@article {pmid39701464,
year = {2024},
author = {Zhang, B and Yuan, F and Zhang, L and Xia, L and Zhu, X and Lu, S and Wang, L and He, Z},
title = {From potential biomarker to clinical predictive models: Integrating socioeconomic status and sleep into leukocyte telomere length of depression and anxiety research.},
journal = {Journal of affective disorders},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jad.2024.12.063},
pmid = {39701464},
issn = {1573-2517},
}

@article {pmid39697975,
year = {2024},
author = {Guillen-Parra, M and Barcenas-Flores, R and Velando, A and Wiley, A and Montoya, B and Torres, R},
title = {Sex-Specific Variation in Foraging Behavior is Related to Telomere Length in a Long-Lived Seabird.},
journal = {Ecology and evolution},
volume = {14},
number = {12},
pages = {e70732},
pmid = {39697975},
issn = {2045-7758},
abstract = {Foraging during breeding is a demanding activity linked to breeding investment and possibly constrained by individual quality. Telomere length, the protective nucleoproteins located at the ends of the chromosomes, is considered a trait reflecting somatic maintenance and individual quality. Therefore, foraging effort and parental investment may be positively related to telomere length, if individuals with longer telomeres are of better quality and thus able to maintain better body condition and allocate more resources to parental activities. In the brown booby (Sula leucogaster), we investigated if telomere length is related to body mass (a proxy of condition) and whether variation in foraging behavior and provisioning effort is related to telomere length or body mass. Then, we explored whether variation in foraging and provisioning influences the chick mass growth rate. In 34 pairs nesting in Isla de San Jorge, in the Gulf of California, México, we sampled their blood to estimate telomere length, measured their body mass, and for 10 days, recorded their foraging behavior via global positioning system (GPS) loggers and their chick provisioning rate and chicks' mass growth rate. We found a positive relationship between parents' body mass and telomere length. Body mass did not affect foraging behavior. Females with longer telomeres were more prone to travel longer distances toward offshore and deeper waters than females with shorter telomeres. In contrast, males with longer telomere lengths performed more nearshore foraging trips than males with shorter telomeres. The chick provisioning rate was unrelated to telomere length or body mass, but females fed the chick at a rate 2.4 times greater than males. Females' offshore foraging, but not males', was positively related to chick mass growth rate. Our results suggest that individual quality, indicated by telomere length, is an important driver of sex-specific, between-individual variation in foraging behavior, indirectly affecting offspring condition.},
}

@article {pmid39695676,
year = {2024},
author = {Skåra, KH and Lee, Y and Jugessur, A and Gjessing, HK and Aviv, A and Brumpton, B and Næss, Ø and Hernáez, Á and Hanevik, HI and Magnus, P and Magnus, MC},
title = {Telomere length in relation to fecundability and use of assisted reproductive technologies: the Norwegian Mother, Father, and Child Cohort Study.},
journal = {BMC medicine},
volume = {22},
number = {1},
pages = {580},
pmid = {39695676},
issn = {1741-7015},
support = {947684//HORIZON EUROPE European Research Council/ ; 947684//HORIZON EUROPE European Research Council/ ; 947684//HORIZON EUROPE European Research Council/ ; 320656//Norges Forskningsråd/ ; 320656//Norges Forskningsråd/ ; 320656//Norges Forskningsråd/ ; 320656//Norges Forskningsråd/ ; 320656//Norges Forskningsråd/ ; 320656//Norges Forskningsråd/ ; 101071773/ERC_/European Research Council/International ; 101071773/ERC_/European Research Council/International ; 101071773/ERC_/European Research Council/International ; 101071773/ERC_/European Research Council/International ; 101071773/ERC_/European Research Council/International ; 101071773/ERC_/European Research Council/International ; R01 1HL134840-01/NH/NIH HHS/United States ; },
mesh = {Humans ; Female ; Norway ; Male ; *Reproductive Techniques, Assisted ; *Fertility/genetics ; Adult ; Cohort Studies ; *Telomere/genetics ; Infertility/genetics ; },
abstract = {BACKGROUND: Telomere length (TL) has been reported to be associated with conditions such as endometriosis and polycystic ovary syndrome, with some studies finding associations with shorter TL and others with longer TL. In men, studies mostly report associations between shorter TL and sperm quality. To our knowledge, no studies have thus far investigated associations between TL and fecundability or the use of assisted reproductive technologies (ART).

METHODS: This study is based on the Norwegian Mother, Father, and Child Cohort (MoBa) Study and uses data from the Medical Birth Registry of Norway (MBRN). We included women (24,645 with genotype data and 1054 with TL measurements) and men (18,339 with genotype data and 965 with TL measurements) participating between 1998 and 2008. We investigated associations between leukocyte TL (LTL) and fecundability (defined as the probability to conceive within a given menstrual cycle), infertility (defined has having spent 12 months or more trying to conceive without success), and ART use. We also repeated the analyses using instrumental variables for LTL consisting of genetic risk scores for LTL and genetically predicted LTL.

RESULTS: Approximately 11% of couples had experienced infertility and 4% had used ART. LTL was not associated with fecundability in women (fecundability ratio [FR], 0.98; 95% confidence interval [CI], 0.92-1.04) or men (FR, 0.99; CI, 0.93-1.06), nor with infertility in women (odds ratio [OR], 1.03; CI, 0.85-1.24) or men (OR, 1.05; CI, 0.87-1.28). We observed an increased likelihood of using ART with increasing LTL in men (OR, 1.22; CI, 1.03-1.46), but not in women (OR, 1.10; CI, 0.92-1.31). No significant associations were observed using the instrumental variables for LTL.

CONCLUSIONS: We found no indication that LTL is a suitable biomarker for assessing fecundability, infertility, or ART use. Additional studies are required to replicate the association observed between LTL and ART use in men.},
}

Humans
Female
Norway
Male
*Reproductive Techniques, Assisted
*Fertility/genetics
Adult
Cohort Studies
*Telomere/genetics
Infertility/genetics

@article {pmid39695460,
year = {2024},
author = {Eren Ozdemir, A},
title = {Evaluation of the effect of melatonin treatment on telomere length of the retinal pigment epithelium in streptozotocin-induced diabetic rat model.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {532},
pmid = {39695460},
issn = {1471-2415},
mesh = {Animals ; *Melatonin/pharmacology/therapeutic use ; *Diabetes Mellitus, Experimental/drug therapy ; *Rats, Sprague-Dawley ; Male ; *Retinal Pigment Epithelium/drug effects/pathology ; *Diabetic Retinopathy/drug therapy ; Rats ; Telomere/drug effects ; Antioxidants/pharmacology ; Streptozocin ; },
abstract = {OBJECTIVES: We aimed to investigate the effect of diabetic retinopathy and melatonin treatment on the relative telomer lengths (RTL) in retinal pigment epithelium (RPE) cells in a streptozotocin-induced diabetic rat model.

BACKGROUND: TL can be used to evaluate diabetes mellitus, its complications, and the effectiveness of its treatment. However, TL assessment has not been performed in retinal cells in a diabetic retinopathy model until now.

METHODS: Forty Sprague-Dawley male rats were randomly divided into four groups. The experimental groups were: Control Group (C): non- diabetic rats; Diabetes Mellitus Group (DM): rats induced to diabetes without treatment; Melatonin and Diabetes Mellitus Group (Mel + DM): rats induced to diabetes and after confirmation, treated with melatonin; Melatonin Group (Mel): rats were not induced to diabetes, treated with melatonin. Diabetes was induced by intraperitoneal administration of streptozotocin solution after 12 h food fasting. For eight weeks after the diabetes was induced, melatonin was administered via subcutaneous injection at a dose of 10 mg / kg. RTLs were measured by qPCR method with modifications. The comparison of averaged data among groups was performed using least significant difference (LSD) and Kruskal - Wallis Test and One way ANOVA test.

RESULTS: RTL was significantly similar in control and melatonin group. RTL was thinnest in DM group, in addition melatonin treatment significantly prevented the RTL shortening in DM + Mel group (p = 0.031).

CONCLUSION: We demonstrated that diabetic retinopathy led to the shortening of RTL in RPE cells in rats and melatonin treatment prevents this shortening.},
}

Animals
*Melatonin/pharmacology/therapeutic use
*Diabetes Mellitus, Experimental/drug therapy
*Rats, Sprague-Dawley
Male
*Retinal Pigment Epithelium/drug effects/pathology
*Diabetic Retinopathy/drug therapy
Rats
Telomere/drug effects
Antioxidants/pharmacology
Streptozocin

@article {pmid39695221,
year = {2024},
author = {Wang, B and Zhang, R and Sun, W and Yang, J},
title = {A nearly telomere-to-telomere diploid genome assembly of Firmiana kwangsiensis, a threatened species in China.},
journal = {Scientific data},
volume = {11},
number = {1},
pages = {1394},
pmid = {39695221},
issn = {2052-4463},
mesh = {*Endangered Species ; *Telomere/genetics ; China ; *Haplotypes ; *Genome, Plant ; Diploidy ; },
abstract = {Firmiana kwangsiensis is a tree species of high ornamental value. The species is critically endangered in the wild, and is listed as a first-class national protected wild plant in China, and a Plant Species with Extremely Small Populations in need of urgent protection. We have assembled a chromosome-scale, haplotype-resolved genome for F. kwangsiensis using a combination of PacBio HiFi sequencing, ONT sequencing, and Hi-C sequencing. The final assembled genome is 2.3 G in size and comprises 2n = 40 chromosomes. All chromosomal ends contain telomeric characteristic motifs (TTTAGGG), and there are only 2 gaps within the rDNA regions, both close to a T2T genome assembly. Two complete sets of haplotypes are present, Haplotype A (1169.19 Mb) and Haplotype B (1157.87 Mb), with contig N50 lengths of 58.37 Mb and 57.27 Mb, respectively. The genome contains a total of 67,527 coding genes, with 62,351 genes functionally annotated here. This is the first report of the genome of F. kwangsiensis, and lays the foundation for future conservation genomics research into this species.},
}

*Endangered Species
*Telomere/genetics
China
*Haplotypes
*Genome, Plant
Diploidy

@article {pmid39695150,
year = {2024},
author = {Zhou, Q and Liu, X and Song, Y and Li, M and Fan, G and Chen, S},
title = {Telomere-to-telomere gapless genome assembly of the giant grouper (Epinephelus lanceolatus).},
journal = {Scientific data},
volume = {11},
number = {1},
pages = {1342},
pmid = {39695150},
issn = {2052-4463},
mesh = {Animals ; *Genome ; *Telomere/genetics ; Bass/genetics ; Chromosomes ; },
abstract = {The giant grouper (Epinephelus lanceolatus) is a large coral reef fish distributed in the Indian Ocean and the Pacific Ocean. With a high market value, this species can grow up to approximately 2.7 meters in length and weigh 440 kilograms. With the rapid development of bioinformatics, higher standards of genome analysis are now required compared to previous reference genomes. This study presents a gapless assembly of the giant grouper genome, which has a length of 1.03 Gb. The sequences were assembled onto 24 chromosomes with a coverage of over 99% (1.02 Gb), and telomeres were detected on 24 chromosomes. Analysis using Merqury indicated a high level of accuracy, with an average consensus quality value of 59.24. The ONT ultralong and PacBio HiFi data were aligned with the assembly using minimap2, resulting in a mapping rate of 99.9%. The study inferred 25,815 protein-coding genes. These results lay a foundation for exploring the evolution and biology of the giant grouper, and advancing molecular breeding techniques.},
}

Animals
*Genome
*Telomere/genetics
Bass/genetics
Chromosomes

@article {pmid39694814,
year = {2024},
author = {Cacchione, S and Cenci, G and Dion-Côté, AM and Barbash, DA and Raffa, GD},
title = {Maintaining Telomeres without Telomerase in Drosophila: Novel Mechanisms and Rapid Evolution to Save a Genus.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041708},
pmid = {39694814},
issn = {1943-0264},
abstract = {Telomere maintenance is crucial for preventing the linear eukaryotic chromosome ends from being mistaken for DNA double-strand breaks, thereby avoiding chromosome fusions and the loss of genetic material. Unlike most eukaryotes that use telomerase for telomere maintenance, Drosophila relies on retrotransposable elements-specifically HeT-A, TAHRE, and TART (collectively referred to as HTT)-which are regulated and precisely targeted to chromosome ends. Drosophila telomere protection is mediated by a set of fast-evolving proteins, termed terminin, which bind to chromosome termini without sequence specificity, balancing DNA damage response factors to avoid erroneous repair mechanisms. This unique telomere capping mechanism highlights an alternative evolutionary strategy to compensate for telomerase loss. The modulation of recombination and transcription at Drosophila telomeres offers insights into the diverse mechanisms of telomere maintenance. Recent studies at the population level have begun to reveal the architecture of telomere arrays, the diversity among the HTT subfamilies, and their relative frequencies, aiming to understand whether and how these elements have evolved to reach an equilibrium with the host and to resolve genetic conflicts. Further studies may shed light on the complex relationships between telomere transcription, recombination, and maintenance, underscoring the adaptive plasticity of telomeric complexes across eukaryotes.},
}

@article {pmid39694812,
year = {2024},
author = {Markiewicz-Potoczny, M and Denchi, EL},
title = {Telomere Protection in Stem Cells.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041686},
pmid = {39694812},
issn = {1943-0264},
abstract = {The natural ends of chromosomes resemble double-strand breaks (DSBs), which would activate the DNA damage response (DDR) pathway without the protection provided by a specialized protein complex called shelterin. Over the past decades, extensive research has uncovered the mechanism of action and the high degree of specialization provided by the shelterin complex to prevent aberrant activation of DNA repair machinery at chromosome ends in somatic cells. However, recent findings have revealed striking differences in the mechanisms of end protection in stem cells compared to somatic cells. In this review, we discuss what is known about the differences between stem cells and somatic cells regarding chromosome end protection.},
}

@article {pmid39694813,
year = {2024},
author = {Ferreira, MG},
title = {Telomere Dynamics in Zebrafish Aging and Disease.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041696},
pmid = {39694813},
issn = {1943-0264},
abstract = {Fish telomere lengths vary significantly across the numerous species, implicating diverse life strategies and environmental adaptations. Zebrafish have telomere dynamics that are comparable to humans and are emerging as a key model in which to unravel the systemic effects of telomere shortening on aging and interorgan communication. Here, we discuss zebrafish telomere biology, focusing on the organismal impact of telomere attrition beyond cellular senescence, with particular emphasis on how telomeric shortening in specific tissues can unleash widespread organ dysfunction and disease. This highlights a novel aspect of tissue communication, whereby telomere shortening in one organ can propagate through biological networks, influencing the aging process systemically. These discoveries position zebrafish as a valuable model for studying the complex interactions between telomeres, aging, and tissue cross talk, providing important insights with direct relevance to human health and longevity.},
}

@article {pmid39693631,
year = {2024},
author = {Su, R and Zhou, H and Yang, W and Moqir, S and Ritu, X and Liu, L and Shi, Y and Dong, A and Bayier, M and Letu, Y and Manxi, X and Chulu, H and Nasenochir, N and Meng, H and Herrid, M},
title = {Near telomere-to-telomere genome assembly of Mongolian cattle: implications for population genetic variation and beef quality.},
journal = {GigaScience},
volume = {13},
number = {},
pages = {},
doi = {10.1093/gigascience/giae099},
pmid = {39693631},
issn = {2047-217X},
support = {//Department of Science and Technology/ ; 2022JBGS0023//Inner Mongolia Autonomous Region/ ; },
mesh = {Animals ; Cattle/genetics ; *Telomere/genetics ; *Genetic Variation ; *Genome ; Molecular Sequence Annotation ; Red Meat/standards ; Genetics, Population ; Whole Genome Sequencing/methods ; Male ; Genomics/methods ; },
abstract = {BACKGROUND: Mongolian cattle, a unique breed indigenous to China, represent valuable genetic resources and serve as important sources of meat and milk. However, there is a lack of high-quality genomes in cattle, which limits biological research and breeding improvement.

FINDINGS: In this study, we conducted whole-genome sequencing on a Mongolian bull. This effort yielded a 3.1 Gb Mongolian cattle genome sequence, with a BUSCO integrity assessment of 95.9%. The assembly achieved both contig N50 and scaffold N50 values of 110.9 Mb, with only 3 gaps identified across the entire genome. Additionally, we successfully assembled the Y chromosome among the 31 chromosomes. Notably, 3 chromosomes were identified as having telomeres at both ends. The annotation data include 54.31% repetitive sequences and 29,794 coding genes. Furthermore, a population genetic variation analysis was conducted on 332 individuals from 56 breeds, through which we identified variant loci and potentially discovered genes associated with the formation of marbling patterns in beef, predominantly located on chromosome 12.

CONCLUSIONS: This study produced a genome with high continuity, completeness, and accuracy, marking the first assembly and annotation of a near telomere-to-telomere genome in cattle. Based on this, we generated a variant database comprising 332 individuals. The assembly of the genome and the analysis of population variants provide significant insights into cattle evolution and enhance our understanding of breeding selection.},
}

Animals
Cattle/genetics
*Telomere/genetics
*Genetic Variation
*Genome
Molecular Sequence Annotation
Red Meat/standards
Genetics, Population
Whole Genome Sequencing/methods
Male
Genomics/methods

@article {pmid39693366,
year = {2024},
author = {Sato, MP and Arafa, RA and Rakha, M and Emeran, AA and Isobe, S and Shirasawa, K},
title = {Near-complete telomere-to-telomere de novo genome assembly in Egyptian clover (Trifolium alexandrinum).},
journal = {DNA research : an international journal for rapid publication of reports on genes and genomes},
volume = {},
number = {},
pages = {},
doi = {10.1093/dnares/dsae036},
pmid = {39693366},
issn = {1756-1663},
abstract = {Egyptian clover (Trifolium alexandrinum L.), also known as berseem clover, is an important forage crop to Semi-arid conditions that was domesticated in ancient Egypt since 6,000 years BC and introduced and well adapted to numerous countries including India, Pakistan, Turkey, and Mediterranean region. Despite its agricultural importance, genomic research on Egyptian clover has been limited to developing efficient modern breeding programs. In the present study, we constructed near-complete telomere-to-telomere-level genome assemblies for two Egyptian clover cultivars, Helaly and Fahl. Initial assemblies were established by using highly-fidelity long-read technology. To extend sequence contiguity, we developed a gap-targeted sequencing (GAP-Seq) method, in which contig ends are targeted for sequencing to obtain long reads bridging two contigs. The total length of the resultant chromosome-level assemblies was 547.7 Mb for Helaly and 536.3 Mb for Fahl. These differences in sequence length can be attributed to the expansion of DNA transposons. Population genomic analysis using single-nucleotide polymorphisms revealed genomic regions highly differentiated between two cultivars and increased genetic uniformity within each cultivar. Gene ontologies associated with metabolic and biosynthetic processes and developmental processes were enriched in these genomic regions, indicating that these genes may determine the unique characteristics of each cultivar. Comprehensive genomic resources can provide valuable insights into genetic improvements in Egyptian clover and legume genomics.},
}

@article {pmid39692822,
year = {2024},
author = {Zhou, K and Liu, X and Wang, M and Duan, J and Zhao, X and Yin, H},
title = {The landscape in telomere related gene prognostic signature for survival and medication treatment effectiveness prediction in hepatocellular carcinoma.},
journal = {Discover oncology},
volume = {15},
number = {1},
pages = {765},
pmid = {39692822},
issn = {2730-6011},
abstract = {OBJECTIVE: Telomeres, made of repetitive DNA sequences and shelterin complexes, which were found at the ends of chromosomes and had been extensively studied in cancer research. However, in hepatocellular carcinoma (HCC) was still relatively scarce. In this study, we investigated the correlation between telomerase-related genes (TRGs) and the prognosis and immunotherapy of HCC patients to enhance clinical outcomes.

METHODS: In this work, TRGs were gathered using TelNet, while clinical information and gene expression data for HCC patients were retrieved from the Cancer Genome Atlas (TCGA) database. A risk prediction model based on TRGs was created using COX and Lasso regression analyses, with ROC curves used to assess prognostic efficacy. Univariate and multifactorial COX regression analyses were used to determine if the risk model had an independent impact on prognosis. Nomograms were created to enhance clinical usability, and calibration curves were used to assess predictive ability at various time points. The Tumor Immune Dysfunction and Exclusion (TIDE) score was used to analyze differences in immune infiltrating cells between risk groups. The study analyzed the relationship between risk ratings and drug treatment effectiveness using data from the CellMiner database. The hub gene was identified and its relationship to prognostic markers of HCC patients was examined. The expression of hub genes in immune cell subpopulations was also investigated by single-cell data.

RESULTS: 2093 TRGs were identified, with 949 showing significant differences in expression between HCC and paracancerous tissues. Seven risk genes were overexpressed in tumor tissues, leading to lower survival rates in high-risk patients. Risk model could independently predict the prognosis of HCC patients. Analysis of tumor immune infiltrating cells revealed significant differences in cell abundance between risk groups, with notable variations in immune subset enrichment between subgroups. Higher risk scores correlated with increased sensitivity to sorafenib, mitoxantrone, oxaliplatin, gemcitabine, and entinostat, while sensitivity decreased for vincristine, etc. CDCA8 was identified as a key gene in the Protein Interaction Network, while high expression associated with poorer overall survival, tumor proliferation and metastasis. The results of single-cell data analysis suggest that CDCA8 may promote the development of HCC by affecting T lymphocytes.

CONCLUSION: The TRG-based risk model could predict HCC patient prognosis and closely linked to tumor immune environment, which could offer new possibilities for clinical treatment.},
}

@article {pmid39689933,
year = {2024},
author = {van Duijvenboden, S and Nelson, CP and Raisi-Estabragh, Z and Ramirez, J and Orini, M and Wang, Q and Aung, N and Codd, V and Stoma, S and Allara, E and Wood, AM and Di Angelantonio, E and Danesh, J and Harvey, NC and Petersen, SE and Munroe, PB and Samani, NJ},
title = {Leucocyte telomere length and conduction system ageing.},
journal = {Heart (British Cardiac Society)},
volume = {},
number = {},
pages = {},
doi = {10.1136/heartjnl-2024-324875},
pmid = {39689933},
issn = {1468-201X},
abstract = {BACKGROUND: Deterioration of the cardiac conduction system is an important manifestation of cardiac ageing. Cellular ageing is accompanied by telomere shortening and telomere length (TL) is often regarded as a marker of biological ageing, potentially adding information regarding conduction disease over and above chronological age. We therefore sought to evaluate the association between leucocyte telomere length (LTL) on two related, but distinct aspects of the cardiac conduction system: ECG measures of conduction (PR interval and QRS duration) and incident pacemaker implantation in a large population-based cohort.

METHODS: In the UK Biobank, we measured PR interval and QRS duration from signal-averaged ECG waveforms in 59 868 and 62 266 participants, respectively. Incident pacemaker implantation was ascertained using hospital episode data from 420 071 participants. Associations with LTL were evaluated in (Cox) multivariable regression analyses adjusted for potential confounders. Putative causal effects of LTL were investigated by mendelian randomisation (MR).

RESULTS: Mean PR interval and QRS duration were 144.2 ms (± 20.4) and 92.3 ms (± 7.8), respectively, and there were 7169 (1.7%) incident pacemaker implantations, during a median follow-up period of 13.6 (IQR 1.5) years. LTL was significantly associated with PR interval (0.19 ms (95% CI: 0.03 to 0.35), per 1 SD shorter LTL, p=0.021), but not QRS duration. After adjusting for age, sex and cardiovascular risk factors, shorter LTL remained associated with an increased risk for incident pacemaker implantation (HR per SD decrease in LTL: 1.03 (95% CI: 1.01 to 1.06), p=0.012). MR analysis showed a trend towards an association of shorter LTL with longer PR interval and higher risk of pacemaker implantation but was likely to be underpowered.

