@article {pmid40563586,
year = {2025},
author = {Baliou, S and Pelagiadis, I and Apetroaei, MM and Vakonaki, E and Arsene, AL and Hatzidaki, E and Tzatzarakis, MN and Ioannou, P and Tsatsakis, A and Stiakaki, E},
title = {The Telomere Length Signature in Leukemias-From Molecular Mechanisms Underlying Telomere Shortening to Immunotherapeutic Options Against Telomerase.},
journal = {Cancers},
volume = {17},
number = {12},
pages = {},
doi = {10.3390/cancers17121936},
pmid = {40563586},
issn = {2072-6694},
abstract = {The nucleoprotein structures known as telomeres provide genomic integrity by protecting the ends of chromosomes. Tumorigenesis is associated with alterations in telomere function and stability. This narrative review provides evidence of the potential prognostic value of telomere length and telomerase in leukemias. On the one hand, oxidative stress and mitochondrial dysfunction can accelerate telomere shortening, leading to higher susceptibility and the progression of leukemia. On the other hand, cytogenetic alterations (such as gene fusions and chromosomal abnormalities) and genomic complexity can result from checkpoint dysregulation, the induction of the DNA damage response (DDR), and defective repair signaling at telomeres. This review thoroughly outlines the ways by which telomere dysfunction can play a key role in the development and progression of four primary leukemias, including chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), and acute leukemias of myeloid or lymphoid origin, highlighting the potential prognostic value of telomere length in this field. However, telomerase, which is highly active in leukemias, can prevent the rate of telomere attrition. In line with this, leukemia cells can proliferate, suggesting telomerase as a promising therapeutic target in leukemias. For this reason, telomerase-based immunotherapy is analyzed in the fight against leukemias, leveraging the immune system to eliminate leukemia cells with uncontrolled proliferation.},
}

@article {pmid40561208,
year = {2025},
author = {Catto, LFB and Aggarwal, N and Shalhoub, RN and Ma, X and Darden, I and Machado, T and Zhang, Y and Redekar, N and Thongon, N and Colla, S and Aubert, G and Dunbar, CE and Wu, CO and Young, NS and Patel, BA and Gutierrez-Rodrigues, F and Groarke, EM},
title = {Clinical and molecular features of immunodeficiency in patients with telomere biology disorders.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024026735},
pmid = {40561208},
issn = {1528-0020},
abstract = {Immunodeficiency in telomere biology disorders (TBDs) has been described in pediatric patients with severe phenotypes, but less characterized within the broader TBD spectrum. We collected complete blood counts, lymphocyte subsets, and infection history from 88 consecutive TBD patients with a median age of 37 years (range 6-76). Most patients were >18 years old (80/88; 90%) and harbored either a TERT (45%) or TERC (32%) germline mutation. Thirty-two patients (36%) experienced significant infections (opportunistic, recurrent, and/or requiring hospitalization); 47% had lymphopenia, and 3% severe neutropenia. Absolute lymphocyte counts (ALC) <0.96 and <1.1 x103/µL, but not severe neutropenia, associated with increased infection risk and lower overall survival, respectively. Decreased CD3+ T-cells, both CD4+ and CD8+, associated with BMF, increased infection risk, and reduced survival. Low CD3+ and CD4+ associated with solid cancers. Telomere length was shortened across the cohort without correlation with ALC or lymphocyte subsets. In a predominantly adult cohort of TBDs, immunodeficiency was marked by T lymphopenia, possibly a consequence of accelerated aging in the hematopoietic compartment. An ALC cut-off of <1.1 x103/µL may be a useful biomarker to identify patients with an increased risk of infection, a major cause of death of TBD patients.},
}

@article {pmid40561046,
year = {2025},
author = {Bae, CY and Kim, IH and Kim, SH and Chun, H and Kim, BS and Jeon, MH},
title = {Effects of lifestyle on telomere length: A study on the Korean population.},
journal = {PloS one},
volume = {20},
number = {6},
pages = {e0325233},
pmid = {40561046},
issn = {1932-6203},
mesh = {Humans ; Female ; Male ; *Life Style ; Middle Aged ; Republic of Korea ; Adult ; *Telomere/genetics ; *Telomere Homeostasis ; Aged ; *Aging/genetics ; Exercise ; Sleep ; Alcohol Drinking ; Smoking ; },
abstract = {Telomere length is a known indicator of biological aging, typically decreasing with age. Biological age is a benchmark for assessing an individual's health and aging. Correlations between telomere length and lifestyle factors have primarily been investigated from the perspective of a single variable and predominantly examined in postmenopausal women in Korea. This study aimed to analyze the effects of multiple lifestyle factors on telomere length in a diverse Korean population comprising 368 healthy adults (174 men and 194 women). We measured anthropometric and blood-related parameters and collected data on lifestyle-related factors, such as exercise, smoking, alcohol consumption, sleep, and stress, using surveys. Telomere length was quantified using monochrome multiplex quantitative real-time polymerase chain reaction (qPCR), and the relationship between lifestyle factors and telomere length was analyzed using correlation and regression analyses (p-value <0.10). Our findings indicated that telomere age, derived from telomere length, significantly increased with each adverse lifestyle factor. For men, significant contributors included exercise, smoking, and stress, whereas for women, significant contributors were exercise, alcohol consumption, sleep, and stress. The results showed that lifestyle and biological age considerably affected telomere age and accelerated the aging process. These results emphasize the importance of lifestyle in the management of biological aging.},
}

