@article {pmid40458946,
year = {2025},
author = {Koç Öztürk, F and Usta Özdemir, S and Karakılıç, E and Sılan, F},
title = {A Comprehensive Diagnostic Assessment of Thyroid Nodules Utilizing Scintigraphy and Telomere Lengths (T/S ratios).},
journal = {Molecular imaging and radionuclide therapy},
volume = {34},
number = {2},
pages = {97-106},
pmid = {40458946},
issn = {2146-1414},
abstract = {OBJECTIVES: This study aims to evaluate the effectiveness and role of telomere length measurements in leukocytes, plasma free cell DNA (cfDNA), and biopsy cells, along with technetium-99m (Tc-99m) methoxyisobutylisonitrile (MIBI) scintigraphy, as non-invasive methods for diagnosing malignant thyroid lesions.

METHODS: Data from 128 patients, who underwent ultrasound, Tc-99m MIBI scintigraphy, and fine-needle biopsy with a preliminary diagnosis of malignant thyroid nodules, were analyzed. In 98 patients, telomere lengths in leukocytes (from blood), cfDNA (from plasma), and biopsy cells were measured using the quantitative polymerase chain reaction method, and the relative telomere/single copy gene (T/S) ratio was calculated. Based on cytological examination results, patients were categorized into three groups: malignant, benign, and suspicious. Group differences were analyzed using the Kruskal-Wallis and Chi-square tests, and correlations between variables were examined with Spearman correlation analysis.

RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of Tc-99m MIBI scintigraphy for diagnosing malignant thyroid nodules were 64.70%, 79.16%, 29.72%, 83.51%, and 67.96%, respectively. While these results align with the literature, the positive predictive value was notably lower. No significant differences were observed in telomere lengths (T/S ratios) in leukocytes, plasma, or tissue between the groups.

CONCLUSION: Tc-99m MIBI scintigraphy demonstrates reasonable diagnostic accuracy for identifying malignancy in thyroid nodules. Contrary to limited reports, telomere length measurements may not be a reliable method for predicting thyroid malignancy. Larger studies are needed to further explore these findings.},
}

@article {pmid40456754,
year = {2025},
author = {Peng, G and Qin, Y and Yan, Z and He, M and Zhao, Y and Jiang, N and Wei, C},
title = {The high-quality telomere-to-telomere genome assembly of the earthworm (Amynthas aspergillum).},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {931},
pmid = {40456754},
issn = {2052-4463},
support = {Grant No. 82473808//National Natural Science Foundation of China (National Science Foundation of China)/ ; Grant No. 82473808//National Natural Science Foundation of China (National Science Foundation of China)/ ; Grant No. 82473808//National Natural Science Foundation of China (National Science Foundation of China)/ ; Grant No. 82473808//National Natural Science Foundation of China (National Science Foundation of China)/ ; Grant No. 82473808//National Natural Science Foundation of China (National Science Foundation of China)/ ; Grant No. 82473808//National Natural Science Foundation of China (National Science Foundation of China)/ ; Grant No. 82473808//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {Animals ; *Oligochaeta/genetics ; *Telomere/genetics ; *Genome ; },
abstract = {Earthworms have been extensively studied as ancient soil invertebrates, that are highly diverse. Previous studies of these invertebrates have mainly focused on their ecosystem services, medicinal value, and ecological habits. However, their genomic analysis remains inadequate. In this study, we generated the first high-quality telomere-to-telomere (T2T) assembly of the genome of the earthworm, Amynthas aspergillum (Perrier, 1872), which belongs to the genus Amynthas of the family Megascolecidae. The T2T assembly was 758.86 Mb with an N50 contig size of 16.59 Mb. The sequences were anchored to 43 chromosomes (2n = 2x = 86) with a coverage of 98.43% (746.95 Mb), and 83 telomeres were detected. In addition, we also predicted 35,723 protein-coding genes with 97.02% being functionally annotated. This T2T genome assembly will establish substantial groundwork for exploring the evolutionary mechanisms of the earthworm genome and enhance the specificity of its pharmacological effects.},
}

Animals
*Oligochaeta/genetics
*Telomere/genetics
*Genome

@article {pmid40456748,
year = {2025},
author = {de Andrade, KC and Pinto, EM and Zhao, T and Zeigler, LP and Kim, J and Giri, N and Haley, JS and McReynolds, LJ and Florez-Vargas, O and Phillips, AH and Kriwacki, RW and Akinniyi, SA and Cohen, SB and Emerson, MR and Smelser, DT and Urban, GM and Fridman, C and Zambetti, GP and Bryan, TM and Carey, DJ and Garcia, CK and Stewart, DR and Savage, SA},
title = {TERT c.3150 G > C (p.K1050N): a founder Ashkenazi Jewish variant associated with telomere biology disorders.},
journal = {NPJ genomic medicine},
volume = {10},
number = {1},
pages = {46},
pmid = {40456748},
issn = {2056-7944},
support = {R01 HL093096/NH/NIH HHS/United States ; },
abstract = {Pathogenic germline variants in telomerase (TERT) cause telomere biology disorders (TBDs) and are associated with bone marrow failure, pulmonary fibrosis, and other complications. TERT c.3150 G > C (p.K1050N) is frequent in the Ashkenazi Jewish (ASH) population and has been identified in ASH families with TBDs. Whole-genome sequencing of 96 p.K1050N heterozygotes from the UK Biobank and All of Us databases revealed a shared haplotype block, supporting a founder effect. Analyses of 15 additional p.K1050N cases validated this haplotype and identified mitochondrial and Y-STR haplogroups consistent with ASH ancestry. Clinical assessments showed that p.K1050N contributes to TBD phenotypes and shortened telomeres, while population data suggest incomplete penetrance. p.K1050N reduces telomerase activity and processivity, and decreases PCNA expression and BrdU incorporation, impairing cell proliferation. Our findings establish TERT p.K1050N as an ASH founder variant associated with TBDs, underscoring the need for genetic screening and long-term clinical studies.},
}

@article {pmid40455262,
year = {2025},
author = {Benetos, A and Fritsch, C and Horton, E and Lenotre, L and Toupance, S and Villemonais, D},
title = {Stochastic branching models for the telomeres dynamics in a model including telomerase activity.},
journal = {Journal of mathematical biology},
volume = {91},
number = {1},
pages = {8},
pmid = {40455262},
issn = {1432-1416},
mesh = {*Telomerase/metabolism ; Stochastic Processes ; Humans ; *Telomere/physiology/metabolism/genetics ; Mathematical Concepts ; *Models, Biological ; Telomere Homeostasis ; Cellular Senescence/genetics ; *Models, Genetic ; Aging/genetics ; Computer Simulation ; },
abstract = {Telomeres are repetitive sequences of nucleotides at the end of chromosomes, whose evolution over time is intrinsically related to biological ageing. In most cells, with each cell division, telomeres shorten due to the so-called end replication problem, which can lead to replicative senescence and a variety of age-related diseases. On the other hand, in certain cells, the presence of the enzyme telomerase can lead to the lengthening of telomeres, which may delay or prevent the onset of such diseases but can also increase the risk of cancer. In this article, we propose a stochastic representation of this biological model, which takes into account multiple chromosomes per cell, the effect of telomerase, different cell types and the dependence of the distribution of telomere length on the dynamics of the process. We study theoretical properties of this model, including its long-term behaviour. In addition, we investigate numerically the impact of the model parameters on biologically relevant quantities, such as the Hayflick limit and the Malthusian parameter of the population of cells.},
}

*Telomerase/metabolism
Stochastic Processes
Humans
*Telomere/physiology/metabolism/genetics
Mathematical Concepts
*Models, Biological
Telomere Homeostasis
Cellular Senescence/genetics
*Models, Genetic
Aging/genetics
Computer Simulation

@article {pmid40452427,
year = {2025},
author = {Szejner-Sigal, A and Heidinger, BJ and Kucera, AC and Kittilson, JD and Torson, AS and Rinehart, JP and Yocum, GD and Bowsher, JH and Greenlee, KJ},
title = {Hypoxia extends lifespan but does not alter telomere length or oxidative stress in a solitary bee (Megachile rotundata).},
journal = {The Journal of experimental biology},
volume = {},
number = {},
pages = {},
doi = {10.1242/jeb.250500},
pmid = {40452427},
issn = {1477-9145},
support = {5P30GM103332//COBRE/ ; NACA 58-3060-5-019//Agricultural Research Service/ ; 3060-21220-03200D//Agricultural Research Service/ ; NSF-IOS-0953297//Division of Integrative Organismal Systems/ ; },
abstract = {Stress can influence lifespan in both positive and negative ways, depending on exposure intensity and duration. However, mechanisms driving positive stress effects on lifespan remain poorly understood. Prolonged hypoxia extends the lifespan of overwintering prepupal Megachile rotundata. Here, we explore telomere length and reduced oxidative stress as potential mechanisms of this extended lifespan. We hypothesized high antioxidant capacity under hypoxia reduces oxidative damage and telomere loss. We exposed prepupae to 10, 21 or 24% oxygen for up to 9 months and measured monthly survival, telomere length, antioxidant capacity, and lipid peroxidation across treatment duration for prepupae and adults. After 9 months of exposure, survival was highest in hypoxia and lowest in hyperoxia. Telomere length did not differ among oxygen treatments but increased in adults compared to prepupae. Total antioxidant capacity and lipid peroxidation showed no significant differences among oxygen treatments, suggesting compensatory responses to maintain baseline oxidative levels.},
}

@article {pmid40451968,
year = {2025},
author = {Li, Q and Yu, X},
title = {Telomere-to-telomere sequence of mouse haploid stem cells.},
journal = {Science China. Life sciences},
volume = {},
number = {},
pages = {},
pmid = {40451968},
issn = {1869-1889},
}

@article {pmid40446331,
year = {2025},
author = {Cabral-de-Mello, DC and Gasparotto, AE and Rico-Porras, JM and Ferretti, ABSM and Mora-Ruiz, P and Alves-Gomes, RT and Lourejan, V and Scudeler, EL and Lorite, P and Bardella, VB},
title = {First insights into the satellitomes and new evidence for the absence of canonical insect telomere in the Neuroptera order.},
journal = {Genome},
volume = {},
number = {},
pages = {},
doi = {10.1139/gen-2025-0018},
pmid = {40446331},
issn = {1480-3321},
abstract = {Repetitive DNA is a major component of eukaryotic genomes, playing structural and evolutionary roles. However, in Neuroptera, its characterization remains unexplored. To address this, we analyzed the satellitomes of two Chrysopini (Chrysopidae) species using cytogenomic tools, also investigating telomeric and ribosomal DNA (rDNA). The canonical insect telomeric motif was absent, and rDNA clusters showed variation compared to other neuropterans, despite karyotype stasis (2n = 12, XY). Satellite DNA (satDNA) abundance varied between Ceraeochrysa cincta and Chrysopa pallens, representing a minor fraction of their repetitive DNA content. Notably, no satDNA sequences were shared between species, suggesting a rapid turnover. Exceptionally, the second most abundant satDNA in each species showed low sequence similarity and a putative common origin. A relationship between satDNAs and transposable elements (TEs) was also observed. Chromosome mapping revealed that abundant satDNAs accumulated in euchromatin, providing insights into their genomic distribution. These findings enhance our understanding of satDNA organization in Neuroptera, offering a foundation for future genome assembly efforts and evolutionary studies in these insects.},
}

@article {pmid40445797,
year = {2025},
author = {Benson, DM and Perez, DJP and DeNardo, DF},
title = {Why are telomeres the length that they are? Insight from a phylogenetic comparative analysis.},
journal = {Evolution; international journal of organic evolution},
volume = {},
number = {},
pages = {},
doi = {10.1093/evolut/qpaf119},
pmid = {40445797},
issn = {1558-5646},
abstract = {Telomeres are short repeating nucleotide sequences at the ends of chromosomes that shorten with every cellular replication. Despite the importance of keeping telomere length within a critical homeostatic range, adult telomere length can differ by two orders of magnitude across vertebrate species. Why telomere length varies so widely remains unknown, though popular hypotheses suggest that body size, lifespan, and endothermy are key variables that have coevolved with telomere length. To test the relationship among telomere length, telomerase activity (which extends telomeres), and these variables, we modeled the evolution of telomere length across 122 vertebrate species. We failed to find an influence of body mass, lifespan, or baseline metabolism on telomere length. However, we found a significant interactive effect between baseline metabolism and body mass. The presence of telomerase activity was positively correlated with telomere length across the 58 species where data for both existed. Taken together, our findings suggest that body mass may have differentially influenced the evolution of telomere length in endotherms and ectotherms and indicate that telomerase activity and telomere length may have coevolved.},
}

@article {pmid40444520,
year = {2025},
author = {Hwa, HL and Feng, JY and Huang, CY and Hsieh, YP and Wei, HS and Shen, AC},
title = {Association between childhood polyvictimization, telomere length, and post-traumatic stress disorder.},
journal = {Pediatrics international : official journal of the Japan Pediatric Society},
volume = {67},
number = {1},
pages = {e70101},
doi = {10.1111/ped.70101},
pmid = {40444520},
issn = {1442-200X},
support = {105-S3060//National Taiwan University Hospital/ ; FR012//National Taiwan University Children and Family Research Center Sponsored by CTBC Charity Foundation/ ; },
mesh = {Humans ; *Stress Disorders, Post-Traumatic/etiology/epidemiology/psychology/genetics ; Male ; Female ; Child ; Taiwan/epidemiology ; *Child Abuse/psychology ; Longitudinal Studies ; *Telomere ; Case-Control Studies ; },
abstract = {BACKGROUND: Child maltreatment is related to adverse psychosocial outcomes and may be associated with telomere erosion. Longitudinal research on mental health problems and telomere length (TL) in victimized children in Asian societies is scarce. In this study, we evaluated the associations of childhood polyvictimization with TL and longitudinal psychological problems.

METHODS: Subcohorts were obtained from a national, proportionately stratified sample of fourth-grade Taiwanese students recruited in 2014; the sample comprised 70 high-risk group participants (experience of polyvictimization) and 129 controls (nonvictims). For these 199 participants, TL was analyzed in 2014, whereas self-report post-traumatic stress disorder (PTSD) symptom scales and psychological disorder/symptom were completed in 2014, 2016, 2018, and 2021.

RESULTS: Childhood polyvictimization was associated with prolonged high PTSD symptom scores in 2014, 2016, 2018, and 2021. TL was significantly shorter among the polyvictims than among the nonvictims.

CONCLUSIONS: This study demonstrated an association between childhood polyvictimization and prolonged PTSD in children. Our findings also support the assertion that childhood polyvictimization is associated with telomere erosion.},
}

Humans
*Stress Disorders, Post-Traumatic/etiology/epidemiology/psychology/genetics
Male
Female
Child
Taiwan/epidemiology
*Child Abuse/psychology
Longitudinal Studies
*Telomere
Case-Control Studies

@article {pmid40444469,
year = {2025},
author = {Travieso, SG and Ortiz, GU},
title = {Increased muscle satellite cell content and preserved telomere length in response to exercise training in FSHD: implications for sarcopenia and longevity.},
journal = {The Journal of physiology},
volume = {},
number = {},
pages = {},
doi = {10.1113/JP288768},
pmid = {40444469},
issn = {1469-7793},
support = {2019/11820-5;2022/15078-4//São Paulo Research Foundation (FAPESP)/ ; },
}

@article {pmid40440898,
year = {2025},
author = {Fan, G and Liu, Q and Fang, Q and Luo, F and Huang, X and Li, H and Guo, W and Liu, B and Yan, L and Hu, L and Xiong, C and Cao, Z and Chen, X and Chen, Z and Wei, J and Wang, Y and Lei, X and Song, L},
title = {Prenatal exposure to PM2.5 constituents and newborn leukocyte telomere length in a prospective study: Windows of susceptibility and modification by maternal folic acid supplementation.},
journal = {Journal of hazardous materials},
volume = {494},
number = {},
pages = {138747},
doi = {10.1016/j.jhazmat.2025.138747},
pmid = {40440898},
issn = {1873-3336},
abstract = {Prenatal exposure to fine particulate matter (PM2.5) is related to alterations in newborn telomere length (TL), an indicator of cellular aging. However, the specific effects of PM2.5 constituents and windows of susceptibility are unknown. We aimed to identify the susceptibility windows for prenatal PM2.5 constituents affecting newborn leukocyte TL (LTL) and examine the modifying role of folic acid (FA) supplementation. This study involved 741 maternal-infant dyads from a birth cohort in Wuhan, China. We applied multiple linear regression, distributed lag models, and three multi-pollutant approaches to explore the effects of PM2.5 constituents on newborn LTL. Prenatal PM2.5 constituent exposures were related to shorter newborn LTL. Each 5 µg/m[3] increase in organic matter (OM) and nitrate (NO3[-]), and each 1 µg/m[3] increase in black carbon (BC), ammonium (NH4[+]), and sulfate (SO4[2-]) during the third trimester were related to reductions in LTL of 3.99 % (95 % confidence interval [CI]: -6.36 %, -1.56 %), 6.31 % (95 % CI: -10.67 %, -1.73 %), 6.63 % (95 % CI: -9.87 %, -3.27 %), 3.69 % (95 % CI: -5.99 %, -1.34 %), and 3.00 % (95 % CI: -5.03 %, -0.92 %), respectively. The mixture of PM2.5 constituents was related to shorter newborn LTL, predominantly driven by OM and BC. The detrimental effects of OM, BC, NH4[+], and NO3[-] on newborn LTL were more pronounced in individuals without FA supplementation (all P for interaction < 0.05). Our findings identify the third trimester as a susceptibility window for PM2.5 constituent-induced LTL shortening, with OM and BC as the primary contributors. FA supplementation may help mitigate these effects, highlighting its potential as an intervention strategy.},
}

@article {pmid40440483,
year = {2025},
author = {Srour, L and Qannan, A and Oshima, J and Megarbane, A and Bejaoui, Y and El Hajj, N},
title = {Investigating telomere length in progeroid syndromes: implications for aging disorders.},
journal = {Aging},
volume = {17},
number = {},
pages = {},
doi = {10.18632/aging.206255},
pmid = {40440483},
issn = {1945-4589},
abstract = {Progeroid syndromes are rare genetic disorders that impact patients' health and lifespans and are characterized by symptoms that mimic the normal aging process. Telomere length is one of the aging hallmarks, a phenomenon linked to cellular aging. Telomere attrition was observed in different progeroid syndromes, such as Nijmegen breakage syndrome patients and Werner syndrome, indicating its contribution to the progeroid phenotype. However, whether it is a common feature in all progeroid syndromes is still unclear. Therefore, in this study, we aimed to estimate telomere length using the DNA methylation-based estimator of human telomere length in publicly available DNA methylation data from patients with Werner Syndrome, Hutchinson-Gilford Progeria Syndrome, Berardinelli-Seip Congenital Lipodystrophy type 2, and Dyskeratosis congenita, along with additional data provided by our laboratory from patients with Cerebroretinal Microangiopathy with Calcifications and Cysts and Wiedemann-Rautenstrauch Syndrome. Our findings revealed that certain progeroid syndromes, including classical Werner Syndrome, Berardinelli-Seip Congenital Lipodystrophy type 2, and Dyskeratosis congenita, have significant telomere attrition conversely to Hutchinson-Gilford Progeria Syndrome, Cerebroretinal Microangiopathy with Calcifications and Cysts, Wiedemann-Rautenstrauch Syndrome, and atypical Werner Syndrome. In conclusion, this study addresses a critical gap by providing new insights into the role of telomere attrition across different progeroid conditions. Further research is needed to elucidate the effect of telomere attrition on progeroid syndromes and its implications.},
}

@article {pmid40438983,
year = {2025},
author = {Nurelegne, HT and Thompson, MB and de Andrade, KC and Thompson, AS and McReynolds, LJ and Niewisch, MR and Savage, SA},
title = {Germline PARN Variants in Telomere Biology Disorders and Challenges in Variant Curation.},
journal = {Molecular genetics & genomic medicine},
volume = {13},
number = {6},
pages = {e70107},
pmid = {40438983},
issn = {2324-9269},
support = {//Division of Cancer Epidemiology and Genetics, National Cancer Institute/ ; },
mesh = {Humans ; *Germ-Line Mutation ; *Exoribonucleases/genetics ; *Telomere/genetics ; Dyskeratosis Congenita/genetics ; },
abstract = {BACKGROUND: PARN encodes poly(A)-specific ribonuclease, a 3 exoribonuclease important in regulating RNA stability and maturation. Rare germline PARN variants have been reported in telomere biology disorders (TBDs) leading to its inclusion on gene panels for bone marrow failure syndromes and pulmonary diseases.

METHODS: To understand the extent of germline PARN variation in human disease, we conducted a comprehensive literature review, curated the TBD-associated PARN variants using AutoGVP and in silico prediction tools (MetaSVM, REVEL, and/or CADD) and assessed their frequency in the gnomAD database.

RESULTS: Ninety-three unique PARN variants were identified in the literature as present in individuals or families affected by TBDs, but clinical features were not consistently reported. Forty-one variants (44.1%) were classified as pathogenic or likely pathogenic. These variants were spread across the entire gene with no obvious clustering. gnomAD data were notable for a paucity of common variants and metrics suggesting PARN variation would be tolerated.

CONCLUSION: The extent to which specific PARN variants can be associated with TBD etiology is limited due to incomplete literature, clinical data, lack of robust functional assays, and high frequency of rare variants.},
}

Humans
*Germ-Line Mutation
*Exoribonucleases/genetics
*Telomere/genetics
Dyskeratosis Congenita/genetics

@article {pmid40437344,
year = {2025},
author = {Huang, HY and Sheen, KH and Hung, CY and Chang-Chien, J and Wang, SL and Ho, CH and Tsai, HJ and Yao, TC},
title = {Association between telomere length and atopic dermatitis among school-age children.},
journal = {Clinical and translational allergy},
volume = {15},
number = {6},
pages = {e70066},
doi = {10.1002/clt2.70066},
pmid = {40437344},
issn = {2045-7022},
support = {MOST 109-2314-B-182-042-MY3//National Science and Technology Council, Taiwan/ ; NSTC 111-2314-B-400-040-MY3//National Science and Technology Council, Taiwan/ ; NSTC 112-2314-B-182-030-MY3//National Science and Technology Council, Taiwan/ ; CMRP3N0371∼3//Chang Gung Medical Foundation/ ; CMRPG3J0121∼3//Chang Gung Medical Foundation/ ; CMRPG3J1711∼2//Chang Gung Medical Foundation/ ; CMRPG3M1831∼3//Chang Gung Medical Foundation/ ; },
abstract = {BACKGROUND: Atopic dermatitis is a common chronic skin disease in children. Whether telomere length is associated with atopic dermatitis remains unclear. This population-based case-control study aimed to investigate the association between telomere length and atopic dermatitis in school-age children.

METHODS: In this cross-sectional analysis, we included 1084 singleton term-born children (608 males; mean age 6.4 years) from the Longitudinal Investigation of Global Health in Taiwanese Schoolchildren cohort. Telomere length was measured using quantitative real-time polymerase chain reaction, log-transformed and was analyzed in quartiles. The main outcome was atopic dermatitis defined as having physician-diagnosed atopic dermatitis and the presence of atopic dermatitis in the last 12 months. Regression analyses were used to assess the relationship between telomere length and atopic dermatitis.

RESULTS: Telomere length was significantly inversely associated with childhood atopic dermatitis after adjusting for child's age, sex, overweight or obesity, birth season, childhood allergic diseases, environmental tobacco smoke, parental history of allergic diseases, parental educational level, and breastfeeding status (p_trend = 0.01). Specifically, when telomere length was classified into quartiles, children in the shortest (fourth) telomere length quartile had a 1.88-fold higher probability of atopic dermatitis compared to those in the longest (first) quartile (95% confidence interval: 1.13-3.14). Stratified analyses showed that the associations were stronger in males and non-breastfed children, with no significant associations observed in females or breastfed children.