CONCLUSIONS: Shorter LTL was significantly, and possibly causally, associated with prolongation of atrioventricular conduction and pacemaker implantation, independent of traditional cardiovascular risk factors. Our findings support further research to explore the role of ageing on cardiac conduction beyond chronological age.},
}

@article {pmid39689244,
year = {2024},
author = {Pickler, RH and Ford, JL and Tan, A and Browning, C and Tarrence, J and Kertes, DA},
title = {Childhood Adversity and Telomere Length.},
journal = {Biological research for nursing},
volume = {},
number = {},
pages = {10998004241309368},
doi = {10.1177/10998004241309368},
pmid = {39689244},
issn = {1552-4175},
abstract = {Purpose: Exposure to adversity during childhood and adolescence is associated with numerous health conditions in adulthood; telomere shortening may be a mechanism through which adversity contributes to poor outcomes. We studied three areas of adversity (parent relational instability, child household instability, and financial instability) occurring during three epochs across childhood and adolescence and their associations with telomere length during adolescence. Methods: Data were obtained from the first wave of a longitudinal cohort study of youth aged 11-17 and their primary caregiver. Caregivers completed demographic and adversity questionnaires; youth provided a saliva sample for DNA extraction for telomere analysis. Results: Of 879 youth, over half experienced some adversity. More than one third experienced parent relational instability in each age epoch, with nearly a quarter experiencing parent relational instability in all age epochs. Youth experienced a similar pattern of financial instability but lower rates of child household instability. Youth experiencing parent relational instability at two or three epochs had shorter telomeres compared to those without any parent relational instability (p < .004). Youth who experienced child household instability in two age epochs had shorter telomeres (p = .003) and youth who experienced financial instability across all three epochs had shorter telomeres (p = .013) compared to youth without these adversities. Conclusion: Continuing exposure to adversity in early childhood may be more likely to affect telomere length. Research is needed to further determine adversities exerting the most effect and to understand if early telomere shortening has long term health effects.},
}

@article {pmid39688874,
year = {2024},
author = {Olsson, M and Miller, E and Rollings, N and Lillie, M and Hufton, J and Hansson, A and Wapstra, E},
title = {The effects of costly telomere maintenance on lifespan - reproductive tradeoffs in sand lizards.},
journal = {Evolution; international journal of organic evolution},
volume = {},
number = {},
pages = {},
doi = {10.1093/evolut/qpae181},
pmid = {39688874},
issn = {1558-5646},
abstract = {Telomeres are DNA-protein structures that primarily protect chromosomes and serve multiple functions of gene regulation. When cells divide, telomeres shorten and their main repair system in ectotherms - telomerase - replaces lost nucleotide complexes ((T2AG3)n in vertebrates). It remains a challenge to experimentally investigate resource requirements for telomere maintenance and its effects on lifespan-reproductive tradeoffs in the wild. In sand lizards (Lacerta agilis), we show that higher female investments into reproduction results in corresponding shortening of telomeres and that males have less frequent and less profound telomere shortening than females; a contributing factor to this may be males' higher telomerase levels. To manipulate resource access for telomere maintenance, we exploit a pseudo-experimental opportunity to analyze 'onboard' resources long-term using lizards that drop their tails with fat and nutrient deposits when attacked by predators. Females with less resources due to regrown tails less often and less profoundly elongate telomeres. Adult lizards with the most TL elongation live the longest, females with the highest lifetime reproductive success shorten telomeres the most, whereas males with the most telomere elongation have the highest lifetime reproductive success. This suggests ongoing evolution of resource-constrained telomere maintenance.},
}

@article {pmid39681615,
year = {2024},
author = {Weisert, N and Majewski, V and Hartleb, L and Luko, K and Lototska, L and Krapoth, NC and Ulrich, HD and Janzen, CJ and Butter, F},
title = {TelAP2 links TelAP1 to the telomere complex in Trypanosoma brucei.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {30493},
pmid = {39681615},
issn = {2045-2322},
mesh = {*Trypanosoma brucei brucei/genetics/metabolism ; *Telomere/metabolism/genetics ; *Protozoan Proteins/metabolism/genetics ; Telomere-Binding Proteins/metabolism/genetics ; Variant Surface Glycoproteins, Trypanosoma/genetics/metabolism ; Protein Binding ; Proteomics/methods ; },
abstract = {The extracellular parasite Trypanosoma brucei evades the immune system of the mammalian host by periodically exchanging its variant surface glycoprotein (VSG) coat. Hereby, only one VSG gene is transcribed from one of 15 subtelomeric so-called bloodstream form expression sites (BES) at any given timepoint, while all other BESs are silenced. VSG gene expression is altered by homologous recombination using a large VSG gene repertoire or by a so-called in situ switch, which activates a previously silent BES. Transcriptional activation, VSG switching and VSG silencing during developmental differentiation from the bloodstream form to the procyclic form present in the tsetse fly vector are tightly regulated. Due to their subtelomeric position, telomere-associated proteins are involved in the regulation of VSG expression. Three functional homologs of mammalian telomere complex proteins have been characterized thus far, and novel telomere-interacting proteins, such as telomere-associated protein 1 (TelAP1), have recently been identified. Here, we used mass spectrometry-based proteomics and interactomics approaches, telomere pull-down assays with recombinant material and immunofluorescence analysis to elucidate the interactions of 21 other putative TelAPs. We investigated the influence on VSG expression and showed that depletion of TelAPs does not ultimately lead to changes in VSG expression. Additionally, we examined the interaction patterns of four TelAPs with the TbTRF/TbTIF2/TbRAP1 telomere complex by reciprocal affinity purification. We further propose that TelAP1 interacts with Tb927.6.4330, now called TelAP2, and that TelAP1 depends on this interaction to form a complex with the telomeric proteins TbTRF, TbTIF2 and TbRAP1.},
}

*Trypanosoma brucei brucei/genetics/metabolism
*Telomere/metabolism/genetics
*Protozoan Proteins/metabolism/genetics
Telomere-Binding Proteins/metabolism/genetics
Variant Surface Glycoproteins, Trypanosoma/genetics/metabolism
Protein Binding
Proteomics/methods

@article {pmid39680438,
year = {2024},
author = {Pearce, EE and Majid, A and Brown, T and Shepherd, RF and Rising, C and Wilsnack, C and Thompson, AS and Gilkey, MB and Ribisl, KM and Lazard, AJ and Han, PK and Werner-Lin, A and Hutson, SP and Savage, SA},
title = {"Crying in the Wilderness"-The Use of Web-Based Support in Telomere Biology Disorders: Thematic Analysis.},
journal = {JMIR formative research},
volume = {8},
number = {},
pages = {e64343},
doi = {10.2196/64343},
pmid = {39680438},
issn = {2561-326X},
mesh = {Humans ; Female ; Male ; Middle Aged ; Adult ; Aged ; *Qualitative Research ; *Internet ; *Social Support ; Information Seeking Behavior ; Telomere/genetics ; Caregivers/psychology ; },
abstract = {BACKGROUND: Web-based information and social support are commonly used in rare disease communities where geographic dispersion and limited provider expertise complicate in-person support. We examined web-based resource use among caregivers of individuals with telomere biology disorders (TBDs), which are rare genetic conditions with long diagnostic odysseys and uncertain prognoses including multiorgan system cancer risk.

OBJECTIVE: This study explored internet-based information-seeking and social support practices and perspectives of patients with TBDs and their caregivers.

METHODS: Our qualitative descriptive study used semistructured interviews of patients with TBDs and caregivers. Data were transcribed verbatim and thematically analyzed by an interdisciplinary team.

RESULTS: A total of 32 adults completed interviews. Participant ages ranged from 27 to 74 years. The majority (n=28, 88%) were female, occupied multiple TBD roles (eg, patient and parent), and had undergone genetic testing. Most engaged in web-based information-seeking (n=29, 91%) and TBD-specific social media (n=26, 81%). Participants found web-based resources useful for information-seeking but reported privacy concerns and frustration with forming supportive relationships. Most participants described ambivalence toward web-based resource use, citing tensions between hunger for information versus distrust, empowerment versus overwhelm, disclosure versus privacy, and accessibility versus connection. Fluctuations in web-based support use arose from perceived harms, information saturation, or decreased relevance over the course of TBD illness experience.

CONCLUSIONS: Individuals with TBDs and their caregivers reported frequent use of web-based informational and emotional support. However, ambivalence about the benefits and liabilities of web-based resources and persistent medical uncertainty may impact the adoption of and adherence to web-based support among patients with TBD and caregivers. Our findings suggest web-based psychosocial support should target long-term and multifaceted informational and emotional needs, be user-initiated, be offered alongside in-person formats, provide expert-informed information, and be attentive to personal privacy and evolving support needs of the TBD community. This study suggests web-based resources will be most effective in the TBD context when they achieve the following features: (1) offer a variety of ways to engage (eg, active and passive), (2) provide privacy protections in moderated "safe spaces" designed for personal disclosure, (3) offer separate venues for informational versus emotional support, (4) combine web-based relationship formation with opportunities for in-person gathering, (5) provide information that is reliable, easy to access, and informed by medical professionals, (6) remain mindful of user distress, and (7) are responsive to variations in levels and types of engagement. Additionally, advocacy organizations may wish to avoid traditional social media platforms when designing safe spaces for web-based emotional support, instead pivoting to internet-based tools that minimize privacy threats and limit the perpetual public availability of shared information.},
}

Humans
Female
Male
Middle Aged
Adult
Aged
*Qualitative Research
*Internet
*Social Support
Information Seeking Behavior
Telomere/genetics
Caregivers/psychology

@article {pmid39675625,
year = {2024},
author = {Xie, JW and Wang, HL and Lin, LQ and Guo, YF and Wang, M and Zhu, XZ and Niu, JJ and Lin, LR},
title = {Telomere-Methylation Genes: Novel Prognostic Biomarkers for Hepatocellular Carcinoma.},
journal = {Clinics and research in hepatology and gastroenterology},
volume = {},
number = {},
pages = {102516},
doi = {10.1016/j.clinre.2024.102516},
pmid = {39675625},
issn = {2210-741X},
abstract = {BACKGROUND: Since telomere length and DNA methylation both correlate with hepatocellular carcinoma (HCC) prognosis, telomere-methylation genes could be novel prognostic markers for HCC.

METHOD: This study first investigated the interaction between telomere length and DNA methylation in HCC through Mendelian randomization analysis. Then, this study identified telomere-methylation genes in HCC by employing the TCGA-LIHC cohort, and explored the expression patterns of these genes in the tumor microenvironment of HCC and potential underlying mechanisms. Finally, the HCC risk-scoring model and prognostic model based on these genes were established, and the performance of the model was assessed.

RESULT: The findings revealed a bidirectional relationship between telomere length and DNA methylation in HCC. Fifty telomere-methylation genes were identified, and the prognosis-related telomere-methylation genes were closely associated with Treg and Tprolif cell subsets within the HCC tumor microenvironment. Telomere-methylation genes could potentially impact the prognosis of HCC patients by modulating chromosome stability and regulating the cell cycle. Additionally, the constructed risk scoring model and prognostic prediction model showcased compelling clinical applicability, as evidenced by the receiver operating characteristic curve, the decision curve analysis, and the calibration curves.

CONCLUSION: This study elucidated the potential of telomere-methylation genes as prognostic biomarkers for HCC and paves the way for novel approaches in prognostication and treatment management for HCC patients.},
}

@article {pmid39667908,
year = {2024},
author = {Jung, JH and Byun, MS and Yi, D and Ahn, H and Lee, JH and Lee, JS and Lee, HS and Lee, JY and Kim, YK and Lee, YS and Kang, KM and Sohn, CH and Lee, DY and , },
title = {Telomere length, in vivo Alzheimer's disease pathologies and cognitive decline in older adults.},
journal = {Journal of neurology, neurosurgery, and psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1136/jnnp-2024-334314},
pmid = {39667908},
issn = {1468-330X},
abstract = {BACKGROUND: Whether telomere length (TL), an indicator of biological ageing, reflects Alzheimer's disease (AD)-related neuropathological change remains unclear. We investigated the relationships between TL, in vivo AD pathologies, including cerebral beta-amyloid and tau deposition, and cognitive outcomes in older adults.

METHODS: A total of 458 older adults were included, encompassing both cognitively normal (CN) individuals and those cognitively impaired (CI), with the CI group consisting of individuals with mild cognitive impairment or AD dementia. All participants underwent clinical and neuropsychological assessments, amyloid positron emission tomography (PET) scan and DNA extraction for measuring TL at baseline. A subset of participants (n=140) underwent tau PET scan. At follow-up, the participants underwent neuropsychological assessments annually for up to 4 years.

RESULTS: Overall, longer TL was associated with greater brain tau deposition (B=0.139, 95% CI 0.040, 0.238) and a faster decline in global cognition (B = - 0.371, 95% CI - 0.720, -0.023). In the subgroup analysis, the association between longer TL and greater in vivo AD pathologies, as well as faster cognitive decline, was observed particularly in the CI group. Mediation analysis suggested that longer TL was associated with cognitive decline through increased tau deposition in the CI group.

CONCLUSION: Our finding suggests that older adults with relatively longer TL, particularly in the CI group, may have greater in vivo AD pathologies and experience more rapid cognitive decline, potentially mediated by brain tau deposition. Further studies are necessary to elucidate the biological links underlying these associations.},
}

@article {pmid39665795,
year = {2024},
author = {Ying, C and Han, C and Li, Y and Zhang, M and Xiao, S and Zhao, L and Zhang, H and Yu, Q and An, J and Mao, W and Cai, Y},
title = {Plasma circulating cell-free DNA integrity and relative telomere length as diagnostic biomarkers for Parkinson's disease and multiple system atrophy: a cross-sectional study.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-24-00599},
pmid = {39665795},
issn = {1673-5374},
abstract = {In clinical specialties focusing on neurological disorders, there is a need for comprehensive and integrated non-invasive, sensitive, and specific testing methods. Both Parkinson's disease and multiple system atrophy are classified as α-synucleinopathies, characterized by abnormal accumulation of α-synuclein protein, which provides a shared pathological background for their comparative study. In addition, both Parkinson's disease and multiple system atrophy involve neuronal death, a process that may release circulating cell-free DNA (cfDNA) into the bloodstream, leading to specific alterations. This premise formed the basis for investigating cell-free DNA as a potential biomarker. Cell-free DNA has garnered attention for its potential pathological significance, yet its characteristics in the context of Parkinson's disease and multiple system atrophy are not fully understood. This study investigated the total concentration, nonapoptotic level, integrity, and cell-free DNA relative telomere length of cell-free DNA in the peripheral blood of 171 participants, comprising 76 normal controls, 62 patients with Parkinson's disease, and 33 patients with multiple system atrophy. In our cohort, 75.8% of patients with Parkinson's disease (stage 1-2 of Hoehn & Yahr) and 60.6% of patients with multiple system atrophy (disease duration less than 3 years) were in the early stages. The diagnostic potential of the cell-free DNA parameters was evaluated using receiver operating characteristic (ROC) analysis, and their association with disease prevalence was examined through logistic regression models, adjusting for confounders such as age, sex, body mass index, and education level. The results showed that cell-free DNA integrity was significantly elevated in both Parkinson's disease and multiple system atrophy patients compared with normal controls (P < 0.001 for both groups), whereas cell-free DNA relative telomere length was markedly shorter (P = 0.003 for Parkinson's disease and P = 0.010 for multiple system atrophy). Receiver operating characteristic analysis indicated that both cell-free DNA integrity and cell-free DNA relative telomere length possessed good diagnostic accuracy for differentiating Parkinson's disease and multiple system atrophy from normal controls. Specifically, higher cell-free DNA integrity was associated with increased risk of Parkinson's disease (odds ratio [OR]: 5.72; 95% confidence interval [CI]: 1.54-24.19) and multiple system atrophy (OR: 10.10; 95% CI: 1.55-122.98). Conversely, longer cell-free DNA relative telomere length was linked to reduced risk of Parkinson's disease (OR: 0.16; 95% CI: 0.04-0.54) and multiple system atrophy (OR: 0.10; 95% CI: 0.01-0.57). These findings suggest that cell-free DNA integrity and cell-free DNA relative telomere length may serve as promising biomarkers for the early diagnosis of Parkinson's disease and multiple system atrophy, potentially reflecting specific underlying pathophysiological processes of these neurodegenerative disorders.},
}

@article {pmid39664691,
year = {2024},
author = {Wang, J and Xu, D and Sang, YL and Sun, M and Liu, C and Niu, M and Li, Y and Liu, L and Han, X and Li, J},
title = {A telomere-to-telomere gap-free reference genome of Chionanthus retusus provides insights into the molecular mechanism underlying petal shape changes.},
journal = {Horticulture research},
volume = {11},
number = {12},
pages = {uhae249},
pmid = {39664691},
issn = {2662-6810},
abstract = {Chionanthus retusus, an arbor tree of the Oleaceae family, is an ecologically and economically valuable ornamental plant for its remarkable adaptability in landscaping. During C. retusus breeding, we observed diverse floral shapes; however, no available genome for C. retusus has hindered the widespread identification of genes related to flower morphology. Thus, a de novo telomere-to-telomere (T2T) gap-free genome was generated. The assembly, incorporating high-coverage and long-read sequencing data, successfully yielded two complete haplotypes (687 and 683 Mb). The genome encompasses 42 864 predicted protein-coding genes, with all 46 telomeres and 23 centromeres in one haplotype. Whole-genome duplication analysis revealed that C. retusus underwent one fewer event of whole-genome duplication after differentiation compared to other species in the Oleaceae family. Furthermore, flower vein diversity was the main reason for the differences in floral shapes. Auxin-related genes were responsible for petal shape formation on genome-based transcriptome analysis. Specifically, the removal and retention of the first intron in CrAUX/IAA20 resulted in the production of two transcripts, and the differences in the expression levels of CrAUX/IAA20 resulted in the variations of flower veins. Compared to transcripts lacking the first intron, transcripts with intron retention caused more severe decreases in the number and length of flower veins in transgenic Arabidopsis thaliana. Our findings will deepen our understanding of flower morphology development and provide important theoretical support for the cultivation of Oleaceae.},
}

@article {pmid39662066,
year = {2024},
author = {Fragkiadaki, P and Apetroaei, MM and Kouvidi, E and Vakonaki, E and Renieri, E and Fragkiadoulaki, I and Spanakis, M and Baliou, S and Alegakis, A and Tsatsakis, A},
title = {The association between short telomere length and cardiovascular disease.},
journal = {Cytogenetic and genome research},
volume = {},
number = {},
pages = {1-18},
doi = {10.1159/000542795},
pmid = {39662066},
issn = {1424-859X},
abstract = {INTRODUCTION: Telomeres, repetitive DNA sequences at chromosome ends, shorten with cell division, countered by telomerase. Short telomeres are linked to cardiovascular disease (CVD), alongside its risk factors like aging, hypertension, diabetes, obesity, inactivity, and smoking. Many studies have claimed the implication of TL in cardiac diseases. This study examines telomere length's (TL) impact on heart conditions using quantitative fluorescence in situ hybridization (Q-FISH) technology.

METHODS: Thirteen CVD patients (nine men and four women) aged 30 to 70 years and aged-matched healthy participants from BIOTEL population TL database, were included in the study. Each chromosome's TL from peripheral blood cells (PBCs) was measured using metaphase Q-FISH. An independent samples t-test was used to compare participants' mean or median TL with various medical factors and habits Results: The mean TL of whole and short telomeres in cardiac disease patients was lower compared to aged-matched healthy controls; however, there was no statistical significance due to the limited patient sample. The mean TL of short telomeres in cardiac disease patients showed a remarkable decline with advanced age. Accordingly, the mean TL of whole and short telomeres in patients with cardiac diseases showed a similar reduced trend.

CONCLUSION: In our study, shorter TL was observed in cardiac disease patients compared to those of healthy controls by using metaphase Q-FISH. However, more cases need to be studied to elucidate the use of TL as a potential biomarker for the diagnosis of patients with CVD.},
}

@article {pmid39661724,
year = {2024},
author = {Peng, D and Hong, Z and Kan, S and Wu, Z and Liao, X},
title = {The telomere-to-telomere (T2T) genome provides insights into the evolution of specialized centromere sequences in sandalwood.},
journal = {GigaScience},
volume = {13},
number = {},
pages = {},
doi = {10.1093/gigascience/giae096},
pmid = {39661724},
issn = {2047-217X},
support = {2021QN02N792//Guangdong Provincial Pearl River Talents Program/ ; 110243160001007//Chinese Academy of Agricultural Sciences/ ; JCYJ20220818103212025//Shenzhen Fundamental Research Program/ ; },
mesh = {*Centromere/genetics ; *Telomere/genetics ; *Genome, Plant ; *Evolution, Molecular ; Chromosomes, Plant ; Genomics/methods ; },
abstract = {BACKGROUND: Sandalwood, a prized hemiparasitic plant, is highly sought in the commercial market because of its aromatic core materia. The structure and stability of the genome are instrumental in the rapid adaptation of parasitic plants to their surroundings. However, there is a conspicuous lack of research on the genomic-level adaptive evolution of sandalwood.

RESULTS: In this study, we assembled a gap-free telomere-to-telomere (T2T) reference genome for Santalum album using PacBio HiFi, Hi-C, and ultra-long ONT data. The T2T reference genome (Sal_t2t) encompassed annotations of 24,171 genes and 25.34% repetitive sequences, in addition to all 10 centromeres and 20 telomeres across the 10 chromosomes. The results revealed that the 3 distinct parasitic species of Santalales had diverse centromeric compositions. The Copia-type long terminal repeat transposon emerged as the most significant in the S. album genome, constituting the primary sequence of the centromere and influencing gene expression. Third, in sandalwood, the presence of Copia affected the size of the centromeres and, consequently, the genome size. Identification of the sandalwood T2T genome in this study also enabled the identification of more precise organelle transfer fragments.

CONCLUSIONS: Our research provides a sandalwood T2T genome, laying the groundwork for future investigations on the evolution of energy organs in parasitic plants. Moreover, it offers novel insights into the function and evolution of centromeres, as well as the mechanisms of adaptation and parasitism.},
}

*Centromere/genetics
*Telomere/genetics
*Genome, Plant
*Evolution, Molecular
Chromosomes, Plant
Genomics/methods

@article {pmid39661387,
year = {2024},
author = {Niewisch, MR and Kim, J and Giri, N and Lunger, JC and McReynolds, LJ and Savage, SA},
title = {Genotype and Associated Cancer Risk in Individuals With Telomere Biology Disorders.},
journal = {JAMA network open},
volume = {7},
number = {12},
pages = {e2450111},
doi = {10.1001/jamanetworkopen.2024.50111},
pmid = {39661387},
issn = {2574-3805},
mesh = {Humans ; Male ; Female ; Adult ; *Neoplasms/genetics/epidemiology ; Longitudinal Studies ; Middle Aged ; Genotype ; Telomere/genetics ; Aged ; Risk Factors ; Genetic Predisposition to Disease ; Bone Marrow Failure Disorders/genetics ; Incidence ; Young Adult ; Adolescent ; },
abstract = {IMPORTANCE: Telomere biology disorders (TBDs) are inherited cancer-prone bone marrow failure syndromes with differences in morbidity and mortality based on mode of inheritance.

OBJECTIVE: To quantify cancer risks in TBDs by genetic subgroups.

This longitudinal cohort study of TBDs assessed cancer occurrences from 2002 through 2022. Participants were individuals with a TBD-associated pathogenic germline variant recruited across institutions by self-referral. Data were collected and analyzed through June 30, 2022.

EXPOSURES: The exposure was TBD genotypes, with subgroups defined by inheritance pattern (autosomal-dominant [AD-non-TINF2] vs autosomal-recessive/X-linked [AR/XLR] vs AD-TINF2).

MAIN OUTCOMES AND MEASURES: The main outcome was cancer; secondary outcomes included death, or organ transplant. Cumulative cancer incidence was determined considering death or transplant as competing events. Observed:expected (O:E) ratios of cancer before and after any organ transplant were calculated using the National Cancer Institute's Surveillance, Epidemiology, and End Results Program.