Humans
Female
Male
*Life Style
Middle Aged
Republic of Korea
Adult
*Telomere/genetics
*Telomere Homeostasis
Aged
*Aging/genetics
Exercise
Sleep
Alcohol Drinking
Smoking

@article {pmid40560939,
year = {2025},
author = {Campbell, AM and Anderson, MG and Haussmann, MF and Rowell, R and Jacobs, L},
title = {Telomere length as a biomarker for cumulative experience in broiler chickens.},
journal = {PloS one},
volume = {20},
number = {6},
pages = {e0326195},
pmid = {40560939},
issn = {1932-6203},
mesh = {Animals ; *Chickens/genetics ; Male ; *Telomere/genetics/metabolism ; Biomarkers/metabolism ; *Telomere Homeostasis ; },
abstract = {Cumulative experience can be defined as the sum of all positive and negative experiences during an animal's lifetime. Telomere length shows promise as a biomarker of cumulative experience in humans and non-human animals but is not yet assessed for broiler chickens. Therefore, our objective was to determine telomere length changes due to positive and negative experiences in fast-growing broiler chickens. In three replicated experiments, male Ross 708 broilers were housed in a 2 × 2 factorial study investigating high environmental complexity as a positive environment (vs. low complexity; 6 pens/treatment) and high stocking density as a negative environment (vs. low density; 6 pens/treatment). Telomere length was quantified at day 48 of age via quantitative RT-PCR (qRT-PCR) from gonad and kidney samples (N = 9 samples/treatment/tissue/experiment). Prior to analysis, raw relative telomere length (rTL) values were z-transformed to allow comparison between experiments. Combined data from the three experiments were analyzed using mixed models with complexity, density, and their interactions as fixed factor and pen nested within experiment and qRT-PCR plate number as random factors. Over all three trials, birds housed in high complexity environments tended (P = 0.0503) to have longer telomeres from kidney tissue than birds housed in low complexity environments. Stocking density did not impact combined kidney telomere length and gonadal telomere length was not impacted by environmental complexity or stocking density. Longer telomeres (statistical trend) in response to positive experience (environmental complexity) when compared to low-complexity indicate that high-complexity environments elicited positive cumulative experience in broiler chickens, although effect size was small. Telomere length has the potential to be a valuable tool in the assessment of cumulative experience in production settings, and future works should replicate these findings and expand upon this work by comparing telomere length with other more traditional animal welfare markers.},
}

Animals
*Chickens/genetics
Male
*Telomere/genetics/metabolism
Biomarkers/metabolism
*Telomere Homeostasis

@article {pmid40560727,
year = {2025},
author = {Analikwu, BT and Deshayes, A and van der Torre, J and Guérin, TM and Katan, AJ and Béneut, C and Barth, R and Phipps, J and Scolari, V and Veaute, X and Busso, D and Dubrana, K and Mattarocci, S and Dekker, C and Marcand, S},
title = {Telomeres stall DNA loop extrusion by condensin.},
journal = {Cell reports},
volume = {44},
number = {7},
pages = {115900},
doi = {10.1016/j.celrep.2025.115900},
pmid = {40560727},
issn = {2211-1247},
abstract = {DNA loop extrusion by SMC proteins is a key process underlying chromosomal organization. It is unknown how loop extruders interact with telomeres where DNA is densely covered with proteins. Using complementary in vivo and in vitro single-molecule approaches, we study how loop-extruding condensin interacts with Rap1, the telomeric DNA-binding protein of Saccharomyces cerevisiae. We show that dense linear Rap1 arrays can completely halt DNA loop extrusion, with a blocking efficiency depending on the array length and the DNA gap size between proteins. In anaphase cells, dense Rap1 arrays are found to accumulate condensin and to cause a local chromatin decompaction, as monitored with a microscopy-based approach, with direct implications for the resolution of dicentric chromosomes produced by telomere fusions. Our findings show that linear arrays of DNA-bound proteins can efficiently halt DNA loop extrusion by SMC proteins, which may impact cellular processes from telomere functions to transcription and DNA repair.},
}

@article {pmid40558975,
year = {2025},
author = {Yang, Y and Huang, J and Dong, G and Hu, X},
title = {Telomere-to-Telomere Assembly of the Cordyceps militaris CH1 Genome and Integrated Transcriptomic and Metabolomic Analyses Provide New Insights into Cordycepin Biosynthesis Under Light Stress.},
journal = {Journal of fungi (Basel, Switzerland)},
volume = {11},
number = {6},
pages = {},
pmid = {40558975},
issn = {2309-608X},
support = {No. 2022EHB047//Program of Hubei Province for International Cooperation/ ; No.20232354C01//Amway (China) Daily-Use Commodity/ ; },
abstract = {Cordyceps militaris, a model species in the genus Cordyceps, is widely distributed globally and is known for its significant medicinal value. It has been traditionally used in Chinese medicine to enhance immunity, alleviate fatigue, and treat tumors, among other therapeutic purposes. Here, we successfully assembled a telomere-to-telomere (T2T) level genome of C. militaris CH1 using PacBio HiFi and Hi-C technologies. The assembled genome is 32.67 Mb in size, with an N50 of 4.70 Mb. Gene prediction revealed a total of 10,749 predicted genes in the C. militaris CH1 genome, with a gene completeness of 99.20%. Phylogenetic analysis showed the evolutionary relationship between C. militaris CH1 and other Cordyceps species, suggesting that the divergence between this strain and C. militaris ATCC 34164 occurred approximately 1.36 Mya. Combined transcriptomic and metabolomic analyses identified 842 differentially expressed genes and 2052 metabolites that were significantly altered under light stress, primarily involving key pathways related to amino acid metabolism, purine metabolism, and secondary metabolite biosynthesis. Joint analysis of genes and metabolites revealed 79 genes coding for enzymes associated with the synthesis of adenine and adenosine, with the expression of 52 genes being upregulated, consistent with the accumulation trends of adenine and adenosine. Four gene clusters related to the synthesis of cordycepin were identified, with a significant upregulation of cns3 (FUN_003263), suggesting that light stress may promote cordycepin biosynthesis. This comprehensive analysis not only provides new insights into the genomics, metabolomics, and functional gene research of C. militaris CH1 but also offers a potential biological foundation for understanding the synthesis mechanisms of cordycepin and its efficient production.},
}