CONCLUSION: This study provides new evidence suggesting an association between shorter telomere length and atopic dermatitis in school-age children.},
}

@article {pmid40431584,
year = {2025},
author = {Dutra, LML and Souza, FS and Vasconcellos, AS and Young, RJ and Schork, IG},
title = {Telomere Tales: Exploring the Impact of Stress, Sociality, and Exercise on Dogs' Cellular Aging.},
journal = {Veterinary sciences},
volume = {12},
number = {5},
pages = {},
pmid = {40431584},
issn = {2306-7381},
support = {309124/2022-0//Fundação de Amparo à Pesquisa do Estado de Minas Gerais/ ; 206418/2014-0//National Council for Scientific and Technological Development/ ; 202351/2015-7//National Council for Scientific and Technological Development/ ; 208427/2017-1//National Council for Scientific and Technological Development/ ; },
abstract = {Animal welfare is influenced by the cumulative life experiences of an individual. Among these, exposure to chronic stressors has a significant impact on both physical and mental health, contributing to premature aging-a process linked to telomere shortening. Conversely, positive experiences have been shown to mitigate, delay, and sometimes reverse telomere attrition. This suggests that telomere length could be a reliable indicator for assessing animal welfare. This study explored the association between telomere length and characteristics such as life history, environment, and health in domestic dogs. Buccal swabs collected DNA samples from 250 dogs, and telomere length was quantified via qPCR. Our findings revealed that environmental factors significantly influenced telomere length. Dogs housed in kennels or subjected to low physical activity levels exhibited shorter telomeres. Similarly, dogs living in groups of more than five dogs had shorter telomeres, and male dogs were found to have longer telomeres than females. Overall, these results highlight the importance of environmental conditions in influencing telomere length in dogs and the potential to use this biological indicator to evaluate animal welfare.},
}

@article {pmid40430074,
year = {2025},
author = {Domínguez-de-Barros, A and Sirvent-Blanco, C and García-Pérez, O and Gajate-Arenas, M and García-Ramos, A and Migliazzo, C and Piñero, JE and Lorenzo-Morales, J and Córdoba-Lanús, E},
title = {Telomere Length, Oxidative Stress Markers, and Related miRNAs in Non-Invasive Samples of Mild COVID-19 Cases.},
journal = {International journal of molecular sciences},
volume = {26},
number = {10},
pages = {},
pmid = {40430074},
issn = {1422-0067},
support = {(CB21/13/00100//Consorcio Centro de Investigación Biomédica (CIBER) de Enfermedades Infecciosas (CIBERINFEC)/ ; 2023-2028, PI-CC202302222, Cabildo.23 and PI-2024/0002347//Cabildo Insular de Tenerife/ ; ACIISI 2024//Agencia Canaria de Investigación, Innovación y Sociedad de la Información/ ; Ministerio de Sanidad, Spain.//Ministerio de Sanidad, Spain./ ; },
mesh = {Humans ; *Oxidative Stress ; *MicroRNAs/genetics/blood/metabolism ; *COVID-19/genetics/metabolism/pathology/blood ; Male ; Female ; Middle Aged ; Biomarkers/blood/metabolism ; Adult ; Aged ; SARS-CoV-2 ; *Telomere/metabolism/genetics ; Case-Control Studies ; 8-Hydroxy-2'-Deoxyguanosine ; Thiobarbituric Acid Reactive Substances/metabolism ; Saliva/metabolism ; *Telomere Homeostasis ; },
abstract = {Oxidative stress and inflammation influence immune response and epigenetic mechanisms in infectious diseases. In mild COVID-19, host-encoded miRNA profiles remain underexplored, although they reveal mechanistic insights into disease pathogenesis. This study evaluated ageing and oxidative stress biomarkers (telomere length (TL), TBARS, 8-OHdG, and circulating related-miRNA expression) in 75 mild cases and 30 non-COVID-19 controls. TL correlated with age (R = -0.384, p = 0.005) and was shorter in cases compared to controls (rTL 1.46 ± 0.51 vs. 0.99 ± 0.37; p < 0.001), being similar between saliva and blood samples (p = 0.917). miR-138-5p was upregulated in COVID-19 cases (p = 0.026) and correlated with 8-OHdG (R = 0.403, p = 0.05), which was increased in cases (p = 0.040); miR-210-3p was downregulated in infected individuals (p = 0.008), while miR-182-5p expression correlated with TBARS (R = 0.582, p = 0.018). miR-34a-5p and miR155-5p expression was not altered in mild COVID-19. These findings suggest early systemic cellular damage in mild COVID-19 and highlight miR-138-5p and miR-182-5p as potential early biomarkers of oxidative stress.},
}

Humans
*Oxidative Stress
*MicroRNAs/genetics/blood/metabolism
*COVID-19/genetics/metabolism/pathology/blood
Male
Female
Middle Aged
Biomarkers/blood/metabolism
Adult
Aged
SARS-CoV-2
*Telomere/metabolism/genetics
Case-Control Studies
8-Hydroxy-2'-Deoxyguanosine
Thiobarbituric Acid Reactive Substances/metabolism
Saliva/metabolism
*Telomere Homeostasis

@article {pmid40429722,
year = {2025},
author = {Mejía-Ortiz, P and Genis-Mendoza, AD and Ramírez Villanueva, R and López Ramírez, S and Guzmán Sánchez, R and Fernández, T and Sigg-Alonso, J and Nicolini-Sánchez, H},
title = {Shorter Telomere Length in Individuals with Neurocognitive Disorder and APOE ε4 Genotype.},
journal = {International journal of molecular sciences},
volume = {26},
number = {10},
pages = {},
doi = {10.3390/ijms26104577},
pmid = {40429722},
issn = {1422-0067},
mesh = {Humans ; Male ; Female ; Aged ; Middle Aged ; *Apolipoprotein E4/genetics ; Genotype ; *Telomere Shortening/genetics ; *Telomere/genetics ; *Neurocognitive Disorders/genetics ; *Cognitive Dysfunction/genetics ; Risk Factors ; Aged, 80 and over ; },
abstract = {Neurocognitive disorders (NCD) are neurodegenerative diseases characterized by decline or loss of cognitive functions. Aging and the APOE genotype have been identified as major risk factors. Telomere length (TL) has been proposed as a biomarker of aging, with shorter TL associated with cognitive decline. This study investigated the relationship between TL and the APOE genotype in individuals with cognitive impairments (CIs). A total of 170 participants aged >55 years were included. Cognitive function was assessed using the MMSE and MoCA tests. Relative telomere quantification and APOE genotype were determined by real-time PCR. A significant association was observed between shorter TL and an increased risk of CI (p < 0.001). Although APOE ε4 is a known genetic risk factor, its association with CI was less clear in this study population, as a considerable proportion of ε4 carriers did not present cognitive impairment (p < 0.05). However, ε4 carriers with CI tended to have shorter TL than those with non-cognitive impairment (NCI-SMC). Furthermore, fewer years of education were strongly correlated with higher CI risk (p < 0.0001). Overall, individuals with both shorter telomeres and lower educational levels exhibited the highest risk of CI. APOE ε4 may contribute to telomere shortening.},
}

Humans
Male
Female
Aged
Middle Aged
*Apolipoprotein E4/genetics
Genotype
*Telomere Shortening/genetics
*Telomere/genetics
*Neurocognitive Disorders/genetics
*Cognitive Dysfunction/genetics
Risk Factors
Aged, 80 and over

@article {pmid40418996,
year = {2025},
author = {Mavioglu, RN and Gumpp, AM and Hummel, EM and Moser, DA and Ammerpohl, O and Behnke, A and Mack, M and Kolassa, IT},
title = {Telomere-mitochondrial dynamics differ depending on childhood maltreatment history, catabolic postpartum state, and developmental period.},
journal = {Brain, behavior, and immunity},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.bbi.2025.05.022},
pmid = {40418996},
issn = {1090-2139},
abstract = {Telomere attrition, a hallmark of aging, is linked to high-energy demand states like early development and biological or psychological stress. Metabolic regulation of telomere length (TL) may occur in these states as part of an energetic trade-off, prioritizing immediate needs over long-term requirements such as telomere maintenance, though this has not been observed in healthy humans. We examined associations between TL and mitochondrial bioenergetics, density, and DNA markers in immune cells of women at 1-week (n = 175) and 1-year postpartum (n = 106), depending on their history of childhood maltreatment (CM), and in their newborns (n = 132). At 1-week postpartum, a catabolic state of high energy demand, women with lower mitochondrial energy production efficiency exhibited shorter TL. One year later, these dynamics appeared only in women with a history of CM. In newborns, TL was shorter when mitochondrial density-normalized routine and ATP production-related respiration was higher. Mitochondrial DNA copy number was associated with TL in both mothers and newborns, regardless of the energetic state. Our findings suggest that telomere-mitochondrial dynamics can adapt to the body's energetic needs.},
}

@article {pmid40418329,
year = {2025},
author = {Mattarocci, S},
title = {The DNA damage tolerance factor Rad5 and telomere replication.},
journal = {Current genetics},
volume = {71},
number = {1},
pages = {11},
pmid = {40418329},
issn = {1432-0983},
mesh = {*Telomere/genetics/metabolism ; *Saccharomyces cerevisiae Proteins/genetics/metabolism ; *DNA Damage ; *DNA Replication ; Saccharomyces cerevisiae/genetics/metabolism ; *DNA Helicases/genetics/metabolism ; Proliferating Cell Nuclear Antigen/genetics/metabolism ; DNA Repair ; DNA Damage Tolerance ; },
abstract = {The DNA Damage Tolerance pathway (DDT) is one of the major mechanisms for resolving replication fork blocks. A key factor in DDT is the fork-associated clamp PCNA, which can undergo to mono- or polyubiquitination, leading to error-prone or error-free modes of DNA damage bypass, respectively. In the yeast Saccharomyces cerevisiae, Rad5[HLTF/SNF2] factor plays important roles in both pathways: (i) promoting the error-free mode through PCNA polyubiquitination and transient template switching and (ii) interacting with specialized DNA polymerases involved in the error-prone pathway. Rad5 also associates with telomeres, the repetitive DNA regions present at the ends of chromosomes. Telomeric DNA, tightly bound by tandem proteins arrays, poses unique challenges to replication fork progression. Here, I review the current understanding of the link between Rad5 and telomeres and provide evidence that Rad5 binds to yeast telomeres, with notable enrichment during telomere replication. This finding highlights a connection between telomeres and an important DDT factor in unperturbed wild-type cells, raising intriguing possibilities regarding the functional interplay between telomere replication and DNA damage tolerance mechanisms.},
}

*Telomere/genetics/metabolism
*Saccharomyces cerevisiae Proteins/genetics/metabolism
*DNA Damage
*DNA Replication
Saccharomyces cerevisiae/genetics/metabolism
*DNA Helicases/genetics/metabolism
Proliferating Cell Nuclear Antigen/genetics/metabolism
DNA Repair
DNA Damage Tolerance

@article {pmid40417237,
year = {2025},
author = {Eremin, A and Sergeev, A and Kopylov, A and Rodin, V and Malyshev, D and Panova, T and Polyakov, I and Zvereva, M},
title = {Long-read sequencing reveals absence of 5mC in Ogataea parapolymorpha DL-1 genome and introduces telomere-to-telomere assembly.},
journal = {Frontiers in genetics},
volume = {16},
number = {},
pages = {1574332},
pmid = {40417237},
issn = {1664-8021},
abstract = {BACKGROUND: Ogataea parapolymorpha DL-1 is a versatile thermotolerant organism with numerous applications in biotechnology, particularly in the production of recombinant proteins and the study of methanol metabolism and peroxisome functions. This study presents a comprehensive genome and methylome analysis of Ogataea parapolymorpha DL-1 using long-read sequencing technology. The research builds upon previous short-read sequencing efforts, revealing enhancements in genome assembly and epigenomic insights.

METHODS: We used long-read sequencing technology to achieve a telomere-to-telomere (T2T) genome assembly of Ogataea parapolymorpha DL-1. High-quality reads were obtained and assembled de novo, followed by polishing to enhance accuracy. The genome was analyzed to identify coding genes, telomeric motifs, rRNA genes, and methylation patterns, including the detection of 5mC and 6 mA modifications. Epigenetic features were further assessed and validated through liquid chromatography-mass spectrometry.

RESULTS: Key findings include the absence of 5 mC DNA modification and the presence of 6 mA in the genome, unusual telomere regulation mechanism based on the addition of non-telomeric dT and the introduction of long-read enhanced telomere-to-telomere assembly.

CONCLUSION: This work provides deeper insights into the yeast's genome organization and methylation patterns, contributing to the understanding of its genetics and therefore potential biotechnological applications.},
}

@article {pmid40414485,
year = {2025},
author = {Yoshitake, K and Shirasawa, K and Kojima, KK and Asakawa, S and Tanaka, N and Kurokochi, H},
title = {Nearly telomere-to-telomere genome assembly of the L. edodes diploid genome.},
journal = {Fungal genetics and biology : FG & B},
volume = {},
number = {},
pages = {104005},
doi = {10.1016/j.fgb.2025.104005},
pmid = {40414485},
issn = {1096-0937},
abstract = {Lentinula edodes (shiitake mushroom) possesses substantial nutritional and medicinal value. Even though the genomes of several strains have been reported, some essential observations, including the exact chromosome number, still need validation. This study reports a near-telomere-to-telomere assembly of the complete diploid genome of L. edodes strain XR1, a commercially important Japanese strain. We employed the PacBio HiFi long-read sequencing technology combined with single-cell genotyping data and manual curation. The assembled diploid genome comprised 20 chromosomes (10 per haplotype), and significant inter-haplotype variation was observed. Additionally, we identified a novel Penelope-like retrotransposon-Coprina-1_LeEd-specifically localized to the telomeres. This study marks the first report of telomere elongation by the transposition of Coprina. Our findings provide a high-resolution genome resource for L. edodes, consequently elucidating its evolution, genomic structure, and breeding potential. Furthermore, this study establishes a foundation for further research on edible mushroom genetics and biotechnology.},
}

@article {pmid40414363,
year = {2025},
author = {Tavares-Marcos, C and Correia, M and de Jesus, BB},
title = {Telomeres as hallmarks of iPSC aging: a review on telomere dynamics during stemness and cellular reprogramming.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {102773},
doi = {10.1016/j.arr.2025.102773},
pmid = {40414363},
issn = {1872-9649},
abstract = {Telomeres, the protective ends of chromosome, are key to tissue repair and regeneration. Telomere shortening is linked to aging and age-related disorders, while excessive telomerase activity may support tissue regeneration or transformation. Some of the functions of telomeres and telomerase may be mediated by its important role in the process of stemness. Active telomerase, and subsequent telomerase-dependent telomere extension, supports stem-cells self-renewal and pluripotency - essential for tissue healing. During cellular reprogramming, differentiated cells are converted into induced pluripotent stem cells (iPSCs), which resemble embryonic stem cells. During iPSC derivation, telomere length is reset, enhancing iPSCs' regenerative potential. During this process, incomplete telomerase activation and telomere extension can lead to genomic instability and/or haltered cell functionality. Understanding the intricate relation of telomeres, telomerase and stemness may be critical when designing novel cell-based therapies targeting degenerative diseases or to unlock strategies to delay aging. Here, we explore the recent bibliography linking these areas, raising awareness of their important when designing novel breakthroughs in health and longevity.},
}

@article {pmid40411290,
year = {2025},
author = {Wu, J and Bao, RX and Liu, Y and Long, YT and Chen, JT and Shi, YN and Zhang, B and Luo, C and Huang, X and Chen, KS and He, XH and Xie, L and Li, BJ},
title = {Gap-free telomere-to-telomere assembly of the Mangifera persiciforma genome and its evolutionary insights on resistance.},
journal = {Plant biotechnology journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/pbi.70070},
pmid = {40411290},
issn = {1467-7652},
support = {2024GXNSFBA010399//Natural Science Foundation of Guangxi Province/ ; Gui Ke AD23026320//Science and Technology Talent Special Project of Guangxi/ ; SKLCUSA- b202302//State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources/ ; //The CARSGIT-Guangxi Mango Industry Project (nycytxgxcxtd-2021-06-02)/ ; },
}

@article {pmid40409468,
year = {2025},
author = {Zhu, H and Manson, JE and Cook, NR and Bekele, BB and Chen, L and Kane, KJ and Huang, Y and Li, W and Christen, W and Lee, IM and Dong, Y},
title = {Vitamin D3 and Marine Omega-3 Fatty Acids Supplementation and Leukocyte Telomere Length: 4-Year Findings from the VITAL Randomized Controlled Trial.},
journal = {The American journal of clinical nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajcnut.2025.05.003},
pmid = {40409468},
issn = {1938-3207},
abstract = {BACKGROUND: Limited studies suggest that vitamin D or omega 3 fatty acids (n-3 FAs) supplementation may be beneficial for telomere maintenance, however, evidence from large randomized clinical trial is lacking. We hypothesized that vitamin D or n-3 FAs supplementation reduce leukocyte telomere length (LTL) attrition overtime by leveraging the VITamin D and OmegA-3 TriaL (VITAL) trial.

METHODS: VITAL is a large, randomized, double-blind, placebo-controlled trial with a 2 x 2 factorial design of vitamin D3 (2,000 IU/day) and marine n-3 FAs (1 g/day) supplements for 5 years among a representative sample of 25,871 US females ≥55 and males ≥50 years of age. The VITAL Telomere study (NCT04386577) included 1054 participants who were evaluated in person at the Harvard Clinical and Translational Science Center. LTL was determined by the Absolute Human Telomere Length Quantification quantitative Polymerase Chain Reaction (PCR) method at baseline, Year 2, and Year 4. The pre-specified primary outcome measures were changes in LTL between baseline, Year 2 and Year 4. Analyses of intervention effect used mixed-effects linear regression models.

RESULTS: LTL was measured in a total of 2,571 samples from the 1031 participants at baseline, year 2, and year 4. Compared to placebo, vitamin D3 supplementation significantly decreased LTL attrition by 0.14 kilo base pairs (kb) (0.01, 0.27) over 4 years (p = 0.039). Overall trend analysis showed that the vitamin D3 supplementation group had LTLs that were about 0.035 kb higher per year of follow-up compared to placebo group (0.002, 0.07, p=0.037). Marine n-3 FAs supplementation had no significant effect on LTL at either year 2 or year 4.

CONCLUSION: 4-years of supplementation with 2000 IU/day vitamin D3 reduced telomere attrition by 140 bp, suggesting that vitamin D3 daily supplementation with or without n-3 FAs might have a role in counteracting telomere erosion or cell senescence. Clinical Trial Registry numberNCT04386577, https://clinicaltrials.gov/study/NCT04386577?term=NCT04386577&rank=1.},
}

@article {pmid40404855,
year = {2025},
author = {Bento, F and Longaretti, M and Pires, VB and Lockhart, A and Luke, B},
title = {RNase H1 and Sen1 ensure that transient TERRA R-loops promote the repair of short telomeres.},
journal = {EMBO reports},
volume = {},
number = {},
pages = {},
pmid = {40404855},
issn = {1469-3178},
support = {552129721- LU 1709/5-1//Deutsche Forschungsgemeinschaft (DFG)/ ; 491145305 - GRK 2859/1//Deutsche Forschungsgemeinschaft (DFG)/ ; 491145305 - GRK 2859/1//Deutsche Forschungsgemeinschaft (DFG)/ ; 552129721- LU 1709/5-1//Deutsche Forschungsgemeinschaft (DFG)/ ; PD/BD/127999/20169//MEC | Fundação para a Ciência e a Tecnologia (FCT)/ ; },
abstract = {Telomere repeat-containing RNA (TERRA) is transcribed at telomeres and forms RNA-DNA hybrids. In budding yeast, the presence of RNA-DNA hybrids at short telomeres promotes homology-directed repair (HDR) and prevents accelerated replicative senescence. RNA-DNA hybrids at telomeres have also been demonstrated to prevent 5'end resection, an essential step for HDR. In accordance, we now demonstrate that, not only the presence, but also the removal, of RNA-DNA hybrids drives HDR at shortened telomeres during replicative senescence. Although RNase H2 is absent from short telomeres, it is quickly compensated for by the recruitment of RNase H1 and Sen1. The recruitment of RNase H1 is essential to allow for the loading of Rad51, consistent with the notion that RNA-DNA hybrids prevent Exo1-mediated end resection. In the absence of RNase H1 or Sen1 function, yeast cultures prematurely enter replicative senescence in the absence of telomerase. Furthermore, the delayed senescence phenotype observed when RNase H2 is deleted, depends on the presence of RNase H1 and Sen1. This study demonstrates the importance of transient RNA-DNA hybrids at short telomeres to regulate senescence.},
}

@article {pmid40404646,
year = {2025},
author = {Nelson, DR and Muvunyi, R and Hazzouri, KM and Tumushime, JC and Nzayisenga, G and Julius, N and Meert, W and Karim, L and Coppieters, W and Munson, KM and Yoo, D and Eichler, EE and Salehi-Ashtiani, K and Twizere, JC},
title = {A near telomere-to-telomere phased reference assembly for the male mountain gorilla.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {842},
pmid = {40404646},
issn = {2052-4463},
support = {R01 HG002385/HG/NHGRI NIH HHS/United States ; },
mesh = {Animals ; *Gorilla gorilla/genetics ; Male ; *Telomere ; *Genome ; Haplotypes ; Endangered Species ; },
abstract = {The endangered mountain gorilla, Gorilla beringei beringei, faces numerous threats to its survival, highlighting the urgent need for genomic resources to aid conservation efforts. Here, we present a near telomere-to-telomere, haplotype-phased reference genome assembly for a male mountain gorilla generated using PacBio HiFi (26.77× ave. coverage) and Oxford Nanopore Technologies (52.87× ave. coverage) data. The resulting non-scaffolded assembly exhibits exceptional contiguity, with contig N50 of ~95 Mbp for the combined pseudohaplotype (3,540,458,497 bp), 56.5 Mbp (3.1 Gbp) and 51.0 Mbp (3.2 Gbp) for each haplotype, an average QV of 65.15 (error rate = 3.1 × 10[-7]), and a BUSCO score of 98.4%. These represent substantial improvements over most other available primate genomes. This first high-quality reference genome of the mountain gorilla provides an invaluable resource for future studies on gorilla evolution, adaptation, and conservation, ultimately contributing to the long-term survival of this iconic species.},
}

Animals
*Gorilla gorilla/genetics
Male
*Telomere
*Genome
Haplotypes
Endangered Species

@article {pmid40397254,
year = {2025},
author = {Li, X and Huang, L and Yan, Y and Rong, Y and Chen, X and Gao, M and Huang, J},
title = {Association of modifiable risk factors and telomere length with five neuroendocrine neoplasms: a bidirectional Mendelian randomization study.},
journal = {Discover oncology},
volume = {16},
number = {1},
pages = {841},
pmid = {40397254},
issn = {2730-6011},
abstract = {BACKGROUND: The timely recognition of modifiable risk factors holds paramount importance in tumor prevention. We aimed to scrutinize the causal relationships between a spectrum of genetically modifiable risk factors and five distinct neuroendocrine neoplasms.

METHODS: A bidirectional two-sample Mendelian randomization (MR) analysis was employed to elucidate the causal relationships between 41 potential risk factors and five neuroendocrine neoplasms.