RESULTS: Among 230 individuals with TBD (135 [58.7%] male; median [range] age at last follow-up, 34.6 [1.4-82.2] years) included, the risk of cancer was 3-fold higher than the general population (O:E, 3.35 [95% CI, 2.32-4.68]). The highest risk was observed in individuals with AR/XLR (O:E, 19.16 [95% CI, 9.19-35.24]) with a significantly younger cancer onset than in individuals with AD-non-TINF2 (median [range] age, 36.7 [25.2-53.6] years vs 44.5 [32.2-67.5] years; P = .01). The risk of solid tumors was highest in individuals with AR/XLR (O:E = 23.97 [95% CI, 10.96-45.50]), predominantly head and neck squamous cell carcinomas (O:E, 276.00 [95% CI, 75.20-706.67]). Hematologic malignant neoplasm risk was highest in individuals with AD-non-TINF2 (O:E, 9.41 [95% CI, 4.30-17.86]). Solid tumor cumulative incidence increased to 12% for individuals with AR/XLR by age 45 years and to 13% for individuals with AD-non-TINF2 by age 70 years. The cumulative incidence of hematologic malignant neoplasms leveled off at 2% by age 30 years and 19% by age 70 years in individuals with AR/XLR and AD-non-TINF2, respectively. Individuals with AD-TINF2 showed the highest cumulative incidence for transplant or death (49% by age 15 years). Following transplant, individuals with AR/XLR (O:E, 136.11 [95% CI, 54.72-280.44) or AD-TINF2 (O:E, 81.07 [95% CI, 16.72-236.92]) had the highest cancer risk, predominantly young-onset head and neck squamous cell carcinomas (median [range] age, 32.2 [10.5-35.5] years).

CONCLUSIONS AND RELEVANCE: This cohort study of individuals with TBDs found an increased cancer risk compared with the general population, with the earliest age at onset for individuals with AR/XLR inheritance. Cancer risks increased after organ transplant across all subgroups. These differences in TBD-associated cancer risks by mode of inheritance suggest cancer screening could be tailored by genotype, but additional research is warranted.},
}

Humans
Male
Female
Adult
*Neoplasms/genetics/epidemiology
Longitudinal Studies
Middle Aged
Genotype
Telomere/genetics
Aged
Risk Factors
Genetic Predisposition to Disease
Bone Marrow Failure Disorders/genetics
Incidence
Young Adult
Adolescent

@article {pmid39658339,
year = {2024},
author = {Lame-Jouybari, AH and Fahami, MS and Hosseini, MS and Moradpour, M and Hojati, A and Abbasalizad-Farhangi, M},
title = {Association Between Maternal Prepregnancy and Pregnancy Body Mass Index and Children's Telomere Length: A Systematic Review and Meta-analysis.},
journal = {Nutrition reviews},
volume = {},
number = {},
pages = {},
doi = {10.1093/nutrit/nuae187},
pmid = {39658339},
issn = {1753-4887},
support = {75731//Tabriz University of Medical Sciences/ ; },
abstract = {CONTEXT: Telomeres maintain chromosome stability and mark cellular aging, and their shortening with age compromises genomic stability.

OBJECTIVE: The purpose of this study was to conduct a meta-analysis of existing evidence to evaluate the relationship between the maternal pregnancy body mass index (BMI) and children's telomere length (TL).

DATA SOURCE: Web of Science, Scopus, and PubMed databases were systematically searched from their inception to August 27, 2023, for pertinent observational studies.

DATA EXTRACTION: The random-effects meta-analysis was conducted on eligible studies that investigated the linear relationship between exposure and the outcomes of interest, utilizing the reported β-coefficient. Cochran's Q test and I2 statistics were used to assess heterogeneity.

DATA ANALYSIS: A significant association was observed between maternal pregnancy BMI and children's TL (32 studies, pooled effect size [ES]: -0.04; 95% CI: -0.06 to -0.01; I2 = 47.51%, P < .001) and maternal prepregnancy BMI and children's TL at birth (16 studies; pooled ES: -0.05; 95% CI: -0.08 to -0.02; I2 = 53.49%, P < .001).

CONCLUSION: The findings indicate an inverse association between maternal prepregnancy BMI and TL in infants, which is evident within the normal to obese BMI range. This underscores the significance of maternal weight status before pregnancy as a determinant of offspring TL.

PROSPERO registration no. CRD42023466425.},
}

@article {pmid39653745,
year = {2024},
author = {Banu, S and Mk, K and George, JK and Siby, E and Bhagat, R and Ms, S and Patil, SJ and Phadke, SR and Sowpati, DT and Tallapaka, KB},
title = {Enhanced resolution of optical genome mapping utilizing telomere-to-telomere reference in genetic disorders.},
journal = {European journal of human genetics : EJHG},
volume = {},
number = {},
pages = {},
pmid = {39653745},
issn = {1476-5438},
abstract = {Reference genomes serve as a baseline criterion for comparison of personal genomes to deduce clinical variants. The widely used reference genome, GRCh38, contains stretches of gaps and unresolved bases particularly in complex regions which could obscure variant discovery. In contrast, the gapless telomere-to-telomere CHM13 (T2T-CHM13) reference genome can be used to assess difficult regions of the genome. Optical genome mapping (OGM), an imaging technique for structural variation identification has improved resolution compared to traditional cytogenetic methods. Our study showcases the utility of the T2T-CHM13 reference genome for enhanced structural variant (SV) detection in complex regions. We illustrate this through two clinical cases, where improved alignment with T2T-CHM13 led to significantly higher confidence scores for critical SVs. We demonstrate improved clinical diagnostic outcomes with the updated T2T-CHM13 reference and advocate its adoption.},
}

@article {pmid39652599,
year = {2024},
author = {Syed, S and Aloe, S and Sutherland, JH and Holloman, WK and Lue, NF},
title = {Ustilago maydis Trf2 ensures genome stability by antagonizing Blm-mediated telomere recombination: Fine-tuning DNA repair factor activity at telomeres through opposing regulations.},
journal = {PLoS genetics},
volume = {20},
number = {12},
pages = {e1011515},
doi = {10.1371/journal.pgen.1011515},
pmid = {39652599},
issn = {1553-7404},
abstract = {TRF2 is an essential and conserved double-strand telomere binding protein that stabilizes chromosome ends by suppressing DNA damage response and aberrant DNA repair. Herein we investigated the mechanisms and functions of the Trf2 ortholog in the basidiomycete fungus Ustilago maydis, which manifests strong resemblances to metazoans with regards to the telomere and DNA repair machinery. We showed that UmTrf2 binds to Blm in vitro and inhibits Blm-mediated unwinding of telomeric DNA substrates. Consistent with a similar inhibitory activity in vivo, over-expression of Trf2 induces telomere shortening, just like deletion of blm, which is required for efficient telomere replication. While the loss of Trf2 engenders growth arrest and multiple telomere aberrations, these defects are fully suppressed by the concurrent deletion of blm or mre11 (but not other DNA repair factors). Over-expression of Blm alone triggers aberrant telomere recombination and the accumulation of aberrant telomere structures, which are blocked by concurrent Trf2 over-expression. Together, these findings highlight the suppression of Blm as a key protective mechanism of Trf2. Notably, U. maydis harbors another double-strand telomere-binding protein (Tay1), which promotes Blm activity to ensure efficient replication. We found that deletion of tay1 partially suppresses the telomere aberration of Trf2-depleted cells. Our results thus point to opposing regulation of Blm helicase by telomere proteins as a strategy for optimizing both telomere maintenance and protection. We also show that aberrant transcription of both telomere G- and C-strand is a recurrent phenotype of telomere mutants, underscoring another potential similarity between double strand breaks and de-protected telomeres.},
}

@article {pmid39650708,
year = {2024},
author = {Wang, J and Xie, F and Zhu, W and Ye, D and Xiao, Y and Shi, M and Zeng, R and Bian, J and Xu, X and Chen, L and Zhu, A and Zhu, K and Fan, T and Liu, B and Xiao, L and Zhang, X},
title = {Relationship between serum carotenoids and telomere length in overweight or obese individuals.},
journal = {Frontiers in nutrition},
volume = {11},
number = {},
pages = {1479994},
doi = {10.3389/fnut.2024.1479994},
pmid = {39650708},
issn = {2296-861X},
abstract = {BACKGROUND: Previous researches have demonstrated an association between carotenoids and elongated telomeres. Nonetheless, there is scant scientific evidence examining this relationship in individuals who are overweight or obese, a demographic more predisposed to accelerated aging. This study aims to elucidate the correlation between serum carotenoid concentrations and telomere length within this population group.

METHODS: Data were sourced from the 2001-2002 National Health and Nutrition Examination Survey, encompassing 2,353 overweight or obese participants. The levels of α-carotene, β-carotene (both trans and cis isomers), β-cryptoxanthin, lutein/zeaxanthin, and trans-lycopene were quantified via high-performance liquid chromatography. Telomere length was assessed using quantitative polymerase chain reaction.

RESULTS: Following adjustment for potential confounders, telomere length exhibited an increase of 1.83 base pairs (bp) per unit elevation in β-carotene levels (β = 1.83; 95% CI: 0.48, 3.18). Within the fully adjusted model, telomere length incremented by 1.7 bp per unit increase in serum β-carotene among overweight individuals (β = 1.7; 95% CI: 0.1, 3.3), and by 2.6 bp per unit increase among obese individuals (β = 2.6; 95% CI: 0.1, 5.0). Furthermore, restricted cubic spline analysis revealed a linear relationship between β-carotene levels and telomere length, whereas a non-linear association was observed between β-cryptoxanthin levels and telomere length.

CONCLUSION: This investigation indicates that higher serum β-carotene concentrations are linked with extended telomere length in overweight and obese populations in the United States. These findings warrant further validation through prospective studies.},
}

@article {pmid39647990,
year = {2024},
author = {Yang, H and Chen, L and Liu, Y},
title = {Association of leukocyte telomere length with the risk of digestive diseases: A large-scale cohort study.},
journal = {Chinese medical journal},
volume = {},
number = {},
pages = {},
pmid = {39647990},
issn = {2542-5641},
abstract = {BACKGROUND: Leukocyte telomere length (LTL) shortening, a biomarker of telomere attrition, has been linked to multiple diseases. However, the relationship between LTL and digestive diseases remains uncertain. This study aimed to investigate the association between LTL and the risk of digestive diseases.

METHODS: A cohort analysis of over 500,000 participants from the UK Biobank (UKB) between 2006 and 2021 was conducted to estimate the associations of LTL with more than 90 common digestive diseases. LTL was quantified using multiplex quantitative polymerase chain reaction, and cases of each disease were determined according to inpatient and primary care data. Multivariable Cox proportional hazards regression analysis was used to evaluate the associations of LTL with the risk of digestive diseases. Furthermore, such associations were also evaluated after stratification by sex and ethnicity.

RESULTS: After a mean follow-up time of 11.8 years, over 20 the International Classification of Diseases 10th Revision (ICD-10) codes were observed to be associated with telomere attrition. LTL shortening is associated with an increased risk of several digestive diseases, including gastroesophageal reflux disease (K21: hazard ratio [HR] = 1.30, 95% confidence interval [95% CI]: 1.19-1.42), esophageal ulcer (K221: HR = 1.81, 95% CI: 1.22-2.71), Barrett's esophagus (K227: HR = 1.58 95% CI: 1.14-2.17), gastritis (K29: HR = 1.39, 95% CI: 1.26-1.52), duodenal ulcer (K26: HR = 1.55, 95% CI: 1.14-2.12), functional dyspepsia (K30X: HR = 1.36, 95% CI: 1.06-1.69), non-alcoholic fatty liver disease (NAFLD) (K760: HR = 1.39, 95% CI: 1.09-1.78), liver cirrhosis (K74: HR = 4.73, 95% CI: 3.27-6.85), cholangitis (K830: HR = 2.55, 95% CI: 1.30-5.00), and hernia (K43: HR = 1.50, 95% CI: 1.17-1.94; K44: HR = 1.29, 95% CI: 1.17-1.42). The risk of rectal polyps (K621: HR = 0.77, 95% CI: 0.63-0.92) decreased per unit shortening of LTL.

CONCLUSIONS: This study suggests that LTL shortening is associated with an increased risk of most digestive diseases except for rectal polyps. These findings may provide some clues for understanding the pathogenesis of digestive diseases.},
}

@article {pmid39647324,
year = {2024},
author = {Li, X and Wang, X and Yu, F and Li, Z and Chen, D and Qi, Y and Lu, Z and Liu, Y and Chen, D and Wu, Y},
title = {Development and validation of a prognostic and drug sensitivity model for gastric cancer utilizing telomere-related genes.},
journal = {Translational oncology},
volume = {52},
number = {},
pages = {102232},
doi = {10.1016/j.tranon.2024.102232},
pmid = {39647324},
issn = {1936-5233},
abstract = {BACKGROUND: Gastric cancer (GC) poses a major global health challenge because of its unfavorable prognosis. Elevated telomerase activity has been linked to the rapid growth and invasiveness of GC tumors. Investigating the expression profiles of telomerase could improve our understanding of the mechanisms underlying telomere-related GC advancement and its applicability as potential targets for diverse therapeutic strategies for GC.

METHODS: The TCGA and GEO databases were utilized to access transcriptome and clinical data related to GC. After assessing differentially expressed genes (DEGs), a prognostic risk model was developed through Cox univariate regression, LASSO-Cox regression. The prognostic risk model was validated using data from the GSE62254 cohort. The significant influence of the risk model on the tumor immune microenvironment (TIME) and its sensitivity to various drugs was assessed.

RESULTS: Differential expression analysis identified 328 significantly telomere-related DEGs in GC, with 35 of them showing a significant association with GC prognosis. A predictive risk model composed of four telomere-related genes (TRGs) was established, enabling the accurate stratification of GC patients into two distinct prognostic groups. The LASSO risk model demonstrated notable variations in immune-cell infiltration and drug sensitivity patterns between high- and low-risk groups.

CONCLUSIONS: The study establishes suggestive relationships between four TRGs (LRRN1, SNCG, GAMT, and PDE1B) and the prognosis of GC. The comprehensive characterization of the TRG model reveals their possible roles in the prognosis, TIME, and drug sensitivity in GC.},
}

@article {pmid39642730,
year = {2024},
author = {Li, R and Chen, G and Liao, W and Yuchi, Y and Yang, X and Zhang, Z and Liu, X and Mao, Z and Li, L and Zhao, J and Li, H and Huo, W and Guo, Y and Li, S and Wu, W and Wang, C and Hou, J},
title = {The role of telomere shortening in ambient ozone exposure-related insulin resistance.},
journal = {Journal of hazardous materials},
volume = {484},
number = {},
pages = {136768},
doi = {10.1016/j.jhazmat.2024.136768},
pmid = {39642730},
issn = {1873-3336},
abstract = {BACKGROUND: Ozone (O3) exposure and telomere shortening are associated with insulin resistance (IR). However, the role of telomere shortening in ambient O3 exposure-related IR is largely unclear.

METHODS: The Henan Rural Cohort recruited participants and performed a random forest method to estimate residential O3 concentration. IR was reflected by homeostasis model assessment-IR, quantitative insulin sensitivity check index, triglyceride and glucose index, etc. Generalized linear model, quantile regression model, and mediation effects analysis were utilized to assess the associations of O3 exposure and relative telomere length (RTL) with longitudinal IR markers and their change rates. Furthermore, the role of telomere homeostasis in O3-exposure-induced IR in vivo and in vitro experiments was verified.

RESULTS: O3 exposure was positively associated with longitudinal IR. The proportions of RTL mediated associations between O3 exposure and longitudinal IR markers ranged from 11.92 % to 60.36 %. O3-exposed mice exhibited a higher glucose load, upregulation of GSK-3β and G-6-Pase expression at mRNA levels, glycogen accumulation reduction, telomere shortening, and decreased telomerase reverse transcriptase activity relative to air-exposed mice. In vitro experiments reveal that overexpression of TERT in HepG2 cells up-regulated G-6-Pase mRNA expression level.

CONCLUSIONS: Impaired telomere homeostasis may be involved in O3 exposure-related IR via inhibition of glycogen synthesis and acceleration of gluconeogenesis and the specific mechanisms are still further elucidated.},
}

@article {pmid39639361,
year = {2024},
author = {Tan, L and Zhong, MM and Zhao, YQ and Feng, Y and Ye, Q and Hu, J and Ou-Yang, ZY and Chen, NX and Su, XL and Zhang, Q and Liu, Q and Yuan, H and Wang, MY and Feng, YZ and Guo, Y},
title = {The role of circulating polyunsaturated fatty acids in mediating the effect of BMI on leukocyte telomere length: analysis using Mendelian randomization.},
journal = {Nutrition & metabolism},
volume = {21},
number = {1},
pages = {104},
pmid = {39639361},
issn = {1743-7075},
support = {202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; },
abstract = {BACKGROUND: polyunsaturated fatty acids (PUFAs) are a category of fatty acids that contain omega-3 and omega-6 fatty acids, which constitute a substantial portion of the Western diet and are vital for maintaining human wellness. The extent to which circulating PUFAs influence the effects of BMI on leukocyte telomere length (LTL) is unknown. Additionally, the impact of circulating PUFA on LTL remains controversial in observational studies.

METHODS: Using publicly accessible datasets, a genome-wide association study (GWAS) was carried out to determine genetic association estimates for BMI, circulating PUFAs, and LTL. The circulating PUFAs considered were omega-3 PUFAs (i.e., docosahexaenoic acid (DHA) and total omega-3 PUFAs) and omega-6 PUFAs (i.e., linoleic acid (LA) and total omega-6 PUFAs). Two-sample Mendelian randomization (MR) was used to investigate the causal relationships between BMI and PUFA with LTL. Additionally, we examined whether certain PUFA mediate the impact of BMI on LTL.

RESULTS: None of the evidence supported a causal effect of genetically predicted DHA and total omega-3 PUFA on LTL (DHA: β = 0.001, 95% CI: -0.023 to 0.026, p = 0.926; total omega-3 PUFA: β = 0.008, 95% CI: -0.013 to 0.029, p = 0.466). After conducting sensitivity analyses to account for various models of horizontal pleiotropy, the causal association between higher levels of LA and longer LTL persisted (β = 0.034, 95% CI 0.016 to 0.052, p < 0.001). Adjusting for LA in genetics reduced the effect of BMI on LTL from β = -0.039 (95% CI: -0.058 to -0.020, p < 0.001) to -0.034 (95% CI: -0.054 to -0.014, p < 0.001).

CONCLUSIONS: This MR study indicates that an increase in genetically predicted circulating LA levels is associated with longer LTL. Additionally, it appears that circulating LA levels play a role in mediating some of the impact that BMI has on LTL.},
}

@article {pmid39639031,
year = {2024},
author = {Dai, M and Li, K and Sacirovic, M and Zemmrich, C and Ritter, O and Bramlage, P and Persson, AB and Buschmann, E and Buschmann, I and Hillmeister, P},
title = {Cell-free plasma telomere length correlated with the risk of cardiovascular events using machine learning classifiers.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {30390},
pmid = {39639031},
issn = {2045-2322},
mesh = {Humans ; *Machine Learning ; Male ; Female ; Middle Aged ; *Coronary Artery Disease/blood/diagnosis ; Retrospective Studies ; Aged ; *Heart Failure/blood/diagnosis ; Telomere ; Biomarkers/blood ; Telomere Homeostasis ; Risk Factors ; },
abstract = {This retrospective study explored the association between circulating cell-free plasma telomere length (cf-TL) and coronary artery disease (CAD) and heart failure (HF). Data from 518 participants were collected, including clinical and laboratory data. cf-TL was measured in plasma samples and machine learning (ML) classification models were developed to differentiate between CAD, HF and control conditions. Our results showed that cf-TL was significantly prolonged in HF patients compared to controls, but no significant difference was observed between CAD patients and controls. Additionally, cf-TL was significantly correlated with nitric oxide metabolites (NOx) and flow-mediated dilation (FMD), suggesting a potential link with endothelial function. To avoid data leakage and ensure the model captured only relationships relevant to the research question, we utilized a temporal data split, holding out the last year's data for testing (n = 81) and using the remaining data for training (n = 324) and validation (n = 109). The ML models using four variables achieved an area under the curve (AUC) of 0.795 in the validation dataset and 0.717 in the test dataset for CAD classification, and 0.829 in the validation dataset and 0.806 in the test dataset for HF classification. SHAP analysis revealed that cf-TL had minimal impact on the predictions of the CAD model, as indicated by consistently low SHAP values, whereas in the HF model, cf-TL exhibited a broader range of SHAP values, indicating a greater contribution to the model's classification. These findings suggest that cf-TL may play a more prominent role in HF pathophysiology and could serve as a valuable biomarker for predicting HF risk. Further studies are warranted to explore cf-TL's diagnostic and prognostic potential across different cardiovascular diseases.},
}

Humans
*Machine Learning
Male
Female
Middle Aged
*Coronary Artery Disease/blood/diagnosis
Retrospective Studies
Aged
*Heart Failure/blood/diagnosis
Telomere
Biomarkers/blood
Telomere Homeostasis
Risk Factors

@article {pmid39638969,
year = {2024},
author = {Sadr, Z and Ghasemi, M and Jafarpour, S and Seyfi, R and Ghasemi, A and Boustanipour, E and Khorshid, HRK and Ehtesham, N},
title = {Beginning at the ends: telomere and telomere-based cancer therapeutics.},
journal = {Molecular genetics and genomics : MGG},
volume = {300},
number = {1},
pages = {1},
pmid = {39638969},
issn = {1617-4623},
mesh = {Humans ; *Neoplasms/genetics/therapy/drug therapy ; *Telomere/genetics/metabolism ; *Telomerase/genetics/metabolism ; *Telomere Homeostasis ; Animals ; },
abstract = {Telomeres, which are situated at the terminal ends of chromosomes, undergo a reduction in length with each cellular division, ultimately reaching a critical threshold that triggers cellular senescence. Cancer cells circumvent this senescence by utilizing telomere maintenance mechanisms (TMMs) that grant them a form of immortality. These mechanisms can be categorized into two primary processes: the reactivation of telomerase reverse transcriptase and the alternative lengthening of telomeres (ALT) pathway, which is dependent on homologous recombination (HR). Various strategies have been developed to inhibit telomerase activation in 85-95% of cancers, including the use of antisense oligonucleotides such as small interfering RNAs and endogenous microRNAs, agents that simulate telomere uncapping, expression modulators, immunotherapeutic vaccines targeting telomerase, reverse transcriptase inhibitors, stabilization of G-quadruplex structures, and gene therapy approaches. Conversely, in the remaining 5-15% of human cancers that rely on ALT, mechanisms involve modifications in the chromatin environment surrounding telomeres, upregulation of TERRA long non-coding RNA, enhanced activation of the ataxia telangiectasia and Rad-3-related protein kinase signaling pathway, increased interactions with nuclear receptors, telomere repositioning driven by HR, and recombination events between non-sister chromatids, all of which present potential targets for therapeutic intervention. Additionally, combinatorial therapy has emerged as a strategy that employs selective agents to simultaneously target both telomerase and ALT, aiming for optimal clinical outcomes. Given the critical role of anti-TMM strategies in cancer treatment, this review provides an overview of the latest insights into the structure and function of telomeres, their involvement in tumorigenesis, and the advancements in TMM-based cancer therapies.},
}

Humans
*Neoplasms/genetics/therapy/drug therapy
*Telomere/genetics/metabolism
*Telomerase/genetics/metabolism
*Telomere Homeostasis
Animals

@article {pmid39638831,
year = {2024},
author = {Zhu, N and Wang, X and Zhu, H and Zheng, Y},
title = {Exploring the role of alternative lengthening of telomere-related genes in diagnostic modeling for non-alcoholic fatty liver disease.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {30309},
pmid = {39638831},
issn = {2045-2322},
mesh = {*Non-alcoholic Fatty Liver Disease/genetics/pathology/diagnosis/metabolism ; Animals ; Mice ; Humans ; Telomere Homeostasis/genetics ; Disease Models, Animal ; Gene Regulatory Networks ; Gene Expression Profiling ; Telomere/genetics/metabolism ; Prognosis ; },
abstract = {Previous studies have reported an association between telomere length and non-alcoholic fatty liver disease (NAFLD). This study aimed to explore the involvement of alternative lengthening of telomere-related genes (ALTRGs) in the pathology of NAFLD, construct a risk signature, and evaluate both treatment and prognosis. Three NAFLD datasets (GSE48452, GSE89632, and GSE63067) were collected from the GEO database and merged into combined GEO datasets. ALTRGs were collected from GeneCards and PubMed databases. Differentially expressed genes (DEGs) were identified, and functional enrichment analysis was performed. This study employed a support vector machine algorithm and least absolute shrinkage and selection operator regression analysis to identify key genes for constructing a diagnostic model. High- and low-risk groups were identified from the combined GEO datasets using the diagnostic model. Gene set enrichment analysis, regulatory network analysis, and intergroup immune infiltration analysis were performed. This study identified the key genes using receiver operating characteristic and Friends analysis. Expression of these genes was validated in a mouse model of NAFLD. Twenty-five genes were differentially expressed, with a positive correlation between FOS and EGR1 and a negative correlation between MYC and CEBPA. A diagnostic model was constructed using 12 genes, and high- and low-risk groups were identified. CAMK2G, ERBB2, FOSB, WT1, and CEBPA showed certain accuracy, and their expression levels were significantly different in the model. Immune infiltration analysis between the risk groups revealed that six immune cells were statistically significant. This includes a strong negative interaction between type 2 T helper cells and SPHK2 in the high-risk group. These findings suggest that ALTRDEGs are potential therapeutic targets and prognostic indicators for NAFLD. However, further investigations are required to elucidate the specific underlying mechanisms.},
}