@article {pmid40556866,
year = {2025},
author = {Vos, S and Martens, DS and De Waele, E and Dewyspelaere, G and Mistiaen, G and Goeminne, P and Nawrot, TS},
title = {Telomere length and COVID-19 disease severity: insights from hospitalized patients.},
journal = {Frontiers in aging},
volume = {6},
number = {},
pages = {1577788},
pmid = {40556866},
issn = {2673-6217},
abstract = {INTRODUCTION: Telomere length is associated with various disease and immune function and may therefore impact COVID-19 disease severity. We studied the associations between telomere length as a geroprotective susceptibility marker and clinical outcomes in hospitalized COVID-19 patients.

METHODS: 283 hospitalised COVID-19 patients (before vaccination, recruited between May 2020 and March 2021) were recruited for this cross-sectional study. Blood telomere length was determined by qPCR. The association between blood telomere length and clinical outcomes was examined using logistic regression, while adjusting for various covariates and confounders including demographic factors, comorbidity, body-mass index and blood cell counts. The primary clinical outcomes assessed were duration of stay, risk of ICU admission, and risk of requiring ventilation support.

RESULTS: Independent of sex and chronological age, an interquartile-range (IQR) increase in blood telomere length was associated with more favourable clinical outcomes in hospitalised COVID-19 patients: specifically, the odds ratio for ICU admission was 0.55 (95%CI: 0.32-0.88). Moreover, the odds ratio for the risk of ventilation was 0.52 (95%CI: 0.31-0.84). Finally, ordinal logistic regression revealed a lower odds for being in a higher quantile of hospital duration (OR: 0.79, 95%CI: 0.58-1.06).

DISCUSSION: To conclude, we found that in hospitalised COVID-19 patients, longer telomeres was associated with lower diseases severity in hospitalised COVID-19 patients, that could not be explained by shifts in blood cell counts. Therefore supporting the geroprotective or immunoprotective effects associated with longer telomeres conferring lower susceptibility to severe COVID-19 outcomes.},
}

@article {pmid40556056,
year = {2025},
author = {Talon, AF and Razia, D and Sum, J and Sista, R},
title = {EXPRESS: Narrative Review: Chronic Lung Allograft Dysfunction with Focus on Short Telomere Syndrome, Adjunctive Therapies, and MRI Detection.},
journal = {Journal of investigative medicine : the official publication of the American Federation for Clinical Research},
volume = {},
number = {},
pages = {10815589251355173},
doi = {10.1177/10815589251355173},
pmid = {40556056},
issn = {1708-8267},
abstract = {Lung transplantation (LTx) is a vital treatment option for patients with end-stage lung diseases, significantly enhancing survival rates and quality of life. Nonetheless, chronic lung allograft dysfunction (CLAD) remains the primary cause of long-term morbidity and mortality in LTx recipients, posing substantial challenges to patient outcomes and healthcare systems. Despite progress in surgical methods and immunosuppressive treatments, CLAD management is complicated by its multifaceted, potentially irreversible nature. This review delves into critical aspects such as short telomere syndrome (STS), innovations in early detection, and adjunctive therapeutic approaches, offering insights into strategies that may extend the survival of LTx recipients. STS exacerbates CLAD by accelerating cellular aging and hindering tissue repair, necessitating a multidisciplinary approach involving pulmonologists, geneticists, hepatologists, and hematologists to devise comprehensive care plans. The review emphasizes dynamic magnetic resonance imaging as a promising tool for early CLAD detection, enhancing patient monitoring capabilities. Additionally, it examines the roles of extracorporeal photopheresis (ECP), total lymphoid irradiation (TLI), and anti-thymocyte globulins as adjunctive therapies, advocating for their inclusion in standard treatment protocols. This could lead to broader adoption and insurance coverage. Furthermore, we attempt to provide a framework to help decide which adjunctive treatments should be pursued based on the available evidence. By assessing these strategies and highlighting the importance of personalized care, this review aims to guide future research and clinical practice, ultimately improving CLAD management in lung transplant recipients.},
}

@article {pmid40552812,
year = {2025},
author = {Hoyer, LL and Souza, CP and Hung, C-C and Hogan, EK and Hernandez, AG},
title = {A telomere-to-telomere genome assembly for Malassezia pachydermatis ATCC 14522 (CBS 1879).},
journal = {Microbiology resource announcements},
volume = {},
number = {},
pages = {e0012525},
doi = {10.1128/mra.00125-25},
pmid = {40552812},
issn = {2576-098X},
abstract = {Pacific Biosciences (PacBio) long-read sequencing was used to generate a telomere-to-telomere genome assembly for the Malassezia pachydermatis type strain ATCC 14522 (CBS 1879). The assembly included six chromosomes. The nuclear genome was 8.4 Mb, with a GC content of 55.3%, and 4,519 predicted genes.},
}