RESULTS: Height, obesity class 1, 2, and 3, overweight, waist-to-hip ratio, waist circumference, and serum uric acid were identified as factors associated with an augmented risk of colorectal neuroendocrine neoplasms (all p < 0.05). Conversely, a negative correlation was observed between fasting glucose and the risk of colorectal neuroendocrine neoplasms (p = 0.031). Platelet count exhibited a negative correlation with lung neuroendocrine neoplasms (p = 0.02). Moreover, the waist-to-hip ratio demonstrated a negative association with the risk of pancreatic neuroendocrine neoplasms. Atrial fibrillation, mean cell heamoglobin, and mean cell volume were positively associated with the risk of small intestine neuroendocrine neoplasms. In gastric neuroendocrine neoplasms, obesity class 1 and 2, overweight, and telomere length were implicated in their heightened risk. Following adjustment for multiple tests, obesity class 1 remained statistically significant to colorectal neuroendocrine neoplasms, and telomere length maintained significance in association with gastric neuroendocrine neoplasms. The outcomes of reverse MR suggested a bidirectional causal relationship between telomere length and gastric neuroendocrine neoplasms.

CONCLUSION: This study provided genetic evidence for the causal relationships between potentially modifiable risk factors and the risk of five neuroendocrine neoplasms. Therapeutic approaches to these factors may provide a basis for preventing neuroendocrine neoplasms.},
}

@article {pmid40392448,
year = {2025},
author = {Wang, KL and Xi, XX and Zheng, JH},
title = {A Novel Telomere Maintenance Gene-Related Model for Prognosis Prediction in Gastric Cancer.},
journal = {Biochemical genetics},
volume = {},
number = {},
pages = {},
pmid = {40392448},
issn = {1573-4927},
abstract = {Gastric cancer (GC) remains a significant clinical challenge due to its frequent late-stage diagnosis and limited treatment stratification. Telomere maintenance genes (TMGs) are crucial in GC progression, but their prognostic value has not been fully explored. This study is the first to integrate TMGs with machine learning to develop a prognostic model for GC. Using clinical and gene expression data from the TCGA database, differentially expressed genes (DEGs) were identified and intersected with TMGs. Prognostic TMGs were determined through Cox regression and machine learning techniques, including Lasso, random forest, and Xgboost algorithms. A five-gene prognostic model (CCT6A, ELOVL4, PC, PLCL1, RPS4Y1) was developed and validated using TCGA data. The model demonstrated strong predictive performance, with AUCs of 0.71, 0.71, and 0.70 at 1-, 3-, and 5-year survival, respectively. High-risk patients had significantly poorer overall survival (OS). Further analysis of the tumor microenvironment (TME) showed that high-risk patients exhibited increased immune cell infiltration, and TMG-associated pathways such as apoptosis, epithelial-mesenchymal transition (EMT), and IL6/JAK/STAT3 signaling were prominent. High EMT scores were linked to worse prognosis. In addition, the hub genes were upregulated in GC patients and cells, correlating with decreased OS. PLCL1 significantly promoted GC cell proliferation, migration, and invasion, and it also activated the inflammation-related pathways in GC. In conclusion, this study not only highlights the prognostic relevance of TMGs in GC but also underscores the clinical translation potential of the prognostic model, offering novel targets for personalized therapeutic strategies in GC.},
}

@article {pmid40389311,
year = {2025},
author = {de Lange, T},
title = {How Shelterin Orchestrates the Replication and Protection of Telomeres.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041685},
pmid = {40389311},
issn = {1943-0264},
abstract = {Efforts to determine how telomeres solve the end-protection problem led to the discovery of shelterin, a conserved six-subunit protein complex that specifically binds to the long arrays of telomeric TTAGGG repeats at vertebrate chromosome ends. The mechanisms by which shelterin prevents telomeres from being detected as sites of DNA damage and how shelterin prevents inappropriate DNA repair pathways are now largely known. More recently, shelterin has emerged as a central player in solving the second major problem at telomeres: how to complete the duplication of telomeric DNA. This end-replication problem results from the inability of the canonical DNA replication machinery to maintain the DNA at chromosome ends. Shelterin solves this problem by recruiting two enzymes that can replenish the lost telomeric repeats: telomerase and CST-Polα/primase. How shelterin accomplishes these critical tasks is reviewed here.},
}

@article {pmid40389285,
year = {2025},
author = {Antipov, D and Rautiainen, M and Nurk, S and Walenz, BP and Solar, SJ and Phillippy, AM and Koren, S},
title = {Verkko2 integrates proximity ligation data with long-read De Bruijn graphs for efficient telomere-to-telomere genome assembly, phasing, and scaffolding.},
journal = {Genome research},
volume = {},
number = {},
pages = {},
doi = {10.1101/gr.280383.124},
pmid = {40389285},
issn = {1549-5469},
abstract = {The Telomere-to-Telomere Consortium recently finished the first truly complete sequence of a human genome. To resolve the most complex repeats, this project relied on the semi-manual combination of long, accurate PacBio HiFi and ultra-long Oxford Nanopore sequencing reads. The Verkko assembler later automated this process, achieving complete assemblies for approximately half of the chromosomes in a diploid human genome. However, the first version of Verkko was computationally expensive and could not resolve all regions of a typical human genome. Here we present Verkko2, which implements a more efficient read correction algorithm, improves repeat resolution and gap closing, introduces proximity-ligation-based haplotype phasing and scaffolding, and adds support for multiple long-read data types. These enhancements allow Verkko to assemble all regions of a diploid human genome, including the short arms of the acrocentric chromosomes and both sex chromosomes. Together, these changes increase the number of telomere-to-telomere scaffolds by twofold, reduce runtime by fourfold, and improve assembly correctness. On a panel of 19 human genomes, Verkko2 assembles an average of 39 of 46 complete chromosomes as scaffolds, with 21 of these assembled as gapless contigs. Together, these improvements enable telomere-to-telomere comparative genomics and pangenomics, at scale.},
}

@article {pmid40384233,
year = {2025},
author = {Ghimire, A and Young, RC and Westneat, DF and Heidinger, BJ},
title = {Repeated Experimental Cold Exposure During Early Life Affects Several Metrics of Success but not Telomeres in a Common Songbird.},
journal = {Journal of experimental zoology. Part A, Ecological and integrative physiology},
volume = {},
number = {},
pages = {},
doi = {10.1002/jez.2927},
pmid = {40384233},
issn = {2471-5646},
support = {//We would like to acknowledge the many graduate students and postdoctoral lab and field workers in Fargo, including: Abigail Dennis, Holland Galante, and Emily Elderbrock. We are also very grateful to Steven Anderson, Todd Molden, Trent Gilbery, Garrett Havelka, and Shane Paasch for their support at the agricultural field site. Funding was provided by NSF award IOS-1656212 to BJH and DFW and IOS-1845974 to BJH. Sampling was conducted with permissions from the NDSU IACUC committee, the State of North Dakota, and USFWS./ ; },
abstract = {Climate change is increasing temperature variability and exposure to extreme temperature events, including cold snaps. Although there is evidence that exposure to cooler developmental temperature can have widespread phenotypic consequences, the degree to which temperature exposures might interact across developmental stages to affect offspring is poorly understood. Here we experimentally exposed free-living house sparrows to repeated bouts of parental absence, which cooled embryos and both cooled and deprived nestlings in a crossed design and examined the effects on growth, body mass, telomeres, and survival. We found that exposure to cooler temperatures during embryonic development had several negative consequences including extending incubation and reducing hatching success and body mass of recent hatchlings. However, there were no significant effects on telomeres. There were also no main effects of cooling and short-term food deprivation during post-hatching development or interactions across developmental stages on any developmental outcomes including telomeres. Taken together, these results suggest that some developmental stages and traits are more sensitive to repeated cooling than others. In songbirds, offspring may be more sensitive to repeated cooling at earlier life stages and telomeres may be largely resilient to these developmental insults.},
}

@article {pmid40383822,
year = {2025},
author = {Wang, XF and Liu, TJ and Feng, T and Huang, HR and Zou, P and Wei, X and Wu, X and Chai, SF and Yan, HF},
title = {A telomere-to-telomere genome assembly of Camellia nitidissima.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {815},
pmid = {40383822},
issn = {2052-4463},
support = {32460103//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {*Camellia/genetics ; *Telomere/genetics ; *Genome, Plant ; Base Composition ; },
abstract = {Camellia nitidissima is the model species of the Camellia sect. Chrysantha Chang, the only lineage within the genus Camellia known to produce golden-yellow flowers. This species holds high aesthetic, germplasm and medical value. Unfortunately, due to excessive collection and habitat loss, C. nitidissima is classified as a critically endangered plant. In this study, we assembled a telomere-to-telomere (T2T) genome of C. nitidissima by incorporating PacBio HiFi and Hi-C data. The assembled genome consisted of 15 pseudo-chromosomes, with a total size estimated to be 2.72 Gb. The GC content and repetitive sequences occupied 38.05% and 84.38% of the assembled genome, respectively. In total, 35,701 protein-coding genes were annotated. Multiple evaluation methods confirmed the contiguity (contig N50: 81.74 Mb), completeness (BUSCOs: 98.80%) and high LTR Assembly Index (LAI: 14.57) of the genome. This high-quality T2T genome will provide valuable insights into the genomic characteristics of C. nitidissima and facilitate conservation efforts as well as functional genomic studies in Camellia sect. Chrysantha species.},
}

*Camellia/genetics
*Telomere/genetics
*Genome, Plant
Base Composition

@article {pmid40383099,
year = {2025},
author = {Zhao, T and Qu, P and Zhao, Y},
title = {Comment on: Prognostic model of osteosarcoma based on telomere-related genes and analysis of immune characteristics.},
journal = {International immunopharmacology},
volume = {158},
number = {},
pages = {114759},
doi = {10.1016/j.intimp.2025.114759},
pmid = {40383099},
issn = {1878-1705},
}

@article {pmid40382655,
year = {2025},
author = {Cao, Z and Tan, Q and Yang, H and Xu, C},
title = {Shared genetic architecture between leukocyte telomere length and Alzheimer's disease.},
journal = {Alzheimer's research & therapy},
volume = {17},
number = {1},
pages = {108},
pmid = {40382655},
issn = {1758-9193},
mesh = {Humans ; *Alzheimer Disease/genetics ; *Leukocytes/metabolism ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Telomere/genetics ; Genetic Predisposition to Disease ; Polymorphism, Single Nucleotide ; Male ; *Telomere Homeostasis/genetics ; Female ; },
abstract = {BACKGROUND: Epidemiological and clinical studies have reported an association between leukocyte telomere length (LTL) and Alzheimer's disease (AD). However, genetic association between the two phenotypes remains largely unknown. We aimed to elucidate the potential shared genetic architecture between LTL and AD.

METHODS: Summary statistics from genome-wide association studies were obtained from large-scale biobank in European-ancestry populations for LTL (N = 472,174) and AD (71,880 cases, 383,378 controls). We examined the global and local genetic correlation between LTL and AD using linkage-disequilibrium score regression and ρ-HESS. We applied the bivariate causal mixture model (MiXeR) to calculate the number of shared genetic causal variants, and the conditional/conjunctional false discovery rate (condFDR/conjFDR) framework to identify specific shared loci between LTL and AD. Bidirectional two-sample Mendelian randomization (MR) were used to explore the causal associations between LTL and AD.

RESULTS: We detected a significant genetic correlation between LTL and AD (rg = -0.168). Partitioning the whole genome into 1703 almost independent regions, we observed a significant local genetic correlation for LTL and AD at 19q13.32. MiXeR estimated a total of 360 variants affecting LTL, of which 16 was estimated to influence AD. The condFDR revealed an essential genetic enrichment in LTL conditional on associations with AD, and vice versa. We next identified 8 shared genomic loci between LTL and AD using conjFDR method, of which 4 are novel loci for both the phenotypes. Moreover, 3 shared loci were identified as eQTLs (rs3098168, rs4780338 and rs2680702). All shared loci mapped a subset of 48 credible genes, including USP8, DEXI and APOE. Gene-set analysis identified 18 putative gene sets enriched with the genes mapped to the shared loci. MR analysis suggested that genetically determined AD was causally associated with LTL.

CONCLUSION: Our study identified specific shared loci between LTL and AD, providing new insights for polygenic overlap and molecular mechanisms, and highlighting new opportunities for future experimental validation.},
}

Humans
*Alzheimer Disease/genetics
*Leukocytes/metabolism
Genome-Wide Association Study
Mendelian Randomization Analysis
*Telomere/genetics
Genetic Predisposition to Disease
Polymorphism, Single Nucleotide
Male
*Telomere Homeostasis/genetics
Female

@article {pmid40379219,
year = {2025},
author = {Konopka, A and Jamali, MS and Fowler, M and Mehta, P and Parakh, S and Takalloo, Z and Farzana, F and Mumtaz, N and Hunter, J and Shadfar, S and Rogers, ML and Atkin, JD},
title = {Pathological forms of TDP-43 in amyotrophic lateral sclerosis (ALS) promote aberrant telomere elongation.},
journal = {Biochimica et biophysica acta. Molecular basis of disease},
volume = {},
number = {},
pages = {167906},
doi = {10.1016/j.bbadis.2025.167906},
pmid = {40379219},
issn = {1879-260X},
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting motor neurons. TAR DNA-binding protein 43 (TDP-43) mis-localisation from the nucleus to the cytoplasm is the major pathological characteristic of ALS. Telomeres are repetitive DNA sequences found in complex with proteins at chromosomal ends. The shelterin protein complex protects telomeres from DNA damage by producing characteristic t-loop structures, and telomere repeat binding factor 2 (TRF2) has an essential role in this process. Telomere dysregulation is reported in ALS, but conflicting findings have been obtained. Here we examined if telomere dysregulation is present in cortical neurons in a mouse model with pathological mis-localisation of TDP-43 to the cytoplasm - TDP-43 rNLS - compared to controls, and in cortical primary neurons expressing TDP-43 ALS associated mutations (A315T, A90V). We demonstrate that telomeres are significantly longer and of more variable in length in this model compared to controls. This was proceeded by downregulation of TRF2 in early disease stages with subsequent upregulation of TRF2 at advanced disease in TDP43 rNLS mice. A trend towards TRF2 upregulation was also present in human ALS. We detected dysregulation of catalytic subunit of telomerase, TERT and trend towards upregulation of telomere interacting protein, Rif 1 in these mice and human ALS spinal cord lysates. The longer telomeres were independent of the alternative lengthening of telomeres (ALT). Similarly, no DNA damage at telomere sites was detected. Our findings imply that telomere protection is compromised, leading to longer telomeres in cortical neurons in ALS associated with TDP-43 pathology.},
}

@article {pmid40378535,
year = {2025},
author = {Selvi, S and Real, CM and Gentiluomo, M and Balounova, K and Vokacova, K and Cumova, A and Mohlenikova-Duchonova, B and Rizzato, C and Halasova, E and Vodickova, L and Smolkova, B and Hemminki, K and Campa, D and Vodicka, P},
title = {Genomic instability, DNA damage response and telomere homeostasis in pancreatic cancer.},
journal = {Seminars in cancer biology},
volume = {113},
number = {},
pages = {59-73},
doi = {10.1016/j.semcancer.2025.05.005},
pmid = {40378535},
issn = {1096-3650},
abstract = {Pancreatic cancer (PC) is becoming one of the most serious health problems at present, but its causes and risk factors are still unclear. One of the drivers in pancreatic carcinogenesis is altered genomic (DNA) integrity with subsequent genomic instability in cancer cells. The latter comprises a) DNA damage response and DNA repair mechanisms, b) DNA replication and mitosis, c) epigenetic regulation, and d) telomere maintenance. In our review we addressed the above aspects in relation to the most abundant and severe form of PC, pancreatic ductal adenocarcinoma (PDAC). In summary, the interactions between the DNA damage response, telomere homeostasis and mitotic regulation are not comprehensively understood at present, including the epigenetic factors entering the trait of genomic stability maintenance. In addition, the complexity of telomere homeostasis in relation to PDAC risk, prognosis and prediction also warrants further investigations.},
}

@article {pmid40372724,
year = {2025},
author = {Cao, C and Miao, J and Xie, Q and Sun, J and Cheng, H and Zhang, Z and Wu, F and Liu, S and Ye, X and Gong, H and Zhang, Z and Wang, Q and Pan, Y and Wang, Z},
title = {A near telomere-to-telomere genome assembly of the Jinhua pig: enabling more accurate genetic research.},
journal = {GigaScience},
volume = {14},
number = {},
pages = {},
pmid = {40372724},
issn = {2047-217X},
support = {2021YFD1200802//National Key Research and Development Program of China/ ; 2022YFF1000500//National Key Research and Development Program of China/ ; 2023YFD1300404//National Key Research and Development Program of China/ ; 32372831//National Natural Science Foundation of China/ ; 32172691//National Natural Science Foundation of China/ ; LZ23C170003//Zhejiang Provincial Natural Science Foundation of China/ ; 2021C02068//Key Research and Development Program of Zhejiang Province/ ; 32402713//Young Scientists Fund of the National Natural Science Foundation of China/ ; },
mesh = {Animals ; *Telomere/genetics ; Swine/genetics ; *Genome ; *Genomics/methods ; Molecular Sequence Annotation ; },
abstract = {BACKGROUND: Pigs are crucial sources of meat and protein, valuable animal models, and potential donors for xenotransplantation. However, the existing reference genome for pigs is incomplete, with thousands of segments and centromeres and telomeres missing, which limits our understanding of the important traits in these genomic regions.

FINDINGS: We present a near-complete genome assembly for the Jinhua pig (JH-T2T) and provide a set of diploid Jinhua reference genomes, constructed using PacBio HiFi, ONT long reads, and Hi-C reads. This assembly includes all 18 autosomes and the X and Y sex chromosomes, with only 6 gaps. It features annotations of 46.90% repetitive sequences, 33 telomeres, 17 centromeres, and 23,924 high-confident genes. Compared to the Sscrofa11.1, JH-T2T closes nearly all gaps, extends sequences by 177 Mb, predicts more intact telomeres and centromeres, and gains 799 more genes and loses 114 genes. Moreover, it enhances the mapping rate for both Western and Chinese local pigs, outperforming Sscrofa11.1 as a reference genome. Additionally, this comprehensive genome assembly will facilitate large-scale variant detection.

CONCLUSIONS: This study produced a near-gapless assembly of the pig genome and provides a set of haploid Jinhua reference genomes. Our findings represent a significant advance in pig genomics, providing a robust resource that enhances genetic research, breeding programs, and biomedical applications.},
}

Animals
*Telomere/genetics
Swine/genetics
*Genome
*Genomics/methods
Molecular Sequence Annotation

@article {pmid40371663,
year = {2025},
author = {Adam, N and Yang, Y and Djamshidi, M and Seifan, S and Ting, NSY and Glover, J and Touret, N and Gordon, PMK and Vineetha Warriyar, KV and Krowicki, H and Garcia, CK and Savage, SA and Goodarzi, AA and Baird, DM and Beattie, TL and Riabowol, K},
title = {hTERT Increases TRF2 to Induce Telomere Compaction and Extend Cell Replicative Lifespan.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e70105},
doi = {10.1111/acel.70105},
pmid = {40371663},
issn = {1474-9726},
support = {PJT-190171//Institute of Aging/ ; },
abstract = {Replicative senescence occurs in response to shortened telomeres and is triggered by ATM and TP53-mediated DNA damage signaling that blocks replication. hTERT lengthens telomeres, which is thought to block damage signaling and the onset of senescence. We find that normal diploid fibroblasts expressing hTERT mutants unable to maintain telomere length do not initiate DNA damage signaling and continue to replicate, despite having telomeres shorter than senescent cells. The TRF1 and TRF2 DNA binding proteins of the shelterin complex stabilize telomeres, and we find that expression of different mutant hTERT proteins decreases levels of the Siah1 E3 ubiquitin ligase that targets TRF2 to the proteasome, by increasing levels of the CDC20 and FBXO5 E3 ligases that target Siah1. This restores the TRF2:TRF1 ratio to block the activation of ATM and subsequent activation of TP53 that is usually associated with DNA damage-induced senescence signaling. All hTERT variants reduce DNA damage signaling, and this occurs concomitantly with telomeres assuming a more compact, denser conformation than senescent cells as measured by super-resolution microscopy. This indicates that hTERT variants induce TRF2-mediated telomere compaction that is independent of telomere length, and it plays a dominant role in regulating the DNA damage signaling that induces senescence and blocks replication of human fibroblasts. These observations support the idea that very short telomeres often seen in cancer cells may fail to induce senescence due to selective stabilization of components of the shelterin complex, increasing telomere density, rather than maintaining telomere length via the reverse transcriptase activity of hTERT.},
}

@article {pmid40370345,
year = {2025},
author = {Rayner, JG and Marshall, A and Adams, DM and Kaiser, J and Armenta, K and Wilkinson, GS},
title = {Sex Differences in Telomere Length in a Bat With Female-Biased Longevity.},
journal = {Ecology and evolution},
volume = {15},
number = {5},
pages = {e71378},
pmid = {40370345},
issn = {2045-7758},
abstract = {Telomeres, protective caps at the ends of linear chromosomes, are frequently found to shorten with age. Telomere length is commonly measured in wild populations to investigate age-related changes in somatic integrity and is considered a hallmark of ageing. Despite interest, there is no clear picture regarding sex differences in telomere length or rate of attrition across species. Bats are of considerable interest in studies of ageing and telomeres, owing to their remarkable longevity and the absence of age-associated telomere attrition observed in some species. Additionally, multiple bat species show evidence of sex differences in longevity. However, few studies of bat telomeres have included both sexes. We collected DNA from wild-caught males and females of the highly polygynous greater spear-nosed bat, Phyllostomus hastatus, in which mortality is strongly male-biased, and measured relative telomere lengths. We found that, while telomeres were shorter in older bats, there was no evidence of shorter telomeres in males. In fact, males tended to have longer telomeres. This runs counter to our prediction of shorter telomeres in the shorter-lived sex but is not completely unexpected in light of other observations, including that of shorter telomeres in longer lived species.},
}

@article {pmid40368912,
year = {2025},
author = {Liu, Y and Chen, Y and Ren, Z and Li, K and Wang, X and Wu, K and Liu, J and Sade, N and He, H and Li, S and Jiang, H and Han, X},
title = {Two haplotype-resolved telomere-to-telomere genome assemblies of Xanthoceras sorbifolium.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {791},
pmid = {40368912},
issn = {2052-4463},
mesh = {*Telomere/genetics ; Haplotypes ; *Genome, Plant ; *Sapindaceae/genetics ; Molecular Sequence Annotation ; },
abstract = {Yellowhorn (Xanthoceras sorbifolium) is widely used in northern China for landscaping, desertification control, and oil production. However, the lack of high-quality genomes has hindered breeding and evolutionary studies. Here, we present the first haplotype-resolved, telomere-to-telomere (T2T) yellowhorn genomes of PBN-43 (white single-flowered) and PBN-126 (white double-flowered) using PacBio HiFi and Hi-C data. These assemblies range from 464.34 Mb to 468.97 Mb and include all centromeres and telomeres. Genome annotation revealed that an average of 67.99% (317.09 Mb) of yellowhorn genomic regions consist of repetitive elements across all haplotypes. The number of protein-coding genes ranges from 35,039 to 35,174 among assemblies, representing an average 50.16% increase over the first published yellowhorn genome. Additionally, 93.90% of the annotated genes have functional annotations. We found yellowhorn experienced an LTR-RT burst during the last 0.45-0.48 Mya. These data provide a resource for investigating genomic variations, phylogenetic relationships, duplication modes, and the distribution of nucleotide-binding leucine-rich repeat (NLR) genes, and support further research into yellowhorn breeding.},
}

*Telomere/genetics
Haplotypes
*Genome, Plant
*Sapindaceae/genetics
Molecular Sequence Annotation

@article {pmid40366866,
year = {2025},
author = {Wang, Y and Hao, X and Chen, C and Wang, H and Gao, P and Yang, X and Dong, X and Qin, H and Li, M and Hou, S and Jian, J and Chang, J and Wu, J and Mu, Z},
title = {Telomere-to-telomere genome of common bean (Phaseolus vulgaris L., YP4).},
journal = {GigaScience},
volume = {14},
number = {},
pages = {},
pmid = {40366866},
issn = {2047-217X},
support = {32241041//National Natural Science Foundation of China/ ; 202101140601027//Major Special Science and Technology Plan in Shanxi Province/ ; 2021YFD1600600//National Key Research and Development Program of China/ ; 202304010930003//Hou Ji Laboratory in Shanxi Province/ ; },
mesh = {*Phaseolus/genetics/classification ; *Genome, Plant ; *Telomere/genetics ; Phylogeny ; Chromosomes, Plant/genetics ; Genomics/methods ; },
abstract = {BACKGROUND: Common bean is a significant grain legume in human diets. However, the lack of a complete reference genome for common beans has hindered efforts to improve agronomic cultivars.