*Non-alcoholic Fatty Liver Disease/genetics/pathology/diagnosis/metabolism
Animals
Mice
Humans
Telomere Homeostasis/genetics
Disease Models, Animal
Gene Regulatory Networks
Gene Expression Profiling
Telomere/genetics/metabolism
Prognosis

@article {pmid39636971,
year = {2024},
author = {Liu, J and Li, Q and Hu, Y and Yu, Y and Zheng, K and Li, D and Qin, L and Yu, X},
title = {The complete telomere-to-telomere sequence of a mouse genome.},
journal = {Science (New York, N.Y.)},
volume = {386},
number = {6726},
pages = {1141-1146},
doi = {10.1126/science.adq8191},
pmid = {39636971},
issn = {1095-9203},
mesh = {Animals ; Mice ; *Telomere/genetics ; *Genome ; Repetitive Sequences, Nucleic Acid ; Sequence Analysis, DNA ; Mouse Embryonic Stem Cells ; Haploidy ; },
abstract = {The current reference genome of Mus musculus, GRCm39, has major gaps in both euchromatic and heterochromatic regions associated with repetitive sequences. In this work, we have sequenced and assembled the telomere-to-telomere genome of mouse haploid embryonic stem cells. The results reveal more than 7.7% of previously uncovered sequences of the mouse genome, including ribosomal DNA arrays and pericentromeric and subtelomeric regions, as well as an additional 140 genes predicted to be protein-coding. This study helps to address knowledge gaps in the mouse genome.},
}

Animals
Mice
*Telomere/genetics
*Genome
Repetitive Sequences, Nucleic Acid
Sequence Analysis, DNA
Mouse Embryonic Stem Cells
Haploidy

@article {pmid39636650,
year = {2024},
author = {Myllymäki, M and Reilly, CR},
title = {Somatic symphony: telomeres and CH.},
journal = {Blood},
volume = {144},
number = {23},
pages = {2369-2371},
doi = {10.1182/blood.2024026841},
pmid = {39636650},
issn = {1528-0020},
}

@article {pmid39635126,
year = {2024},
author = {Burkert, M and Blanc, E and Thiessen, N and Weber, C and Toedling, J and Monti, R and Dombrowe, VM and Stella de Biase, M and Kaufmann, TL and Haase, K and Waszak, SM and Eggert, A and Beule, D and Schulte, JH and Ohler, U and Schwarz, RF},
title = {Copy-number dosage regulates telomere maintenance and disease-associated pathways in neuroblastoma.},
journal = {iScience},
volume = {27},
number = {10},
pages = {110918},
pmid = {39635126},
issn = {2589-0042},
abstract = {Telomere maintenance in neuroblastoma is linked to poor outcome and caused by either telomerase reverse transcriptase (TERT) activation or through alternative lengthening of telomeres (ALT). In contrast to TERT activation, commonly caused by genomic rearrangements or MYCN amplification, ALT is less well understood. Alterations at the ATRX locus are key drivers of ALT but only present in ∼50% of ALT tumors. To identify potential new pathways to telomere maintenance, we investigate allele-specific gene dosage effects from whole genomes and transcriptomes in 115 primary neuroblastomas. We show that copy-number dosage deregulates telomere maintenance, genomic stability, and neuronal pathways and identify upregulation of variants of histone H3 and H2A as a potential alternative pathway to ALT. We investigate the interplay between TERT activation, overexpression and copy-number dosage and reveal loss of imprinting at the RTL1 gene associated with poor clinical outcome. These results highlight the importance of gene dosage in key oncogenic mechanisms in neuroblastoma.},
}

@article {pmid39633874,
year = {2024},
author = {Almuraikhy, S and Naja, K and Anwardeen, N and Sellami, M and Al-Amri, HS and Al-Sulaiti, H and Bashraheel, SS and Aden, AA and Elrayess, MA},
title = {Metabolic signatures of combined exercise and fasting: an expanded perspective on previous telomere length findings.},
journal = {Frontiers in aging},
volume = {5},
number = {},
pages = {1494095},
pmid = {39633874},
issn = {2673-6217},
abstract = {INTRODUCTION: Aging is a complex process marked by a gradual decline in physiological function and increased susceptibility to diseases. Telomere length is frequently regarded as one of the primary biomarkers of aging. Metabolic profiles are key features in longevity and have been associated with both age and age-related diseases. We previously reported an increase in the telomere length in healthy female subjects when Ramadan fasting was combined with physical training. This study aims to characterize the metabolic signature differentiating the combined effects of exercise and fasting from exercise alone and explore the correlations with the previously reported telomere length changes.

METHODS: Twenty-nine young, non-obese, and healthy female subjects were previously randomized into two groups: one group followed a 4-week exercise program, while the other group followed the same 4-week exercise program but also fasted during Ramadan. Metabolic profiles were assessed pre- and post-intervention using untargeted metabolomics.

RESULTS AND DISCUSSION: Our results showed a significant decrease in many lipid metabolites in the exercise-while-fasting group, particularly ceramides. Our study sheds light on the dynamic changes in lipid metabolism and its potential role in inflammation and age-related diseases, and contributes to the broader understanding of how lifestyle factors can influence cellular aging and metabolic health.},
}

@article {pmid39633416,
year = {2024},
author = {Wang, Q and Gao, Y and Song, J and Taiwaikuli, D and Ding, H and Yang, X and Tang, B and Zhou, X},
title = {DNA methylation-based telomere length is more strongly associated with cardiovascular disease and long-term mortality than quantitative polymerase chain reaction-based telomere length: evidence from the NHANES 1999-2002.},
journal = {Clinical epigenetics},
volume = {16},
number = {1},
pages = {177},
pmid = {39633416},
issn = {1868-7083},
support = {82260064//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Cardiovascular Diseases/genetics/mortality ; Female ; Male ; Middle Aged ; Aged ; *DNA Methylation/genetics ; *Nutrition Surveys ; *Telomere/genetics ; Telomere Homeostasis/genetics ; Polymerase Chain Reaction/methods ; Proportional Hazards Models ; Cohort Studies ; },
abstract = {BACKGROUND: Telomere length (TL) serves as a pivotal gauge of cellular aging, with shorter TL linked to various age-related ailments. Recently, a DNA methylation-based TL estimator, known as DNAmTL, has emerged as a novel TL measurement tool. Our current investigation scrutinized the correlation between DNAmTL and the risks of cardiovascular disease (CVD) and enduring mortality among middle-aged and elderly individuals.

METHODS: We enrolled a nationwide, population-based cohort of subjects from the National Health and Nutrition Examination Survey spanning 1999 to 2002, possessing data on both DNAmTL and quantitative polymerase chain reaction-based TL (qPCRTL). Logistic regression models and Cox proportional hazards models were employed to evaluate the associations of DNAmTL with CVD risk and mortality, respectively.

RESULTS: The cohort comprised 2532 participants, with a weighted CVD prevalence of 19.06%. Notably, each one-kilobase increase in DNAmTL was linked to a 53% diminished CVD risk [odds ratio (OR): 0.47, 95% confidence interval (CI): 0.23-0.95, P = 0.035]. Over a median follow-up period of 206 months, 1361 deaths were recorded (53.75%), with 590 (23.30%) ascribable to CVD. Individuals with the lengthiest DNAmTL exhibited a 36% lower risk of all-cause mortality (hazard ratio (HR): 0.64, 95% CI: 0.49-0.85, P = 0.002) and a 35% decrease in CVD mortality (HR: 0.65, 95% CI: 0.43-0.98, P = 0.044) compared to those with shortest DNAmTL. Notably, a stronger association with age was observed for DNAmTL compared to qPCRTL (r = -0.58 vs. r = - 0.25). Analysis of receiver operating characteristic (ROC) curves suggested superior predictive performance of DNAmTL over qPCRTL for CVD (area under curve (AUC): 0.63 vs. 0.55, P < 0.001), all-cause (AUC: 0.74 vs. 0.62, P < 0.001), and CVD mortality (AUC: 0.75 vs. 0.64, P < 0.001).

CONCLUSION: Longer DNAmTL was positively correlated with reduced CVD risk and long-term mortality in middle-aged and elderly cohorts. Notably, DNAmTL outperformed qPCRTL as an aging biomarker in the stratification of CVD risks and mortality.},
}

Humans
*Cardiovascular Diseases/genetics/mortality
Female
Male
Middle Aged
Aged
*DNA Methylation/genetics
*Nutrition Surveys
*Telomere/genetics
Telomere Homeostasis/genetics
Polymerase Chain Reaction/methods
Proportional Hazards Models
Cohort Studies

@article {pmid39633034,
year = {2024},
author = {Saraswati, S and Martínez, P and Serrano, R and Mejías, D and Graña-Castro, O and Álvarez Díaz, R and Blasco, MA},
title = {Author Correction: Renal fibroblasts are involved in fibrogenic changes in kidney fibrosis associated with dysfunctional telomeres.},
journal = {Experimental & molecular medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s12276-024-01370-4},
pmid = {39633034},
issn = {2092-6413},
}

@article {pmid39628055,
year = {2024},
author = {Wang, X and Sun, Z and Qi, F and Zhou, Z and Du, P and Shi, L and Dong, W and Huang, B and Han, S and Pavan, S and Zhang, M and Cui, M and Xu, J and Liu, H and Qin, L and Zhang, Z and Dai, X and Gao, W and Miao, L and Zhao, R and Wang, J and Wang, M and Zhi, C and Hu, Y and Zhao, H and Chen, L and Jin, X and Sun, Y and Zheng, Z and Zhang, X},
title = {A telomere-to-telomere genome assembly of the cultivated peanut.},
journal = {Molecular plant},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.molp.2024.12.001},
pmid = {39628055},
issn = {1752-9867},
}

@article {pmid39624822,
year = {2024},
author = {Saretzki, G},
title = {Editorial: Chronic stress, telomeres and aging.},
journal = {Frontiers in endocrinology},
volume = {15},
number = {},
pages = {1504405},
pmid = {39624822},
issn = {1664-2392},
}

@article {pmid39623492,
year = {2024},
author = {Sumesh, D and Lin, J and Wojcicki, JM},
title = {High school diploma is associated with longer postpartum leukocyte telomere length in a cohort of primarily Latina women.},
journal = {Maternal health, neonatology and perinatology},
volume = {10},
number = {1},
pages = {25},
pmid = {39623492},
issn = {2054-958X},
abstract = {OBJECTIVE: This study investigates correlates of maternal leukocyte telomere length (LTL) in the immediate postpartum period using a cross-sectional study design from an existing prospective longitudinal birth cohort of primarily Latina women. The study focuses on the role of maternal health and dietary habits in pregnancy and maternal education level and LTL at delivery.

STUDY DESIGN: Latina mothers were recruited during the immediate postpartum period prior to 24 h at two San Francisco hospitals and dried blood spots were collected for LTL analysis via quantitative polymerase chain reaction (qPCR). We used multivariable linear regression models to determine independent predictors of maternal LTL during the postpartum period.

RESULTS: In multivariable regression models, increasing maternal age was associated with shorter LTL during the immediate postpartum period (Coeff - 0.015; p < 0.01) whereas having a high school diploma was associated with longer LTL versus not having graduated from high school (Coeff 0.12; p < 0.01).

CONCLUSION: Maternal education level as a potential marker of exposure to life stressors and socioeconomic status was associated with maternal LTL after adjusting for age and other potential confounders in women of reproductive age.},
}

@article {pmid39618119,
year = {2024},
author = {Chen, J and Liu, H and Pang, Y and Wang, Y and Ren, Z and Liu, J and Nan, Y and Liu, D},
title = {Genetic Association of Chronic Pains and Analgesics With Telomere Length: A Mendelian Randomization Study.},
journal = {Biological research for nursing},
volume = {},
number = {},
pages = {10998004241303536},
doi = {10.1177/10998004241303536},
pmid = {39618119},
issn = {1552-4175},
abstract = {Objective: The aim of this study was to explore the causal relationships between chronic pains (back pain, facial pain, general pain, headaches, knee pain, hip pain, neck/shoulder pain, stomach/abdominal pain) and analgesics (codeine, diclofenac, ibuprofen, morphine, paracetamol, tramadol) with telomere length using Mendelian randomization methods. Methods: In the study, various statistical methods including inverse variance weighted (IVW), Mendelian Randomization-Egger, weighted median, simple mode, and weighted mode were used to investigate the relationships between chronic pains, analgesics, and telomere length. Heterogeneity and pleiotropy tests were conducted to ensure the accuracy of the results. Results: The results of the IVW analysis revealed positive causal relationships between hip pain (odds ratio (OR): 1.145; 95% confidence interval (CI): 1.021-1.285; p = .020), and stomach/abdominal pain (OR: 1.100; 95% CI: 1.008-1.200; p = 0.033) with telomere length. Use of tramadol (OR: 0.074; 95% CI: 0.009-0.605; p = 0.015) had a negative causal relationships with telomere length. Conclusion: This study found positive associations between hip pain and stomach/abdominal pain with telomere length, and a negative association between tramadol and telomere length. However, no significant causal relationships were found with other types of chronic pains and analgesics. This could help develop healthier chronic pain treatments, avoiding the abuse of analgesics.},
}

@article {pmid39616267,
year = {2024},
author = {Kvarnung, M and Pettersson, M and Chun-On, P and Rafati, M and McReynolds, LJ and Norberg, A and Moura, PL and Pesonen, I and Chaireti, R and Grönros Söderholm, B and Burlin, J and Rydén, J and Lindberg, EH and Giri, N and Savage, SA and Agarwal, S and Nordgren, A and Tesi, B},
title = {Identification of biallelic POLA2 variants in two families with an autosomal recessive telomere biology disorder.},
journal = {European journal of human genetics : EJHG},
volume = {},
number = {},
pages = {},
pmid = {39616267},
issn = {1476-5438},
support = {SLS-973171//Svenska Läkaresällskapet (Swedish Society of Medicine)/ ; FoUI-985957//Stockholms Läns Landsting (Stockholm County Council)/ ; FoUI-972766//Stockholms Läns Landsting (Stockholm County Council)/ ; },
abstract = {POLA2 encodes the accessory subunit of DNA polymerase α (polα)/primase, which is crucial for telomere C-strand fill-in. Incomplete fill-in of the C-rich telomeric strand after DNA replication has been proposed as a mechanism for Coats plus syndrome, a phenotype within the broader spectrum of telomere biology disorders (TBD). Coats plus syndrome has so far been associated with pathogenic variants in POT1, CTC1, and STN1. Here we report the findings of biallelic deleterious rare variants in POLA2 gene detected by whole genome sequencing and segregation analysis in five young adults from two unrelated families. All five individuals displayed abnormally short telomeres and a clinical phenotype suggesting a TBD disorder with Coats plus features including retinal and gastrointestinal telangiectasias. Our results suggest POLA2 as a novel autosomal recessive gene for a TBD with Coats plus features.},
}

@article {pmid39616073,
year = {2024},
author = {Modi, P and Pennington, K and Shah, S and Mangaonkar, A and Goswami, U},
title = {Clinical Outcomes of Lung Transplant Recipients with Myelodysplastic Syndrome and Short Telomere Syndrome-Case Series.},
journal = {Transplantation proceedings},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.transproceed.2024.10.038},
pmid = {39616073},
issn = {1873-2623},
abstract = {Limited data exists concerning the postlung transplantation outcomes of patients diagnosed with myelodysplastic syndrome (MDS). We delineate the clinical trajectories and outcomes for 3 patients with MDS and Short Telomere Syndrome (STS) who underwent lung transplantation. Our findings suggest that patients with STS and low-risk MDS, especially those harboring the SF3B1 mutation, tolerated standard immunosuppression and antimicrobial prophylaxis well without significant deviation from a typical post-transplant course. Therefore, individuals with low-risk MDS should not be automatically excluded from lung transplantation consideration. Post-transplant monitoring is crucial to promptly detect and manage cytopenias. Conversely, our patient, diagnosed with high-risk MDS post-transplantation faced a poor prognosis, with severe cytopenias limiting immunosuppression treatment and resulting in rejection. Thus, abundance of caution is warranted when contemplating lung transplantation for individuals with high-risk MDS and STS. Further research is necessary to validate these findings.},
}

@article {pmid39615158,
year = {2024},
author = {Tilekli, MM and Yılmaz, AK and Yasul, Y and Çon, N and Mercan, S and Tek, N},
title = {Influence of diet and exercise on leukocyte telomere length, markers of oxidative stress and inflammation in rats.},
journal = {Experimental and molecular pathology},
volume = {140},
number = {},
pages = {104947},
doi = {10.1016/j.yexmp.2024.104947},
pmid = {39615158},
issn = {1096-0945},
abstract = {Telomere length is an important biomarker of biological aging and is affected by nutrition and physical activity. This study investigated the effects of diets with different fat contents and increased physical activity on certain pro/anti-inflammatory and oxidative stress markers and aging. The study is performed in a randomized, experimental, and controlled design with 48 rats, 8 weeks old, divided into 6 different groups (Control (C), exercise (E), unsaturated fat diet (USF), saturated fat diet (SF), unsaturated fat diet + exercise (USF + E), and saturated fat diet + exercise (SF + E)). The rats performed aerobic swimming exercise for 50 days and were fed a diet with different fat content. TAS, TOS, and MDA levels were determined by colorimetric analysis while 8-OHdG, IL-10, and TNF-α were determined by ELISA. Additionally, leukocyte telomere length is determined by the PCR method. Weight changes were also recorded. Plasma TOS, OSI, and TNF-α were lowest in the USF group and highest in the SF and SF + E groups. MDA, 8-OHdG and TG levels were highest in the SF group. The lowest IL-10 level was detected in group C. TL level was the highest in the USF group. There was also a moderate, negative, and significant correlation between telomeres and TOS, OSI, and TNF-α. The groups with the highest body weight gain were C, SF, and SF + E. Diets low in saturated fat or high in unsaturated fat, and physical activity were associated with leukocyte telomere length and alteration of oxidative and pro/anti-inflammatory markers.},
}

@article {pmid39614920,
year = {2024},
author = {Taseva, T and Koycheva, Y and Racheva, R and Raycheva, T and Hodzhev, Y and Nikolova, E and Ilieva, M and Krasteva, M},
title = {Altered Mitochondrial DNA Copy Number and Telomere Length in Patients with Substance Use Disorder: Correlation with Age, Sex, and Chronic Diseases.},
journal = {Biochemical genetics},
volume = {},
number = {},
pages = {},
pmid = {39614920},
issn = {1573-4927},
support = {Grant number KP-06-H25/5//Bulgarian National Science Fund (BNSF), Ministry of Education and Science, Bulgaria/ ; Grant number KP-06-H25/5//Bulgarian National Science Fund (BNSF), Ministry of Education and Science, Bulgaria/ ; Grant number KP-06-H25/5//Bulgarian National Science Fund (BNSF), Ministry of Education and Science, Bulgaria/ ; Grant number KP-06-H25/5//Bulgarian National Science Fund (BNSF), Ministry of Education and Science, Bulgaria/ ; Grant number KP-06-H25/5//Bulgarian National Science Fund (BNSF), Ministry of Education and Science, Bulgaria/ ; Grant number KP-06-H25/5//Bulgarian National Science Fund (BNSF), Ministry of Education and Science, Bulgaria/ ; },
abstract = {Substance use disorder (SUD) is a complex condition involving psychological, sociocultural, and genetic factors. In this study, we examined the alternations in mitochondrial DNA copy number (mtDNAcn) and telomere length (TL) and their relationship to demographic, medical, heredity, and substance use characteristics in patients with SUD and healthy controls. We investigated a total cohort of 54 participants: 21 healthy individuals, 17 patients with alcohol dependence (AD), and 16 patients with drug dependence (DD). TL and mtDNAcn were measured using quantitative real-time PCR, with statistical methods used to assess the association between variables. We observed a significant decrease in mtDNAcn in both SUD groups, particularly associated with chronic diseases in the AD group. No significant differences in TL were found among the three groups. Sex-associated analysis revealed a significant mtDNAcn reduction in the DD males and elevated TL in AD males compared to control males. Correlation analyses showed associations between the two biomarkers and age, sex, and chronic diseases. Our findings suggest that leukocyte mtDNAcn is a more sensitive marker than TL in patients with SUD, indicating sex-specific patterns of alterations. These findings require confirmation through larger cohort recruitment.},
}

@article {pmid39614014,
year = {2024},
author = {Jones-Weinert, C and Mainz, L and Karlseder, J},
title = {Telomere function and regulation from mouse models to human ageing and disease.},
journal = {Nature reviews. Molecular cell biology},
volume = {},
number = {},
pages = {},
pmid = {39614014},
issn = {1471-0080},
abstract = {Telomeres protect the ends of chromosomes but shorten following cell division in the absence of telomerase activity. When telomeres become critically short or damaged, a DNA damage response is activated. Telomeres then become dysfunctional and trigger cellular senescence or death. Telomere shortening occurs with ageing and may contribute to associated maladies such as infertility, neurodegeneration, cancer, lung dysfunction and haematopoiesis disorders. Telomere dysfunction (sometimes without shortening) is associated with various diseases, known as telomere biology disorders (also known as telomeropathies). Telomere biology disorders include dyskeratosis congenita, Høyeraal-Hreidarsson syndrome, Coats plus syndrome and Revesz syndrome. Although mouse models have been invaluable in advancing telomere research, full recapitulation of human telomere-related diseases in mice has been challenging, owing to key differences between the species. In this Review, we discuss telomere protection, maintenance and damage. We highlight the differences between human and mouse telomere biology that may contribute to discrepancies between human diseases and mouse models. Finally, we discuss recent efforts to generate new 'humanized' mouse models to better model human telomere biology. A better understanding of the limitations of mouse telomere models will pave the road for more human-like models and further our understanding of telomere biology disorders, which will contribute towards the development of new therapies.},
}

@article {pmid39613012,
year = {2024},
author = {Liu, Q and Fan, G and Bi, J and Fang, Q and Luo, F and Huang, X and Li, H and Liu, B and Yan, L and Guo, W and Hu, L and Mei, S and Wang, Y and Song, L},
title = {Exposure to multiple metals and leukocyte telomere length in children and adolescents: The mediating effect of thyroid hormones.},
journal = {Environmental research},
volume = {},
number = {},
pages = {120483},
doi = {10.1016/j.envres.2024.120483},
pmid = {39613012},
issn = {1096-0953},
abstract = {Exposure to metals has been related to alterations in leukocyte telomere length (LTL), an aging marker. However, the evidence regarding this relationship in children and adolescents, as well as the underlying mechanisms, remains unclear. Therefore, we aimed to explore the individual and mixture effects of metals on LTL in children and adolescents and to assess the mediating role of thyroid hormones and the modifying effect of a healthy lifestyle. In a cross-sectional study performed in Liuzhou, China, we assessed 5 serum thyroid hormones, 18 urinary metals, and LTL among 1050 children and adolescents aged 6-18 years. We employed multivariate linear regression and weighted quantile sum (WQS) regression to assess the associations of urinary metals with LTL in children and adolescents. Mediation analyses were conducted to explore the effects of thyroid hormones on these relationships. Urinary cobalt (Co), nickel (Ni), strontium (Sr), mercury (Hg), cadmium (Cd), and thallium (Tl) were related to a shorter LTL in children and adolescents. The WQS regression showed a 6.31% (95% CI: -8.76%, -3.79%) decrease in LTL per quartile increase in the WQS index, and identified Ni (23.3%), Sr (21.7%), and Tl (18.0%) as the major contributors. Mediation analyses showed that triiodothyronine (T3) mediated 14.8% and 8.1% of the associations of urinary Sr and Hg with LTL, respectively, and suppressed 9.3% of the association with urinary Co. Furthermore, the inverse associations of Sr, Cd, and Tl with LTL were attenuated among participants who adopted a healthy lifestyle. Our findings suggested that exposure to Co, Ni, Sr, Cd, Hg, Tl, and their mixture were related to a shorter LTL in children and adolescents, potentially mediated by thyroid hormones. Additionally, adopting a healthy lifestyle may alleviate these adverse effects.},
}