@article {pmid40552254,
year = {2025},
author = {Andreikos, DA and Spandidos, DA},
title = {Telomere length and skin cancer risk: A systematic review and meta-analysis of melanoma, basal cell carcinoma and squamous cell carcinoma.},
journal = {Oncology letters},
volume = {30},
number = {2},
pages = {395},
pmid = {40552254},
issn = {1792-1082},
abstract = {Skin cancer is one of the most prevalent types of cancer worldwide, with its global incidence rising despite prevention efforts. Telomere length (TL) has emerged as a potential biomarker for cancer risk; however, its relationship with skin cancer risk remains incompletely understood. To explore the association between TL and the risk of melanoma, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), a systematic review and meta-analysis was conducted. Longer TL was significantly associated with an increased risk in melanoma (pooled odds ratio: 0.51; 95% confidence interval: 0.38-0.69; P<0.0001). A significant association between longer TL and increased melanoma risk was identified in both familial melanoma and the general population. Subgroup analyses revealed consistent associations across sex, population source and adjustments for confounding factors. Geographic stratification indicated stronger associations in studies conducted in the USA compared with those from European populations. A meta-analysis of BCC and SCC studies did not achieve statistical significance, although qualitative synthesis suggested a potential association between shortened TL and increased risk. The significant association of longer TL and increased melanoma risk diverges from the conventional hypothesis that telomere shortening elevates cancer risk, highlighting a cancer-type specific telomeric relationship. The inconclusive findings for BCC and SCC underscore the necessity for further detailed investigation. Large-scale prospective studies with standardized methodologies are imperative to validate these findings and explore the underlying mechanisms. The present findings suggested that TL could potentially serve as a valuable biomarker for melanoma risk stratification in dermatologic oncology.},
}

@article {pmid40551485,
year = {2025},
author = {Wen, W and Chen, S and Coulter, K and Kim, SY},
title = {The association of depressive symptoms and telomere length among Mexican-origin youth: How it varies by family environment.},
journal = {Journal of research on adolescence : the official journal of the Society for Research on Adolescence},
volume = {35},
number = {2},
pages = {e70047},
pmid = {40551485},
issn = {1532-7795},
support = {1651128//National Science Foundation/ ; 0956123//National Science Foundation/ ; 1R21MD012706-01A1/MD/NIMHD NIH HHS/United States ; 3R21MD-012706-02S1/MD/NIMHD NIH HHS/United States ; 5R03HD060045-02//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; 2P2CHD042849-21A1//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; 2T32HD007081-46A1//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; 2699//Russell Sage Foundation/ ; 10023427//Spencer Foundation/ ; JRG-102//Hogg Foundation for Mental Health/ ; //Office of the Vice President for Research and Creative Grant and Special Research Grant from the University of Texas at Austin/ ; //College of Natural Sciences Catalyst Grant from the University of Texas at Austin/ ; 1K99MD019319/MD/NIMHD NIH HHS/United States ; },
mesh = {Humans ; Female ; Adolescent ; Male ; *Depression/ethnology/psychology/genetics ; *Mexican Americans/psychology/statistics & numerical data ; *Telomere Shortening ; Child ; Parenting/psychology/ethnology ; *Emigrants and Immigrants/psychology ; *Telomere ; Socialization ; White ; },
abstract = {Telomere length is an important indicator of aging and related diseases. Identifying risk and protective factors for telomere shortening early in life among youth from Mexican immigrant families is critical for reducing ethnic health disparities. This study investigates how familial environmental factors (i.e., culture-general and culture-specific parenting and parentification experiences) shape individual differences in the association between depressive symptoms and telomere length. Adolescents from immigrant families (n = 325; Mwave1.age = 12.81) self-reported their perceptions of maternal hostility, warmth, cultural socialization, and parentification experiences across three waves during adolescence, as well as depressive symptoms in late adolescence (Mwave3.age = 17.61). Youth also provided dried blood spots for telomere length assessment at Wave 3. Moderation models were conducted in Mplus 8.3 with basic sociodemographic variables and BMI controlled. Maternal hostility, cultural socialization, and parentification during adolescence, but not maternal warmth, were critical family context factors impacting biological (i.e., telomere length) responses to depressive symptoms. Higher depressive symptoms were related to shorter telomere length in late adolescence only for youth who experienced high levels of maternal hostility, lower cultural socialization, or lower parentification experiences during adolescence. This study highlights the importance of cultivating cultural assets through culturally specific parenting and family experiences during adolescence, demonstrating their role in mitigating the link between depressive symptoms and accelerated cellular aging as shown by telomere length.},
}

Humans
Female
Adolescent
Male
*Depression/ethnology/psychology/genetics
*Mexican Americans/psychology/statistics & numerical data
*Telomere Shortening
Child
Parenting/psychology/ethnology
*Emigrants and Immigrants/psychology
*Telomere
Socialization
White