FINDINGS: Herein, we present the first telomere-to-telomere (T2T) genome assembly of common bean (Phaseolus vulgaris L., YP4) using PacBio High-Fidelity reads, ONT ultra-long sequencing, and Hi-C technologies. The assembly resulted in a genome size of 560.30 Mb with an N50 of 55.11 Mb, exhibiting high completeness and accuracy (BUSCO score: 99.5%, quality value (QV): 54.86). The sequences were anchored into 11 chromosomes, with 20 of 22 telomeres identified, leading to the formation of 9 T2T pseudomolecules. Furthermore, we identified repetitive elements accounting for 61.20% of the genome and predicted 29,925 protein-coding genes. Phylogenetic analysis suggested an estimated divergence time of approximately 11.6 million years ago between P. vulgaris and Vigna angularis. Comparative genome analysis revealed the expanded gene families and variations between YP4 and G19833 associated with defense response.

CONCLUSIONS: The T2T reference genome and genomic insights presented here are crucial for future genetic studies not only in common bean but also in other legumes.},
}

*Phaseolus/genetics/classification
*Genome, Plant
*Telomere/genetics
Phylogeny
Chromosomes, Plant/genetics
Genomics/methods

@article {pmid40364833,
year = {2025},
author = {Mendez, KJW and Lai, TP and Spellman, SR and Verhulst, S and Anderson, J and Saber, W and Gadalla, SM and Aviv, A},
title = {Long donor leukocyte telomeres raise risk of severe COVID-19 in recipients of allogeneic hematopoietic cell transplant.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1524608},
pmid = {40364833},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/mortality/immunology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Male ; Middle Aged ; Female ; *SARS-CoV-2 ; *Telomere/genetics ; Adult ; *Leukocytes ; Aged ; Transplantation, Homologous ; Tissue Donors ; Severity of Illness Index ; Telomere Homeostasis ; Risk Factors ; },
abstract = {INTRODUCTION: Short leukocyte telomeres are associated with an increased risk of severe COVID-19 in the general population, likely due to a weakened T-cell response to SARS-CoV-2. This may lead to an amplified neutrophil response, causing pulmonary damage. Allogeneic hematopoietic cell transplant (HCT) offers an experimental setting to examine further the role of telomere length (TL) in COVID-19 severity, as leukocyte TL in recipients post-HCT reflects TL in donor leukocytes before HCT and SARS-CoV-2 infection.

METHODS: We examined the relationship between donor leukocyte TL pre-HCT and COVID-19 severity post-HCT in 87 HCT recipients hospitalized for COVID-19 between March 2020 and January 2022. Using the Telomere Shortest Length Assay (TeSLA), we measured leukocyte TL and the percentage of telomeres shorter than 3 kilobases.

RESULTS: The risk of severe COVID-19 in HCT recipients was associated with long telomeres (P=0.005) and a lower percentage of telomeres shorter than 3 kilobases (P=0.01) in donor leukocytes. Moreover, long donor leukocyte telomeres were associated with an increased risk of recipient mortality within four months after COVID-19 hospitalization (P=0.03).

CONCLUSIONS: These findings suggest that long donor leukocyte telomeres may trigger an excessive neutrophil response and severe COVID-19 in allogeneic HCT recipients, potentially due to a transplant-related but TL-independent weak T-cell response.},
}

Humans
*COVID-19/mortality/immunology
*Hematopoietic Stem Cell Transplantation/adverse effects
Male
Middle Aged
Female
*SARS-CoV-2
*Telomere/genetics
Adult
*Leukocytes
Aged
Transplantation, Homologous
Tissue Donors
Severity of Illness Index
Telomere Homeostasis
Risk Factors

@article {pmid40362411,
year = {2025},
author = {Hakobyan, M and Binder, H and Arakelyan, A},
title = {Telomere Maintenance Pathways in Lower-Grade Gliomas: Insights from Genetic Subtypes and Telomere Length Dynamics.},
journal = {International journal of molecular sciences},
volume = {26},
number = {9},
pages = {},
doi = {10.3390/ijms26094175},
pmid = {40362411},
issn = {1422-0067},
support = {21AG-1F021//Science Committee of the MESCS of Armenia/ ; },
mesh = {Humans ; *Glioma/genetics/pathology ; *Telomere Homeostasis/genetics ; *Telomere/genetics/metabolism ; Telomerase/genetics/metabolism ; *Brain Neoplasms/genetics/pathology ; Mutation ; X-linked Nuclear Protein/genetics ; Isocitrate Dehydrogenase/genetics ; Neoplasm Grading ; },
abstract = {Telomere maintenance mechanisms (TMMs) play a critical role in cancer biology, particularly in lower-grade gliomas (LGGs), where telomere dynamics and pathway activity remain poorly understood. In this study, we analyzed TCGA-LGG and CGGA datasets, focusing on telomere length variations, pathway activity, and survival data across IDH subtypes. Additional validation was performed using the GEO COPD and GBM datasets, ensuring consistency in data processing and batch effect correction. Our analysis revealed significant differences in TEL pathway activation between Short- and Long-TL groups, emphasizing the central role of TERT in telomere maintenance. In contrast, ALT pathway activation displayed subtype-specific patterns, with IDH-wt tumors exhibiting the highest ALT activity, primarily driven by the RAD51 branch. Validation using CGGA data confirmed these findings, demonstrating consistent TEL and ALT pathway behaviors across datasets. Additionally, genetic subtype analysis revealed substantial telomere length variability associated with ATRX and IDH mutation status. Notably, IDHwt-ATRX WT tumors exhibited the shortest telomere length and the highest ALT pathway activity. These findings highlight distinct telomere regulatory dynamics across genetic subtypes of LGG and provide new insights into potential therapeutic strategies targeting telomere maintenance pathways.},
}

Humans
*Glioma/genetics/pathology
*Telomere Homeostasis/genetics
*Telomere/genetics/metabolism
Telomerase/genetics/metabolism
*Brain Neoplasms/genetics/pathology
Mutation
X-linked Nuclear Protein/genetics
Isocitrate Dehydrogenase/genetics
Neoplasm Grading

@article {pmid40360522,
year = {2025},
author = {Han, X and Li, X and Xu, L and Liu, Q and Su, S and Yao, W and He, W},
title = {The telomere-to-telomere genome assembly and annotation of the rock carp (Procypris rabaudi).},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {781},
pmid = {40360522},
issn = {2052-4463},
support = {32071651//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {Animals ; *Genome ; *Telomere/genetics ; Molecular Sequence Annotation ; *Cyprinidae/genetics ; *Carps/genetics ; },
abstract = {Procypris rabaudi, commonly known as the rock carp, is an endemic economic fish in the middle-upper reaches of the Yangtze River. To enhance the understanding the biology of rack carps, a high-quality reference genome is required in different areas of study. Here, we generated the first telomere-to-telomere genome assembly and annotation of the rock carp, which spans 1.64 Gb with a contig N50 of 32.36 Mb. Hi-C assembly suggested that 99.83% sequences were positioned to 50 pseudo-chromosomes. Notably, 43 chromosomes were assembled without any gap. Through the integration of homologous-based predictions and RNA-sequencing technology, we identified 44,402 protein-coding genes, with 43,663 of them (98.3%) predicted to be functional. Furthermore, our assembled genome achieved 98.1% BUSCO completeness. This work improves the quality of the rock carp genome and provides valuable foundation for the future studies of genomics, biology and the fishery resources breeding.},
}

Animals
*Genome
*Telomere/genetics
Molecular Sequence Annotation
*Cyprinidae/genetics
*Carps/genetics

@article {pmid40358587,
year = {2025},
author = {Celestin, GF and Pierce, LJ and Valdes, V and Urbina-Johanson, SA and Barrero-Castillero, A and Vyas, CM and Senese, S and De Vivo, I and Nelson, CA},
title = {Telomere Length and Change Among Infants Growing up in Low- to Mid-Income Households.},
journal = {Developmental psychobiology},
volume = {67},
number = {3},
pages = {e70047},
doi = {10.1002/dev.70047},
pmid = {40358587},
issn = {1098-2302},
support = {//JPB Research Network on Toxic Stress: A project of the Center on the Developing Child at Harvard University as well as the Jacobs Foundation/ ; },
mesh = {Humans ; Female ; Male ; Infant ; *COVID-19 ; Longitudinal Studies ; *Stress, Psychological ; *Telomere ; Adult ; *Child Development/physiology ; *Poverty ; Mothers ; *Psychological Distress ; },
abstract = {Telomere biology is a molecular mechanism that may underlie relationships between stress and health outcomes and has been shown to vary across racial and ethnic groups. Telomere length may also be susceptible to the deleterious impacts of stress during early development. However, limited research has examined these associations in diverse samples using repeated measures in infancy. This study assessed longitudinal change in telomere length across three time points in the first year of life (n = 90) in a diverse sample of infants (53.3% female, 30% Black, and 35.6% Hispanic) from low- to middle-income backgrounds. We also examined associations between maternal psychological stress, sociodemographic characteristics, COVID-19 pandemic onset, and infant telomere length. In this sample, female infants had longer telomeres than male infants. Additionally, visit timepoint significantly predicted infant telomere length, showing nonlinear patterns of change over time. Maternal psychological distress, sociodemographic characteristics, and the onset of the COVID-19 pandemic were not associated with infant telomere length. Overall, these findings suggest that infant telomere length is dynamic in the first year of life, although larger and more socioeconomically heterogeneous samples may be needed to detect the effects of stress on infant telomere length.},
}

Humans
Female
Male
Infant
*COVID-19
Longitudinal Studies
*Stress, Psychological
*Telomere
Adult
*Child Development/physiology
*Poverty
Mothers
*Psychological Distress

@article {pmid40356370,
year = {2025},
author = {Song, H and Kim, S and Lim, DS and Choi, HJ and Lee, J},
title = {Robust Binding Capability and Occasional Gene Loss of Telomere-Binding Proteins Underlying Telomere Evolution in Nematoda.},
journal = {Genome biology and evolution},
volume = {},
number = {},
pages = {},
doi = {10.1093/gbe/evaf085},
pmid = {40356370},
issn = {1759-6653},
abstract = {Telomeres, the nucleoprotein complexes that protect the ends of linear chromosomes, are essential for maintaining the stability of eukaryotic genomes. As telomeres generally consist of repetitive DNA associated with specifically bound proteins, telomeric repeat motifs (TRMs) are thought to be difficult to evolve. However, a recent study identified nematodes with telomeric repeats distinct from the canonical TTAGGC motif. Here, we investigated how telomere repeats could have evolved despite the challenge posed by the specificity of telomere-binding proteins (TBPs) to the telomeric DNA in Nematoda. We performed a phylogenetic analysis and electrophoresis mobility shift assays to assess the binding affinities of two TBPs, which displayed different conservation patterns. Our results revealed that the well-conserved protein CEH-37 exhibits limited specificity, unable to distinguish telomeric repeats found in nematodes except for the TTAGGG motif, while the less conserved POT proteins displayed rigid specificity. These findings suggest that the emergence of novel telomeric repeat motifs correlated with the characteristics and evolutionary outcomes of TBPs in Nematoda. Our study not only revealed the dynamics of telomere evolution but also enhanced the understanding of the evolutionary relationship between proteins and DNAs.},
}

@article {pmid40355908,
year = {2025},
author = {Sung, JY and Kim, JH and Kim, YJ},
title = {Alternative lengthening of telomeres confers favorable prognosis in chondrosarcomas.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {536},
pmid = {40355908},
issn = {1479-5876},
support = {RS-2023-00213119//National Research Foundation of Korea/ ; RS-2024-00440273//National Research Foundation of Korea/ ; RS-2025-00517430//National Research Foundation of Korea/ ; },
mesh = {Humans ; *Chondrosarcoma/genetics/pathology/immunology/diagnosis ; Prognosis ; *Telomere Homeostasis/genetics ; Tumor Microenvironment/genetics ; Gene Expression Regulation, Neoplastic ; *Bone Neoplasms/genetics/pathology ; Single-Cell Analysis ; Telomerase/metabolism ; Female ; Telomere/metabolism ; },
abstract = {BACKGROUND: Cancer cells achieve replicative immortality through telomere maintenance mechanisms (TMMs), primarily via telomerase activation or alternative lengthening of telomeres (ALT). Sarcomas frequently employ the ALT pathway, which traditionally correlates with adverse clinical outcomes. However, chondrosarcomas represent a unique context where the role and prognostic significance of ALT remain largely unexplored.

METHODS: We performed comprehensive analyses of single-cell RNA-sequencing data from patients with chondrosarcoma and integrated this with 90 bulk RNA-seq datasets. This approach enabled detailed characterization of TMM at single-cell resolution, identification of ALT-specific signatures, and evaluation of the tumor microenvironment in chondrosarcomas.

RESULTS: Patients with ALT-like chondrosarcomas exhibited significantly improved survival compared to those with non-ALT-like chondrosarcomas. Analysis of the tumor immune microenvironment revealed distinct metabolic and immune landscapes between the ALT-like and non-ALT-like groups. Single-cell analysis showed that high-entropy stem-like cells in high-grade chondrosarcomas predominantly adopted telomerase activation over the ALT pathway as their TMM. Additionally, we identified a 100-gene signature that reliably distinguishes ALT-like chondrosarcomas, providing a robust molecular marker for classification and prognosis.

CONCLUSIONS: Our study reveals ALT-like state as a marker of favorable prognosis in chondrosarcomas-contrasting with its typically adverse implications in other sarcomas. We establish a robust 100-gene signature that reliably identifies ALT-like chondrosarcomas and characterize their distinct immune microenvironment profile.},
}

Humans
*Chondrosarcoma/genetics/pathology/immunology/diagnosis
Prognosis
*Telomere Homeostasis/genetics
Tumor Microenvironment/genetics
Gene Expression Regulation, Neoplastic
*Bone Neoplasms/genetics/pathology
Single-Cell Analysis
Telomerase/metabolism
Female
Telomere/metabolism

@article {pmid40352198,
year = {2025},
author = {Sasmita, DM and Anwar, SL and Heriyanto, DS and Paramita, DK and Hendrawan, F and Aryandono, T},
title = {Prognosis value of circulating telomere repeat binding factor 2 and leukocyte telomere length in breast cancer mortality.},
journal = {Narra J},
volume = {5},
number = {1},
pages = {e1601},
pmid = {40352198},
issn = {2807-2618},
mesh = {Humans ; *Breast Neoplasms/mortality/blood/genetics ; Female ; *Telomeric Repeat Binding Protein 2/blood ; Middle Aged ; Prognosis ; *Leukocytes/metabolism ; Retrospective Studies ; *Telomere ; Biomarkers, Tumor/blood ; Adult ; Aged ; },
abstract = {Telomere repeat binding factor 2 (TRF2) is currently a novel tumor marker, yet its clinical implication has not been investigated. The aim of this study was to investigate the prognostic value of circulating TRF2 and leukocyte telomere length in 5-year mortality in breast cancer patients. In this cohort retrospective study, breast cancer patients were included and the length of telomeres and circulating TRF2 were quantified. Receiver operating characteristics and the Youden index were used to determine the optimal cut-off. To analyze the overall survival rate in five years, Kaplan Meier analysis was used, while the prognostic value of both variables was analyzed in Cox proportional hazard regression on both univariate and multivariate models. Our data indicated that the optimal cut-off points for TRF2 and leukocyte telomere length were 598 pg/mL and 0.93 kb, respectively. Based on the optimal cut-off points, the participant's data was grouped, and our data indicated that the high TRF2 group had a poorer overall survival rate in comparison to the low group (91.3% vs 83.87%; log-rank test; p < 0.01). The overall survival between short and long telomeres was comparable (88.24% vs 88.37%; log-rank test; p = 0.64). TRF2 (hazard ratio (HR): 3.66; 95%CI: 1.45-9.29) and molecular subtype (p = 0.04) were identified as independent factors to predict mortality. In conclusion, a high circulating TRF2 in breast cancer participants was associated with lower overall 5-year survival rates in comparison with the low TRF2 group. Moreover, high TRF2 could predict the mortality of the breast cancer population to be 3.66 times higher than the lower group. In contrast, telomere length was not associated with overall survival rate nor predicting mortality in five years.},
}

Humans
*Breast Neoplasms/mortality/blood/genetics
Female
*Telomeric Repeat Binding Protein 2/blood
Middle Aged
Prognosis
*Leukocytes/metabolism
Retrospective Studies
*Telomere
Biomarkers, Tumor/blood
Adult
Aged

@article {pmid40351047,
year = {2025},
author = {Affonso, JM and D'Amico, TP and Horst, MA and Moreno, FS and Heidor, R},
title = {Telomeres and Telomerase: Targets for Chemoprevention of Hepatocellular Carcinoma With Bioactive Food Compounds.},
journal = {Molecular nutrition & food research},
volume = {},
number = {},
pages = {e70088},
doi = {10.1002/mnfr.70088},
pmid = {40351047},
issn = {1613-4133},
support = {2013/07914-8//São Paulo Research Foundation (FAPESP)/ ; },
abstract = {The maintenance of telomere length by telomerase plays an essential role in senescence, aging, and cancer. Mutations in the TERT promoter, a telomerase subunit, are frequent in human cancers. In hepatocellular carcinoma (HCC), telomere shortening contributes to preneoplastic conditions such as cirrhosis. Telomerase activation during cirrhosis may reduce chromosomal instability, while its suppression in early dysplastic nodules may prevent hepatocarcinogenesis. Evidence suggests that bioactive food compounds (BFCs) can reduce the incidence and/or delay the onset of HCC by modulating telomerase activity. A systematic review was conducted on the role of BFCs in telomerase activity during hepatocarcinogenesis. BFCs were analyzed in isolated form or as part of extracts and categorized into fatty acids, isoprenoids, isothiocyanates, and phenolic compounds. Despite structural diversity, BFCs modulate telomerase through common mechanisms, including inhibition of activating proteins at the TERT promoter, activation of nuclear receptors, or histone H3 hyperacetylation. Indirectly, telomerase can also be modulated via activation of antioxidant defense pathways. Understanding telomerase reactivation and its modulation by BFCs is key to establishing effective HCC chemoprevention strategies targeting telomerase.},
}

@article {pmid40347215,
year = {2025},
author = {Yang, Z and Li, F},
title = {From gaps to insights: telomere-to-telomere cotton genome deciphers centromere dynamics after polyploidization.},
journal = {Science China. Life sciences},
volume = {},
number = {},
pages = {},
pmid = {40347215},
issn = {1869-1889},
}

@article {pmid40345564,
year = {2025},
author = {Hannan, SJ and Iasella, CJ and Sciullo, M and Moore, C and Rivosecci, R and Sacha, L and Sutton, RM and Koshy, R and Shigemura, N and Sanchez, PG and Farah, R and Hage, CA and Alder, JK and McDyer, JF},
title = {Belatacept as an Alternative Immunosuppressive Agent for Bone Marrow-Sparing in Idiopathic Pulmonary Fibrosis Lung Transplant Recipients with Short Telomeres.},
journal = {The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.healun.2025.04.022},
pmid = {40345564},
issn = {1557-3117},
abstract = {As we have previously shown, Idiopathic pulmonary fibrosis lung transplant recipients (IPF-LTRs) with short-telomere length (STL) are prone to develop significant cytopenias and poor tolerance to cell cycle inhibitors, specifically Mycophenolate mofetil (MMF), post-transplant. We investigated the use of Belatacept as an alternative immunosuppressive agent in a prospective, open-label cohort of 9 ST-IPF-LTRs at our institution. These patients were either challenged with MMF (majority) or immediately started on Belatacept post-transplant with the goal to bridge to Everolimus, an mTOR inhibitor that is commonly used post-transplant. We describe outcomes in the first-year post-transplant including the incidence of Acute Cellular Rejection (ACR), Epstein-Barr Virus (EBV) viremia, and one case of Post-Transplant Lymphoproliferative Disorder (PTLD) at 13 months. The use of Belatacept post-lung transplant may be an acceptable short-term alternative therapy to cell cycle inhibitors in ST-IPF-LTRs with cytopenias but may lead to higher risk of EBV viremia and PTLD when Belatacept is used long-term in these patients.},
}

@article {pmid40344431,
year = {2025},
author = {Straniero, L and Rimoldi, V and Cereda, E and Soldà, G and Calandrella, D and Duga, S and Mazzetti, S and Cappelletti, G and Isaias, IU and Pezzoli, G and Asselta, R},
title = {Genetics Influences Telomere Length in Parkinson's Disease: A Study in Monozygotic Discordant Twins.},
journal = {Movement disorders : official journal of the Movement Disorder Society},
volume = {},
number = {},
pages = {},
doi = {10.1002/mds.30224},
pmid = {40344431},
issn = {1531-8257},
support = {2017228L3J//Ministero dell'Università e della Ricerca/ ; //Fondazione Pezzoli per la Malattia di Parkinson/ ; },
abstract = {BACKGROUND: Parkinson's disease (PD) results from complex interactions among environmental, genetic, and aging factors. Telomeres, which ensure chromosome stability, naturally shorten with cell division, contributing to aging and cellular senescence. However, studies investigating telomere length (TL) in PD have produced inconsistent results.

OBJECTIVE: This study aims to explore the relationship between TL and PD using a unique PD-discordant monozygotic twin design, which minimizes confounding factors such as age, gender, and genetic background. We also examined the impact of PD-related genetic mutations on TL.

METHODS: We analyzed relative telomere length (RTL) in blood samples from 29 pairs of monozygotic twins discordant for PD. Data was stratified by disease duration, and we investigated the influence of genetic variants (GBA1 and LRRK2) on RTL.

RESULTS: No significant difference in RTL was observed between PD-affected twins and their healthy co-twins overall. However, twins with longer disease duration (≥8 years) showed a significant decline in RTL (0.90 ± 0.18 vs. 1.07 ± 0.24; P = 0.046), which was more pronounced with a 10-year disease duration cutoff (0.85 ± 0.18 vs. 1.06 ± 0.22; P = 0.015). GBA1-mutated PD twins exhibited significantly longer RTL than non-mutated twins, a result replicated in non-twin GBA1 carriers and extended to LRRK2 carriers.