@article {pmid39608550,
year = {2024},
author = {Fang, H and Wu, J and Xie, L and Li, Y and Huang, J and Yan, X and He, X and Deng, W and Chen, J and Ji, Y and Li, R and Wen, C and Yu, W and Wang, P},
title = {Telomere-to-telomere genome assembly of eggplant (Solanum melongena L.) promotes gene fine localization of the green stripe (GS) in pericarp.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {138094},
doi = {10.1016/j.ijbiomac.2024.138094},
pmid = {39608550},
issn = {1879-0003},
abstract = {Fruit appearance of eggplant is a key commercial trait, and the precise selection of new varieties with diverse aesthetics aligns with current breeding objectives. However, functional genomics research in eggplant remains underdeveloped. Here, we assembled the first telomere-to-telomere (T2T) eggplant genome, as well as chloroplast and mitochondrial genomes for the inbred line 'NO211'. The 1.06-Gb SmT2T genome is anchored to 12 chromosomes, nine of which are gap-free, totaling three gaps. This assembly harbors 36,505 genes and 64.08 % repetitive sequences, identifying 12 centromeres and 22 telomeres. Utilizing the SmT2T genome for bulked segregant analysis (BSA) and forward genetic approach with green-striped 'NO211' and pure green 'P13' as parents, the green stripe (GS) locus was finely mapped to a 9-Kb region on Chr4, containing a single gene, eggplant.04G07850 (GLK protein). Sequence analysis and qRT-PCR revealed that a single-base deletion in the exon of SmGLK in 'P13' led to premature stop codon, and SmGLK expression was significantly higher in the pericarp of 'NO211' compared to 'P13'. A marker was developed and validated in 36 germplasms, demonstrating co-segregation with green-striped rind trait. This study provides an ideal reference genome for eggplant functional genomics studies, facilitating mechanistic research on peel stripe formation and molecular-assisted selection for fruit appearance.},
}

@article {pmid39608081,
year = {2024},
author = {Tan, MY and Zhang, P and Gao, M},
title = {Letter to the editor - "Association of healthy and unhealthy plant-based diets with telomere length".},
journal = {Clinical nutrition (Edinburgh, Scotland)},
volume = {44},
number = {},
pages = {12-13},
doi = {10.1016/j.clnu.2024.11.030},
pmid = {39608081},
issn = {1532-1983},
}

@article {pmid39605578,
year = {2024},
author = {Lin, SY and Futeran, H and Levine, MT},
title = {Adaptive protein coevolution preserves telomere integrity.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.11.11.623029},
pmid = {39605578},
issn = {2692-8205},
abstract = {Many essential conserved functions depend, paradoxically, on proteins that evolve rapidly under positive selection. How such adaptively evolving proteins promote biological innovation while preserving conserved, essential functions remains unclear. Here, we experimentally test the hypothesis that adaptive protein-protein coevolution within an essential multi-protein complex mitigates the deleterious incidental byproducts of innovation under pressure from selfish genetic elements. We swapped a single, adaptively evolving subunit of a telomere protection complex from Drosophila yakuba into its close relative, D. melanogaster . The heterologous subunit uncovered a catastrophic interspecies incompatibility that caused lethal telomere fusions. Restoring six adaptively evolving sites on the protein-protein interaction surface, or introducing the D. yakuba interaction partner, rescued telomere integrity and viability. Our in vivo , evolution-guided manipulations illuminate how adaptive protein-protein coevolution preserves essential functions threatened by an evolutionary pressure to innovate.},
}

@article {pmid39603404,
year = {2024},
author = {Teng, Y and Gao, Y and Liu, L and Zhang, W and Li, C and Lian, B and Sun, H and Sun, L},
title = {Sex differential effects of early maternal separation on PTSD susceptibility in adult rats accompanied by telomere shortening in the hippocampus.},
journal = {Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuroscience.2024.11.058},
pmid = {39603404},
issn = {1873-7544},
abstract = {Early life stress (ELS) is thought to be a leading cause of mental disorders in adulthood, including PTSD. Recent studies have found that such stress has a gender and resilient specific effect on adult PTSD. This study aimed to assess emotion, and cognitive behavior, and to examine the sex differences and resilience of ELS on adult PTSD. At the same time, the expression of hippocampal telomere length and telomere repeat binding factors (TRF1 and TRF2) were detected to explore the mechanism of telomere length change. Rat offspring were separated from their dams (3 h/day or 6 h/day from PND2 ∼ PND14). Then, pups were treated with a single prolonged stress (SPS) procedure when they reached adulthood (PND80). Rats exposed early to MS and SPS showed anxiety-like and depression-like behaviors as well as impaired learning and memory. The rats exposed to MS3h showed reduced anxiety-like and depression-like behavior upon re-experiencing "secondary stress" compared to the SPS and MS6h groups. Behavioral results showed no significant gender difference. However, gender and SPS factors significantly affected telomere length and TRF1 and TRF2 gene expression in hippocampus. The SPS effect and MS*SPS interaction significantly impacted TRF1 and TRF2 protein expression. In conclusion, this study shows that MS has different effects on anxiety, depression, and cognitive memory deficits in rats experiencing "secondary stress" in adulthood and is accompanied by telomere shortening in the hippocampus. This reveals the potential impact of early MS on PTSD and provides a new perspective for further research in the field of psychological stress.},
}

@article {pmid39603108,
year = {2024},
author = {Li, X and Li, M and Cheng, J and Guan, S and Hou, L and Zu, S and Yang, L and Wu, H and Li, H and Fan, Y and Zhang, B},
title = {"Reply - Letter to the editor" - "Association of healthy and unhealthy plant-based diets with telomere length".},
journal = {Clinical nutrition (Edinburgh, Scotland)},
volume = {44},
number = {},
pages = {9-11},
doi = {10.1016/j.clnu.2024.11.032},
pmid = {39603108},
issn = {1532-1983},
}

@article {pmid39596838,
year = {2024},
author = {Tucker, LA and Bates, CJ},
title = {Telomere Length and Biological Aging: The Role of Strength Training in 4814 US Men and Women.},
journal = {Biology},
volume = {13},
number = {11},
pages = {},
doi = {10.3390/biology13110883},
pmid = {39596838},
issn = {2079-7737},
abstract = {Telomere length is an index of cellular aging. Healthy lifestyles are associated with reduced oxidative stress and longer telomeres, whereas unhealthy behaviors are related to shorter telomeres and greater biological aging. This investigation was designed to determine if strength training accounted for differences in telomere length in a random sample of 4814 US adults. Data from the National Health and Nutrition Examination Survey (NHANES) were employed to answer the research questions using a cross-sectional design. Time spent strength training was calculated by multiplying days of strength training per week by minutes per session. Participation in other forms of physical activity was also calculated based on reported involvement in 47 other activities. Weighted multiple regression and partial correlation were used to calculate the mean differences in telomere length across levels of strength training, adjusting for differences in potential confounders. With the demographic covariates controlled, strength training and telomere length were linearly related (F = 14.7, p = 0.0006). Likewise, after adjusting for all the covariates, the linear association remained strong and significant (F = 14.7, p = 0.0006). In this national sample, 90 min per week of strength training was associated with 3.9 years less biological aging, on average. Regular strength training was strongly related to longer telomeres and less biological aging in 4814 US adults.},
}

@article {pmid39596019,
year = {2024},
author = {Zhao, L and Li, Z and Jiang, S and Xia, C and Deng, K and Liu, B and Wang, Z and Liu, Q and He, M and Zou, M and Xia, Z},
title = {The Telomere-to-Telomere Genome of Jaboticaba Reveals the Genetic Basis of Fruit Color and Citric Acid Content.},
journal = {International journal of molecular sciences},
volume = {25},
number = {22},
pages = {},
doi = {10.3390/ijms252211951},
pmid = {39596019},
issn = {1422-0067},
support = {ZDYF2022XDNY149//Hainan Province Science and Technology Special Fund/ ; },
mesh = {*Fruit/genetics/metabolism ; *Citric Acid/metabolism ; *Genome, Plant ; Telomere/genetics/metabolism ; Myrtaceae/genetics/metabolism ; Gene Expression Regulation, Plant ; Pigmentation/genetics ; Phylogeny ; },
abstract = {Jaboticaba is a typical tropical plant that blossoms and bears fruit on the tree trunks and branches. The fruits resemble grapes in appearance and texture and are also known as "treegrapes". Currently, research on the genomics of jaboticaba is lacking. In this study, we constructed an integrated, telomere-to-telomere (T2T) gap-free reference genome and two nearly complete haploid genomes, thereby providing a high-quality genomic resource. Furthermore, we unveiled the evolutionary history of several species within the Myrtaceae family, highlighting significant expansions in metabolic pathways such as the citric acid cycle, glycolysis/gluconeogenesis, and phenylpropanoid biosynthesis throughout their evolutionary process. Transcriptome analysis of jaboticaba fruits of different colors revealed that the development of fruit skin color in jaboticaba is associated with the phenylpropanoid and flavonoid biosynthesis pathways, with the flavanone 3-hydroxylase (F3H) gene potentially regulating fruit skin color. Additionally, by constructing the regulatory pathway of the citric acid cycle, we found that low citric acid content is correlated with high expression levels of genes such as thiamin diphosphate (ThDP) and low expression of phosphoenolpyruvate carboxykinase (PEPCK), indicating that PEPCK positively regulates citric acid content. These T2T genomic resources will accelerate jaboticaba pepper genetic improvement and help to understand jaboticaba genome evolution.},
}

*Fruit/genetics/metabolism
*Citric Acid/metabolism
*Genome, Plant
Telomere/genetics/metabolism
Myrtaceae/genetics/metabolism
Gene Expression Regulation, Plant
Pigmentation/genetics
Phylogeny

@article {pmid39595175,
year = {2024},
author = {Lv, J and Zhao, X and Zhao, L and Gong, C and Zheng, W and Guo, L and Wang, J and Liang, T},
title = {The Notable Role of Telomere Length Maintenance in Complex Diseases.},
journal = {Biomedicines},
volume = {12},
number = {11},
pages = {},
pmid = {39595175},
issn = {2227-9059},
support = {62171236//National Natural Science Foundation of China/ ; BE2022799//the Key Project of Social Development in Jiangsu Province, China/ ; 22KJA180006//the Key Projects of Natural Science Research in Universities of Jiangsu Province, China/ ; NA//the Priority Academic Program Development of Jiangsu Higher Education Institution (PAPD)/ ; },
abstract = {Telomere length function serves as a critical biomarker for biological aging and overall health. Its maintenance is linked to cancer, neurodegenerative conditions, and reproductive health. This review mainly examines genetic variations and environmental influences on telomere dynamics, highlighting key regulatory genes and mechanisms. Advances in telomere measurement methodologies are also reviewed, underscoring the importance of precise telomere assessment for disease prevention and treatment. Telomerase activation offers potential for cellular lifespan extension and anti-aging effects, whereas its inhibition emerges as a promising therapeutic approach for cancer. Regulatory mechanisms of tumor suppressor genes on telomerase activity are analyzed, with a comprehensive overview of the current state and future potential of telomerase inhibitors. In addition, the association between telomeres and neurodegenerative diseases is discussed, detailing how telomere attrition heightens disease risk and outlining multiple pathways by which telomerase protects neurons from damage and apoptosis.},
}

@article {pmid39590949,
year = {2024},
author = {Jiang, Y and Xu, Z and Wang, M and Liu, H and Li, Y and Xu, S},
title = {Association Between Prenatal Exposure to Organochlorine Pesticides and Telomere Length in Neonatal Cord Blood.},
journal = {Toxics},
volume = {12},
number = {11},
pages = {},
doi = {10.3390/toxics12110769},
pmid = {39590949},
issn = {2305-6304},
support = {(91643207, 81273083)//National Natural Science Foundation of China/ ; (2017YFC0212003)//National Key R&D Program of China/ ; (JCYJ20210324131213037)//Shenzhen Science and Technology Innovation Committee/ ; (SZSM202103008)//High-Level Project of Medicine in Nanshan, Shenzhen; Sanming Project of Medicine in Shenzhen/ ; },
abstract = {Objectives: Environmental exposure may affect the telomere length (TL) of newborns, which is considered as an early biomarker indicating susceptibility for later life diseases. However, the effects of prenatal organochlorine pesticide (OCP) exposure on newborn TL remain unclear. This study aimed to investigate the association between prenatal exposure levels of OCPs during pregnancy and TL in neonatal cord blood. Methods: A total of 168 mother-infant pairs from a birth cohort in Wuhan, China, were included this study. The concentrations of hexachlorocyclohexanes (HCHs, including β-HCH, α-HCH, and γ-HCH), p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) and its metabolites (p,p'-dichlorodiphenyldichloroethane, p,p'-DDD; p,p'-dichlorodiphenyldichloroethylene, p,p'-DDE) were measured in cord blood. The associations between the OCPs and the TL in newborns were analyzed by a generalized linear regression model. Stratified analyses by newborn sex, maternal gestational weight gain, and pregnancy body mass index (BMI) were performed to evaluate if the associations were modified by these factors. Results: The detection rates of various OCPs ranged from 50.9% to 100.0%. The median concentration of p,p'-DDE was the highest (33.90 ng/g lipid), followed by β-HCH (8.67 ng/g lipid), and the median concentrations of the other OCPs were between 0.12 and 0.33 ng/g lipid. Among the all newborns, a two-fold increase in the γ-HCH concentration in the cord blood was significantly associated with a 0.024 (95% CI: -0.041, -0.007) decrease in the TL. After stratification by newborn sex, the inverse association between γ-HCH and the TL was only statistically significant in boys, but not in girls (P for interaction <0.05). In addition, after stratification by pre-pregnancy BMI, β-HCH and p,p'-DDT concentrations were significantly associated with a decreased TL in the overweight pre-pregnancy BMI group [-0.111 (95% CI: -0.203, -0.018) and -0.036 (95% CI: -0.049, -0.023), respectively]. Conclusions: Prenatal exposure to OCPs during pregnancy was associated with a decreased neonatal telomere length, which may be affected by the newborn sex and pre-pregnancy BMI. These findings may provide new insights into the mechanisms underlying OCP-induced adverse health effects.},
}

@article {pmid39589440,
year = {2024},
author = {Hong, L and Xu, XD and Yang, L and Wang, M and Li, S and Yang, H and Ye, SY and Chen, LL and Song, JM},
title = {Construction and analysis of telomere-to-telomere genomes for 2 sweet oranges: Longhuihong and Newhall (Citrus sinensis).},
journal = {GigaScience},
volume = {13},
number = {},
pages = {},
doi = {10.1093/gigascience/giae084},
pmid = {39589440},
issn = {2047-217X},
support = {KYLX20240900007//Chongqing Municipal Financial Science and Technology Innovation Project/ ; NKY-2022AB005//Ministry of Agriculture/ ; },
mesh = {*Citrus sinensis/genetics ; *Genome, Plant ; *Telomere/genetics ; Genomics/methods ; },
abstract = {BACKGROUND: Sweet orange (Citrus sinensis Osbeck) is a fruit crop of high nutritional value that is widely consumed around the world. However, its susceptibility to low-temperature stress limits its cultivation and production in regions prone to frost damage, severely impacting the sustainable development of the sweet orange industry. Therefore, developing cold-resistant sweet orange varieties is of great necessity. Traditional hybrid breeding methods are not feasible due to the polyembryonic phenomenon in sweet oranges, necessitating the enhancement of its germplasm through molecular breeding. High-quality reference genomes are valuable for studying crop resistance to biotic and abiotic stresses. However, the lack of genomic resources for cold-resistant sweet orange varieties has hindered the progress in developing such varieties and researching their molecular mechanisms of cold resistance.

FINDINGS: This study integrated PacBio HiFi, ONT, Hi-C, and Illumina sequencing data to assemble telomere-to-telomere (T2T) reference genomes for the cold-resistant sweet orange mutant "Longhuihong" (Citrus sinensis [L.] Osb. cv. LHH) and its wild-type counterpart "Newhall" (C. sinensis [L.] Osb. cv. Newhall). Comprehensive evaluations based on multiple criteria revealed that both genomes exhibit high continuity, completeness, and accuracy. The genome sizes were 340.28 Mb and 346.33 Mb, with contig N50 of 39.31 Mb and 36.77 Mb, respectively. In total, 31,456 and 30,021 gene models were annotated in the respective genomes. Leveraging these assembled genomes, comparative genomics analyses were performed, elucidating the evolutionary history of the sweet orange genome. Moreover, the study identified 2,886 structural variants between the 2 genomes, with several SVs located in the upstream, downstream, or intronic regions of homologous genes known to be associated with cold resistance.

CONCLUSIONS: The study de novo assembled 2 T2T reference genomes of sweet orange varieties exhibiting different levels of cold tolerance. These genomes serve as valuable foundational resources for genomic research and molecular breeding aimed at enhancing cold tolerance in sweet oranges. Additionally, they expand the existing repository of reference genomes and sequencing data resources for C. sinensis. Moreover, these genomes provide a critical data foundation for comparative genomics analyses across different plant species.},
}

*Citrus sinensis/genetics
*Genome, Plant
*Telomere/genetics
Genomics/methods

@article {pmid39587573,
year = {2024},
author = {Hassan, R and Bhat, GR and Mir, FA and Ganie, HA and Mushtaq, I and Bhat, MA and Asimi, RP and Afroze, D},
title = {Concomitant telomere attrition is associated with spinal muscular atrophy in highly inbred region of North India: unraveling the thread in Kashmir region.},
journal = {BMC medical genomics},
volume = {17},
number = {1},
pages = {275},
pmid = {39587573},
issn = {1755-8794},
mesh = {Humans ; *Muscular Atrophy, Spinal/genetics ; India ; Male ; Female ; *Telomere Shortening ; *Telomere/genetics ; Child, Preschool ; Child ; Case-Control Studies ; Adolescent ; Infant ; Survival of Motor Neuron 1 Protein/genetics ; Adult ; },
abstract = {Spinal muscular atrophy (SMA) is a rare genetic disorder that unequivocally results in the degeneration of motor neurons, leading to muscle weakness and atrophy. This condition is caused by a mutation in the survival motor neuron 1 (SMN1) gene, which inevitably results in a deficiency of the SMN protein. In present study, we investigated the potential role of telomere attrition in SMA patients. Relative telomere length in peripheral blood lymphocytes was measured by Monochrome Multiplex Quantitative Polymerase Chain Reaction (MMQPCR) in 98 subjects and we conclusively found that SMA cases exhibit telomere attrition compared to healthy controls (P = 4 × 10[- 2]). Moreover, significant attrition was also observed in severe form of SMA, i.e. SMA type 0 (P = 0.04) as well.Although, the exact mechanism through which telomere shortening contributes to the pathogenesis of SMA is not fully understood and is yet to be delineated. However, one possibility is that telomere shortening leads to genomic instability and DNA damage, which can contribute to motor neuron degeneration. Another possibility is that telomere shortening leads to cellular senescence, which can impair the ability of motor neurons to regenerate and repair themselves. Recent studies have suggested that telomere shortening may be a potential therapeutic target in SMA. Thus, understanding the role of SMN1 gene in disease pathogenesis & its effect on telomere length will aid in estimating the risk & prognosis of SMA in genetically less explored & highly inbred region of Kashmir, Northern India.},
}

Humans
*Muscular Atrophy, Spinal/genetics
India
Male
Female
*Telomere Shortening
*Telomere/genetics
Child, Preschool
Child
Case-Control Studies
Adolescent
Infant
Survival of Motor Neuron 1 Protein/genetics
Adult

@article {pmid39586626,
year = {2024},
author = {Baird, DM},
title = {Telomere Dynamics in Human Health and Disease.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041701},
pmid = {39586626},
issn = {1943-0264},
abstract = {Telomere function is critical for genomic stability; in the context of a functional TP53 response, telomere erosion leads to a G1/S cell-cycle arrest and the induction of replicative senescence, a process that is considered to underpin the ageing process in long-lived species. Abrogation of the TP53 pathway allows for continued cell division, telomere erosion, and the complete loss of telomere function; the ensuing genomic instability facilitates clonal evolution and malignant progression. Telomeres display extensive length heterogeneity in the population that is established at birth, and this affects the individual risk of a broad range of diseases, including cardiovascular disease and cancer. In this perspective, I discuss telomere length heterogeneity at the levels of the population, individual, and cell, and consider how the dynamics of these essential chromosomal structures contribute to human disease.},
}

@article {pmid39582797,
year = {2025},
author = {Kaliman, P and Álvarez-López, MJ and Lehodey, A and Fernández, D and Chocat, A and Schlosser, M and de La Sayette, V and Vivien, D and Marchant, NL and Chételat, G and Lutz, A and Poisnel, G and , },
title = {Effect of an 18-Month Meditation Training on Telomeres in Older Adults: A Secondary Analysis of the Age-Well Randomized Controlled Trial.},
journal = {Biological psychiatry global open science},
volume = {5},
number = {1},
pages = {100398},
pmid = {39582797},
issn = {2667-1743},
abstract = {BACKGROUND: Shorter telomeres are associated with increased risk of cognitive decline and age-related diseases. Developing interventions to promote healthy aging by preserving telomere integrity is of paramount importance. Here, we investigated the effect of an 18-month meditation intervention on telomere length (TL) measures in older people without cognitive impairment.

METHODS: A total of 137 adults age ≥65 years were randomized to one of the 3 groups (meditation training, non-native language training, or passive control). We evaluated the 50th and 20th percentile TL and the percentage of critically short telomeres (<3 kbp) in peripheral blood mononuclear cells.

RESULTS: Mixed model analysis showed a time effect indicating a general decrease on the 50th percentile TL (F = 80.72, p adjusted < .001), without a significant group effect or time × group interaction. No significant effect was detected in the 20th percentile TL or the percentage of critically short telomeres. Secondary analysis showed that only in the meditation training group 1) the 50th percentile TL positively correlated with class attendance time (r = 0.45, p adjusted < .011), 2) the 50th and 20th percentile TL positively correlated with responsiveness to the intervention, evaluated through a composite score (r = 0.46, p adjusted < .010 and r = 0.41, p adjusted = .029, respectively), and 3) lower scores on a measure of the personality trait "openness to experience" correlated with a lower percentage of critically short telomeres after the intervention (r = 0.44, p adjusted = .015).

CONCLUSIONS: In older adults, we found no evidence for a main effect of an 18-month meditation training program on TL compared with the control groups. Our findings highlight the importance of considering the impact of moderating factors when measuring the effectiveness of meditation-based trainings.},
}

@article {pmid39580387,
year = {2024},
author = {Li, P and Meng, L and Tu, H and Luo, S and Gong, X},
title = {The impact of Radioresistant-Related Telomere Genes in the prognosis and immune infiltration in lung adenocarcinoma.},
journal = {Cancer cell international},
volume = {24},
number = {1},
pages = {387},
pmid = {39580387},
issn = {1475-2867},
support = {82473378//National Natural Science Foundation of China/ ; 2021071//Shanghai Talents Development Fund Project/ ; SKPY2021006//Clinical Research fundation of Shanghai Pulmonary Hospital/ ; fkzr2436//National Natural Science Foundation Cultivation Project of Shanghai Pulmonary Hospital/ ; },
abstract = {INTRODUCTION: Lung adenocarcinoma (LUAD), a common subtype of NSCLC, has a high mortality rate. Telomere genes are influenced by radiation therapy, affecting treatment response. Additionally, immune cell presence in the tumor microenvironment plays a crucial role in cancer prognosis. However, the role of Radioresistant-Related Telomere Genes (RRTGs) in LUAD prognosis and immune infiltration remains unclear.