@article {pmid40550303,
year = {2025},
author = {Janet Chik, HY and Gillings, MM and Ton, R and van der Velde, M and Taylor, MP and Swaddle, JP and Dugdale, HL and Griffith, SC},
title = {Telomere length declines with mean blood lead concentration in an urban passerine.},
journal = {Environmental research},
volume = {},
number = {},
pages = {122210},
doi = {10.1016/j.envres.2025.122210},
pmid = {40550303},
issn = {1096-0953},
abstract = {Lead (Pb) is a highly toxic and widespread environmental pollutant and can severely harm body tissues as well as DNA. Pb could potentially damage telomeres, whose length and shortening rate are linked with cellular senescence, physiological state, and mortality. Yet, studies investigating Pb and telomere dynamics in natural systems remain inconclusive. In this study, we used a free-living house sparrow (Passer domesticus) population in Broken Hill, Australia, chronically exposed to varying levels of environmental Pb, to assess the effects of Pb on telomere length and telomere rate of change. Using all data from adults and juveniles, we found that mean blood Pb concentration had a negative relationship with telomere lengths measured at capture sites, such that a standard deviation increase in the concentration of blood Pb was associated with an 8% decrease in telomere length. In a series of robustness analyses we found that this negative relationship existed at both the individual and the site levels. Although not statistically significant, the relationship between telomere length and soil Pb also appeared to be consistent with that found for blood Pb. Our results demonstrated that while exposure to Pb damages telomeres in free-living house sparrows, the biological effect is relatively weak, and is only identified with a sample size of over 500 individuals. Nevertheless, our data reveal that in this urban setting in Australia, a human commensal bird is suffering from lead-induced damage to telomeres. Given the well-established relationship between telomere shortening and life-span, our study highlights a clear risk of Pb contamination on the biota of the urban area, including humans.},
}

@article {pmid40544370,
year = {2025},
author = {Martin, C and Ruthsatz, K and Gomez-Mestre, I and Burraco, P},
title = {Growth but Not Corticosterone, Oxidative Stress, or Telomere Length Is Negatively Affected by Microplastic Exposure in a Filter-Feeding Amphibian.},
journal = {Journal of experimental zoology. Part A, Ecological and integrative physiology},
volume = {},
number = {},
pages = {},
doi = {10.1002/jez.70005},
pmid = {40544370},
issn = {2471-5646},
support = {//The German Research Foundation (DFG) project (533973724); a new actor on the stage of global change: A multi-level perspective on the toxicity of microplastics pollution in amphibians) supported C.M. and K.R. Ramón y Cajal Fellowship RYC 2023-044964-I (Spanish Ministry of Science and Innovation) supported P.B./ ; },
abstract = {Microplastics (MPs) are of increasing global concern for species inhabiting aquatic habitats. However, the mechanisms behind animal responses to MPs still require comprehensive exploration. Amphibians are the most threatened vertebrate group with most species having a complex life cycle, commonly with an aquatic larval stage. Here, we investigated whether exposure to an environmentally relevant concentration of MPs affects the growth of filter-feeding larvae of the African clawed frog (Xenopus laevis), and the consequences for their stress physiology (corticosterone [CORT] levels), or health and ageing physiology (oxidative stress and telomere length, the latter in the liver and gut). We conducted a 3 × 2 experiment with three levels of fiber exposure (fibers absent -control-, and MP and cellulose fiber treatments), and two stress levels (CORT absent -control-, and CORT present simulating a stressful condition). We observed a negative impact of MP exposure on larval growth; however, this did not alter the CORT levels, oxidative stress. or telomere length. Our study shows that realistic concentrations of MPs are not enough to induce major alterations on the stress or health and ageing physiology of a filter-feeding amphibian. Whether compensatory growth responses during the post-metamorphic stages could lead to detrimental effects later in life should be explored in amphibians and other organisms with complex life cycles.},
}

@article {pmid40540389,
year = {2025},
author = {Huang, YC and Lu, HY and Zhang, L and Olivier, A and Wu, TL and Hsu, CY and LeGrand, C and Zeng, H and Curran, S and Wang, Q and Nannapaneni, R and Zhang, X and Ticó, M and Mariotti, M and Wu, RTY and Combs, GF and Cheng, WH},
title = {Dietary Selenium Deficiency Accelerates the Onset of Aging-Related Gut Microbial Changes in Aged Telomere-Humanized Mice, With Akkermansia muciniphila Being the Most Prominent and Alleviating Selenium Deficiency-Induced Type 2 Diabetes.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e70130},
doi = {10.1111/acel.70130},
pmid = {40540389},
issn = {1474-9726},
support = {DK117407/NH/NIH HHS/United States ; 3062-51000-050-00D//Agricultural Research Service/ ; },
abstract = {Previous studies have shown that dietary selenium (Se) deficiency in mice reshapes gut microbiota, exacerbates healthspan deterioration (e.g., type 2 diabetes), and paradoxically activates beneficial longevity pathways. This study demonstrated that dietary Se deficiency accelerated many age-related gut microbial changes in aged telomere-humanized C57BL/6J diabetic mice in a sexually dimorphic manner, with Akkermansia muciniphila showing the greatest enrichment in males. However, dietary Se deficiency did not enrich A. muciniphila in mature or middle-aged male C57BL/6J wild-type mice. Oral gavage of A. muciniphila alleviated Se deficiency-induced type 2 diabetes-like symptoms, reversed mucosal barrier dysfunction and gut inflammation, and resulted in a trend of symbiotic and competitive suppression changes in certain gut bacteria in mature wild-type mice under conventional conditions. The beneficial effects of A. muciniphila appeared to be independent of selenoproteins sensitive to dietary Se deficiency, such as GPX1, SELENOH, and SELENOW, in the liver and muscle. Altogether, these results show that dietary Se deficiency accelerates age-related A. muciniphila enrichment specifically in aged male mice with severe insulin resistance and pancreatic senescence, indicating a potential hormetic response to Se deficiency through reshaped gut microbiota, which alleviates hyperglycemia and partially compensates for healthspan decline.},
}