CONCLUSIONS: Our findings suggest that aging and cellular senescence primarily drive sporadic PD, whereas genetic forms are linked to disruptions in cellular pathways, such as lysosomal or mitochondrial functions. These insights highlight the role of genetics in telomere dynamics in PD. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.},
}

@article {pmid40343350,
year = {2025},
author = {Li, YP and Su, LY and Huang, T and Liu, H and Tan, SS and Deng, YJ and Wang, YH and Xiong, AS},
title = {The telomere-to-telomere genome of Pucai () (Typha angustifolia L.): a distinctive semiaquatic vegetable with lignin and chlorophyll as quality characteristics.},
journal = {Horticulture research},
volume = {12},
number = {7},
pages = {uhaf079},
doi = {10.1093/hr/uhaf079},
pmid = {40343350},
issn = {2662-6810},
abstract = {Pucai () (Typha angustifolia L.), within the Typha spp., is a distinctive semiaquatic vegetable. Lignin and chlorophyll are two crucial traits and quality indicators for Pucai. In this study, we assembled a 207.00-Mb high-quality gapless genome of Pucai, telomere-to-telomere (T2T) level with a contig N50 length of 13.73 Mb. The most abundant type of repetitive sequence, comprising 16.98% of the genome, is the long terminal repeat retrotransposons (LTR-RT). A total of 30 telomeres and 15 centromeric regions were predicted. Gene families related to lignin, chlorophyll biosynthesis, and disease resistance were greatly expanded, which played important roles in the adaptation of Pucai to wetlands. The slow evolution of Pucai was indicated by the σ whole-genome duplication (WGD)-associated Ks peaks from different Poales and the low activity of recent LTR-RT in Pucai. Meanwhile, we found a unique WGD event in Typhaceae. A statistical analysis and annotation of genomic variations were conducted in interspecies and intraspecies of Typha. Based on the T2T genome, we constructed lignin and chlorophyll metabolic pathways of Pucai. Subsequently, the candidate structural genes and transcription factors that regulate lignin and chlorophyll biosynthesis were identified. The T2T genomic resources will provide molecular information for lignin and chlorophyll accumulation and help to understand genome evolution in Pucai.},
}

@article {pmid40342949,
year = {2024},
author = {Verly, E and Meyer, A and Sichieri, R and Rosa, ACS and Faerstein, E},
title = {Inverse and Direct Effect of Serum DDE Exposure on the Distribution of Leukocyte Telomere Length in Brazilian Adults: The Pró-Saúde Study.},
journal = {Journal of health & pollution},
volume = {12},
number = {1-4},
pages = {017003},
doi = {10.1289/JHP1033},
pmid = {40342949},
issn = {2156-9614},
abstract = {BACKGROUND: The current literature on associations between organochlorine pesticides and leukocyte telomere length (LTL) is conflicted, showing positive, inverse, or no association, findings that might be related to methodological issues and population characteristics, including the baseline LTL. Alternative exploration of this relationship over the whole LTL distribution may add information to help understand the role of pesticides in telomere shortening or enlargement.

OBJECTIVE: We evaluated the association between environmental dichlorodiphenyldichloroethylene (DDE) exposure and percentiles of LTL in a sample of adults living in the urban area of Rio de Janeiro, Brazil.

METHODS: LTL, serum pesticide concentration, and the covariates were determined cross-sectionally in a sample of 471 adults from the Pró-Saúde Study, a cohort of civil servants at a university campus in Rio de Janeiro, Brazil, conducted from July 2012 to October 2013. The percentiles (5th to 95th) of LTL (outcome variable) were modeled using quantile regression (QR) models with DDE as exposure and adjusted for age, sex, educational level, total body fat mass, total serum lipids, smoking, alcohol intake, and caloric share of in natura and ultra-processed foods.

RESULTS: Mean ± standard deviation  (SD) LTL and serum DDE were 0.578 ± 0.158 telomere to single-copy gene ratio (T/S ratio) and 0.17 ± 0.34  ng / mL , respectively. Serum DDE was not detected in 44% of the samples. QR coefficients were positive and significant in the first percentiles (up to the 15th percentile) and inverse and significant at the 95th percentile. No significant association was observed between serum DDE and mean LTL (β = - 0.001 ; p = 0.93).

DISCUSSION: DDE exposure predicts some quantiles of LTL distribution, with a positive relationship in the first quantiles and inverse at the highest quantile. This study added new information to help understand the role of pesticides in telomere shortening or enlargement; however, given the few studies and the conflicting results, longitudinal investigations are needed to clarify this association. https://doi.org/10.1289/JHP1033.},
}

@article {pmid40340407,
year = {2025},
author = {Lin, XJ and Wang, ML and Kong, WW and Mo, BX},
title = {Molecular Studies on Plant Telomeres: Expanding Horizons in Plant Biology.},
journal = {ACS synthetic biology},
volume = {},
number = {},
pages = {},
doi = {10.1021/acssynbio.4c00846},
pmid = {40340407},
issn = {2161-5063},
abstract = {The integrity of plant genomes is intricately safeguarded by telomeres, the protective caps located at the ends of the chromosome. This review provides a comprehensive analysis of the molecular mechanisms governing the structure, maintenance, and dynamics of plant telomeres, highlighting their genetic and epigenetic regulation and their pivotal roles in plant development, longevity, stress adaptation, and disease resistance. Recent advancements, such as next-generation sequencing and single-molecule imaging, have revolutionized our understanding of telomere biology, unveiling new insights into telomerase activity and telomere-associated genetic variants. Additionally, the review also discusses the challenges and future directions of telomere research, including the potential applications of telomere biology in plant breeding and genetic engineering.},
}

@article {pmid40335681,
year = {2025},
author = {Yu, J and Zhang, Y and Pang, CP and Tham, CC and Yam, JC and Chen, LJ},
title = {Association between leukocyte telomere length and incident glaucoma: A prospective UK biobank study.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {40335681},
issn = {1476-5454},
abstract = {BACKGROUND: Leukocyte telomere length (LTL) has been associated with various diseases, including age-related eye diseases such as cataract and age-related macular degeneration. However, the role of LTL in the longitudinal development of glaucoma is still unknown. Here we prospectively evaluate the association of LTL with glaucoma incidence and related traits, in the UK Biobank cohort.

METHODS: The study cohort included 419,603 participants with complete baseline data for glaucoma analyses. Multivariable Cox proportional hazards models were used to evaluate the association between LTL and the risk of glaucoma incidence, and multivariable linear regression was employed to test the association between LTL and glaucoma-related traits.

RESULTS: During a 13.58-year follow-up period, 7385 (1.76%) participants developed glaucoma. No association between LTL and incident glaucoma was found in either Model 1 (adjusted for age, sex, ethnicity and the ancestry components; HR = 1.011, 95% CI: 0.990-1.033; P = 0.311), or Model 2 (additionally adjusted for smoking status, alcohol consumption, body mass index, systolic blood pressure, education level, Townsend Deprivation Index, polygenic risk score for glaucoma, and history of diabetes and cardiovascular diseases; HR = 1.010, 95% CI: 0.988-1.032; P = 0.367). Non-significant associations were also observed for glaucoma-related traits, including the retinal nerve fibre layer, ganglion cell-inner plexiform layer, and intraocular pressure with LTL (all P-values > 0.05), but LTL was associated with a slightly increased vertical cup-to-disc ratio (P = 0.009).

CONCLUSIONS: This study suggested that LTL is not a major biomarker for incident glaucoma in the UK Biobank population. Further studies in different populations are warranted.},
}

@article {pmid40335638,
year = {2025},
author = {Nourazarian, A and Aghaei-Zarch, SM and Panahi, Y},
title = {Delayed complications of sulfur mustard poisoning: a focus on inflammation and telomere footprint.},
journal = {Archives of toxicology},
volume = {},
number = {},
pages = {},
pmid = {40335638},
issn = {1432-0738},
support = {403000027//Khoy University of Medical Sciences, Department of Basic Medical Sciences/ ; },
abstract = {Sulfur mustard (SM), a potent alkylating agent, has been widely used in chemical warfare, causing severe acute and long-term health complications. While its immediate toxic effects are well documented, the late-onset complications remain poorly understood. Chronic exposure to SM has been linked to persistent oxidative stress, inflammation, and genomic instability, contributing to the progression of various diseases, including pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), and cancer. This review explores the emerging role of telomere biology in the delayed pathophysiology of SM exposure. Evidence suggests that telomere shortening and dysregulation of telomeric repeat-containing RNA (TERRA) may serve as key molecular indicators of SM-induced aging and cellular dysfunction. Furthermore, inflammatory pathways, particularly NF-κB and TGF-β signaling, appear to be closely associated with telomere attrition, perpetuating chronic inflammation and fibrosis. By integrating oxidative stress, inflammation, and telomere dynamics, we propose a novel model linking telomere biology to SM-induced late complications. Understanding these mechanisms could pave the way for targeted therapeutic strategies, including antioxidant and epigenetic interventions, to mitigate long-term effects. Future research should focus on validating telomere-based biomarkers for early detection and exploring novel interventions to alleviate SM-induced chronic health conditions.},
}

@article {pmid40335534,
year = {2025},
author = {Wang, H and Yang, X and Liu, J and Wang, H and Yu, Y and Su, X and Fan, Y and Liu, H and Yang, R},
title = {Telomere-to-telomere gap-free genome assembly of Euchiloglanis kishinouyei.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {757},
pmid = {40335534},
issn = {2052-4463},
mesh = {Animals ; *Catfishes/genetics ; *Genome ; *Telomere ; China ; Repetitive Sequences, Nucleic Acid ; },
abstract = {Euchiloglanis kishinouyei is a typical endemic torrent catfish found in the Jinsha River system of the upper Yangtze River in China. It inhabits fast-flowing streams with steep elevation gradients and has evolved unique biological adaptations to thrive in these extreme environments. A high-quality genome provides key insights into the adaptive mechanisms driving its evolution in these harsh conditions. In this study, we successfully assembled the first telomere-to-telomere (T2T) genome of E. kishinouyei, marking the first T2T genome assembly of torrent catfish. The genome spans 886.74 Mb, anchored to 27 chromosomes, with over 99% coverage. The quality value (QV) and Benchmarking Universal Single-Copy Ortholog (BUSCO) scores were 46.96 and 98.50%, respectively, reflecting the high quality of the assembly. We identified repetitive elements accounting for 45.59% (404.23 Mb) of the genome and predicted 24,403 protein-coding genes, 94.37% of which were annotated. This high-fidelity genome assembly provides a valuable resource for future research and lays the foundation for exploring the ecological adaptation mechanisms and evolutionary biology of torrent catfish.},
}

Animals
*Catfishes/genetics
*Genome
*Telomere
China
Repetitive Sequences, Nucleic Acid

@article {pmid40334844,
year = {2025},
author = {Kapse, B and Mohanty, RP and Wax, M and Gao, Y and Tran, L and Wolters, PJ and Pellegrini, M and Singer, JP and Greenland, JR},
title = {Frailty in lung transplant recipients is associated with anemia and telomere dysfunction but independent of epigenetic age.},
journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajt.2025.05.002},
pmid = {40334844},
issn = {1600-6143},
abstract = {Frailty is a syndrome of vulnerability to stressors linked to worse outcomes pre- and post-lung transplantation. However, the biological basis of this association is unknown. Biological correlates of aging include epigenetic reprograming, chronic inflammation, telomere dysfunction, and anemia. We hypothesized that these aging-associated biological processes would be associated with frailty in lung transplant recipients. In a nested case-control study, we compared 43 lung transplant recipients who were frail pre- and post-transplant with 43 non-frail matched controls. We quantified peripheral blood leukocyte epigenetic aging (Horvath) and longevity (GrimAge) clocks, telomere length, cytokine profiles, and hemoglobin before transplant. Epigenetic clocks were correlated with age but not frailty. However, we observed hypermethylation of multiple gene pathways, including hedgehog signaling and angiogenesis, and an associated decreased levels of plasma cytokines in frail recipients. Frailty was also associated with telomere dysfunction and anemia. Overall, telomere dysfunction and anemia of chronic disease were most linked to frailty in this cohort, while epigenetic aging and chronic inflammation were not. Understanding the heterogeneity of aging syndromes my help target interventions in frail lung transplant recipients.},
}

@article {pmid40330857,
year = {2025},
author = {Fernandez, A and Zhou, T and Esworthy, S and Shen, C and Liu, H and Hess, JD and Yuan, H and Liu, N and Shi, G and Zhou, M and Kosiyatrakul, S and Gaur, V and Sommers, J and Edelman, W and Li, GM and Brosh, R and Chai, W and Lee, MYWT and Zhang, D and Schildkraut, C and Zheng, L and Shen, B},
title = {DNA2 and MSH2 activity collectively mediate chemically stabilized G4 for efficient telomere replication.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.04.04.647332},
pmid = {40330857},
issn = {2692-8205},
abstract = {G-quadruplexes (G4s) are widely existing stable DNA secondary structures in mammalian cells. A long-standing hypothesis is that timely resolution of G4s is needed for efficient and faithful DNA replication. In vitro , G4s may be unwound by helicases or alternatively resolved via DNA2 nuclease mediated G4 cleavage. However, little is known about the biological significance and regulatory mechanism of the DNA2-mediated G4 removal pathway. Here, we report that DNA2 deficiency or its chemical inhibition leads to a significant accumulation of G4s and stalled replication forks at telomeres, which is demonstrated by a high-resolution technology: Single molecular analysis of replicating DNA (SMARD). We further identify that the DNA repair complex MutSα (MSH2-MSH6) binds G4s and stimulates G4 resolution via DNA2-mediated G4 excision. MSH2 deficiency, like DNA2 deficiency or inhibition, causes G4 accumulation and defective telomere replication. Meanwhile, G4-stabilizing environmental compounds block G4 unwinding by helicases but not G4 cleavage by DNA2. Consequently, G4 stabilizers impair telomere replication and cause telomere instabilities, especially in cells deficient in DNA2 or MSH2.},
}

@article {pmid40325439,
year = {2025},
author = {Urban, JM and Gerbi, SA and Spradling, AC},
title = {Chromosome-scale scaffolds of the fungus gnat genome reveal multi-Mb-scale chromosome-folding interactions, centromeric enrichments of retrotransposons, and candidate telomere sequences.},
journal = {BMC genomics},
volume = {26},
number = {1},
pages = {443},
pmid = {40325439},
issn = {1471-2164},
support = {NIH/GM121455/NH/NIH HHS/United States ; },
mesh = {*Telomere/genetics ; *Centromere/genetics ; *Retroelements/genetics ; *Genome, Fungal ; *Chromosomes, Fungal/genetics ; Genomics ; },
abstract = {BACKGROUND: The lower Dipteran fungus gnat, Bradysia (aka Sciara) coprophila, has compelling chromosome biology. Paternal chromosomes are eliminated during male meiosis I and both maternal X sister chromatids are retained in male meiosis II. Embryos start with three copies of the X chromosome, but 1-2 copies are eliminated from somatic cells as part of sex determination, and one is eliminated in the germline to restore diploidy. In addition, there is gene amplification in larval polytene chromosomes, and the X polytene chromosome folds back on itself mediated by extremely long-range interactions between three loci. These developmentally normal events present opportunities to study chromosome behaviors that are unusual in other systems. Moreover, little is known about the centromeric and telomeric sequences of lower Dipterans in general, and there are recent claims of horizontally-transferred genes in fungus gnats. Overall, there is a pressing need to learn more about the fungus gnat chromosome sequences.

RESULTS: We produced the first chromosome-scale models of the X and autosomal chromosomes where each somatic chromosome is represented by a single scaffold. Extensive analysis supports the chromosome identity and structural accuracy of the scaffolds, demonstrating they are co-linear with historical polytene maps, consistent with evolutionary expectations, and have accurate centromere positions, chromosome lengths, and copy numbers. The positions of alleged horizontally-transferred genes in the nuclear chromosomes were broadly confirmed by genomic analyses of the chromosome scaffolds using Hi-C and single-molecule long-read datasets. The chromosomal context of repeats shows family-specific biases, such as retrotransposons correlated with the centromeres. Moreover, scaffold termini were enriched with arrays of retrotransposon-related sequence as well as nucleosome-length (~ 175 bp) satellite repeats. Finally, the Hi-C data captured Mb-scale physical interactions on the X chromosome that are seen in polytene spreads, and we characterize these interesting "fold-back regions" at the sequence level for the first time.

CONCLUSIONS: The chromosome scaffolds were shown to be of exceptional quality, including loci harboring horizontally-transferred genes. Repeat analyses demonstrate family-specific biases and telomere repeat candidates. Hi-C analyses revealed the sequences of ultra-long-range interactions on the X chromosome. The chromosome-scale scaffolds pave the way for further studies of the unusual chromosome movements in Bradysia coprophila.},
}

*Telomere/genetics
*Centromere/genetics
*Retroelements/genetics
*Genome, Fungal
*Chromosomes, Fungal/genetics
Genomics

@article {pmid40324704,
year = {2025},
author = {Quintanilla, I and Azeroglu, B and Sagar, AK and Stracker, TH and Denchi, EL and Pegoraro, G},
title = {Optical pooled screening for the discovery of regulators of the alternative lengthening of telomeres pathway.},
journal = {Methods (San Diego, Calif.)},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymeth.2025.05.001},
pmid = {40324704},
issn = {1095-9130},
abstract = {Telomere elongation is essential for the proliferation of cancer cells. Telomere length control is achieved by either the activation of the telomerase enzyme, or by the recombination-based Alternative Lengthening of Telomeres (ALT) pathway. ALT is active in about 10-15% of human cancers, but its molecular underpinnings remain poorly understood, preventing the discovery of potential novel therapeutic targets. Pooled CRISPR-based functional genomic screens enable the unbiased discovery of molecular factors involved in cancer biology. Recently, Optical Pooled Screens (OPS) have significantly extended the capabilities of pooled functional genomics screens to enable sensitive imaging-based readouts at the single cell level and large scale. To gain a better understanding of the ALT pathway, we developed a novel OPS assay that employs telomeric native DNA FISH (nFISH) as an optical quantitative readout to measure ALT activity. The assay uses standard OPS protocols for library preparation and sequencing. As a critical element, an optimized nFISH protocol is performed before in situ sequencing to maximize the assay performance. We show that the modified nFISH protocol faithfully detects changes in ALT activity upon CRISPR knock-out (KO) of the FANCM and BLM genes which were previously implicated in ALT. Overall, the OPS-nFISH assay is a reliable method that can provide deep insights into the ALT pathway in a high-throughput format.},
}

@article {pmid40323481,
year = {2025},
author = {Boccardi, V},
title = {From telomeres and senescence to integrated longevity medicine: redefining the path to extended healthspan.},
journal = {Biogerontology},
volume = {26},
number = {3},
pages = {107},
pmid = {40323481},
issn = {1573-6768},
mesh = {Humans ; *Longevity/physiology ; *Telomere/metabolism/genetics ; *Aging/genetics/physiology ; *Cellular Senescence ; Oxidative Stress ; Animals ; Precision Medicine ; *Telomere Homeostasis ; Biomarkers/metabolism ; },
abstract = {Despite significant advances in aging research, translating these findings into clinical practice remains a challenge. Aging is a complex, multifactorial process shaped by many factors including genetic, metabolic, and environmental factors. While medical advancements have extended lifespan, healthspan remains constrained by cellular senescence, telomere attrition, and systemic inflammation-core hallmarks of biological aging. However, emerging evidence suggests that telomere dynamic is not inevitable but can be influenced by oxidative stress, lifestyle choices, and metabolic regulation. This review examines how telomere-based biomarkers and metabolic interventions can drive personalized longevity medicine, enabling targeted strategies to delay aging. Furthermore, it highlights the integration of geroscience into clinical practice-integrated longevity medicine leveraging biomarker tracking, metabolic therapies, and preventive interventions-to redefine aging as a modifiable process, ultimately extending both lifespan and healthspan.},
}

Humans
*Longevity/physiology
*Telomere/metabolism/genetics
*Aging/genetics/physiology
*Cellular Senescence
Oxidative Stress
Animals
Precision Medicine
*Telomere Homeostasis
Biomarkers/metabolism

@article {pmid40321212,
year = {2025},
author = {Lee, J and Sohn, EJ and Lee, J and Taglialatela, A and Ciccia, A and Min, J},
title = {Distinct mechanisms underlying extrachromosomal telomere DNA generation in ALT cancers.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.04.15.648952},
pmid = {40321212},
issn = {2692-8205},
abstract = {Alternative lengthening of telomeres (ALT) is a telomerase-independent telomere maintenance mechanism observed in 15% of human cancers. A hallmark of ALT cancers is the presence of C-circles, circular single-stranded DNAs (ssDNAs) enriched with cytosine-rich telomere (C-rich, CCCTAA) sequences. G-circles, containing guanosine-rich telomere (G-rich, GGGTTA) ssDNAs, also exist but are much less abundant. Recent studies indicate that excessive displacement of Okazaki fragments during lagging-strand synthesis is a unique feature of ALT telomeres and responsible for generating C-circles/C-rich ssDNAs. However, the distinct characteristics of C-circles compared to G-circles remain unclear. Here, we demonstrate that co-deficiency of the DNA translocases SMARCAL1 and FANCM leads to abundant generation of G-circle/G-rich ssDNAs. These G-rich ssDNAs mainly exist in linear form, ranging in size from 500 to 3000 nucleotides, which differs significantly from the structure and size of C-circle/C-rich ssDNAs. Mechanistically, both C-rich and G-rich ssDNAs originate from BLM/POLD-mediated excessive strand displacement; however, they differ in their origins and initiation mechanisms. Specifically, C-rich ssDNAs arise from lagging daughter strands initiated by the CST complex, whereas G-rich ssDNAs originate from leading daughter strands through RAD51-dependent G-strand synthesis. Our findings propose two distinct mechanisms for generating two different extrachromosomal telomere DNAs, C-and G-circles, during ALT-mediated telomere elongation.},
}

@article {pmid40320141,
year = {2025},
author = {Guo, Z and Guo, JF and Wei, ZY and Zhang, RG and McMahan, S and Nie, S and Yan, XM and Zhou, SS and Yun, QZ and Wu, JY and Ge, J and Yang, Y and Xue, JY and Mao, JF},
title = {Near-gapless telomere-to-telomere reference nuclear genome and variable mitochondrial genome of Amborella trichopoda.},
journal = {Journal of genetics and genomics = Yi chuan xue bao},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jgg.2025.04.016},
pmid = {40320141},
issn = {1673-8527},
}

@article {pmid40318230,
year = {2025},
author = {Chen, L and Wang, H and Xu, T and Liu, R and Zhu, J and Li, H and Zhang, H and Tang, L and Jing, D and Yang, X and Guo, Q and Wang, P and Wang, L and Liu, J and Duan, S and Liu, Z and Huang, M and Li, X and Lu, Z},
title = {A telomere-to-telomere gap-free assembly integrating multi-omics uncovers the genetic mechanism of fruit quality and important agronomic trait associations in pomegranate.},
journal = {Plant biotechnology journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/pbi.70107},
pmid = {40318230},
issn = {1467-7652},
support = {32402506//National Natural Science Foundation of China/ ; 242300421597//Natural Science Foundation of Henan Province/ ; CAAS-ASTIP-2024-ZFRI//Agricultural Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences/ ; 2021YFD1600800//National Key Research and Development Program of China/ ; },
abstract = {Pomegranate is an important perennial fruit tree distributed worldwide. Reference genomes with gaps and limit gene identification controlling important agronomic traits hinder its functional genomics and genetic improvements. Here, we reported a telomere-to-telomere (T2T) gap-free genome assembly of the distinctive cultivar 'Moshiliu'. The Moshiliu reference genome was assembled into eight chromosomes without gaps, totalling ~366.71 Mb, with 32 158 predicted protein-coding genes. All 16 telomeres and eight centromeres were characterized; combined with FISH analysis, we revealed the atypical telomere units in pomegranate as TTTTAGGG. Furthermore, a total of 16 loci associated with 15 important agronomic traits were identified based on GWAS of 146 accessions. Gene editing and biochemical experiments demonstrated that a 37.2-Kb unique chromosome translocation disrupting the coding domain sequence of PgANS was responsible for anthocyanin-less, knockout of PgANS in pomegranate exhibited a defect in anthocyanin production; a unique repeat expansion in the promoter of PgANR may affected its expression, resulting in black peel; notably, the G → A transversion located at the 166-bp coding domain of PgNST3, which caused a E56K mutation in the PgNST3 protein, closely linked with soft-seed trait. Overexpression of PgNST3[A] in tomato presented smaller and softer seed coats. The E56K mutation in PgNST3 protein, eliminated the binding ability of PgNST3 to the PgMYB46 promoter, which subsequently affected the thickness of the inner seed coat of soft-seeded pomegranates. Collectively, the validated gap-free genome, the identified genes controlling important traits and the CRISPR-Cas9-mediated gene knockout system all provided invaluable resources for pomegranate precise breeding.},
}

@article {pmid40316493,
year = {2025},
author = {Jiang, S and Jiang, X and Li, D and Lyu, Q and Li, W},
title = {Telomere length of granulosa cells is positively associated with oocyte maturation and fertilization.},
journal = {Reproductive biomedicine online},
volume = {},
number = {},
pages = {104803},
doi = {10.1016/j.rbmo.2025.104803},
pmid = {40316493},
issn = {1472-6491},
abstract = {RESEARCH QUESTION: Is it feasible to use the telomere length of granulosa cells as a biomarker for ovarian function and embryological outcomes during IVF?