METHODS: In this research, we utilized diverse bioinformatics techniques to examine our personally tested information along with publicly accessible datasets. We conducted a comprehensive study on the genetic and transcriptional differences, predictive significance, and expression profiles of RRTGs. Afterwards, a RRTGs score was developed to forecast the overall survival (OS) and ascertain its reliable predictive capacity for patients with LUAD. Following this, dependable nomograms were developed to enhance the practicality of RRTGs scoring in a clinical setting. Furthermore, the investigation delved into the associations among RRTGs, infiltration of immune cells, prognosis, and clinical treatments of patients. Gene Set Enrichment Analysis (GSEA) was conducted to explore the potential mechanisms by which RRTGs influence the regulation of LUAD. Then, Western blot, qRT-PCR and Immunohistochemistry were used to detect the expression levels of RRTGs in cell lines and LUAD tumor tissues.

RESULTS: Our research indicates that certain genes related to telomeres have a notable correlation with the prognosis of patients diagnosed with LUAD. The RRTGs score, which includes three key genes (ARRB1, PLK1, and DSG2), was developed to forecast the OS and its dependable predictive capability for individuals diagnosed with LUAD was ascertained. Afterwards, extremely reliable nomograms were developed to improve the practicality of the RRTGs score. Moreover, as illustrated, genetic characteristics can be utilized to assess the infiltration of immune cells in tumors, as well as clinical attributes and prognosis. RRTGs score characterizes tumor mutational burden, immune activity, and notable survival probabilities in addition. Furthermore, GSEA results revealed that RRTGs may influence LUAD by modulating immune-related pathways in high-risk groups and regulating cell cycle and DNA repair processes in low-risk groups. The RRTGs (ARRB1 and PLK1) were upregulated in A549 cells and radiosensitive NSCLC tissues compared to radioresistant A549 cells and NSCLC tissues.

CONCLUSION: In conclusion, this research emphasizes the significance of RRTGs in the outlook of LUAD. The findings contributed to a better understanding of the link between radiotherapy, telomere-related genes, and prognosis in LUAD, and identified potential therapeutic targets for patients with LUAD.},
}

@article {pmid39578472,
year = {2024},
author = {Lu, S and Liu, Y and Li, M and Ge, Q and Wang, C and Song, Y and Zhou, B and Chen, S},
title = {Gap-free telomere-to-telomere haplotype assembly of the tomato hind (Cephalopholis sonnerati).},
journal = {Scientific data},
volume = {11},
number = {1},
pages = {1268},
pmid = {39578472},
issn = {2052-4463},
mesh = {*Haplotypes ; *Telomere/genetics ; *Solanum lycopersicum/genetics ; Animals ; High-Throughput Nucleotide Sequencing ; Genome, Plant ; Bees/genetics ; },
abstract = {The tomato hind (Cephalopholis sonnerati) is an emerging economically important grouper in recent years. With the increasing maturity of sequencing technologies and assembly methodologies, a higher quality reference genome has become both accessible and necessary. In this study, we present two telomere-to-telomere (T2T) gap-free haplotype assemblies of the tomato hind with lengths of 1039.53 Mb (YSFRI_Csonn_HA_1.0, N50 43.83 Mb) and 1039.91 Mb (YSFRI_Csonn_HB_1.0, N50 44.09 Mb). Reads from next-generation sequencing, ONT ultra-long sequencing, and PacBio HiFi sequencing exhibited mapping rates exceeding 99.8% when aligned to these two assemblies. Evaluation using Merqury indicated high accuracy for both assemblies, with average quality values of 51.80 and 51.83, respectively. Percentages of 97.9% and 97.8% of complete BUSCOs were achieved, and a total of 23,270 and 23,184 protein-code genes were inferred in each assembly. Moreover, telomere identification, centromere prediction, and repetitive sequence annotation were also successfully performed. These two assemblies provide robust foundation for the genetic analysis and development of molecular genetic breeding technologies in C. sonnerati.},
}

*Haplotypes
*Telomere/genetics
*Solanum lycopersicum/genetics
Animals
High-Throughput Nucleotide Sequencing
Genome, Plant
Bees/genetics

@article {pmid39574740,
year = {2024},
author = {Mohanty, SK and Chiaromonte, F and Makova, KD},
title = {Evolutionary Dynamics of G-Quadruplexes in Human and Other Great Ape Telomere-to-Telomere Genomes.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.11.05.621973},
pmid = {39574740},
issn = {2692-8205},
abstract = {G-quadruplexes (G4s) are non-canonical DNA structures that can form at approximately 1% of the human genome. G4s contribute to point mutations and structural variation and thus facilitate genomic instability. They play important roles in regulating replication, transcription, and telomere maintenance, and some of them evolve under purifying selection. Nevertheless, the evolutionary dynamics of G4s has remained underexplored. Here we conducted a comprehensive analysis of predicted G4s (pG4s) in the recently released, telomere-to-telomere (T2T) genomes of human and other great apes-bonobo, chimpanzee, gorilla, Bornean orangutan, and Sumatran orangutan. We annotated tens of thousands of new pG4s in T2T compared to previous ape genome assemblies, including 41,236 in the human genome. Analyzing species alignments, we found approximately one-third of pG4s shared by all apes studied and identified thousands of species- and genus-specific pG4s. pG4s accumulated and diverged at rates consistent with divergence times between the studied species. We observed a significant enrichment and hypomethylation of pG4 shared across species at regulatory regions, including promoters, 5' and 3'UTRs, and origins of replication, strongly suggesting their formation and functional role in these regions. pG4s shared among great apes displayed lower methylation levels compared to species-specific pG4s, suggesting evolutionary conservation of functional roles of the former. Many species-specific pG4s were located in the repetitive and satellite regions deciphered in the T2T genomes. Our findings illuminate the evolutionary dynamics of G4s, their role in gene regulation, and their potential contribution to species-specific adaptations in great apes, emphasizing the utility of high-resolution T2T genomes in uncovering previously elusive genomic features.},
}

@article {pmid39574517,
year = {2024},
author = {Peker Eyüboğlu, İ and Koca, S and Çelik, B and Güllü Amuran, G and Uğurlu, MÜ and Alan, Ö and Akın Telli, T and Yumuk, PF and Akkiprik, M},
title = {Neoadjuvant Chemotherapy Shortens the cfDNA Telomere Length in Breast Cancer Patients.},
journal = {International journal of breast cancer},
volume = {2024},
number = {},
pages = {6117394},
pmid = {39574517},
issn = {2090-3170},
abstract = {Introduction: Cancer is a genetic disease that affects people worldwide, and breast cancer is the most common cancer in women. Studies have been conducted on molecular parameters to predict tumor behavior and develop therapeutic strategies. Telomeres, which are at the end of chromosomes, have been studied for their relationship with breast cancer, but more research is needed to understand their role in the disease. Circulating-free DNA (cfDNA) is DNA that is free in the bloodstream and is considered a promising target for early cancer detection, treatment response monitoring, and prognosis assessment. This study is aimed at comparing cfDNA telomere length of breast cancer patients and healthy individuals and analyzing the impact of neoadjuvant chemotherapy on telomere length in cfDNA. Materials and Methods: Blood samples were collected from 33 breast cancer patients undergoing neoadjuvant chemotherapy before and after treatment. The quantitative PCR method is used to measure the average telomere lengths. Results: This study found that the telomere length of cfDNA in breast cancer patients before and after treatment is significantly shorter than in the control group. Neoadjuvant chemotherapy is found to shorten the cfDNA telomere length, especially in the treatment-responsive group. Conclusion: Our study suggests that telomere length in cfDNA may be a useful biomarker for predicting therapy response and possible reoccurrence of the disease in breast cancer patients.},
}

@article {pmid39574146,
year = {2024},
author = {Wang, L and Zhang, J and Liu, F and Shi, Q and Gao, F and Li, J and Liu, Y and Kong, F and Xu, D},
title = {Maternal infection of SARS-CoV-2 during the first and second trimesters leads to newborn telomere shortening.},
journal = {Journal of translational medicine},
volume = {22},
number = {1},
pages = {1049},
pmid = {39574146},
issn = {1479-5876},
mesh = {Humans ; Female ; Infant, Newborn ; *COVID-19/virology ; Pregnancy ; *Telomere Shortening ; Adult ; *Pregnancy Complications, Infectious/virology ; *SARS-CoV-2/physiology ; Pregnancy Trimester, Second ; Placenta/virology/metabolism ; Fetal Blood/virology ; Telomere/metabolism ; Cytokines/metabolism/blood ; Male ; },
abstract = {BACKGROUND: Initial telomere length (TL) in newborns is the major determinant for TL in later life while TL in newborn/early-life predicts long-term health and lifespan. It is important to identify key factors that affect telomere homeostasis throughout embryonic development for precision interventions to maintain optimal TL in fetus/prenatal infants. SARS-CoV-2 has caused a widespread global pandemic of COVID-19, but it remains unclear whether maternal SARS-CoV-2 infection impairs prenatal telomere homeostasis.

METHODS: We recruited 413 normally delivered newborns whose mothers were either non-infected or infected with SARS-CoV-2 during different trimesters of pregnancy (otherwise healthy). Telomere length (TL) in cord blood (CB) was assessed using qPCR. CB and maternal blood were analyzed for cytokine levels. Placental senescence was determined using senescence-associated β-galactosidase staining.

RESULTS: Control (non-infected maternal) newborn TL was significantly longer than that from maternal infection (1.568 ± 0.340 vs 1.390 ± 0.350, P = 0.005). Such shorter TL was observed only if maternal infection of SARS-CoV-2 occurred in the first and second trimesters of pregnancy (1.261 ± 0.340 and 1.346 ± 0.353, P < 0.0001 and 0.001, respectively). There were no differences in TL between controls and infection at the third trimester (1.568 ± 0.340 vs 1.565 ± 0.329, P > 0.05). Across the first trimester, there was a positive correlation between newborn TL and gestational weeks with maternal infection, suggesting that the earlier maternal infection occurs, the worse effect is taken on fetal telomere homeostasis. Placental senescence coupled with the downregulated expression of telomerase reverse transcriptase was significantly more frequent from the maternal infection at the first trimester. There were no differences in IL-6, C reactive protein and other cytokine levels in CB and maternal serum or placentas.

CONCLUSIONS: Maternal SARS-CoV-2 infection at the first and second trimesters leads to significantly shorter TL and earlier infection causes much more severe TL damage. The infection-mediated cell senescence and other histopathological abnormalities result in defective placental function through which fetal telomere homeostasis is impaired. Thus, vaccination against COVID-19 should be done in advance for women who plan pregnancy.},
}

Humans
Female
Infant, Newborn
*COVID-19/virology
Pregnancy
*Telomere Shortening
Adult
*Pregnancy Complications, Infectious/virology
*SARS-CoV-2/physiology
Pregnancy Trimester, Second
Placenta/virology/metabolism
Fetal Blood/virology
Telomere/metabolism
Cytokines/metabolism/blood
Male

@article {pmid39568075,
year = {2024},
author = {Di Pietro, E and Burla, R and La Torre, M and González-García, MP and Dello Ioio, R and Saggio, I},
title = {Telomeres: an organized string linking plants and mammals.},
journal = {Biology direct},
volume = {19},
number = {1},
pages = {119},
pmid = {39568075},
issn = {1745-6150},
support = {A0375E0189-2020-36640//POR FESR Lazio 2014-2020/ ; 20229LHY5L//Ministero dell'Università e della Ricerca/ ; IG-24614//Fondazione AIRC per la ricerca sul cancro ETS/ ; },
abstract = {Telomeres are pivotal determinants of cell stemness, organismal aging, and lifespan. Herein, we examined similarities in telomeres of Arabidopsis thaliana, mice, and humans. We report the common traits, which include their composition in multimers of TTAGGG sequences and their protection by specialized proteins. Moreover, given the link between telomeres, on the one hand, and cell proliferation and stemness on the other, we discuss the counterintuitive convergence between plants and mammals in this regard, focusing on the impact of niches on cell stemness. Finally, we suggest that tackling the study of telomere function and cell stemness by taking into consideration both plants and mammals can aid in the understanding of interconnections and contribute to research focusing on aging and organismal lifespan determinants.},
}

@article {pmid39567477,
year = {2024},
author = {Wu, H and Luo, LY and Zhang, YH and Zhang, CY and Huang, JH and Mo, DX and Zhao, LM and Wang, ZX and Wang, YC and He-Hua, E and Bai, WL and Han, D and Dou, XT and Ren, YL and Dingkao, R and Chen, HL and Ye, Y and Du, HD and Zhao, ZQ and Wang, XJ and Jia, SG and Liu, ZH and Li, MH},
title = {Telomere-to-telomere genome assembly of a male goat reveals variants associated with cashmere traits.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {10041},
pmid = {39567477},
issn = {2041-1723},
support = {2021YFD1200900//Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology)/ ; },
mesh = {Animals ; *Goats/genetics ; *Telomere/genetics ; Male ; *Polymorphism, Single Nucleotide ; *Genome/genetics ; Breeding ; Genetic Variation ; Y Chromosome/genetics ; Genomic Structural Variation ; },
abstract = {A complete goat (Capra hircus) reference genome enhances analyses of genetic variation, thus providing insights into domestication and selection in goats and related species. Here, we assemble a telomere-to-telomere (T2T) gap-free genome (2.86 Gb) from a cashmere goat (T2T-goat1.0), including a Y chromosome of 20.96 Mb. With a base accuracy of >99.999%, T2T-goat1.0 corrects numerous genome-wide structural and base errors in previous assemblies and adds 288.5 Mb of previously unresolved regions and 446 newly assembled genes to the reference genome. We sequence the genomes of five representative goat breeds for PacBio reads, and use T2T-goat1.0 as a reference to identify a total of 63,417 structural variations (SVs) with up to 4711 (7.42%) in the previously unresolved regions. T2T-goat1.0 was applied in population analyses of global wild and domestic goats, which revealed 32,419 SVs and 25,397,794 SNPs, including 870 SVs and 545,026 SNPs in the previously unresolved regions. Also, our analyses reveal a set of selective variants and genes associated with domestication (e.g., NKG2D and ABCC4) and cashmere traits (e.g., ABCC4 and ASIP).},
}

Animals
*Goats/genetics
*Telomere/genetics
Male
*Polymorphism, Single Nucleotide
*Genome/genetics
Breeding
Genetic Variation
Y Chromosome/genetics
Genomic Structural Variation

@article {pmid39563242,
year = {2024},
author = {Ferguson, S and Bar-Ness, YD and Borevitz, J and Jones, A},
title = {Correction: A telomere-to-telomere Eucalyptus regnans genome: unveiling haplotype variance in structure and genes within one of the world's tallest trees.},
journal = {BMC genomics},
volume = {25},
number = {1},
pages = {1107},
doi = {10.1186/s12864-024-10952-5},
pmid = {39563242},
issn = {1471-2164},
}

@article {pmid39561615,
year = {2024},
author = {Panelli, DM and Mayo, JA and Wong, RJ and Becker, M and Feyaerts, D and Marić, I and Wu, E and Gotlib, IH and Gaudillière, B and Aghaeepour, N and Druzin, ML and Stevenson, DK and Shaw, GM and Bianco, K},
title = {Corrigendum to "Mode of delivery predicts postpartum maternal leukocyte telomere length" [Eur. J. Obstetr. Gynecol. Reprod. Biol. 300 (2024) 224-229].},
journal = {European journal of obstetrics, gynecology, and reproductive biology},
volume = {304},
number = {},
pages = {35},
doi = {10.1016/j.ejogrb.2024.11.017},
pmid = {39561615},
issn = {1872-7654},
}

@article {pmid39561502,
year = {2024},
author = {Pedklang, N and Navasumrit, P and Chompoobut, C and Promvijit, J and Hunsonti, P and Ruchirawat, M},
title = {Effects of particulate air pollution on BPDE-DNA adducts, telomere length, and mitochondrial DNA copy number in human exhaled breath condensate and BEAS-2B cells.},
journal = {International journal of hygiene and environmental health},
volume = {263},
number = {},
pages = {114488},
doi = {10.1016/j.ijheh.2024.114488},
pmid = {39561502},
issn = {1618-131X},
abstract = {Traffic-related particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs) have been linked to respiratory diseases and cancer risk in humans. Genomic damage, including benzo[a]pyrene diolepoxide (BPDE)-DNA adducts as well as alterations in telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN) are associated with respiratory diseases. This study aimed to investigate the association between exposure to traffic-related particulate pollutants and genomic damage in exhaled breath condensate (EBC) in human subjects and a bronchial epithelial cell line (BEAS-2B). Among the 60 healthy recruited subjects, residents living in high-traffic-congested areas were exposed to higher concentrations of PM2.5 (1.66-fold, p < 0.01), UFPs (1.79-fold, p < 0.01), PM2.5-PAHs (1.50-fold, p < 0.01), and UFPs-PAHs (1.35-fold, p < 0.05), than those in low-traffic-congested areas. In line with increased exposure to particulate air pollution, the high-traffic-exposed group had significantly increased BPDE-DNA adducts (1.40-fold, p < 0.05), TL shortening (1.24-fold, p < 0.05), and lower mtDNA-CN (1.38-fold, p < 0.05) in EBC. The observations in the human study linking exposure to PM2.5, UFPs, PM2.5-PAHs, and UFPs-PAHs with the aforementioned biological effects were confirmed by an in vitro cell-based study, in which BEAS-2B cells were treated with diesel exhaust particulate matter (DEP) containing fine and ultrafine PM and PAHs. Increased BPDE-DNA adducts levels, shortened TL, and decreased mtDNA-CN were also found in treated BEAS-2B cells. The shortened TL and decreased mtDNA-CN were in part mediated by decreased transcript levels of hTERT, and SIRT1, which are involved in telomerase activity and mitochondrial biogenesis, respectively. These results suggest that exposure to traffic-related particulate pollutants can cause genomic instability in respiratory cells, which may increase the health risk of respiratory diseases and the development of cancer.},
}

@article {pmid39556024,
year = {2024},
author = {Laemmerer, A and Lehmann, C and Mayr, L and Bruckner, K and Gabler, L and Senfter, D and Meyer, P and Balber, T and Pirker, C and Jaunecker, CN and Kirchhofer, D and Vician, P and Griesser, M and Spiegl-Kreinecker, S and Schmook, MT and Traub-Weidinger, T and Kuess, P and Eckert, F and Federico, A and Madlener, S and Stepien, N and Robl, B and Baumgartner, A and Hainfellner, JA and Dieckmann, K and Dorfer, C and Roessler, K and Corsini, NS and Holzmann, K and Schmidt, WM and Peyrl, A and Azizi, AA and Haberler, C and Beck, A and Pfister, SM and Schueler, J and Loetsch-Gojo, D and Knoblich, JA and Berger, W and Gojo, J},
title = {Alternative lengthening of telomere-based immortalization renders H3G34R -mutant diffuse hemispheric glioma hypersensitive to PARP inhibitor combination regimens.},
journal = {Neuro-oncology},
volume = {},
number = {},
pages = {},
doi = {10.1093/neuonc/noae228},
pmid = {39556024},
issn = {1523-5866},
abstract = {BACKGROUND: Diffuse hemispheric glioma, H3G34R/V-mutant (DHG-H3G34) is characterized by poor prognosis and lack of effective treatment options. DHG-H3G34R further harbor deactivation of Alpha-Thalassemia/Mental Retardation Syndrome X-linked protein (ATRX; DHG-H3G34R_ATRX) suggesting a unique interaction of these two oncogenic alterations. In this study, we dissect their cell biological interplay, investigate the impact on telomere stabilization and, consequently, validate a targeted therapy approach.

METHODS: We characterized patient-derived primary pediatric high-grade glioma (pHGG) models for telomere-maintenance mechanisms, DNA damage stress (including protein expression, pH2AX/Rad51 foci, cell-cycle arrest) and their sensitivity towards poly-ADP polymerase inhibitor (PARPi) combinations. Human induced pluripotent stem cells (iPSCs) were used for modelling the disease. The anticancer activity of PARPi combinations in vivo was studied in Chorioallantoic Membrane (CAM) and orthotopic in vivo experiments. Finally, we treated a DHG-H3G34R_ATRX patient with a PARPi combination therapy.

RESULTS: We elaborate that alternative lengthening of telomeres (ALT) is a key characteristic of DHG-H3G34R_ATRX. A dominant cooperative effect between H3G34R and ATRX loss in ALT activation also became apparent in iPSCs, which endogenously exert telomerase activity. In both, patient-derived DHG-H3G34R_ATRX models and H3G34R+/ATRX- iPSCs, the ALT phenotype was associated with increased basal DNA damage stress, mediating synergistic susceptibility towards PARPi (talazoparib, niraparib) combinations with topoisomerase-I inhibitors (topotecan, irinotecan). In a first-of-its-kind case, treatment of a DHG-H3G34R_ATRX patient with the brain-penetrant PARP inhibitor niraparib and topotecan resulted in a significant tumor reduction.

CONCLUSION: Our preclinical and clinical data strongly support the further development of PARPis together with DNA damage stress-inducing treatment regimens for DHG-H3G34R_ATRX.},
}

@article {pmid39554689,
year = {2024},
author = {Pearce, E and Majid, A and Brown, T and Wilsnack, C and Rising, C and Thompson, AS and Shepherd, RF and Niknafs, A and Werner-Lin, A and Gilkey, MB and Ribisl, KM and Hutson, SP and Han, PKJ and Savage, SA},
title = {A "rotating menu" of medical uncertainty for families affected by telomere biology disorders: A qualitative interview study.},
journal = {SSM. Qualitative research in health},
volume = {6},
number = {},
pages = {},
pmid = {39554689},
issn = {2667-3215},
abstract = {BACKGROUND: Medical uncertainty may cause distress and challenge medical decision-making for patients with rare diseases and their caregivers. Few studies have examined the experience and management of medical uncertainty in rare disease and the dynamics of multiple medical uncertainty sources, issues, and management strategies.

OBJECTIVE: We explored the experience and management of uncertainty in individuals with telomere biology disorders (TBDs), a set of rare cancer-prone bone marrow failure syndromes, and their caregivers.

DESIGN: Participants (N=32) in this qualitative-descriptive study were individuals with a TBD (n=17) and/or their caregivers (n=15). We thematically analyzed transcripts to describe the presence and dynamics of medical uncertainty in TBDs using categories from a previously published taxonomy.

RESULTS: Individuals with TBDs and caregivers described medical uncertainty as a chronic burden embodied amidst a range of interrelated sources and issues. Scientific uncertainty included diagnostic and prognostic ambiguity. Practical uncertainty focused on logistical challenges of building and maintaining medical care teams. Personal uncertainty included difficulty realigning self-identity, goals, and relationship expectations post-diagnosis. Scientific, practical, and personal uncertainty issues were entangled. The rarity of TBDs resulted in limited scientific knowledge, which gave rise to practical and personal uncertainties affecting medical decision-making and relationship formation (e.g., creating trusted care teams where patient knowledge of TBDs may exceed that of clinicians). Participants used multiple strategies for uncertainty management, particularly information-seeking and community-building. However, these management strategies could intensify, rather than resolve, participants' medical uncertainty.

CONCLUSION: In TBDs, medical uncertainty manifests as a network of multiple, interrelated, sources and issues, which require evolving management strategies. Researchers must be mindful that complex, synergistic uncertainty networks contribute to psychosocial challenges in TBDs. Additional research is warranted to address scientific uncertainty in TBDs, including clinical manifestations and underlying biology, and to develop psychosocial interventions that recognize and anticipate evolving uncertainty.},
}

@article {pmid39554068,
year = {2024},
author = {Chung, G and Piano, F and Gunsalus, KC},
title = {TeloSearchLR: an algorithm to detect novel telomere repeat motifs using long sequencing reads.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.10.29.617943},
pmid = {39554068},
issn = {2692-8205},
abstract = {Telomeres are eukaryotic chromosome end structures that guard against sequence loss and aberrant chromosome fusions. Telomeric repeat motifs (TRMs), the minimal repeating unit of a telomere, vary from species to species, with some evolutionary clades experiencing a rapid sequence divergence. To explore the full scope of this evolutionary divergence, many bioinformatic tools have been developed to infer novel TRMs using repetitive sequence search on short sequencing reads. However, novel telomeric motifs remain unidentified in up to half of the sequencing libraries assayed with these tools. A possible reason may be that short reads, derived from extensively sheared DNA, preserve little to no positional context of the repetitive sequences assayed. On the other hand, if a sequencing read is sufficiently long, telomeric sequences must appear at either end rather than in the middle. The TeloSearchLR algorithm relies on this to help identify novel TRMs on long reads, in many cases where short-read search tools have failed. In addition, we demonstrate that TeloSearchLR can reveal unusually long telomeric motifs not maintained by telomerase, and it can also be used to anchor terminal scaffolds in new genome assemblies.},
}

@article {pmid39553389,
year = {2024},
author = {Packer, A and Habiballa, L and Tato-Barcia, E and Breen, G and Brooker, H and Corbett, A and Arathimos, R and Ballard, C and Hampshire, A and Palmer, A and Dima, D and Aarsland, D and Creese, B and Malanchini, M and Powell, TR},
title = {Telomere length and cognitive changes in 7,877 older UK adults of European ancestry.},
journal = {Frontiers in aging},
volume = {5},
number = {},
pages = {1480326},
pmid = {39553389},
issn = {2673-6217},
abstract = {BACKGROUND: Telomere length (TL) has been linked to cognitive function, decline and dementia. This study aimed to explore whether both measured TL and genetic disposition for TL predict dimensions of cognitive performance in a longitudinal sample of older UK adults.