@article {pmid40539277,
year = {2025},
author = {Sharma, A and Sowpati, DT},
title = {Analysis of tandem repeats in seven telomere-to-telomere primate genomes.},
journal = {Journal of genetics},
volume = {104},
number = {},
pages = {},
pmid = {40539277},
issn = {0973-7731},
mesh = {Animals ; *Telomere/genetics ; Humans ; *Primates/genetics ; *Tandem Repeat Sequences/genetics ; *Genome ; High-Throughput Nucleotide Sequencing ; Evolution, Molecular ; Y Chromosome/genetics ; },
abstract = {Tandem repeats (TRs) are highly polymorphic low complexity regions present in all the genomes. The length variation in TRs, particularly that of short TRs (STRs), is associated with several cellular functions such as gene expression and genome organization. In humans, an abnormal expansion of a few STR loci is linked to neurodegenerative diseases. Despite their importance, limitations and gaps in reference genomes prohibit the comprehensive analysis of TRs. Recent advances in high-throughput sequencing technologies have enabled the generation of gapless, telomere-to-telomere (T2T) genomes of humans and other ape species. Here, we report the TR landscape of seven primate T2T genomes, including humans. Our analysis indicates that TRs of 1-100 nucleotide (nt) motifs cover 3.5-6.9% of large primate genomes, with the highest density observed in gorilla (69 kb per Mbp). Large motif size TRs are prevalent and contribute abundantly to higher-order repeats. As an example, we describe a species-specific 32 nt A/T rich motif that contributes to subtelomeric repeats. Finally, we present the motif decomposition and substructure of pentameric repeats in Y chromosomes of six ape species. Our work illutrates the dynamics of TRs in large genomes, and showcases the utility of complete genomes for better understanding the role of low complexity sequences.},
}

Animals
*Telomere/genetics
Humans
*Primates/genetics
*Tandem Repeat Sequences/genetics
*Genome
High-Throughput Nucleotide Sequencing
Evolution, Molecular
Y Chromosome/genetics

@article {pmid40537010,
year = {2025},
author = {Zhang, Q and Xu, C and Fan, J and Lou, C and Chen, J and Zhang, J and Mo, J},
title = {Telomere length as a predictive marker for long-term cognitive function in a mouse model of subarachnoid hemorrhage.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-24-01150},
pmid = {40537010},
issn = {1673-5374},
abstract = {Subarachnoid hemorrhage is a subtype of stroke that causes severe neurological damage and is associated with poor long-term prognosis. Cognitive impairment is a major manifestation of long-term neurological dysfunction in patients with subarachnoid hemorrhage. However, there is notable absence of biological markers to predict long-term prognosis in this patient population. Given the aging-like neurocognitive phenomena associated with subarachnoid hemorrhage, this study postulates that telomere length, a recognized biomarker for aging, could be used as a prognostic indicator for subarachnoid hemorrhage. A left internal carotid artery intravascular puncture mouse model was used to simulate subarachnoid hemorrhage. Comprehensive neurological test scores were obtained through neurobehavioral assessments conducted at one-month intervals. Concurrently, the relative telomere length was analyzed by quantitative polymerase chain reaction, which was performed using DNA extracted from ear notch and brain tissue after each assessment. Furthermore, proteomic analysis was employed to investigate differential protein expression in hippocampal tissue. Subarachnoid hemorrhage mice exhibited persistent neurocognitive impairment over a prolonged period of time. There was a significant positive correlation between telomere length and neurological test scores, confirming the usefulness of telomere length as a prognostic indicator in subarachnoid hemorrhage. Hippocampal tissue from subarachnoid hemorrhage mice showed reduced expression of acetyl-coenzyme A synthetase-2 and abnormalities in the expression of proteins related to ribosomes, energy metabolism, and cellular signal transduction. This study confirmed telomere shortening in the brain and metabolic disturbances in the hippocampi of subarachnoid hemorrhage mice. Thus, telomere length is a predictive marker for long-term impairment of cognitive function in mice following experimental subarachnoid hemorrhage.},
}

@article {pmid40536886,
year = {2025},
author = {Yadav, HK and Singh, N and Singh, B and Kaur, V and Sawant, SV},
title = {Telomere-to-telomere genome assembly of linseed (Linum usitatissimum L.) for functional genomics and accelerated genetic improvement.},
journal = {Plant biotechnology journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/pbi.70183},
pmid = {40536886},
issn = {1467-7652},
support = {//Department of Biotechnology, Ministry of Science and Technology, India/ ; },
abstract = {Linseed (Linum usitatissimum L.), a member of the Linaceae family, is a versatile crop valued for its oil, fibre, nutritional and medicinal applications. Recognized as a superfood, linseed is rich in omega-3 fatty acid (~55%), lignans, high-quality proteins, dietary fibre and bioactive secondary metabolites. Previously published genome assemblies of linseed are quite fragmented and non-contiguous. In this study, we present a telomere-to-telomere (T2T) chromosome-scale genome assembly of the Indian linseed variety T397 using advanced sequencing approaches. The assembly comprises ~595 Mb of genomic sequences, with a scaffold N50 of 32.86 Mb, spanning 15 chromosomes, including 29 telomeres and 15 centromeres. A total of 34 572 protein-encoding genes were predicted with an average length of 2980.7 bp and an average of 5.0 exons per gene. Gene family analysis determines a considerable number of unique genes in linseed and its close relationship with Manihot esculenta and Ricinus communis. The higher expression of oleosin and FAD3 genes in linseed highlights their roles in oil accumulation and enrichment for omega-3 fatty acid. The metabolites found in the seeds were enriched for the biosynthesis of unsaturated fatty acids. Various potential key structural genes and transcription factors that regulate oil metabolism especially unsaturated fatty acids biosynthesis has been identified. Overall, the present study provides the potential genomic resources for accelerated genetic studies and improvement of linseed.},
}