DESIGN: This prospective cohort study included 240 patients undergoing their first IVF cycle between October 2022 and December 2022. The main outcomes were the associations between relative telomere length of granulosa cells, collected during oocyte retrieval, and ovarian reserve, ovarian response and embryological outcomes.

RESULTS: The mean ± SD relative telomere length was -5.35 ± 2.55. No significant relationships were found between telomere length and ovarian reserve and ovarian response. Telomere length was positively correlated with maturation rate (r = 0.386, P < 0.001) and fertilization rate (retrieved oocytes: r = 0.408, P < 0.001; matured oocytes: r = 0.203, P = 0.002). However, telomere length was not significantly correlated with oocyte retrieval or viable embryo rate. On multifactor linear regression, relative telomere length was associated with oocyte maturation rate (P < 0.001) and fertilization rate of matured oocytes (P = 0.011). The receiver operating characteristic curve of telomere length as a predictor of oocyte maturity showed that the area under the curve (AUC) was 0.719 (P < 0.001), while the AUC of telomere length as a predictor of fertilization (of matured oocytes) was 0.613 (P = 0.005).

CONCLUSION: Telomere length is correlated with embryological outcomes in IVF, mainly by affecting oocyte maturation and fertilization, rather than early embryo development. Telomere length alone cannot be used as a biomarker for ovarian reserve or ovarian response. When dealing with recurrent oocyte maturity or fertilization disorders, therapies oriented to lengthen telomeres or increase telomerase expression or function would facilitate cell division of granulosa cells, leading to higher oocyte maturation and fertilization rates.},
}

@article {pmid40313080,
year = {2025},
author = {Macha, SJ and Koneru, B and Burrow, TA and Zhu, C and Savitski, D and Rahman, RL and Ronaghan, CA and Nance, J and McCoy, K and Eslinger, C and Reynolds, CP},
title = {Correction: Alternative Lengthening of Telomeres in Cancer Confers a Vulnerability to Reactivation of p53 Function.},
journal = {Cancer research},
volume = {85},
number = {9},
pages = {1738},
doi = {10.1158/0008-5472.CAN-25-0818},
pmid = {40313080},
issn = {1538-7445},
}

@article {pmid40305614,
year = {2025},
author = {Byers, SMH and Rocker, A and Nguyen, TNT and Rosas, NC and Taiaroa, G and Tan, KS and Li, Y and Wilksch, JJ and Steele, JR and Schittenhelm, RB and Dunstan, RA and Short, FL and Lithgow, T},
title = {Telomere bacteriophages are widespread and equip their bacterial hosts with potent interbacterial weapons.},
journal = {Science advances},
volume = {11},
number = {18},
pages = {eadt1627},
pmid = {40305614},
issn = {2375-2548},
mesh = {*Bacteriophages/genetics/physiology ; *Telomere/genetics/virology ; *Klebsiella/virology/genetics ; *Bacteria/virology/genetics ; Genome, Viral ; },
abstract = {Bacteriophages (phages) are viruses that can kill bacteria, thereby editing and shaping microbial communities. The telomere phages are a curious form using telomere-like structures to replicate their genomes as linear extrachromosomal elements. Here, we find that telomere phages are widely distributed in bacteria, being highly prevalent in Klebsiella species. We establish a model system to investigate telomere phage biology by isolating the virions of telomere phages and infecting naïve strains to create isogenic lines with and without a phage. We find that only a small set of telomere phage proteins is expressed in phage-host cells, including a toxin-the telocin-that kills other Klebsiella strains. We identify and validate a set of telocins in the genomes of other prevalent Klebsiella telomere phages. Thus, telomere phages are widespread elements encoding diverse antibacterial weapons and we discuss the prospect of using telocins for precision editing of microbial populations.},
}

*Bacteriophages/genetics/physiology
*Telomere/genetics/virology
*Klebsiella/virology/genetics
*Bacteria/virology/genetics
Genome, Viral

@article {pmid40303469,
year = {2025},
author = {Barros, AGA and Soares, TO and Lage, AFA and Cintra, MTG and de Paula, JJ and Malheiro, OB and Falcão, AE and Nogueira, CAC and de Carvalho, LB and Romano Silva, MA and de Miranda, DM and Viana, BM and Rosa, DVF and Bicalho, MAC},
title = {Leukocyte telomere attrition in cognitive decline: associations with APOE genotype and cardiovascular risk factors.},
journal = {Frontiers in aging neuroscience},
volume = {17},
number = {},
pages = {1557016},
pmid = {40303469},
issn = {1663-4365},
abstract = {Telomere shortening represents a fundamental mechanism of cellular aging potentially implicated in neurodegenerative processes. This study investigated the complex associations among leukocyte telomere length, cardiovascular risk profiles, and APOE polymorphisms in age-related cognitive decline. Through a cross-sectional analysis of 90 participants stratified by cognitive status into three groups: cognitively unimpaired (CU), mild cognitive impairment (MCI), and Alzheimer's Disease (AD), we quantified relative telomere length using quantitative PCR, performed APOE genotyping and assessed cardiovascular risk factors. Quantitative analysis revealed significantly reduced telomere length in the AD group compared to CU and MCI groups. Multivariate regression analysis identified cognitive status as an independent predictor of telomere length (β = -0.468, p < 0.001). APOE ε4 carrier status showed higher prevalence in AD subjects as expected. Cardiovascular risk factors demonstrated no significant correlation with telomere length across cognitive groups. Our findings establish a robust association between telomere shortening and advanced cognitive impairment in AD, suggesting potential utility as a neurodegenerative biomarker. This relationship appears independent of traditional cardiovascular risk factors, highlighting the complexity of cellular aging mechanisms in neurodegeneration.},
}

@article {pmid40299325,
year = {2025},
author = {Wei, G and Chen, R and Liu, S and Cai, S and Feng, Z},
title = {Telomere Length as Both Cause and Consequence in Type 1 Diabetes: Evidence from Bidirectional Mendelian Randomization.},
journal = {Biomedicines},
volume = {13},
number = {4},
pages = {},
pmid = {40299325},
issn = {2227-9059},
abstract = {Background/Objectives: Diabetes is the most prevalent metabolic disease globally, characterized by dysregulated glucose control and accompanied by multiple refractory complications. As a critical marker of cellular homeostasis, telomere length (TL) may be associated with the progression of diabetes. However, the causal relationship between diabetes and TL remains unclear, particularly whether cellular homeostasis imbalance acts as a consequence of diabetic complications or a precipitating factor in disease development. Methods: We performed a bidirectional Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data. Following the three core assumptions of MR analysis, we conducted quality control on all instrumental variables to ensure methodological rigor. The inverse variance weighted (IVW) method served as the primary analytical method, supplemented by additional MR methods to evaluate the significance of the results. Furthermore, we performed sensitivity analyses to ensure the reliability and robustness of the findings. Results: Forward analysis revealed that shortened TL significantly increases the risk of broadly defined Type 1 diabetes (T1D) and unspecified types of diabetes (p < 0.05). Additionally, we identified a positive causal relationship between TL and several diabetes-related complications, including co-morbidities, diabetic nephropathy, and diabetic ketoacidosis (p < 0.05). Interestingly, the reverse analysis demonstrated a positive causal effect of T1D and its complications on TL (p < 0.05); however, this effect disappeared after adjusting for insulin use (p > 0.05). Conclusions: Bidirectional MR analyses revealed a complex relationship between TL and T1D, where shortened telomeres increase T1D risk while T1D itself may trigger compensatory mechanisms affecting telomere maintenance, with insulin playing a crucial regulatory role in this relationship. These findings suggest telomere biology may be fundamentally involved in T1D pathogenesis and could inform future therapeutic approaches.},
}

@article {pmid40299209,
year = {2025},
author = {Yang, B and Bi, J and Zeng, W and Chen, M and Yao, Z and Cheng, S and Jiang, Z and Zhang, C and Liao, H and Gu, X and Xian, Z and Yu, Y},
title = {Causal effect between telomere length and thirteen types of cancer in Asian population: a bidirectional Mendelian randomization study.},
journal = {Aging clinical and experimental research},
volume = {37},
number = {1},
pages = {134},
pmid = {40299209},
issn = {1720-8319},
support = {2021A1515111219//Guangdong Basic and Applied Basic Research Foundation/ ; 2021A1515111219//Guangdong Basic and Applied Basic Research Foundation/ ; KS0120220268//Department of Finance of Guangdong Province/ ; KS0120220268//Department of Finance of Guangdong Province/ ; KS0120220268//Department of Finance of Guangdong Province/ ; KS0120220268//Department of Finance of Guangdong Province/ ; KS0120220268//Department of Finance of Guangdong Province/ ; KS0120220268//Department of Finance of Guangdong Province/ ; KS0120220268//Department of Finance of Guangdong Province/ ; KS0120220268//Department of Finance of Guangdong Province/ ; KS0120220268//Department of Finance of Guangdong Province/ ; 2023LNS26880//Bureau of Science and Technology of Ganzhou Municipality/ ; },
mesh = {Humans ; Mendelian Randomization Analysis ; *Neoplasms/genetics ; *Asian People/genetics ; *Telomere/genetics ; Male ; *Telomere Homeostasis/genetics ; Leukocytes ; Genetic Predisposition to Disease ; Female ; Polymorphism, Single Nucleotide ; },
abstract = {BACKGROUND: The relationship between leukocyte telomere length (LTL) and the risk of developing various cancers has always been controversial and predominantly focused on European populations. Hence, Mendelian randomization (MR) was applied to the Asian population to explore the causal relationships between LTL and the risk of developing various cancers.

METHODS: We explored the causal connection between LTL and the risk of developing thirteen types of cancer in Asian populations using freely available genetic variation data. The primary analytical method employed was the inverse variance weighted (IVW) method, complemented by sensitivity and validation analyses. Following Bonferroni correction, P < 0.0038 was considered to indicate statistical significance, and P values ranging from 0.0038 to 0.05 were considered to indicate a nominally significant association.

RESULTS: The findings indicated significant positive associations between LTL and the risk of developing lung cancer [odds ratio (OR) = 1.6009, 95% confidence interval (CI) 1.3056-1.9629, P = 6.08 × 10[-6]] and prostate cancer (OR = 1.4200, 95% CI 1.1489-1.7550, P = 0.0012). Additionally, there was a nominally significant association between LTL and the risk of developing hematological malignancy (OR = 1.5119, 95% CI 1.0810-2.1146, P = 0.0157). No statistically significant relationships between LTL and the risk of developing the other ten kinds of cancer were detected. No causal link between the risk of developing various cancers and LTL was discovered.

CONCLUSIONS: Asians with longer telomeres are more prone to developing lung and prostate cancer. There is also a nominally significant association between longer telomeres and the risk of developing hematological malignancy.},
}

Humans
Mendelian Randomization Analysis
*Neoplasms/genetics
*Asian People/genetics
*Telomere/genetics
Male
*Telomere Homeostasis/genetics
Leukocytes
Genetic Predisposition to Disease
Female
Polymorphism, Single Nucleotide

@article {pmid40299122,
year = {2025},
author = {Asanov, MA and Poddubnyak, AO and Sinitskaya, AV and Khutornaya, MV and Khryachkova, OV and Sinitsky, MY},
title = {Telomere Length of Cardiomyocytes in Wistar Rat Treated with Doxorubicin: In Vivo Experimental Study.},
journal = {Bulletin of experimental biology and medicine},
volume = {},
number = {},
pages = {},
pmid = {40299122},
issn = {1573-8221},
abstract = {The effect of doxorubicin on the relative telomere length of cardiomyocytes in Wistar rats was studied. Doxorubicin (2 mg/kg body weight) was injected into the caudal vein once a week for 4 weeks, the control group was injected with 0.9% NaCl solution in an equivalent volume. The serum concentrations of proinflammatory cytokines (MCP-1 and TNFα), oxidative stress marker 8-hydroxydeoxyguanosine (8-OHdG), and telomerase reverse transcriptase (TERT) were measured. In rats treated with doxorubicin, the relative length of cardiomyocyte telomeres and serum levels of 8-OHdG were higher than the in control. Thus, molecular effects of subchronic low-dose doxorubicin exposure in rats were revealed: telomeric regions of cardiomyocyte DNA were lengthened, and the level of oxidative stress marker increased.},
}

@article {pmid40298841,
year = {2025},
author = {Torres-Oteros, D and Parilli-Moser, I and Laveriano Santos, EP and Becerra-Tomás, N and Sanz-Lamora, H and Hurtado-Barroso, S and Haro, D and Marrero, PF and Lamuela-Raventos, RM and Relat, J and Canudas, S},
title = {Unveiling the Impact of Peanut Consumption on Telomere Length in Young and Healthy Individuals: Insights from the ARISTOTLE Study: A Randomized Clinical Trial.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {4},
pages = {},
doi = {10.3390/antiox14040467},
pmid = {40298841},
issn = {2076-3921},
support = {The Peanut Institut 2019//The Peanut Institut 2019/ ; },
abstract = {Diet is a potential modulator of telomere length (TL), but the impact of individual dietary components, such as nuts, on TL in young, healthy individuals remains underexplored. Peanuts are rich in bioactive compounds that may influence TL. Therefore, to fill this gap of knowledge, this study aimed to investigate the effect of peanut consumption on TL in this specific population. Fifty-eight young, healthy individuals were randomized to one of three different intervention groups for 6 months each: (1) 25 g/day of skin-roasted peanuts (SRP); (2) 32 g/day of peanut butter (PB); (3) 32 g/day of a control butter (CB) (based on peanut oil). TL was measured by quantitative real-time PCR in saliva at baseline and at the end of the intervention. Our findings revealed significant between-group differences in TL changes, particularly between the SRP and CB groups over 6 months (mean difference: 0.53; 95% CI: 0.01, 1.05; p-value = 0.048). No significant difference was observed between PB and CB groups (mean difference: 0.12; 95% CI: -0.42, 0.66; p-value = 0.66). This study provides novel insights into the impact of peanut consumption on TL maintenance in young and healthy individuals. The findings highlight the potential benefits of incorporating peanuts into the diet as a means of promoting cellular health and longevity. Further research is warranted to elucidate the underlying mechanisms and validate these findings across diverse populations and longer time frames.},
}

@article {pmid40292316,
year = {2025},
author = {Pierpoint, M and Floyd, W and Wisdom, AJ and Luo, L and Ma, Y and Dickson, BC and Waitkus, MS and Kirsch, DG},
title = {Loss of function of Atrx recapitulates phenotypes of alternative lengthening of telomeres in a primary mouse model of sarcoma.},
journal = {iScience},
volume = {28},
number = {5},
pages = {112357},
pmid = {40292316},
issn = {2589-0042},
abstract = {The development of a telomere maintenance mechanism is essential for immortalization in human cancer. While most cancers elongate their telomeres by expression of telomerase, 10-15% of human cancers utilize a pathway known as alternative lengthening of telomeres (ALT). ALT is commonly associated with loss-of-function mutations in ATRX. Here, we developed a genetically engineered primary mouse model of sarcoma in CAST/EiJ mice to investigate the extent to which telomerase deficiency and Atrx-inactivation lead to ALT induction. We observed increases in multiple ALT-associated phenotypic indicators in tumors with loss of function mutations of Atrx. Furthermore, we found that loss of Atrx leads to an increase in telomeric instability and telomere sister chromatid exchange. However, Atrx-deficient tumors did not show productive telomere length maintenance in the absence of telomerase. This primary mouse model of sarcoma could facilitate future investigations into the molecular features of ALT in vivo.},
}

@article {pmid40286639,
year = {2025},
author = {Lin, SY and Levine, MT},
title = {Paternal effects on telomere integrity during the sperm-to-embryo transition.},
journal = {Current opinion in genetics & development},
volume = {93},
number = {},
pages = {102348},
doi = {10.1016/j.gde.2025.102348},
pmid = {40286639},
issn = {1879-0380},
abstract = {Telomeres are essential nucleoprotein structures that preserve our terminal DNA sequence and protect chromosome ends from fusion. Our vast knowledge of telomeres comes almost entirely from studies of healthy and diseased somatic cells. However, building evidence suggests that the molecules and mechanisms required for telomere integrity in somatic cells are insufficient to preserve telomere integrity during the sperm-to-embryo transition. Here, we review this growing body of work on telomere 'paternal effects', wherein zygotic telomere integrity is determined not by the genotype of the zygote but instead by the genotype of the father. Direct inheritance of sperm-specific proteins establishes paternal telomere epigenetic identity, while direct inheritance of sperm telomere length contributes to telomere length inheritance. Together, these investigations of telomere integrity through the sperm-to-embryo transition reveal potent paternal effects on zygotic telomere functions, with implications for human infertility.},
}

@article {pmid40280988,
year = {2025},
author = {Yang, J and Peng, Y and Yang, F and Meng, G and Kong, W},
title = {The telomere-to-telomere genome assembly of the wild mulberry, Morus mongolica.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {694},
pmid = {40280988},
issn = {2052-4463},
support = {20JS003//Education Department of Shaanxi Province (Department of Education of Shaanxi Province)/ ; 2021NY-216//Shaanxi Provincial Science and Technology Department (Science and Technology Department, Shaanxi Province)/ ; },
mesh = {*Morus/genetics ; *Telomere/genetics ; *Genome, Plant ; Centromere ; },
abstract = {Morus mongolica is a wild mulberry native to China and North Korea. In the current study, we assembled a high-quality telomere-to-telomere genome sequence of M. mongolica using NGS, HiFi, ONT, and Hi-C technologies. The genome was determined to be 341.88 Mb in size with a contig N50 of 23.82 Mb. The numbers of telomeres and centromeres were 28 and 14, with average lengths of 9.86 kb and 1.91 Mb, accounting for 0.08% and 7.84% of the total genome, respectively. A total of 21,657 protein-coding genes and 186.50 Mb repeat sequences were annotated. Genome integrity evaluation by BUSCO revealed a completeness score of 99.44% and a quality value of 46.7. Collinearity analysis between M. mongolica and either Morus alba or Morus notabilis showed that the breakage and fusion of chromosomes in Morus occurred at the centromere region of M. notabilis, which provided important genomic evidence for the evolution and chromosome breakage-fusion mechanism of Morus species.},
}

*Morus/genetics
*Telomere/genetics
*Genome, Plant
Centromere

@article {pmid40280966,
year = {2025},
author = {Zhao, D and Zang, Z and Li, H and Li, R and Wang, G and Zhang, K and Diao, T and Fu, Q},
title = {Telomere-related gene risk model predicts prognostic and immune microenvironment alterations in prostate cancer.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {14536},
pmid = {40280966},
issn = {2045-2322},
support = {ZR2021QH366//Natural Science Foundation of Shandong Province/ ; 2021YFC2009300//National Key Research and Development Program of China/ ; 82071635//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Prostatic Neoplasms/genetics/immunology/pathology/mortality ; Male ; *Tumor Microenvironment/immunology/genetics ; Prognosis ; *Telomere/genetics ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor ; Dendritic Cells/immunology/metabolism ; Biomarkers, Tumor/genetics ; },
abstract = {The improvement of the prediction of prostate cancer (PCa) is a major challenge in disease management. This study analysed a total of 147,856 cells and identified 15 distinct cell types using single-cell RNA-sequencing (scRNA-seq) and bulk RNA-seq data from TCGA and GEO databases. Of these cells, 31,256 exhibited a high telomere-related gene score and were predominantly composed of myeloid dendritic cells (mDCs). Simultaneously, pseudo-temporal analysis indicated that mDCs are in the later stages of the differentiation trajectory, suggesting the significant role of mDCs as telomere-active cells in the development of PCa. Analysis of cell-cell communication revealed significant differences, particularly an increase in communication between mDCs and CTLs, alongside a decrease in communication between mDCs and B cells. These variations may represent critical nodes influencing the development of PCa. Additionally, two hub genes were utilized to create risk models, with ROC curves confirming their predictive efficacy for 3-, 5-, and 10-year survival rates in patients. Functional analysis of these genes was conducted, and NPY siRNA transfection notably inhibited proliferation in LNCaP and DU145 cells. Furthermore, the models demonstrated that high-risk patients had poorer overall survival, greater immune infiltration, and reduced sensitivity to chemotherapeutic drugs.},
}

Humans
*Prostatic Neoplasms/genetics/immunology/pathology/mortality
Male
*Tumor Microenvironment/immunology/genetics
Prognosis
*Telomere/genetics
Gene Expression Regulation, Neoplastic
Cell Line, Tumor
Dendritic Cells/immunology/metabolism
Biomarkers, Tumor/genetics

@article {pmid40278882,
year = {2025},
author = {Zhang, H and Zhou, J and Cao, Y and Zhang, X and Chang, H and Zhao, Y and Bo, Y and Zhang, H and Yu, Z and Zhao, X},
title = {Association between telomere length and psychiatric disorders: a bidirectional Mendelian randomization study.},
journal = {European archives of psychiatry and clinical neuroscience},
volume = {},
number = {},
pages = {},
pmid = {40278882},
issn = {1433-8491},
support = {SBGJ202101020//Tianjian Laboratory of Advanced Biomedical Sciences and Major Project of Medical Science and Technology Jointly Constructed by the Provincial and Ministerial Departments/ ; },
abstract = {Observational studies have suggested that shorter telomere length (TL) may be a risk factor for psychiatric disorders. However, whether this association underlie causal effects remains unknown. This study aims to investigate the potential association between TL and psychiatric disorders by conducting a bidirectional Mendelian randomization (MR) study. Summary statistics for TL were obtained from the UK Biobank (n = 472,174), while summary statistics for ten psychiatric disorders were acquired from the Psychiatric Genomics Consortium (PGC). The inverse-variance weighted (IVW) method was used as primary analysis, with the MR-Egger, weighted median, MR-PRESSO, simple mode, and weighted mode approaches were utilized as sensitivity analyses. Our findings indicated a potential association between genetic predisposition to attention deficit hyperactivity disorder (ADHD) and shortened TL (Beta = - 0.039, SE = 0.011, P = 4.00E-04). Additionally, posttraumatic stress disorder (PTSD) may be was potentially associated with TL (Beta = - 0.014, SE = 0.006, P = 0.019). Our findings suggest a potential correlation between ADHD and TL, yet no significant association exists between TL and other psychiatric disorders. Nevertheless, considering the small effect size and the fact that it might have limited practical clinical significance, TL may not function as a biomarker for psychiatric disorders.},
}

@article {pmid40278194,
year = {2025},
author = {Foffa, I and Esposito, A and Simonini, L and Berti, S and Vecoli, C},
title = {Telomere Length and Clonal Hematopoiesis of Indeterminate Potential: A Loop Between Two Key Players in Aortic Valve Disease?.},
journal = {Journal of cardiovascular development and disease},
volume = {12},
number = {4},
pages = {},
pmid = {40278194},
issn = {2308-3425},
abstract = {Aortic valve stenosis (AVS) is the most common valvular heart disease that was considered, for a long time, a passive degenerative disease due to physiological aging. More recently, it has been recognized as an active, modifiable disease in which many cellular processes are involved. Nevertheless, since aging remains the major risk factor for AVS, a field of research has focused on the role of early (biological) aging and its dependent pathways in the initiation and progression of AVS. Telomeres are regions at the ends of chromosomes that are critical for maintaining genome stability in eukaryotic cells. Telomeres are the hallmarks and molecular drivers of aging and age-related degenerative pathologies. Clonal hematopoiesis of indeterminate potential (CHIP), a condition caused by somatic mutations of leukemia-associated genes in individuals without hematologic abnormalities or clonal disorders, has been reported to be associated with aging. CHIP represents a new and independent risk factor in cardiovascular diseases, including AVS. Interestingly, evidence suggests a causal link between telomere biology and CHIP in several pathological disorders. In this review, we discussed the current knowledge of telomere biology and CHIP as possible mechanisms of aortic valve degeneration. We speculated on how a better understanding of the complex relationship between telomere and CHIP might provide great potential for an early diagnosis and for developing novel medical therapies to reduce the constant increasing health burden of AVS.},
}

@article {pmid40274277,
year = {2025},
author = {Hanley, SM and Schutte, NS and Bellamy, J and Denham, J},
title = {Shorter Telomeres and Faster Telomere Attrition in Individuals With Five Syndromic Forms of Intellectual Disability: A Systematic Review and Meta-Analysis.},
journal = {Journal of intellectual disability research : JIDR},
volume = {},
number = {},
pages = {},
doi = {10.1111/jir.13244},
pmid = {40274277},
issn = {1365-2788},
abstract = {BACKGROUND: People with intellectual disability suffer complex challenges due to adaptive functioning limitations, high rates of chronic diseases and shortened lifespans compared with the general population. Telomere shortening is a hallmark of ageing, and short telomeres are linked to neurological disorders. The main objective of this systematic review and meta-analysis was to identify any differences in telomere length and the rate of telomere attrition in leukocytes and fibroblasts from people with intellectual disability and controls.