METHODS: We analysed data from PROTECT study participants aged ≥50 years without a dementia diagnosis, who had completed longitudinal cognitive testing. We calculated polygenic scores for telomere length (PGS-TL) for 7,877 participants and measured relative telomere length (RTL) in a subgroup of 846 participants using DNA extracted from saliva samples collected within 6 months either side of their baseline cognitive testing. Latent growth models were used to examine whether RTL and PGS-TL predict both baseline and longitudinal changes in cognitive performance (4 time-points, annually).

RESULTS: In the whole sample, we did not observe significant associations between either measure of telomere length and initial or longitudinal changes in cognitive performance. Stratifying by median age, in older adults (≥ ∼62 years), longer baseline RTL showed a nominal association with poorer baseline verbal reasoning performance (n = 423, M intercept = 47.58, B = -1.05, p = .011) and PGS-TL was associated with performance over time (n = 3,939; slope factor, M slope = 3.23, B = -0.45, p = .001; slope [2] factor, M slope [2] = 0.21, B = 0.13, p = .002).

CONCLUSION: Our findings suggest either the absence of a significant relationship between telomere length (RTL and PGS-TL) and cognitive performance (baseline and change over time), or possibly a weak age-dependent and domain-specific relationship, in older adults of European ancestry. More research is needed in representative and ancestrally diverse samples over a longer assessment period. Alternative biological ageing indicators may still provide utility in the early detection of individuals at risk for cognitive decline (e.g., pace-of ageing epigenetic clocks).},
}

@article {pmid39553152,
year = {2024},
author = {Xie, S and Xiao, H and Zhang, F and Lan, Y and Luo, M},
title = {Identification and Validation of Telomere-Related Gene Signature in Intervertebral Disc Degeneration.},
journal = {Cureus},
volume = {16},
number = {10},
pages = {e71735},
pmid = {39553152},
issn = {2168-8184},
abstract = {This study investigates the role of telomere-related differentially expressed genes (TRDEGs) in intervertebral disc degeneration (IVDD) through comprehensive bioinformatics analyses. Data were sourced from the Gene Expression Omnibus (GEO) with datasets GSE245147 and GSE124272 used for initial identification and validation, respectively. The GSE245147 dataset comprised transcriptional profiles from nucleus pulposus cells of both degenerated and non-degenerated human nucleus pulposus (NP) tissues. Using the limma package, 198TRDEGs were identified by intersecting differentially expressed genes (DEGs) with telomere-related genes (TRGs) from the TelNet database. Functional enrichment analyses using the Database for Annotation, Visualization and Integrated Discovery (DAVID) revealed that TRDEGs are significantly involved in cell division, chromosome segregation, and other mitotic processes. Protein-protein interaction (PPI) networks constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and visualized with Cytoscape (Cytoscape Consortium, San Diego, CA, USA) identified key hub genes such as CDK1, CCNA2, and AURKB. Pearson correlation and receiver operating characteristic (ROC) analyses highlighted five hub genes (ASPM, BUB1B, CDC20, KIF2C, TTK) with significant predictive value for IVDD. Additionally, mRNA-microRNA (miRNA) interaction analysis using NetworkAnalyst identified key miRNAs interacting with these hub genes. This study provides insights into the molecular mechanisms of IVDD and identifies potential targets for therapeutic intervention.},
}

@article {pmid39548087,
year = {2024},
author = {Piras, M and Lin, J and Sadler, MC and Ranjbar, S and Grosu, C and Laaboub, N and Preisig, M and Gamma, F and Plessen, KJ and von Gunten, A and Conus, P and Kutalik, Z and Eap, CB},
title = {Psychotropic-induced weight gain and telomere length: results from a one-year longitudinal study and a large population-based cohort.},
journal = {Translational psychiatry},
volume = {14},
number = {1},
pages = {471},
pmid = {39548087},
issn = {2158-3188},
mesh = {Humans ; *Weight Gain/drug effects/genetics ; Male ; Female ; Longitudinal Studies ; *Psychotropic Drugs/adverse effects ; Middle Aged ; *Telomere Shortening/drug effects ; Adult ; *C-Reactive Protein ; Body Mass Index ; Telomere/drug effects/genetics ; Aged ; },
abstract = {Weight-inducing psychotropic treatments are risk factors for age-related diseases such as cardiovascular disorders, which are associated with both inflammation and telomere length shortening. With a longitudinal design, the present study evaluates telomere length trajectories after 1 year of weight-inducing psychotropic medication, accounting for weight changes and the inflammatory biomarker high-sensitivity C-Reactive Protein (CRP). Among 200 patients, an overall median telomere shortening of -41.2 bp was observed (p = 0.014), which is comparable with the general population's yearly telomere attrition. Linear regression showed on average -93.1 and -58.9 bp of further telomere shortening per five units of BMI for BMI values < or ≥30 kg/m[2], respectively (p = 0.003 and p = 0.009, respectively). Importantly, the overall telomere shortening was predicted to be increased four-fold among patients with low baseline weight (i.e., 50 kg) and with clinically relevant weight gain (≥ 7%) after 1 year of treatment (interaction term between relevant weight gain and baseline weight: +6.3 bp, p = 0.016). Patients with relevant weight gain showed greater CRP levels (+ 49%; p = 0.016), and a telomere shortening of -36.2 bp (p = 0.010) was estimated whenever CRP level doubled. Mendelian randomization using UKBiobank data showed a causal effect of BMI on telomere shortening, notably stronger among patients receiving weight-inducing psychotropic treatments (n = 9798) than among psychiatric patients without such drugs (n = 16228) and non-psychiatric controls (n = 252932) (beta: -0.37, -0.12, -0.06, respectively; p = 0.004, p < 0.001, p < 0.001, respectively). Ultimately, telomere trajectories were associated with 1 year weight gain and increases in CRP levels, with telomere shortening strongly enhanced by BMI increments among patients receiving weight-inducing psychotropic treatments.},
}

Humans
*Weight Gain/drug effects/genetics
Male
Female
Longitudinal Studies
*Psychotropic Drugs/adverse effects
Middle Aged
*Telomere Shortening/drug effects
Adult
*C-Reactive Protein
Body Mass Index
Telomere/drug effects/genetics
Aged

@article {pmid39543404,
year = {2024},
author = {Muñoz-Pardeza, J and López-Gil, JF and Huerta-Uribe, N and Hormazábal-Aguayo, I and Ojeda-Rodríguez, A and Del Moral, AM and Izquierdo, M and García-Hermoso, A},
title = {Is physical fitness associated with leucocyte telomere length in youth with type 1 diabetes?.},
journal = {Pediatric research},
volume = {},
number = {},
pages = {},
pmid = {39543404},
issn = {1530-0447},
abstract = {BACKGROUND: In type 1 diabetes, telomere length (TL) may predict complications and could be influenced by glycaemic control and physical activity, but its relationship with physical fitness in youths remains unexplored. The aim of the study was to assess the association between physical fitness and TL in youth with type 1 diabetes, both at baseline and one year later.

METHODS: Eighty-three children and adolescents (aged 6-18 years; 44.6% girls) with type 1 diabetes from the Diactive-1 Cohort Study were involved in this study. Physical fitness was assessed using spirometry on a cycloergometer (i.e., peak oxygen consumption), dynamometry, and maximal isometric strength (one-repetition maximum [1RM]), and muscle power. Leucocyte TL was assessed using multiplex monochrome real-time quantitative polymerase chain reaction.

RESULTS: Positive cross-sectional associations were identified between 1RM (unstandardized beta coefficient [B] = 0.042, 95% bias corrected and accelerated [BCa] confidence interval [CI] 0.012-0.069), muscle power (B = 0.056, 95% BCa CI 0.02-0.250), and overall physical fitness (B = 0.043, 95% BCa CI 0.015-0.071) with TL independent of maturation, glycated haemoglobin, and diabetes duration. However, no associations were observed one year later.

CONCLUSION: Higher levels of fitness, particularly muscle strength, may play a role in telomere dynamics in youth with type 1 diabetes, suggesting that strength training exercise could be beneficial.

IMPACT: This is the first study to examine cross-sectional and longitudinal perspectives on the correlation among muscle strength, peak oxygen consumption [VO2peak] and telomere length in youths with type 1 diabetes. Higher physical fitness levels, as assessed by measures such as one-repetition maximum, muscle power, and overall physical fitness, are positively associated with telomere length in youths with type 1 diabetes. Understanding this link could improve management strategies, prioritizing muscle strength training for better long-term health in type 1 diabetes.},
}

@article {pmid39538053,
year = {2024},
author = {da Cunha Agostini, L and da Silva, GN},
title = {Telomere length as a biomarker for cerebrovascular diseases: current evidence.},
journal = {Molecular biology reports},
volume = {51},
number = {1},
pages = {1150},
pmid = {39538053},
issn = {1573-4978},
support = {001//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; 314486/2023-2//Conselho Nacional de Desenvolvimento Científico e Tecnológico , Brasil/ ; APQ-03555-22//Fundação de Amparo à Pesquisa do Estado de Minas Gerais , Brasil/ ; 23109.016819/2023-81//Pró-Reitoria de Pesquisa e Pós-Graduação, Universidade Federal de Ouro Preto/ ; 23109.009436/2023-56//Pró-Reitoria de Pesquisa e Pós-Graduação, Universidade Federal de Ouro Preto/ ; },
abstract = {Cerebrovascular disease (CVD) includes a range of conditions affecting the brain's blood vessels, which can result in reduced blood flow to brain tissue. The most common manifestation of CVD is stroke, the second leading cause of death and the third leading cause of disability worldwide. Major risk factors for CVD encompass gender, age, smoking, hypertension, diabetes, physical inactivity, obesity, alcohol consumption, and metabolic syndrome. Research suggests a link between telomere length and an increased risk of CVD, particularly in ischemic stroke cases. This review highlights key findings on the relationship between telomere length and CVD, underscoring its clinical importance. The analysis utilizes scientific literature from PubMed, Scopus, and SciELO up to 2024. Results show that shorter telomere length is associated with various types of CVD, including stroke, ischemic stroke, hemorrhagic stroke, and cardioembolic stroke. Some studies propose that telomere length measurement could be a valuable biomarker for CVD, potentially improving prevention, diagnosis, and management strategies.},
}

@article {pmid39537670,
year = {2024},
author = {Katneni, VK and Krishnan, K and Prabhudas, SK and Jayaraman, R and Quraishi, N and Vasagam, K and Jangam, AK and Angel, JRJ and Kaikkolante, N and Jayaraman, K and Mudagandur, SS},
title = {Genome assembly at chromosome scale with telomere ends for Pearlspot, Etroplus suratensis.},
journal = {Scientific data},
volume = {11},
number = {1},
pages = {1226},
pmid = {39537670},
issn = {2052-4463},
support = {BT/PR34518/AAQ/3/965/2019//Department of Biotechnology, Ministry of Science and Technology (DBT)/ ; },
mesh = {Animals ; *Cichlids/genetics ; *Genome ; *Telomere/genetics ; Chromosomes ; Salinity ; },
abstract = {The pearlspot, Etroplus suratensis is a climate resilient cichlid fish that exhibits unusual adaptation to salinity. The fish is able to complete full life cycle in diverse salinity habitats ranging from fresh water to marine environments. High-quality primary and phased genome assemblies were generated for pearlspot fish using PacBio HiFi and Arima HiC sequencing technologies, for the first time. The primary assembly is highly contiguous with contig N50 length of 36 Mb. The final assembly is of 1.247 Gb with N50 length of 51.57 Mb and 98% of the genome length anchored to 24 chromosomes. The genome was assessed to be 99.9% complete based on BUSCO evaluation and was predicted to contain 52.96% repeat elements. We have predicted 27,192 protein encoding genes, of which 21,580 were functionally annotated. The genome offers an invaluable resource to understand adaptation of pearlspot fish to diverse salinity habitats.},
}

Animals
*Cichlids/genetics
*Genome
*Telomere/genetics
Chromosomes
Salinity

@article {pmid39533571,
year = {2024},
author = {Li, J and Hu, L and Huang, X},
title = {Causal relationship between leukocyte telomere length and two cardiomyopathies based on a bidirectional Mendelian randomization approach.},
journal = {Medicine},
volume = {103},
number = {45},
pages = {e40308},
doi = {10.1097/MD.0000000000040308},
pmid = {39533571},
issn = {1536-5964},
support = {No. 2022YFC3500102//National Key Research and Development Program of China/ ; },
mesh = {Humans ; *Mendelian Randomization Analysis ; *Leukocytes ; Telomere/genetics ; Cardiomyopathy, Dilated/genetics ; Cardiomyopathies/genetics ; Cardiomyopathy, Hypertrophic/genetics ; Genetic Predisposition to Disease ; },
abstract = {This study aims to employ the Mendelian randomization (MR) approach to investigate the relationship between leukocyte telomere length (TL) and 2 prevalent forms of cardiomyopathies. Using R software (4.3.1) for MR study, independent genetic variants associated with leukocyte TL were extracted from the Integrative Epidemiology Unit database, while cardiomyopathies data were pooled from FinnGen and European Bioinformatics Institute databases. Analytical methodologies included inverse-variance weighting, MR-Egger regression, and weighted median methods. Further analyses involved MR-Egger intercept and MR-PRESSO for handling horizontal pleiotropy and Cochran Q test for study heterogeneity. Our forward Mendelian randomization study indicates a positive correlation between longer leukocyte TL and the risk of 2 forms of cardiomyopathies: the longer the leukocyte telomere, the higher is the risk of cardiomyopathies. Specifically, for hypertrophic obstructive cardiomyopathy the OR is 2.23 (95% CI: 1.19-4.14, P = .01), for hypertrophic cardiomyopathy the OR is 1.80 (95% CI: 1.14-2.85, P = .01), and for dilated cardiomyopathy the OR is 1.32 (95% CI: 1.01-1.71, P = .04). In contrast, our reverse Mendelian randomization showed that cardiomyopathies were not directly associated with TL, and the inverse-variance-weighted test was not statistically significant for any of the 3 (P > .05). The reliability tests for the forward Mendelian randomization, including both MR-Egger intercept and MR-PRESSO tests, show no evidence of horizontal pleiotropy, and Cochran Q test indicates no heterogeneity. The "leave-one-out" sensitivity analysis revealed no outlier genes. The reliability tests for the reverse Mendelian randomization, including both MR-Egger intercept and MR-PRESSO tests, also indicate no genetic pleiotropy. Despite the heterogeneity shown in our study between hypertrophic cardiomyopathy and leukocyte TL, the sensitivity analysis did not identify any anomalies. Our Mendelian randomization study suggests that longer leukocyte TL is associated with an increased risk of hypertrophic obstructive cardiomyopathy, hypertrophic cardiomyopathy, and dilated cardiomyopathy. However, the onset of these 2 kinds of disease does not directly lead to changes in leukocyte TL.},
}

Humans
*Mendelian Randomization Analysis
*Leukocytes
Telomere/genetics
Cardiomyopathy, Dilated/genetics
Cardiomyopathies/genetics
Cardiomyopathy, Hypertrophic/genetics
Genetic Predisposition to Disease

@article {pmid39525171,
year = {2024},
author = {Mazumdar, J and Chowdhury, P and Mondal, BC and Das, AK and Ghosh, U},
title = {Elevated Telomeric Repeat-Containing RNA (TERRA) Levels Linked to Telomere Dysfunction and Telomerase Inactivity in Blood Cells of Children With Aplastic Anemia.},
journal = {Cureus},
volume = {16},
number = {10},
pages = {e71241},
pmid = {39525171},
issn = {2168-8184},
abstract = {Background Aplastic anemia (AA) is characterized by pancytopenia and hypocellularity of the bone marrow. Certain inherited or genetic forms of AA have also been associated with telomere dysfunction. Here, we report the clinical manifestations of eleven AA patients aged between one and 12 years, along with the expression of a few candidate genes involved in the telomere length (TL) maintenance pathway. Methods The clinical manifestations were recorded for all the patients. The average telomere length of peripheral blood mononuclear cells (PBMC), the expression of telomerase subunits, telomere-associated proteins, and chromosome-specific telomeric repeat-containing RNA (TERRA) in whole blood cells of each patient was compared with an age-matched control group consisting of five clinically confirmed normal individuals. Results Out of 11 AA patients, four were found to have upper limb anomalies, and two showed short stature along with other defects. All the patients showed significantly shorter telomere length compared with the age-matched control group. The essential subunits of telomerase (hTERT and hTERC) were significantly low, and the shelterin protein is abnormally expressed in all patients implicating a compromised TL maintenance pathway. Notably, AA with combined androgen and prednisolone treatment showed a marked reduction of TERRA level than that of AA without androgen/prednisolone therapy. Conclusion Based on the findings and observations made, it appears that there might be an association between telomere dysfunction and elevated levels of TERRA in patients diagnosed with aplastic anemia who are 12 years of age or younger.},
}

@article {pmid39514990,
year = {2024},
author = {Amatya, S and Bhatia, P and Raina, S and Sreedharanunni, S and Singh, M and Rahman, E and Archana, MV and Trehan, A},
title = {Corrigendum to "Clinical utility of relative telomere length analysis in pediatric bone marrow failure" [Blood Cells Mol. Dis. 109 (2024) 102882].},
journal = {Blood cells, molecules & diseases},
volume = {110},
number = {},
pages = {102899},
doi = {10.1016/j.bcmd.2024.102899},
pmid = {39514990},
issn = {1096-0961},
}

@article {pmid39513855,
year = {2024},
author = {Knecht, H and Petrogiannis-Haliotis, T and Louis, S and Mai, S},
title = {3D-Q-FISH/Telomere/TRF2 Nanotechnology Identifies a Progressively Disturbed Telomere/Shelterin/Lamin AC Complex as the Common Pathogenic, Molecular/Spatial Denominator of Classical Hodgkin Lymphoma.},
journal = {Cells},
volume = {13},
number = {21},
pages = {},
doi = {10.3390/cells13211748},
pmid = {39513855},
issn = {2073-4409},
mesh = {*Hodgkin Disease/genetics/pathology/virology/metabolism/diagnosis ; Humans ; *Telomere/metabolism ; Cell Line, Tumor ; In Situ Hybridization, Fluorescence ; Nanotechnology/methods ; Reed-Sternberg Cells/metabolism/pathology ; Shelterin Complex/metabolism ; },
abstract = {The bi- or multinucleated Reed-Sternberg cell (RS) is the diagnostic cornerstone of Epstein-Barr Virus (EBV)-positive and EBV-negative classical Hodgkin lymphoma (cHL). cHL is a germinal center (GC)-derived B-cell disease. Hodgkin cells (H) are the mononuclear precursors of RS. An experimental model has to fulfill three conditions to qualify as common pathogenic denominator: (i) to be of GC-derived B-cell origin, (ii) to be EBV-negative to avoid EBV latency III expression and (iii) to support permanent EBV-encoded oncogenic latent membrane protein (LMP1) expression upon induction. These conditions are unified in the EBV-, diffuse large B-Cell lymphoma (DLBCL) cell line BJAB-tTA-LMP1. 3D reconstructive nanotechnology revealed spatial, quantitative and qualitative disturbance of telomere/shelterin interactions in mononuclear H-like cells, with further progression during transition to RS-like cells, including progressive complexity of the karyotype with every mitotic cycle, due to BBF (breakage/bridge/fusion) events. The findings of this model were confirmed in diagnostic patient samples and correlate with clinical outcomes. Moreover, in vitro, significant disturbance of the lamin AC/telomere interaction progressively occurred. In summary, our research over the past three decades identified cHL as the first lymphoid malignancy driven by a disturbed telomere/shelterin/lamin AC interaction, generating the diagnostic RS. Our findings may act as trailblazer for tailored therapies in refractory cHL.},
}

*Hodgkin Disease/genetics/pathology/virology/metabolism/diagnosis
Humans
*Telomere/metabolism
Cell Line, Tumor
In Situ Hybridization, Fluorescence
Nanotechnology/methods
Reed-Sternberg Cells/metabolism/pathology
Shelterin Complex/metabolism

@article {pmid39512472,
year = {2024},
author = {Zhu, S and Zheng, W and Rao, D and Tang, Z and Liao, X},
title = {Leukocyte telomere length and lung function: a mendelian randomization study in European population.},
journal = {Frontiers in physiology},
volume = {15},
number = {},
pages = {1373064},
pmid = {39512472},
issn = {1664-042X},
abstract = {BACKGROUND: The telomere has long been regarded as a dependable biomarker for cellular senescence. The lung function can reflect the function and status of the lungs. As individuals age beyond adulthood, there is a gradual decline in lung function. However, the existence of a associated between leukocyte telomere length (LTL) and lung function remains uncertain.

METHODS: A two-sample Mendelian randomization (MR) analysis was used. The Single-nucleotide polymorphisms (SNPs) of LTL from the genome-wide association (GWAS) study were used as exposure instruments variable, and the lung function indicator including Forced expiratory volume in 1-s (FEV1), FEV1 Best measure, FEV1 predicted and Forced vital capacity (FVC) from the Neale Lab and MRC-IEU were used as outcomes. The associated between the exposures and outcomes was assessed using inverse-variance weighted (IVW), MR-Egger, and weighted median methods. Sensitivity analysis was conducted using Cochran's Q-test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and Steriger test.

RESULTS: Using the IVW method, a significant association was identified between genetically determined telomere length extension and enhanced lung function in FEV1, with ukb-a-336 (P = 0.127, OR = 1.028,95CI% = 1.003-1.042) and ukb-b-19657 (P = 7.26E-05, OR = 1.051,95CI% = 1.025-1.077),in FEV1 predicted, ukb-a-234 (P = 0.013, OR = 1.029,95CI% = 1.003-1.042), ukb-b-8428 (P = 0.001, OR = 1.032,95CI% = 1.012-1.052), in FEV1 best measure, ukb-a-231 (P = 7.24E-05, OR = 1.050,95CI% = 1.025-1.075), ukb-b-11141 (P = 1.40E-09, OR = 1.067,95CI% = 1.045-1.090).The sensitivity analysis did not reveal heterogeneity or horizontal pleiotropy.Meanwhile, the Steriger test results also indicate that the directionality between exposure and outcome is correct. Therefore, the results indicated robustness.