@article {pmid40533492,
year = {2025},
author = {Zhou, Y and Chen, C and Fang, D and Wang, C and Peng, Y and Wang, B and Zhang, M and You, Y and Liu, Y and Deng, G and Jian, J and Xu, D},
title = {Telomere-to-telomere genome assembly of Phoxinus lagowskii.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {1025},
pmid = {40533492},
issn = {2052-4463},
mesh = {*Telomere/genetics ; *Genome ; Animals ; DNA Transposable Elements ; *Cyprinidae/genetics ; },
abstract = {As an important economic and ecological fish, Amur minnow (Phoxinus lagowskii) plays a significant role in food products as well as evolutionary, ecological research. However, a high-quality chromosome-level genome of P. lagowskii is not currently available. In this study, we report a T2T (Telomere-to-telomere) genome for P. lagowskii with chromosome-level. The finally assembled genome size is 1.04 G, with a contig N50 of 41.7 Mb, comprising 25 chromosomes. The transposable elements constituted 512.40 Mb (49.22%) of the assembled P. lagowskii genome, with DNA transposons 25.02% being the predominant repeat type. A total of 2,4610 protein-coding genes were predicted in P. lagowskii genome, with 99.96% of these genes being functionally annotated. The identification of telomeres, BUSCO assessment, mapping coverage, and sequencing depth collectively demonstrated the high quality of the genome assembly. The T2T genomic information serves as an invaluable resource for studies in evolution, comparative genomics, fish breeding applications, and ecological research.},
}

*Telomere/genetics
*Genome
Animals
DNA Transposable Elements
*Cyprinidae/genetics

@article {pmid40531666,
year = {2025},
author = {Liu, F and Li, Y and Wang, G and Zhang, D and Yang, X and Zhou, C and Zhou, R and Liu, H},
title = {The telomere-to-telomere gapless genome of grass carp provides insights for genetic improvement.},
journal = {GigaScience},
volume = {14},
number = {},
pages = {},
doi = {10.1093/gigascience/giaf059},
pmid = {40531666},
issn = {2047-217X},
support = {2024B03J1082//Guangzhou Key R&D Program/ ; U23A20249//National Natural Science Foundation of China/ ; },
mesh = {*Carps/genetics ; Animals ; *Telomere/genetics ; *Genome ; Molecular Sequence Annotation ; Genomics/methods ; Centromere/genetics ; Chromosomes/genetics ; },
abstract = {BACKGROUND: The grass carp (Ctenopharyngodon idella) is a large herbivorous freshwater fish belonging to the Cyprinidae family. It is widely cultivated as a food source in China and is renowned as one of the Four Great Domestic Fishes. Despite its economic importance, the published genome assemblies of grass carp remain incomplete due to gaps, thereby hindering molecular research and genetic improvement.

RESULTS: In this study, we report the assembly of a telomere-to-telomere (T2T) gap-free genome of the grass carp with total length of 890,918,310 bp for 24 chromosomes without gaps, representing the highest completeness and assembly quality to date. Our assembly contains 27,446 protein-coding genes, and 93.04% of all were annotated with multiple databases, with 48 telomeres and 24 centromeres characterized. Gap-free reference genomes enable us to study the structure of centromeres and identify conserved centromere-specific satellite motifs for grass carp. Furthermore, we identified 108 gene-related gaps across 12 chromosomes and 38 structural variations across 17 chromosomes in this T2T assembly.

CONCLUSIONS: The validated gap-free genome provides invaluable resource for future genomic studies grass carp, offering new insights into its genetic architecture and evolutionary dynamics.},
}

*Carps/genetics
Animals
*Telomere/genetics
*Genome
Molecular Sequence Annotation
Genomics/methods
Centromere/genetics
Chromosomes/genetics

@article {pmid40531189,
year = {2025},
author = {Roy, S and Azzalin, CM},
title = {Reading the DNA of telomeres.},
journal = {eLife},
volume = {14},
number = {},
pages = {},
pmid = {40531189},
issn = {2050-084X},
mesh = {*Telomere/genetics/metabolism ; Humans ; *DNA Damage ; *DNA/metabolism/genetics ; Neoplasms/genetics ; },
abstract = {Experiments with tools designed to detect DNA damage reveal unique and conserved features of telomeres in cancer cells.},
}

*Telomere/genetics/metabolism
Humans
*DNA Damage
*DNA/metabolism/genetics
Neoplasms/genetics

@article {pmid40530773,
year = {2025},
author = {Zhou, J and Antinori, ME and Bellotti, G and Chalot, M and Puglisi, E},
title = {Telomere-to-telomere genome assembly of Talaromyces purpureogenus strain ISA502 isolated from maize rhizosphere.},
journal = {Microbiology resource announcements},
volume = {},
number = {},
pages = {e0012225},
doi = {10.1128/mra.00122-25},
pmid = {40530773},
issn = {2576-098X},
abstract = {We present a telomere-to-telomere genome assembly of Talaromyces purpureogenus strain ISA502, isolated from the maize rhizosphere. The 30.33 Mb genome, assembled using hybrid sequencing, comprises 8 chromosomes with 99% BUSCO completeness, offering improved resolution over existing fragmented genomes and advancing studies on its ecological and biotechnological significance.},
}