METHODS: PubMed, Scopus and ScienceDirect were searched. Articles that compared telomere length in individuals with intellectual disability to apparently healthy age-matched controls were included. Risk of bias was assessed using the AXIS tool and data were analysed using CMA.

RESULTS: Fifteen studies comprised of 17 comparisons provided data and were included in meta-analyses. Compared with healthy controls (N = 481), people with intellectual disability (N = 366) from a known genetic syndrome (Cri du chat, Down, Hoyeraal-Hreidarsson, Williams or Nicolaides-Baraitser) possessed shorter leukocyte telomeres (SMD: -0.853 [95% CI: -1.622 to -0.084], p = 0.03). Similarly, relative to controls (N = 16), people with syndromic intellectual disability (N = 21) possessed shorter fibroblast telomeres (-1.389 [-2.179 to -0.599], p = 0.001). Furthermore, people with syndromic forms of intellectual disability also demonstrated a faster rate (2.09-fold) of telomere shortening.

CONCLUSIONS: Consistent with epidemiological findings on mortality and morbidity risk, people with syndromic intellectual disability appear to undergo a faster rate of biological ageing compared to the general population. These findings emphasise the need for healthy ageing lifestyle (i.e., exercise and stress management) and therapeutic interventions for people with syndromic intellectual disability.},
}

@article {pmid40272729,
year = {2025},
author = {Valeeva, EV and Nikitin, DO and Nikiforova, LS and Semina, II and Ahmetov, II},
title = {Effects of Pharmacological Treatment on Telomere Length and the Expression of Telomerase/Shelterin-Related Genes in Rat Models of Autism.},
journal = {Journal of molecular neuroscience : MN},
volume = {75},
number = {2},
pages = {55},
pmid = {40272729},
issn = {1559-1166},
support = {23-25-00325//Russian Science Foundation/ ; 23-25-00325//Russian Science Foundation/ ; 23-25-00325//Russian Science Foundation/ ; 23-25-00325//Russian Science Foundation/ ; },
mesh = {Animals ; Male ; Rats ; *Telomerase/genetics/metabolism ; Rats, Wistar ; Female ; Valproic Acid/toxicity ; Risperidone/pharmacology/therapeutic use ; *Telomere-Binding Proteins/genetics/metabolism ; Hippocampus/metabolism/drug effects ; *Telomere/metabolism/drug effects ; Shelterin Complex ; Prefrontal Cortex/metabolism/drug effects ; *Telomere Homeostasis/drug effects ; Antipsychotic Agents/pharmacology/therapeutic use ; },
abstract = {Telomeres are increasingly recognized for their potential role in the etiology of autism spectrum disorder (ASD) due to their involvement in cellular aging and telomerase-shelterin function. Although shorter telomeres have been observed in individuals with ASD, studies linking telomere dynamics in blood cells and brain regions remain limited. Using the valproic acid (VPA, 500 mg/kg) rodent model, this study aimed to assess the impact of three drugs commonly used in ASD treatment (amitriptyline, risperidone, and nooclerin) on telomere length and the expression of telomerase/shelterin-related genes (Dkc1, Gar1, Pot1a, Pot1b, Tep1, Terc, Terf2ip, Tert, Tinf2, Tnks, Tpp1, Trf1, and Trf2) in blood cells, the prefrontal cortex, and hippocampus of VPA-exposed Wistar rats. Telomere length and gene expression were measured using quantitative PCR. Risperidone treatment in VPA males resulted in telomere elongation and increased expression of Tnks in blood cell and Trf1, Trf2 genes in prefrontal cortex. Nooclerin treatment also showed beneficial effects on telomere length of blood cell in males, alongside increased Trf1 expression. Long telomeres in male blood cells were associated with reduced anxiety, while a positive correlation was found between Tpp1 expression and stereotypical behavior in both male and female VPA rats. These findings suggest that nooclerin and risperidone influence telomere length and gene expression related to the telomere-telomerase complex in a sex-dependent manner, offering insights into the neurobiological mechanisms underlying ASD.},
}

Animals
Male
Rats
*Telomerase/genetics/metabolism
Rats, Wistar
Female
Valproic Acid/toxicity
Risperidone/pharmacology/therapeutic use
*Telomere-Binding Proteins/genetics/metabolism
Hippocampus/metabolism/drug effects
*Telomere/metabolism/drug effects
Shelterin Complex
Prefrontal Cortex/metabolism/drug effects
*Telomere Homeostasis/drug effects
Antipsychotic Agents/pharmacology/therapeutic use

@article {pmid40269921,
year = {2025},
author = {Jiang, Q and Yu, C and Zhu, S and Liu, Y and Ye, M},
title = {Bidirectional Mendelian randomization reveals associations between telomere length and autoimmune diseases.},
journal = {Trials},
volume = {26},
number = {1},
pages = {137},
pmid = {40269921},
issn = {1745-6215},
mesh = {Humans ; *Mendelian Randomization Analysis ; *Autoimmune Diseases/genetics/diagnosis ; *Telomere/genetics ; Genetic Predisposition to Disease ; *Telomere Homeostasis/genetics ; Risk Factors ; *Telomere Shortening ; },
abstract = {BACKGROUND: Autoimmune diseases are a group of complex chronic illnesses that affect multiple organs or body systems. These diseases are characterized by tissue damage, impaired organ function, and increased risk of malignancies, and elevated mortality. Nevertheless, the casual correlation between autoimmune diseases and telomere length remains uncertain.

OBJECTIVE: Our bidirectional Mendelian randomization analysis was aimed to evaluate the causal association between autoimmune diseases and telomere length.

METHODS: To minimize bias, four demographic factors including body mass index (BMI), alcohol consumption, smoking, and income were assessed using two-sample Mendelian randomization analysis. Furthermore, this analysis was conducted to explore the causal relationships between telomere length and autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes (T1D), Graves' disease (GD), and psoriasis using two separate datasets from FinnGen and the UK Biobank.

RESULTS: When using inverse variance weighting (IVW) to assess the relationship between four available demographic factors and overall autoimmune diseases, no significant association was found (p > 0.05). However, a significant negative causal effect of telomere length on autoimmune diseases was observed (IVW: OR = 0.906, 95% CI = 0.832-0.986, p = 0.022). Reverse Mendelian randomization analysis revealed no significant correlation. Further analysis using two separate datasets for five common autoimmune diseases confirmed significant negative associations between telomere length and RA (UKB biobank: OR = 0.997, 95% CI 0.994-0.999, p = 0.025; FinnGen: OR = 0.860, 95% CI 0.741-0.998, p = 0.047), GD (UK Biobank: OR = 0.519, 95% CI 0.430-0.625, p < 0.001; FinnGen: OR = 0.623, 95% CI 0.496-0.785, p < 0.001), and psoriasis (UK Biobank: OR = 0.772, 95%CI = 0.642-0.928, p = 0.006; FinnGen: OR = 0.841, 95%CI = 0.727-0.973, p = 0.020). A significant positive association was found for SLE in the UK Biobank (OR = 1.718, 95% CI = 95% CI 1.155-2.558, p = 0.007). Reverse Mendelian randomization analysis identified a significant negative association between telomere length and SLE (UK Biobank: OR = 0.995, 95% CI 0.991-0.998, p = 0.014; FinnGen: OR = 0.988, 95% CI 0.977-0.998, p = 0.029) and psoriasis (FinnGen: OR = 0.992, 95% CI 0.988-0.997, P = 0.005), and a positive association with RA (UK Biobank: OR = 1.988 95% CI 1.056-3.743, p = 0.031).

CONCLUSIONS: This Mendelian randomization analysis reveals a significant association between telomere length and autoimmune diseases such as RA, GD, and psoriasis, while a positive relationship was validated with SLE. These findings underscore the need for further investigation to better understand the underlying mechanisms and their potential clinical applications.},
}

Humans
*Mendelian Randomization Analysis
*Autoimmune Diseases/genetics/diagnosis
*Telomere/genetics
Genetic Predisposition to Disease
*Telomere Homeostasis/genetics
Risk Factors
*Telomere Shortening

@article {pmid40261310,
year = {2025},
author = {Shibuya, H},
title = {Telomeres, the nuclear lamina, and membrane remodeling: Orchestrating meiotic chromosome movements.},
journal = {The Journal of cell biology},
volume = {224},
number = {5},
pages = {},
pmid = {40261310},
issn = {1540-8140},
support = {//RIKEN/ ; },
mesh = {Humans ; *Telomere/metabolism/genetics ; Animals ; *Meiosis ; *Nuclear Lamina/metabolism/genetics ; *Nuclear Envelope/metabolism/genetics ; *Chromosomes/metabolism ; },
abstract = {Telomeres, the DNA-protein complex located at the ends of linear eukaryotic chromosomes, not only safeguard genetic information from DNA erosion and aberrant activation of the DNA damage response pathways but also play a pivotal role in sexual reproduction. During meiotic prophase I, telomeres attach to the nuclear envelope and migrate along its surface, facilitating two-dimensional DNA homology searches that ensure precise pairing and recombination of the paternal and maternal chromosomes. Recent studies across diverse model systems have revealed intricate molecular mechanisms, including modifications to telomere- and nuclear envelope-binding proteins, the nuclear lamina, and even membrane composition. Emerging evidence reveals mutations in the genes encoding these meiotic telomere and nuclear envelope-associated proteins among infertile patients. This review highlights recent advances in the field of meiotic telomere research, particularly emphasizing mammalian model systems, contextualizes these findings through comparisons with other eukaryotes, and concludes by exploring potential future research directions in the field.},
}

Humans
*Telomere/metabolism/genetics
Animals
*Meiosis
*Nuclear Lamina/metabolism/genetics
*Nuclear Envelope/metabolism/genetics
*Chromosomes/metabolism

@article {pmid40259036,
year = {2025},
author = {Castro, JDS and Teixeira, CM and Rocha, DMUP and Ribeiro, AQ and Kravchychyn, ACP and Hermsdorff, HHM},
title = {Dietary inflammatory index (DII) and telomere length: a systematic review.},
journal = {Biogerontology},
volume = {26},
number = {3},
pages = {95},
pmid = {40259036},
issn = {1573-6768},
support = {001//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior , Brasil/ ; },
mesh = {Humans ; *Inflammation ; *Diet/adverse effects ; *Telomere ; Aged ; *Telomere Homeostasis ; *Aging/genetics ; Middle Aged ; Male ; Female ; Adult ; Aged, 80 and over ; Adolescent ; *Telomere Shortening ; },
abstract = {Dietary intake influences inflammation and may impact telomere length (TL), a biomarker of biological aging. However, the relationship between the inflammatory potential of the diet and TL remains unclear. This review systematically assessed whether higher Dietary Inflammatory Index (DII) scores, indicative of pro-inflammatory diets, are associated with shorter TL. Searches in PubMed, Embase, Scopus, Web of Science, and Cochrane up to October 2024 identified nine eligible studies, involving 123,923 participants (53% women), aged 9-80 years. Seven studies were cross-sectional, and two were longitudinal, with follow-ups of 5-10 years. Most studies (n = 4) examined adult and older adult populations of both sexes. DII values ranged from -6.48 (anti-inflammatory) to 3.98 (pro-inflammatory). None included all DII parameters, and three adjusted for energy intake. Four studies linked higher DII to shorter TL, focusing on European adults with and without cardiovascular risk, healthy American adults, and Chinese older adults with mild cognitive impairment. This systematic review presents limited data to provide a definitive conclusion on the association between higher DII and shorter TL. Additional studies that address the limitations identified in this review are needed.},
}

Humans
*Inflammation
*Diet/adverse effects
*Telomere
Aged
*Telomere Homeostasis
*Aging/genetics
Middle Aged
Male
Female
Adult
Aged, 80 and over
Adolescent
*Telomere Shortening

@article {pmid40258723,
year = {2025},
author = {Wei, Z and Hu, Y and Zhang, Y and Wang, G and Zhou, C and Wang, Y},
title = {Identification of a telomere-related gene signature for the prognostic and immune landscape prediction in head and neck squamous cell carcinoma by integrated analysis of machine learning and Mendelian randomization.},
journal = {Medicine},
volume = {104},
number = {16},
pages = {e42211},
doi = {10.1097/MD.0000000000042211},
pmid = {40258723},
issn = {1536-5964},
support = {2023S078//Ningbo Social Public Welfare Research Project/ ; },
mesh = {Humans ; *Squamous Cell Carcinoma of Head and Neck/genetics/immunology/mortality ; *Machine Learning ; Prognosis ; *Head and Neck Neoplasms/genetics/immunology/mortality ; Mendelian Randomization Analysis ; *Telomere/genetics ; Male ; Female ; Biomarkers, Tumor/genetics ; Middle Aged ; },
abstract = {Telomere-related genes (TRGs) are vital in diverse tumor types. Nevertheless, there is a notable lack of in-depth research concerning their significance in head and neck squamous cell carcinoma (HNSCC). In this context, the present study aims to assess the predictive value of TRGs in HNSCC. Gene expression data and clinical data for HNSCC were sourced from The Cancer Genome Atlas and the Gene Expression Omnibus database. A new prognostic signature for TRGs was formulated through the application of machine learning techniques. Based on this signature, risk scores were computed for individual samples, effectively classifying individuals into low- and high-risk categories. The signature was evaluated in terms of its association with survival outcomes, tumor mutation burden, functional enrichment, immune cell infiltration, and its predictive capacity regarding immunotherapy efficacy. Additionally, Mendelian randomization analysis was utilized to ascertain the potential causal association between the expression of model genes and the development of HNSCC. A sum of 24 TRGs was recognized and utilized to develop the predictive signature. The areas under the receiver operating characteristic (ROC) curves for 1-, 3-, and 5-year overall survival were computed as 0.654, 0.734, and 0.711, respectively. Kaplan-Meier survival analysis demonstrated that individuals classified as high-risk had notably poorer prognoses relative to those placed in the low-risk. Those with lower risk scores demonstrated better survival outcomes, marked by elevated immune scores, augmented immune-related functions, and greater immune cell infiltration. Furthermore, these lower-risk patients exhibited an enhanced response to immunotherapy in comparison to high-risk patients. Mendelian randomization findings indicated a possible causal link between MAD1L1 expression and the occurrence of HNSCC. This research established an innovative TRG-based risk model to forecast the survival outcomes and immune landscape of individuals with HNSCC. This reliable and validated prognostic indicator has the potential to inform and enhance the creation of innovative treatment approaches for individuals with HNSCC.},
}

Humans
*Squamous Cell Carcinoma of Head and Neck/genetics/immunology/mortality
*Machine Learning
Prognosis
*Head and Neck Neoplasms/genetics/immunology/mortality
Mendelian Randomization Analysis
*Telomere/genetics
Male
Female
Biomarkers, Tumor/genetics
Middle Aged

@article {pmid40257417,
year = {2025},
author = {Gheytaspour, P and Bahadoran, S and Hassanpour, H},
title = {The Impact of Dietary Melatonin on Heart and Lung Telomere Length and Shelterin Protein Gene Expression of Pulmonary Hypertensive Broiler Chickens.},
journal = {Veterinary medicine and science},
volume = {11},
number = {3},
pages = {e70355},
doi = {10.1002/vms3.70355},
pmid = {40257417},
issn = {2053-1095},
mesh = {Animals ; *Melatonin/administration & dosage/pharmacology/metabolism ; *Chickens ; *Poultry Diseases/drug therapy/genetics/metabolism ; Lung/drug effects/metabolism ; Dietary Supplements/analysis ; *Hypertension, Pulmonary/veterinary/drug therapy/genetics/metabolism ; Diet/veterinary ; *Telomere/drug effects ; Male ; Animal Feed/analysis ; *Gene Expression/drug effects ; Avian Proteins/metabolism/genetics ; Myocardium/metabolism ; *Antioxidants/administration & dosage/pharmacology ; *Telomere-Binding Proteins/genetics/metabolism ; Shelterin Complex ; Heart/drug effects ; },
abstract = {OBJECTIVES: Pulmonary hypertension syndrome (PHS) is a common metabolic disease in broiler chickens linked to oxidative stress. This study explored the potential of melatonin, an antioxidant, to improve PHS response and telomere structure in chickens with cold-induced PHS.

METHODS: We investigated the effects of dietary melatonin supplementation on telomere length and the expression of genes related to telomere protection (shelterin genes) in the heart and lungs of broiler chickens with PHS.

RESULTS: Melatonin supplementation improved telomere length in the heart tissue of chickens with PHS. We also observed changes in the expression of genes (TRF1, RAP1, and TPP1) responsible for protecting telomeres, suggesting a potential mechanism for melatonin's beneficial effects. Melatonin's impact was more pronounced in the heart than in the lungs.

CONCLUSIONS: Melatonin may help protect cardiac cells during PHS by improving telomere length and influencing the activity of genes involved in telomere protection. These findings suggest that melatonin could be a valuable tool in managing heart cell dysfunction associated with PHS in poultry.},
}

Animals
*Melatonin/administration & dosage/pharmacology/metabolism
*Chickens
*Poultry Diseases/drug therapy/genetics/metabolism
Lung/drug effects/metabolism
Dietary Supplements/analysis
*Hypertension, Pulmonary/veterinary/drug therapy/genetics/metabolism
Diet/veterinary
*Telomere/drug effects
Male
Animal Feed/analysis
*Gene Expression/drug effects
Avian Proteins/metabolism/genetics
Myocardium/metabolism
*Antioxidants/administration & dosage/pharmacology
*Telomere-Binding Proteins/genetics/metabolism
Shelterin Complex
Heart/drug effects

@article {pmid40254557,
year = {2025},
author = {Xu, S and Ye, J and Cai, X},
title = {Identification of telomere-related diagnostic markers in osteoarthritis based on bioinformatics analysis and machine learning.},
journal = {The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology},
volume = {29},
number = {3},
pages = {359-372},
doi = {10.4196/kjpp.24.322},
pmid = {40254557},
issn = {1226-4512},
abstract = {Osteoarthritis (OA) is one of the most prevalent joint disorders, with aging considered a primary, irreversible factor contributing to its progression. Telomere-related cellular senescence may be a crucial factor influencing the OA process, yet biomarkers for OA based on telomere-related genes have not been clearly identified. The datasets GSE51588, GSE12021, and GSE55457 were retrieved from the Gene Expression Omnibus database. Initially, R software was utilized to identify differentially expressed genes between OA and normal samples. Subsequently, differentially expressed telomere-related genes (DETMRGs) were obtained, and their functional enrichment was analyzed. Feature genes for OA diagnosis were selected from DETMRGs using a combination of least absolute shrinkage and selection operator, support vector machine-recursive feature elimination, and Random Forest algorithms. The diagnostic value of these feature genes was then validated through receiver operating characteristic (ROC) curves and decision curve analysis. Additionally, CIBERSORT and xCell were employed to assess the infiltration of immune cells in OA tissues. Finally, potential drugs targeting candidate genes were predicted. Three telomere-related genes, PGD, SLC7A5, and TKT, have been identified as biomarkers for OA diagnosis and were confirmed through ROC diagnostic tests. The immune infiltration of mast cells, neutrophils, common lymphoid precursors, and eosinophils associated with PGD, SLC7A5, and TKT was reduced. Recognizing telomere-related genes PGD, SLC7A5, and TKT as potential diagnostic biomarkers for OA is significant, as it offers valuable insights into the role of telomere-related genes in OA. This discovery also provides valuable information for the diagnosis and treatment of OA.},
}

@article {pmid40253647,
year = {2025},
author = {McLester-Davis, LWY and Norton, D and Papale, LA and James, TT and Salazar, H and Asthana, S and Johnson, SC and Gooding, DC and Roy, TR and Alisch, RS and Hogan, KJ and Drury, SS and Gleason, CE and Zuelsdorff, M},
title = {Telomere Length and Cognitive Function Among Middle-Aged and Older Participants From Communities Underrepresented in Aging Research: A Preliminary Study.},
journal = {Journal of aging and health},
volume = {},
number = {},
pages = {8982643251331260},
doi = {10.1177/08982643251331260},
pmid = {40253647},
issn = {1552-6887},
abstract = {ObjectiveAccelerated biological aging is a plausible and modifiable determinant of dementia burden facing minoritized communities but is not well-studied in these historically underrepresented populations. Our objective was to preliminarily characterize relationships between telomere length and cognitive health among American Indian/Alaska Native (AI/AN) and Black/African American (B/AA) middle-aged and older adults.MethodsThis study included data on telomere length and neuropsychological test performance from 187 participants, enrolled in one of two community-based cognitive aging cohorts and who identified their primary race as AI/AN or B/AA.ResultsNested multivariable regression models revealed preliminary evidence for associations between telomere length and cognitive performance, and these associations were partially independent of chronological age.DiscussionSmall sample size limited estimate precision; however, findings suggest future work on telomere length and cognitive health in underrepresented populations at high risk for dementia is feasible and valuable as a foundation for social and behavioral intervention research.},
}

@article {pmid40252362,
year = {2025},
author = {Wai, KM and Paing, AM and Swe, T},
title = {Understanding physical aging in relation to biological aging, telomere length: A systematic review.},
journal = {Archives of gerontology and geriatrics},
volume = {134},
number = {},
pages = {105854},
doi = {10.1016/j.archger.2025.105854},
pmid = {40252362},
issn = {1872-6976},
abstract = {BACKGROUND: Telomere length (TL) serves as a marker for biological aging, influenced by chronological aging but distinct from it. This systematic review aims to synthesize the evidence on the associations between components of physical aging and TL in the elderly population.

METHODS: A comprehensive search was conducted in online databases of PubMed, Web of Science, ProQuest, and ScienceDirect to identify the eligible papers published until 1st August 2024. The authors independently extracted data using the standardized form. The quality of the included studies was evaluated for the risks of biases.

RESULTS: A total of 1080 records were initially identified using the predefined search strategy. A total of 40 eligible records were included in this review. When assessing physical aging, the nature and type of measurements across studies vary, including subjective, objective, and a combination of both approaches. Subjective assessments of general health or physical limitations may be linked with TL, while frailty, whether measured subjectively or objectively, shows associations with TL in less than 35 percent of total studies. In contrast, composite measures of physical performance/ability are consistently associated with TL in the elderly population.