CONCLUSION: There is a correlation between longer LTL and better lung function in the European dataset.},
}

@article {pmid39511975,
year = {2024},
author = {Hu, T and Duan, L and Shangguan, L and Zhao, Q and Hang, Y and Wang, X and Li, X and Yang, N and Yan, F and Lv, Q and Tang, L and Liu, M and Qiang, W and Wang, X and Wang, X and Zhang, M},
title = {Haploid-Phased Chromosomal Telomere-to-Telomere Genome Assembly of Medicinal Plant Uncaria rhynchophylla Dissects Genetic Controls on the Biosynthesis of Bioactive Alkaloids.},
journal = {Plant, cell & environment},
volume = {},
number = {},
pages = {},
doi = {10.1111/pce.15257},
pmid = {39511975},
issn = {1365-3040},
support = {//This work was supported by the Key Core Technology Research Project for Mountainous Agriculture in Guizhou (GZNYGJHX-2023011); the Major Special Project of Science and Technology Programme in Guizhou (2017-5411-06); the Construction Project of State Engineering Technology Institute for Karst Desertification Control of China (2012FU125X13); the Construction Project of Modern Industry Technology system of traditional Chinese Medicinal Materials in Guizhou (GZCYTX-02); Guizhou Provincial Basic Research Programme (Natural Science) (Qian Ke He Ji Chu-ZK [2022] General 096) and the Scientific Research Project of Ordinary Undergraduate Colleges and Universities of Guizhou Provincial Department of Education (Qian Jiao Ji [2022] No. 145)./ ; },
abstract = {Natural indole alkaloids provide important medicinal resources and defences to environmental stresses. The Uncaria genus is a recorded traditional medicinal woody plant with high alkaloids. Genomic insights into alkaloid variation remain elusive. Here, we have dissected the haploid-resolved chromosomal T2T genome assembly of Uncaria rhynchophylla with a size of ~634 Mb and contig N50 of 27 Mb using PacBio HiFi long-reads plus Hi-C reads and anchored the contigs on 22 pairs of confirmed chromosomes. This genome contains 56% repeat sequences and ~29 000 protein-encoding genes. U. rhynchophylla diverged from a common ancestor shared with Coffea around 20 million years ago and contains expanded and contracted gene families associated with secondary metabolites and defences/resistance to stresses. We constructed the pathway and mined genes for rhynchophylline alkaloid biosynthesis. Fifty-three alkaloids in this pathway and eight differentially expressed genes are the keys to alkaloid accumulation. Elevated alkaloid levels are driven by high copy numbers of critical genes STRs and SGRs involved in strictosidine synthesis and hydrolysis as evidenced by phylogenetic, expression and RNA interference analyses. These results advance our genetic understanding and guide further breeding improvements, stress adaptation studies and pharmaceutical development.},
}

@article {pmid39509271,
year = {2024},
author = {Lynskey, ML and Brown, EE and Bhargava, R and Wondisford, AR and Ouriou, JB and Freund, O and Bowman, RW and Smith, BA and Lardo, SM and Schamus-Hayes, S and Hainer, SJ and O'Sullivan, RJ},
title = {HIRA protects telomeres against R-loop-induced instability in ALT cancer cells.},
journal = {Cell reports},
volume = {43},
number = {11},
pages = {114964},
doi = {10.1016/j.celrep.2024.114964},
pmid = {39509271},
issn = {2211-1247},
abstract = {Inactivating mutations in chromatin modifiers, like the α-thalassemia/mental retardation, X-linked (ATRX)-death domain-associated protein (DAXX) chromatin remodeling/histone H3.3 deposition complex, drive the cancer-specific alternative lengthening of telomeres (ALT) pathway. Prior studies revealed that HIRA, another histone H3.3 chaperone, compensates for ATRX-DAXX loss at telomeres to sustain ALT cancer cell survival. How HIRA rescues telomeres from the consequences of ATRX-DAXX deficiency remains unclear. Here, using an assay for transposase-accessible chromatin using sequencing (ATAC-seq) and cleavage under targets and release using nuclease (CUT&RUN), we establish that HIRA-mediated deposition of new H3.3 maintains telomeric chromatin accessibility to prevent the detrimental accumulation of nucleosome-free single-stranded DNA (ssDNA) in ATRX-DAXX-deficient ALT cells. We show that the HIRA-UBN1/UBN2 complex deposits new H3.3 to prevent TERRA R-loop buildup and transcription-replication conflicts (TRCs) at telomeres. Furthermore, HIRA-mediated H3.3 incorporation into telomeric chromatin links productive ALT to the phosphorylation of serine 31, an H3.3-specific amino acid, by Chk1. Therefore, we identify a critical role for HIRA-mediated H3.3 deposition that ensures the survival of ATRX-DAXX-deficient ALT cancer cells.},
}

@article {pmid39531590,
year = {2024},
author = {Zhang, B and Zhao, Y},
title = {Association Analysis of Telomere Length and Vision in a Large Community-Based Survey.},
journal = {Ophthalmic epidemiology},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/09286586.2024.2422349},
pmid = {39531590},
issn = {1744-5086},
abstract = {PURPOSE: To investigate whether there is a direct, age-independent association between telomere length and visual acuity decline in a large community-based cohort study.

METHODS: Participants older than 40 with linked leukocyte telomere length (LTL) were enrolled in NHANES. LTL was assayed using qPCR from the participants' blood samples. Best corrected visual acuity (BCVA) of the better-seeing eye was analyzed, with visual impairment (VI) defined as BCVA ≥ 20/40. LTL was grouped into quartiles, and its association with BCVA and VI was evaluated after adjusting for covariates.

RESULTS: Among the 4,480 enrolled participants, the weighted means of age, BCVA, and telomere length were 56.1 ± 11.9 years, 0.05 ± 0.08 logMAR, and 5,662 ± 36 base pairs, respectively. The proportion of VI was 2.6%. After adjusting for covariates including sex, ethnicity, education, family poverty income ratio, general health status, hypertension, diabetes, smoking, and body mass index, BCVA was significantly worse in participants with shorter LTL, with a significant trend (p = 0.002). However, after further adjusting for age, the association between LTL and BCVA was no longer significant, without a trend (p = 0.640). No significant association or trend between LTL and VI was found in the stepwise logistic model.

CONCLUSIONS: No age-independent association between LTL and BCVA was found. Our study indicates LTL may not serve as a biomarker for age-related visual acuity decline.},
}

@article {pmid39529015,
year = {2024},
author = {Zeng, F and Chen, Y and Lin, J},
title = {Identification of alternative lengthening of telomeres-related genes prognosis model in hepatocellular carcinoma.},
journal = {BMC cancer},
volume = {24},
number = {1},
pages = {1386},
pmid = {39529015},
issn = {1471-2407},
mesh = {Humans ; *Carcinoma, Hepatocellular/genetics/pathology/mortality ; *Liver Neoplasms/genetics/pathology/mortality ; Prognosis ; *Biomarkers, Tumor/genetics ; *Gene Expression Regulation, Neoplastic ; Telomere Homeostasis/genetics ; Cell Proliferation/genetics ; Nomograms ; Cell Line, Tumor ; Female ; Male ; Gene Expression Profiling ; Kaplan-Meier Estimate ; },
abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide, characterized by high mortality. This study aimed to explore the prognostic value and function of alternative lengthening of telomeres (ALT)-related genes in HCC.

METHODS: Differentially expressed genes (DEGs) were identified based on The Cancer Genome Atlas (TCGA) and then intersected with ALT-related genes to obtain ALTDEGs. Risk score model was constructed using the least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression and validated with Gene Expression Omnibus (GEO) datasets. The predictive efficacy of the risk score and ALTs-score was evaluated by Kaplan-Meier curves, time-ROC curves, and the nomogram analyses. The impacts of SMG5 silencing on the HCC cell behaviors were assessed by CCK-8, wound healing, and Transwell assays.

RESULTS: A total of 500 ALTDEGs were screened and 13 genes (CDCA8, SMG5, RAD54B, FOXD2, NOL10, RRP12, CCT5, CCT4, HDAC1, DDX1, HRG, HDAC2, and PPP1CB) were identified for constructing a prognostic model. The overall survival (OS) curves, time-ROC curves, and nomograms based on the risk score or ALTs-score were developed to optimally predict the survival of HCC patients. ALTs-score was correlated with immune infiltration and confirmed its value in predicting immunotherapy outcomes. Furthermore, RT-qPCR demonstrated that eight risk signature genes were up-regulated in HCC cells. SMG5 silencing suppressed the proliferation, migration, and invasion of HCC cells. It was also found that SMG5 silencing reduced C-circle level in SNU-387 cells.

CONCLUSION: We identified new ALT-related prognostic biomarkers for HCC. SMG5 knockdown inhibited the HCC progression, which might be a promising target for HCC therapy.},
}

Humans
*Carcinoma, Hepatocellular/genetics/pathology/mortality
*Liver Neoplasms/genetics/pathology/mortality
Prognosis
*Biomarkers, Tumor/genetics
*Gene Expression Regulation, Neoplastic
Telomere Homeostasis/genetics
Cell Proliferation/genetics
Nomograms
Cell Line, Tumor
Female
Male
Gene Expression Profiling
Kaplan-Meier Estimate

@article {pmid39528945,
year = {2024},
author = {Kezer, CA and Kusztos, V and Kassmeyer, B and Lennon, R and Rattan, P and Kamath, PS and Shah, VH and Simonetto, DA},
title = {Impact of sociodemographic disparities on sarcopenia, telomere length, and mortality in patients with liver disease in the US population.},
journal = {BMC gastroenterology},
volume = {24},
number = {1},
pages = {404},
pmid = {39528945},
issn = {1471-230X},
mesh = {Humans ; *Sarcopenia/mortality ; Male ; Female ; Middle Aged ; *Liver Diseases/mortality ; United States/epidemiology ; Aged ; Adult ; *Nutrition Surveys ; Age Factors ; Telomere/genetics ; Proportional Hazards Models ; Telomere Shortening ; Sociodemographic Factors ; Socioeconomic Factors ; Comorbidity ; },
abstract = {BACKGROUND & AIMS: Sarcopenia is common in patients with liver disease and both sarcopenia and short telomeres are associated with mortality, however their relationship in patients with liver disease remains unknown.

METHODS: A cohort of 16,072 adults from the National Health and Nutrition Examination Survey from 1999 to 2006 was analyzed. Liver disease was defined by aminotransferases and classified into etiology-based categories. Sarcopenia was defined by dual-energy x-ray absorptiometry. All analyses were conducted separately on each multiple imputation data set and combined via Rubin's rules. P-values for group comparisons were calculated by testing logistic regression parameter estimates. Cox proportional hazards regression was used for mortality analysis with mortality data available until 2015.

RESULTS: Sarcopenia was present in 9.5% of patients with liver disease. Age, race, income, education, physical inactivity, and certain medical comorbidities were associated with sarcopenia. Patients with liver disease and sarcopenia had significantly shorter telomeres than patients with liver disease without sarcopenia when unadjusted for age. The interaction between telomere length and sarcopenia was significantly associated with all-cause mortality.

CONCLUSIONS: The implications of telomere length on all-cause mortality in patients with liver disease varied by age and sarcopenia status. Shorter telomeres appear to be more highly associated with increased mortality in older patients without sarcopenia.},
}

Humans
*Sarcopenia/mortality
Male
Female
Middle Aged
*Liver Diseases/mortality
United States/epidemiology
Aged
Adult
*Nutrition Surveys
Age Factors
Telomere/genetics
Proportional Hazards Models
Telomere Shortening
Sociodemographic Factors
Socioeconomic Factors
Comorbidity

@article {pmid39528488,
year = {2024},
author = {Giaccherini, M and Clay-Gilmour, AI and Liotti, R and Macauda, A and Gentiluomo, M and Brown, EE and Machiela, MJ and Chanock, SJ and Hildebrandt, MAT and Norman, AD and Manasanch, E and Rajkumar, SV and Hofmann, JN and Berndt, SI and Bhatti, P and Giles, GG and Ziv, E and Kumar, SK and Camp, NJ and Cozen, W and Slager, SL and Canzian, F and Gemignani, F and Vachon, CM and Campa, D},
title = {Genetically determined telomere length in monoclonal gammopathy of undetermined significance, multiple myeloma risk and outcome.},
journal = {Blood cancer journal},
volume = {14},
number = {1},
pages = {200},
pmid = {39528488},
issn = {2044-5385},
}

@article {pmid39527203,
year = {2025},
author = {Zhang, H and Kerr, C and Audry, J and Runge, KW},
title = {A Rapidly Inducible DNA Double-Strand Break to Monitor Telomere Formation, DNA Repair, and Checkpoint Activation.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2862},
number = {},
pages = {209-221},
pmid = {39527203},
issn = {1940-6029},
mesh = {*DNA Breaks, Double-Stranded ; *Schizosaccharomyces/genetics/metabolism ; *DNA Repair ; *Telomere/metabolism/genetics ; Cell Cycle Checkpoints ; Deoxyribonucleases, Type II Site-Specific/metabolism ; DNA, Fungal/genetics/metabolism ; Schizosaccharomyces pombe Proteins/metabolism/genetics ; },
abstract = {The study of processes that govern genome integrity has been augmented by the ability to create a precise DNA double-strand break (DSB) in a short period of time that allows the kinetics of DNA metabolism and protein recruitment to be followed. Defined DSBs are made by expressing endonucleases with long recognition sites that are rare or absent in the genome, and require that the endonuclease is only active when induced. Research in this area in Schizosaccharomyces pombe was limited because rapidly inducible promoters were not available until around 2005, and several rapidly inducible DSB systems are now available. Here, we describe a system to rapidly induce a modified I-SceI endonuclease that can generate a DSB 20 min after induction. I-SceI has no recognition sites in the S. pombe genome, allowing the introduction of complex substrates to monitor the effects of a new DSB in real time. This chapter describes how I-SceI can be most efficiently induced and a simple cell length measurement assay to monitor cell cycle checkpoint activation from a single DSB.},
}

*DNA Breaks, Double-Stranded
*Schizosaccharomyces/genetics/metabolism
*DNA Repair
*Telomere/metabolism/genetics
Cell Cycle Checkpoints
Deoxyribonucleases, Type II Site-Specific/metabolism
DNA, Fungal/genetics/metabolism
Schizosaccharomyces pombe Proteins/metabolism/genetics

@article {pmid39526375,
year = {2024},
author = {Blanchard, M and Lin, J and Hurley, S and Goldberg, D and Von Behren, J and Wang, SS and Reynolds, P and Clague DeHart, J},
title = {Telomere length and chronotype among women in the California Teachers Study (CTS).},
journal = {Chronobiology international},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/07420528.2024.2422865},
pmid = {39526375},
issn = {1525-6073},
abstract = {While links between certain chronotypes and poorer health outcomes have been well established in previous studies, few studies have examined the relationship between chronotype and cellular aging. Using data from the California Teachers Study (CTS), the present study evaluates the relationship between cellular aging and chronobiology through an analysis of leukocyte telomere length (LTL) and chronotype among 817 predominantly postmenopausal women with no history of cancer and occupations not associated with night-shift work. Unconditional logistic regression models were run to estimate odds ratios (ORs) for each chronotype category, adjusted for age, ethnicity, and smoking status. Analyses were then stratified by potential modifiers to assess whether results varied among specific subgroups within the sample. Women who reported being current evening types and evening types from teen years to now were significantly less likely to have short LTL compared to women who reported being current morning types or morning types from teen years to now (OR = 0.72; 95% CI = 0.53-0.98; OR = 0.57; 95% CI = 0.39-0.84). Our results suggest that women with no history of cancer who identify as evening chronotypes may undergo decreased cellular aging compared to women in the same population who identify as morning types. Further studies on populations of postmenopausal women are warranted.},
}

@article {pmid39523870,
year = {2024},
author = {Qi, X and Gao, L and Qi, L},
title = {Genetic Determinants of Telomere Length and Risk of Aneurysmal Subarachnoid Hemorrhage: A Bidirectional Two-Sample Mendelian Randomization Study.},
journal = {The International journal of neuroscience},
volume = {},
number = {},
pages = {1-22},
doi = {10.1080/00207454.2024.2414285},
pmid = {39523870},
issn = {1563-5279},
abstract = {BACKGROUND: Our objective is to investigate the potential causal relationship between telomere length (TL) and aneurysmal subarachnoid hemorrhage (aSAH) and intracranial aneurysms (IAs) by conducting a bidirectional two-sample Mendelian Randomization (MR) study.

METHODS: We utilized publicly available summary data from genome-wide association studies (GWAS) for comprehensive analysis. Telomere length-associated data were sourced from the Epidemiology Unit (IEU) GWAS database (n = 472,174), while data pertaining to intracranial aneurysms were derived from a GWAS meta-analysis conducted by Bakker et al, encompassing aneurysmal subtypes including aSAH (n = 77,074), IAs (n = 79,429), and unruptured intracranial aneurysms (uIA) (n = 74,004), all sampled from European populations. The primary method for MR analysis employed was the Inverse Variance Weighted (IVW) method. Additionally, we conducted various sensitivity analyses to assess the heterogeneity and pleiotropy of study findings. Reverse MR analysis was employed to explore potential reverse causality.

RESULTS: In the forward MR analysis, the IVW method indicated a negative association between TL and aSAH (OR = 0.636, 95% CI: 0.459-0.883, p = 0.006) as well as IAs (OR = 0.670, 95% CI: 0.499-0.900, p = 0.0079). There was no evidence of heterogeneity or horizontal pleiotropy in the forward MR analysis. Reverse MR analysis did not reveal any causal relationship between aSAH, IAs, uIA and TL.

CONCLUSIONS: In European populations, there exists a causal relationship between longer TL and reduced risks of aSAH and IAs Further research is warranted to elucidate the underlying mechanisms and the potential of TL as an intervention target for lowering the incidence of aSAH and IAs.},
}

@article {pmid39522643,
year = {2024},
author = {Heaphy, CM and Patel, S and Smith, K and Wondisford, AR and Lynskey, ML and O'Sullivan, RJ and Fuhrer, K and Han, X and Seethala, RR and Liu, TC and Cao, D and Ertunc, O and Zheng, Q and Stojanova, M and Zureikat, AH and Paniccia, A and Lee, K and Ongchin, MC and Pingpank, JF and Zeh, HJ and Hogg, ME and Geller, D and Marsh, JW and Brand, RE and Chennat, JS and Das, R and Fasanella, KE and Gabbert, C and Khalid, A and McGrath, K and Lennon, AM and Sarkaria, S and Singh, H and Slivka, A and Hsu, D and Zhang, JY and Nacev, BA and Nikiforova, MN and Wald, AI and Vaddi, N and De Marzo, AM and Singhi, AH and Bell, PD and Singhi, AD},
title = {Detection of Alternative Lengthening of Telomeres via Chromogenic in situ Hybridization (ALT-CISH) for the Prognostication of PanNETs and Other Neoplasms.},
journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc},
volume = {},
number = {},
pages = {100651},
doi = {10.1016/j.modpat.2024.100651},
pmid = {39522643},
issn = {1530-0285},
abstract = {Molecular studies have shown ALT to be an important prognostic biomarker of shorter relapse-free survival (RFS) for patients with pancreatic neuroendocrine tumors (PanNETs) and other neoplasms. However, the preferred method of detecting ALT in tissue is by fluorescence in situ hybridization (FISH), which has several clinical limitations. These issues necessitate the creation of a chromogenic ALT assay that can be easily implemented into routine practice. A CISH assay was developed using genetically modified osteosarcoma cell lines, 20 normal pancreata, 20 ALT-positive PanNETs, and 20 ALT-negative PanNETs. Thereafter, it was validated on a multi-institutional cohort of 360 surgically resected PanNETs and correlated with multiple clinicopathologic features, RFS, and FISH results. Separately, 109 leiomyosarcomas (LMS) were evaluated by both CISH and FISH, and, similarly, the prognostic significance of ALT status was assessed. Upon optimization, ALT-CISH was identified in 112 of 360 (31%) primary PanNETs and was 100% concordant with FISH testing. ALT correlated with several adverse prognostic findings and distant metastasis (all p<0.004). The 5-year RFS for patients with ALT-positive PanNETs was 35% as compared to 94% for ALT-negative PanNETs. By multivariate analysis, ALT was an independent prognostic factor for shorter RFS. Similarly, ALT was associated with shorter RFS in LMS patients and, analogous to PanNETs, a negative, independent prognostic factor. ALT-CISH was developed and validated in not only PanNETs, but also sarcomas, specifically LMS. CISH testing has multiple advantages over FISH that facilitate its widespread clinical use in the detection of ALT and prognostication of patients with diverse neoplasms.},
}

@article {pmid39520989,
year = {2024},
author = {Mostovoy, Y and Boone, PM and Huang, Y and Garimella, KV and Tan, KT and Russell, BE and Salani, M and de Esch, CEF and Lemanski, J and Curall, B and Hauenstein, J and Lucente, D and Bowers, T and DeSmet, T and Gabriel, S and Morton, CC and Meyerson, M and Hastie, AR and Gusella, J and Quintero-Rivera, F and Brand, H and Talkowski, ME},
title = {Resolution of ring chromosomes, Robertsonian translocations, and complex structural variants from long-read sequencing and telomere-to-telomere assembly.},
journal = {American journal of human genetics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajhg.2024.10.006},
pmid = {39520989},
issn = {1537-6605},
abstract = {Delineation of structural variants (SVs) at sequence resolution in highly repetitive genomic regions has long been intractable. The sequence properties, origins, and functional effects of classes of genomic rearrangements such as ring chromosomes and Robertsonian translocations thus remain unknown. To resolve these complex structures, we leveraged several recent milestones in the field, including (1) the emergence of long-read sequencing, (2) the gapless telomere-to-telomere (T2T) assembly, and (3) a tool (BigClipper) to discover chromosomal rearrangements from long reads. We applied these technologies across 13 cases with ring chromosomes, Robertsonian translocations, and complex SVs that were unresolved by short reads, followed by validation using optical genome mapping (OGM). Our analyses resolved 10 of 13 cases, including a Robertsonian translocation and all ring chromosomes. Multiple breakpoints were localized to genomic regions previously recalcitrant to sequencing such as acrocentric p-arms, ribosomal DNA arrays, and telomeric repeats, and involved complex structures such as a deletion-inversion and interchromosomal dispersed duplications. We further performed methylation profiling from long-read data to discover phased differential methylation in a gene promoter proximal to a ring fusion, suggesting a long-range position effect (LRPE) with heterochromatin spreading. Breakpoint sequences suggested mechanisms of SV formation such as microhomology-mediated and non-homologous end-joining, as well as non-allelic homologous recombination. These methods provide some of the first glimpses into the sequence resolution of Robertsonian translocations and illuminate the structural diversity of ring chromosomes and complex chromosomal rearrangements with implications for genome biology, prediction of LRPEs from integrated multi-omics technologies, and molecular diagnostics in rare disease cases.},
}

@article {pmid39506437,
year = {2024},
author = {Song, B and Lou, J and Mu, L and Lu, X and Sun, J and Tang, B},
title = {An Innovative Telomere-associated Prognosis Model in AML: Predicting Immune Infiltration and Treatment Responsiveness.},
journal = {Current medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0109298673334218241021044800},
pmid = {39506437},
issn = {1875-533X},
abstract = {AIMS: To build an innovative telomere-associated scoring model to predict prognosis and treatment responsiveness in acute myeloid leukemia (AML).

BACKGROUND: AML is a highly heterogeneous malignant hematologic disorder with a poor prognosis. While telomere maintenance is frequently observed in tumors, investigations into telomere-related genes (TRGs) in AML remain limited.

OBJECTIVES: This study aimed to identify prognostic TRGs using the least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression, evaluate their predictive value, explore the association between TRG scores and immune cell infiltration, and assess the sensitivity of high-scoring AML patients to chemotherapeutic agents.

METHOD: Univariate Cox regression analysis was conducted on the TCGA cohort to identify prognostic TRGs and to develop the TRG scoring model using LASSO-Cox and multivariate Cox regression. Validation was performed on the GSE37642 cohort. Immune cell infiltration patterns were assessed through computational analysis, and the sensitivity to chemotherapeutic agents was evaluated.

RESULTS: Thirteen prognostic TRGs were identified, and a seven-TRG scoring model (including NOP10, OBFC1, PINX1, RPA2, SMG5, MAPKAPK5, and SMN1) was developed. Higher TRG scores were associated with a poorer prognosis, as confirmed in the GSE37642 cohort, and remained an independent prognostic factor even after adjusting for other clinical characteristics. The high-score group was characterized by elevated infiltration of B cells, T helper cells, natural killer cells, tumor-infiltrating lymphocytes, regulatory T (Treg) cells, M2 macrophages, neutrophils, and monocytes, along with reduced infiltration of gamma delta T cells, CD4- T cells, and resting mast cells. Moreover, high infiltration of M2 macrophages and Tregs was associated with poor overall survival compared to low infiltration. Notably, high-risk AML patients were resistant to Erlotinib, Parthenolide, and Nutlin-3a, but sensitive to AC220, Midostaurin, and Tipifarnib. Additionally, using RT-qPCR, we observed significantly higher expression of two model genes, OBFC1 and SMN1, in AML tissues compared to control tissues.

CONCLUSION: This innovative TRG scoring model demonstrates considerable predictive value for AML patient prognosis, offering valuable insights for optimizing treatment strategies and personalized medicine approaches. The identified TRGs and associated scoring models could aid in risk stratification and guide tailored therapeutic interventions in AML patients.},
}