CONCLUSIONS: In conclusion, we demonstrated that the associations between physical aging and TL varies depending on the type and nature of physical aging assessments. Composite measures of physical performance/ability demonstrate a strong and consistent parameter of physical aging to link with TL. Future research should prioritize standardized, multidimensional approaches to measure physical aging to understand better its association with TL to support healthy aging strategies.},
}

@article {pmid40250166,
year = {2025},
author = {Tian, Y and Kong, S and Mao, L and Wang, G and He, J and Lei, F and Lin, L and Li, J},
title = {Association of life's essential 8 with leukocyte telomere length and mitochondrial DNA copy number: Findings from the population-based UK Biobank study.},
journal = {The journal of nutrition, health & aging},
volume = {29},
number = {7},
pages = {100557},
doi = {10.1016/j.jnha.2025.100557},
pmid = {40250166},
issn = {1760-4788},
abstract = {OBJECTIVES: To explore the association of Life's Essential 8 (LE8) levels with leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNA-CN).

DESIGN: A cross-sectional study.

SETTING AND PARTICIPANTS: 225,692 participants aged 37-73 year from the UK Biobank cohort enrolled from 2006 to 2010.

MEASUREMENTS: The LE8 score (0-100) was divided into low (<50), moderate (50-79), and high cardiovascular health (CVH) (≥80) categories, based on health behaviors and factors defined by the American Heart Association. LTL was measured by a validated quantitative polymerase chain reaction method. mtDNA-CN was reacted by standardized SNP probe intensities. The association of CVH (as both a continuous and categorical variable) with LTL and mtDNA-CN was examined using multiple linear regression.

RESULTS: Of 225,692 participants, 5.3% had low CVH, 81.2% had moderate CVH, and 13.4% had high CVH. Participants with higher CVH were usually younger, female, better educated, of higher socioeconomic status, and with a lower prevalence of comorbidities. After adjusting for confounders, a higher LE8 score is associated with longer LTL (Beta = 0.075, P < 0.05) and increased mtDNA-CN (Beta = 0.094, P < 0.05). We also observed that this association was evident in the health behavior score (diet, physical activity, nicotine exposure, and sleep) and the health factors score (BMI, non-HDL cholesterol, blood glucose, and blood pressure), with a stronger positive association of health factors with LTL and mtDNA-CN (Beta = 0.019, P < 0.05; Beta = 0.037, P < 0.05).

CONCLUSIONS: Higher CVH is associated with longer LTL and increased mtDNA-CN.},
}

@article {pmid40247641,
year = {2025},
author = {Ryall, C and Denham, J},
title = {A systematic review and meta-analysis highlights a link between aerobic fitness and telomere maintenance.},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
volume = {},
number = {},
pages = {},
doi = {10.1093/gerona/glaf068},
pmid = {40247641},
issn = {1758-535X},
abstract = {Cardiorespiratory fitness declines with ageing and is a major risk factor of cardiometabolic diseases and early death. Although the benefits of regular exercise are well established, whether maximal oxygen uptake (V̇O2max) is associated with biological ageing remains unclear. Given that telomere shortening is a hallmark of ageing, the purpose of this systematic review and meta-analysis was to determine the association between V̇O2max and telomere length. Articles were retrieved from PubMed, Scopus, and ScienceDirect and deemed eligible if they: 1) involved human participants with relatively low and high V̇O2max values objectively assessed by pulmonary analysis; 2) quantified telomere length using an established technique; and 3) were peer-reviewed journal articles written in English. Relative to individuals with below average V̇O2max based on age- and sex-adjusted norms, fit participants with relative V̇O2max values in the 70th percentile or higher possessed longer telomeres (SMD [95%CI]: 0.36 [0.14-0.59], p=0.002). A similar difference was observed between individuals with below average V̇O2max and those above the 90th percentile (0.28 [0.03-0.53], p=0.03). However, no statistically significant telomere length differences were observed between individuals in the 70th to 90th percentile compared to those above the 90th (-0.08 [-0.40-0.24], p=0.62). The findings provide evidence linking metabolism to telomere biology. They encourage individuals to regularly engage in endurance exercise to attenuate telomere attrition and promote healthy biological ageing. Importantly, the results suggest that extensive endurance training may not be required to protect the telomeres, rather moderate amounts of training may be sufficient to reach more achievable V̇O2max targets.},
}

@article {pmid40246468,
year = {2025},
author = {Ma, N and Yip, R and Woodward, M and Lewis, S and Crane, M and Jirapatnakul, A and Aloman, C and Bansal, MB and Dieterich, D and Gros, L and Valvi, D and Colicino, E and Yankelevitz, D and Henschke, C and Branch, AD},
title = {Mixture analysis of associations between environmental and workplace toxins and liver damage and telomere length, stratified by race/ethnicity.},
journal = {Journal of environmental sciences (China)},
volume = {155},
number = {},
pages = {316-328},
doi = {10.1016/j.jes.2024.08.020},
pmid = {40246468},
issn = {1001-0742},
mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Cadmium ; Cross-Sectional Studies ; *Environmental Exposure/statistics & numerical data ; *Environmental Pollutants/toxicity/blood ; Ethnicity/statistics & numerical data ; Lead ; Liver/drug effects ; Nutrition Surveys ; *Occupational Exposure/statistics & numerical data ; Polychlorinated Biphenyls ; *Telomere ; United States/epidemiology ; Racial Groups ; White ; Black or African American ; },
abstract = {This study aimed to identify the worst "bad actors" in mixtures of pollutants contributing to liver damage and shorter telomeres in the U.S. population, using weighted quantile sum (WQS) modeling with stratification by race/ethnicity. We conducted a comprehensive cross-sectional analysis of mixtures of pollutants in National Health and Nutrition Examination Survey datasets: (1) 33,979 adults with blood levels of cadmium (Cd), lead (Pb), and mercury, including subsets with measurements of per-/polyfluoroalkyl substances (PFAS), and polychlorinated biphenyls (PCBs)/polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs); and (2) 7360 adults with measurements of telomeres, Cd, and Pb. Multivariable-adjusted WQS regression examined associations between WQS mixture indices and liver injury (alanine aminotransferase (ALT)-elevation), advanced liver-fibrosis (LF), and telomere length. WQSmetal indices were associated with advanced-LF in all racial/ethnic groups. The top contributor was Cd in the total population and in non-Hispanic Whites (NHW), while Pb was the top contributor in non-Hispanic Blacks (NHB). The WQSmetal-PCB-PCDD/F index was associated with ALT-elevation, with PCB126, Cd and Pb as main contributors; the odds ratio (OR) per decile was 1.50 (95 % CI, 1.26-1.78), while the OR per decile of the WQSmetal-PFAS index was 1.03 (95 % CI, 0.98-1.05), not significant. WQSmetal indices were associated with shorter telomeres. Cd was main contributor associated with advanced-LF in NHW, while Pb was the major bad actor in NHB, suggesting that NHB may be especially susceptible to Pb toxicity. Metals were associated with shorter telomeres. Metal and PCB/PCDD/F mixtures were associated with ALT-elevation. Heavy metals and organic chemicals may contribute to liver-related morbidity and healthcare disparities.},
}

Adult
Female
Humans
Male
Middle Aged
Cadmium
Cross-Sectional Studies
*Environmental Exposure/statistics & numerical data
*Environmental Pollutants/toxicity/blood
Ethnicity/statistics & numerical data
Lead
Liver/drug effects
Nutrition Surveys
*Occupational Exposure/statistics & numerical data
Polychlorinated Biphenyls
*Telomere
United States/epidemiology
Racial Groups
White
Black or African American

@article {pmid40245101,
year = {2025},
author = {Calugaru, K and Yu, EY and Huang, S and González-Rodríguez, N and Coloma, J and Lue, NF},
title = {The yeast CST and Polα/primase complexes act in concert to ensure proper telomere maintenance and protection.},
journal = {Nucleic acids research},
volume = {53},
number = {7},
pages = {},
doi = {10.1093/nar/gkaf245},
pmid = {40245101},
issn = {1362-4962},
support = {MCB-2246561//National Science Foundation/ ; GM107287/NH/NIH HHS/United States ; AEI/10.13039/501100011 033//Agencia Estatal de Investigación/ ; PID2020-114429RB-I00//Ministerio de Ciencia e Innovación/ ; //National Institute of Health Carlos III/ ; },
mesh = {*DNA Polymerase I/metabolism/genetics/chemistry ; *DNA Primase/metabolism/genetics/chemistry/ultrastructure ; *Telomere/metabolism/genetics ; *Telomere-Binding Proteins/genetics/metabolism/chemistry ; *Telomere Homeostasis/genetics ; Telomerase/metabolism/genetics/chemistry ; *Saccharomyces cerevisiae Proteins/genetics/metabolism/chemistry ; Humans ; Cryoelectron Microscopy ; Candida glabrata/genetics/metabolism ; Mutation ; DNA Replication ; Cell Cycle Proteins/genetics/metabolism ; Saccharomyces cerevisiae/genetics ; },
abstract = {Polα/primase (PP), the polymerase that initiates DNA synthesis at replication origins, also completes the task of genome duplication by synthesizing the telomere C-strand under the control of the CTC1/CDC13-STN1-TEN1 (CST) complex. Using cryo-electron microscopy (cryo-EM) structures of the human CST-Polα/primase-DNA complex as guides in conjunction with AlphaFold modeling, we identified structural elements in yeast CST and PP that promote complex formation. Mutating these structures in Candida glabrata Stn1, Ten1, Pri1, and Pri2 abrogated the stimulatory activity of CST on PP in vitro, supporting the functional relevance of the physical contacts in cryo-EM structures as well as the conservation of mechanisms between yeast and humans. Introducing these mutations into C. glabrata yielded two distinct groups of mutants. One group exhibited progressive, telomerase-dependent telomere elongation without evidence of DNA damage. The other manifested slow growth, telomere length heterogeneity, single-stranded DNA accumulation and elevated C-circles, which are indicative of telomere deprotection. These telomere deprotection phenotypes are altered or suppressed by mutations in multiple DNA damage response (DDR) and DNA repair factors. We conclude that in yeast, the telomerase inhibition and telomere protection function previously ascribed to the CST complex are mediated jointly by both CST and Polα/primase, highlighting the critical importance of a replicative DNA polymerase in telomere regulation.},
}

*DNA Polymerase I/metabolism/genetics/chemistry
*DNA Primase/metabolism/genetics/chemistry/ultrastructure
*Telomere/metabolism/genetics
*Telomere-Binding Proteins/genetics/metabolism/chemistry
*Telomere Homeostasis/genetics
Telomerase/metabolism/genetics/chemistry
*Saccharomyces cerevisiae Proteins/genetics/metabolism/chemistry
Humans
Cryoelectron Microscopy
Candida glabrata/genetics/metabolism
Mutation
DNA Replication
Cell Cycle Proteins/genetics/metabolism
Saccharomyces cerevisiae/genetics

@article {pmid40244253,
year = {2025},
author = {Murillo-Ortiz, BO and Romero-Vázquez, MJ and Luevanos-Aguilera, AJ and Meza-Herrán, PM and Ramos-Rodriguez, EM and Martínez-Garza, S and Murguia-Perez, M},
title = {Association Between Telomere Shortening and Erythropoietin Resistance in Patients with Chronic Kidney Disease Undergoing Hemodialysis.},
journal = {International journal of molecular sciences},
volume = {26},
number = {7},
pages = {},
doi = {10.3390/ijms26073405},
pmid = {40244253},
issn = {1422-0067},
mesh = {Humans ; *Renal Dialysis ; Female ; Male ; *Erythropoietin/therapeutic use ; *Renal Insufficiency, Chronic/therapy/genetics ; Middle Aged ; *Drug Resistance/genetics ; *Telomere Shortening ; Cross-Sectional Studies ; Aged ; Anemia/drug therapy ; Hematinics/therapeutic use ; Telomere ; Adult ; },
abstract = {The relationship between telomere shortening and patients with chronic kidney disease (CKD) has recently been investigated. Although most patients respond adequately to erythropoiesis-stimulating agents (ESAs), approximately 10% do not, and this is referred to as ESA resistance. The aim of our study was to investigate the relationship between telomere shortening and erythropoietin resistance in patients with CKD on hemodialysis. This cross-sectional, comparative, analytical, and observational study was conducted in patients of both sexes over 18 years of age diagnosed with CKD. Two groups of patients were identified. The first group consisted of 40 patients receiving erythropoiesis-stimulating agents with erythropoietin resistance. The second group consisted of 40 patients with the same characteristics but without erythropoietin resistance. Telomere length was measured by real-time PCR. Eighty patients were included in the study. Mean hemoglobin levels were lower in the erythropoietin resistance group (8.8 ± 1.67 vs. 11.95 ± 1.81, p = 0.001). Differences were observed in hematocrit and albumin levels, which were lower in patients with erythropoietin resistance, while PTH levels were higher in this group (788 ± 538.47 vs. 535.65 ± 603.06, p = 0.001). A significant difference in telomere length (T/S) was observed between the two groups, with shorter telomere length in the erythropoietin resistance group (0.45 ± 0.04 vs. 0.56 ± 0.03, p = 0.01). Telomere shortening may be associated with anemia and erythropoietin resistance in patients with CKD undergoing hemodialysis. This relationship suggests the need to explore whether telomere length recovery improves the response to ESAs.},
}

Humans
*Renal Dialysis
Female
Male
*Erythropoietin/therapeutic use
*Renal Insufficiency, Chronic/therapy/genetics
Middle Aged
*Drug Resistance/genetics
*Telomere Shortening
Cross-Sectional Studies
Aged
Anemia/drug therapy
Hematinics/therapeutic use
Telomere
Adult

@article {pmid40243865,
year = {2025},
author = {Dos Reis, GG and Silvestre, RT and Alves, G and Delmonico, L and Chantre-Justino, M and Moreira, ADS and Müller, BLA and do Nascimento, CR and da Silva, DLP and Dos Santos, LS and Mattos-Guaraldi, AL and Ornellas, MH},
title = {Leukocyte telomere length and telomerase activity in Long COVID patients from Rio de Janeiro, Brazil.},
journal = {Memorias do Instituto Oswaldo Cruz},
volume = {120},
number = {},
pages = {e240129},
doi = {10.1590/0074-02760240129},
pmid = {40243865},
issn = {1678-8060},
mesh = {Humans ; *Telomerase/blood/metabolism ; *COVID-19/enzymology ; Male ; Female ; *Leukocytes/enzymology ; *Telomere/genetics ; Middle Aged ; Brazil ; Real-Time Polymerase Chain Reaction ; Adult ; SARS-CoV-2 ; Case-Control Studies ; Aged ; },
abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by the new coronavirus 2 (severe acute respiratory syndrome coronavirus 2 - SARS-CoV-2). Long COVID is a new condition associated with persistent COVID-19 symptoms and/or new emerging symptoms. Telomeres are specialised structures for genome protection at the end of chromosomes and telomerase is the enzyme that synthesises telomere DNA.

OBJECTIVES: Patients with Long COVID symptoms were recruited at the Pedro Ernesto University Hospital (HUPE) in Rio de Janeiro, Brazil, with the main purpose of investigating the association between telomere length and Long COVID.

METHODS: Leukocyte telomere length (LTL) was determined by quantitative real-time polymerase chain reaction (qPCR) in 34 Long COVID patients compared to a control group (n = 122). Telomerase activity was determined by qPCR assays using the commercial kit from ScienCell. A questionnaire on symptoms, vaccine doses and blood count was completed.

FINDINGS: The Long COVID patients were found to have an increase in LTL. Telomerase activity was also examined in a smaller number of patients and found to be reactivated in the blood.

MAIN CONCLUSIONS: It will be necessary to conduct further studies and monitor Long COVID patients to determine if future health issues could be linked to telomerase activity and elongated telomeres.},
}

Humans
*Telomerase/blood/metabolism
*COVID-19/enzymology
Male
Female
*Leukocytes/enzymology
*Telomere/genetics
Middle Aged
Brazil
Real-Time Polymerase Chain Reaction
Adult
SARS-CoV-2
Case-Control Studies
Aged

@article {pmid40243583,
year = {2025},
author = {Dmitrenko, O and Karpova, N and Nurbekov, M},
title = {Increased Preeclampsia Risk in GDM Pregnancies: The Role of SIRT1 rs12778366 Polymorphism and Telomere Length.},
journal = {International journal of molecular sciences},
volume = {26},
number = {7},
pages = {},
doi = {10.3390/ijms26072967},
pmid = {40243583},
issn = {1422-0067},
support = {FGFU-2025-0007: Search for diagnostically significant biochemical, immunological and other markers of disorders of normal functioning of organs and systems.//Federal State Budgetary Institution the "Research Institute of Pathology and Pathophysiology"/ ; },
mesh = {Humans ; Female ; Pregnancy ; *Pre-Eclampsia/genetics ; *Sirtuin 1/genetics ; *Diabetes, Gestational/genetics ; Adult ; *Polymorphism, Single Nucleotide ; *Telomere/genetics ; *Genetic Predisposition to Disease ; Case-Control Studies ; Risk Factors ; Genotype ; *Telomere Homeostasis ; Telomere Shortening ; },
abstract = {Preeclampsia (PE) and gestational diabetes mellitus (GDM) are common pregnancy disorders with shared pathophysiological mechanisms. This study examined the association between SIRT1 polymorphisms (rs12778366 and rs7895833) and relative telomere length (RTL) in women with PE and GDM. The DNA from pregnant women with GDM with and without PE was analyzed. The RTL and genotyping were measured using quantitative real-time PCR. The women with GDM and PE had significantly shorter telomeres. The rs12778366 TC genotype was associated with a 4.48-fold increased risk of PE (OR = 4.48; 95% CI 1.54-13.08; p = 0.003). The PE group had a higher prevalence of the heterozygous TC rs12778366 genotype with short telomeres. The SIRT1 variant rs12778366 is associated with shorter telomeres and an increased risk of developing preeclampsia, suggesting it may be a useful biomarker for preeclampsia risk assessment in GDM pregnancies.},
}

Humans
Female
Pregnancy
*Pre-Eclampsia/genetics
*Sirtuin 1/genetics
*Diabetes, Gestational/genetics
Adult
*Polymorphism, Single Nucleotide
*Telomere/genetics
*Genetic Predisposition to Disease
Case-Control Studies
Risk Factors
Genotype
*Telomere Homeostasis
Telomere Shortening

@article {pmid40239997,
year = {2025},
author = {Pirota, V and Iachettini, S and Platella, C and Zizza, P and Fracchioni, G and Di Vito, S and Carachino, A and Battistini, F and Orozco, M and Freccero, M and Biroccio, A and Montesarchio, D and Doria, F},
title = {Naphthalene diimide-naphthalimide dyads promote telomere damage by selectively targeting multimeric G-quadruplexes.},
journal = {Nucleic acids research},
volume = {53},
number = {7},
pages = {},
doi = {10.1093/nar/gkaf301},
pmid = {40239997},
issn = {1362-4962},
support = {//European Union/ ; //Fondazione Umberto Veronesi/ ; 21579//National Center for Gene Therapy and Drugs/ ; 25046//Fondazione AIRC/ ; },
mesh = {*G-Quadruplexes/drug effects ; *Telomere/drug effects/chemistry ; Humans ; *Imides/chemistry/pharmacology ; *Naphthalenes/chemistry/pharmacology ; *Naphthalimides/chemistry/pharmacology ; *Antineoplastic Agents/pharmacology/chemistry/chemical synthesis ; Cell Line, Tumor ; Ligands ; Cell Survival/drug effects ; },
abstract = {G-quadruplex (G4) nucleic acid ligands have attracted significant attention as putative anticancer agents for selectively stabilizing telomeric structures. In our pursuit of targeting the most biologically relevant telomeric structures, we have investigated a new class of naphthalene diimide (NDI)-based ligands designed to bind multimeric G4s. The NDI unit covalently linked with one 1,8-naphthalimide (NI) moiety, results in ligands able to fold into a sandwich-like conformation fitting into the binding pockets of telomeric multimeric G4s, thus optimizing binding complementarity. Varying the NDI decorations, we synthesized a small library of NDI-NI dyads and then examined their capability of stabilizing G4s by biophysical assays. Given the relevance of G4 stabilizing agents in fighting cancer, the most promising NDI-NIs were evaluated for their antitumoral activity on a panel of human cell lines originating from different tumor histotypes. Obtained results evidenced that three of the selected ligands promoted an accumulation of telomere-localized damage leading to a robust impairment of cell viability, regardless of homologous recombination status. These data, then confirmed in advanced 3D models, paved the way for the advancement of NDI-NIs as a new class of clinically relevant antitumoral agents. Finally, computational analyses gained deeper insight into their binding modality.},
}

*G-Quadruplexes/drug effects
*Telomere/drug effects/chemistry
Humans
*Imides/chemistry/pharmacology
*Naphthalenes/chemistry/pharmacology
*Naphthalimides/chemistry/pharmacology
*Antineoplastic Agents/pharmacology/chemistry/chemical synthesis
Cell Line, Tumor
Ligands
Cell Survival/drug effects

@article {pmid40236780,
year = {2025},
author = {Zong, W and Chen, L and Zhang, D and Zhang, Y and Wang, J and Hou, X and Chai, J and An, Y and Tian, M and He, X and Song, C and He, J and Liu, X and Wang, L and D'Alessandro, E and Wang, L and Yin, Y and Li, M and Liu, D and Wang, J and Zhang, L},
title = {Two telomere-to-telomere pig genome assemblies and pan-genome analyses provide insights into genomic structural landscape and genetic adaptations.},
journal = {iMeta},
volume = {4},
number = {2},
pages = {e70013},
pmid = {40236780},
issn = {2770-596X},
abstract = {This study presented two high-precision telomere-to-telomere genome assemblies for Min and Rongchang pigs, including a detailed exploration of the telomeric and centromeric regions. By integrating pan-genome and multi-omics analyses, structural variations linked to genetic adaptation were identified, providing a valuable resource for advancing pig breeding and genetic improvement.},
}

@article {pmid40236733,
year = {2025},
author = {Song, WL and Chen, BZ and Feng, L and Chen, G and He, SM and Hao, B and Zhang, GH and Dong, Y and Yang, SC},
title = {Telomere-to-telomere genome assembly and 3D chromatin architecture of Centella asiatica insight into evolution and genetic basis of triterpenoid saponin biosynthesis.},
journal = {Horticulture research},
volume = {12},
number = {5},
pages = {uhaf037},
pmid = {40236733},
issn = {2662-6810},
abstract = {Centella asiatica is renowned for its medicinal properties, particularly due to its triterpenoid saponins, such as asiaticoside and madecassoside, which are in excess demand for the cosmetic industry. However, comprehensive genomic resources for this species are lacking, which impedes the understanding of its biosynthetic pathways. Here, we report a telomere-to-telomere (T2T) C. asiatica genome. The genome size is 438.12 Mb with a contig N50 length of 54.12 Mb. The genome comprises 258.87 Mb of repetitive sequences and 25 200 protein-coding genes. Comparative genomic analyses revealed C. asiatica as an early-diverging genus within the Apiaceae family with a single whole-genome duplication (WGD, Apiaceae-ω) event following the ancient γ-triplication, contrasting with Apiaceae species that exhibit two WGD events (Apiaceae-α and Apiaceae-ω). We further constructed 3D chromatin structures, A/B compartments, and topologically associated domains (TADs) in C. asiatica leaves, elucidating the influence of chromatin organization on expression WGD-derived genes. Additionally, gene family and functional characterization analysis highlight the key role of CasiOSC03 in α-amyrin production while also revealing significant expansion and high expression of CYP716, CYP714, and UGT73 families involved in asiaticoside biosynthesis compared to other Apiaceae species. Notably, a unique and large UGT73 gene cluster, located within the same TAD, is potentially pivotal for enhancing triterpenoid saponin. Weighted gene coexpression network analysis (WGCNA) further highlighted the pathways modulated in response to methyl jasmonate (MeJA), offering insights into the regulatory networks governing saponin biosynthesis. This work not only provides a valuable genomic resource for C. asiatica but also sheds light on the molecular mechanisms driving the biosynthesis of pharmacologically important metabolites.},
}