@article {pmid40530700,
year = {2025},
author = {Smoom, R and May, CL and Lichtental, D and Bar-Ness, K and Rangel, R and Khoury, J and Nachmani, D and Avrahami, D and Ahangari, F and Skordalakes, E and Kaminski, N and Kaestner, KH and Tzfati, Y},
title = {Separation of telomere protection from length regulation by two different point mutations at amino acid 492 of RTEL1.},
journal = {Nucleic acids research},
volume = {53},
number = {11},
pages = {},
doi = {10.1093/nar/gkaf507},
pmid = {40530700},
issn = {1362-4962},
support = {2071/18//Israel Science Foundation/ ; 1342/23//Israel Science Foundation/ ; 2166/24//Israel Science Foundation/ ; 1R01DK139049-01/DK/NIDDK NIH HHS/United States ; R01-CA249929/DK/NIDDK NIH HHS/United States ; U01-DK-134995/DK/NIDDK NIH HHS/United States ; R01-HL-127349/DK/NIDDK NIH HHS/United States ; R01-HL-141852/DK/NIDDK NIH HHS/United States ; //Israel-UK-Palestine GROWTH/ ; },
mesh = {Animals ; Mice ; *Point Mutation ; *Telomere/genetics/metabolism ; *DNA Helicases/genetics/metabolism ; *Telomere Homeostasis/genetics ; Humans ; Microcephaly/genetics/pathology ; DNA Damage ; Intellectual Disability/genetics/pathology ; Disease Models, Animal ; X-Linked Intellectual Disability/genetics/pathology ; Growth Disorders/genetics/pathology ; Dyskeratosis Congenita/genetics/pathology ; Limb Deformities, Congenital/genetics/pathology ; Hematopoiesis/genetics ; Lung/pathology ; Amino Acid Substitution ; Fetal Growth Retardation ; },
abstract = {RTEL1 is an essential DNA helicase that plays multiple roles in genome stability and telomere length regulation. The ultra-long telomeres of the house mouse hinder its utility as a model for telomere-related diseases. We have previously generated a mouse model with human-length telomeres, termed "Telomouse," by substituting methionine 492 of mouse Rtel1 to a lysine (Rtel1M492K). In humans, a methionine to isoleucine mutation at this position causes the fatal telomere biology disorder Hoyeraal-Hreidarsson syndrome (HHS). Here, we introduced the Rtel1M492I point mutation into the mouse genome, generating another mouse model, which we termed "HHS mouse." The HHS mouse telomeres are not as short as those of the Telomouse but nevertheless display higher levels of telomeric DNA damage, fragility, and recombination, associated with anaphase bridges and micronuclei. The HHS mouse also exhibits aberrant hematopoiesis and pre-fibrotic alterations in the lung. These observations indicate that the two mutations at the same codon separate critical functions of RTEL1: Rtel1M492K mainly reduces the telomere length setpoint, while Rtel1M492I predominantly disrupts telomere protection. The two mouse models enable dissecting the mechanistic roles of RTEL1 and the different contributions of short telomeres and DNA damage to telomere biology disorders and genomic instability.},
}

Animals
Mice
*Point Mutation
*Telomere/genetics/metabolism
*DNA Helicases/genetics/metabolism
*Telomere Homeostasis/genetics
Humans
Microcephaly/genetics/pathology
DNA Damage
Intellectual Disability/genetics/pathology
Disease Models, Animal
X-Linked Intellectual Disability/genetics/pathology
Growth Disorders/genetics/pathology
Dyskeratosis Congenita/genetics/pathology
Limb Deformities, Congenital/genetics/pathology
Hematopoiesis/genetics
Lung/pathology
Amino Acid Substitution
Fetal Growth Retardation

@article {pmid40527455,
year = {2025},
author = {Kletkiewicz, H and Kowalski, K and Kęsy, J and Trzeciak, P and Nowak, A and Jefimow, M and Przybylska-Piech, A},
title = {Unpredictable warm spells in winter increase blood cortisol level but lengthen telomeres in a seasonal rodent Phodopus sungorus.},
journal = {Proceedings. Biological sciences},
volume = {292},
number = {2049},
pages = {20250819},
doi = {10.1098/rspb.2025.0819},
pmid = {40527455},
issn = {1471-2954},
mesh = {Animals ; *Phodopus/physiology/blood/genetics ; Seasons ; *Hydrocortisone/blood ; Photoperiod ; Male ; *Telomere ; Stress, Physiological ; *Telomere Shortening ; Female ; },
abstract = {Global warming and the increased frequency of unpredictable weather events may disrupt the proper timing of seasonal adjustments of a phenotype. This may lead to the deterioration of the animal's condition and shorten its lifespan. We tested whether warm spells in winter affect the baseline and stress-induced cortisol level and leukocyte relative telomere length in two winter phenotypes of Siberian hamster, Phodopus sungorus, responding and non-responding to short photoperiod. We found that both phenotypes increased cortisol levels in winter and that warm spells augmented this response. Under stable cold conditions, non-responding individuals were more vulnerable to short-term stress than responding ones. However, telomere length increased, suggesting that animals have a high potential to cope with stress and prevent telomere shortening or that these two variables are not directly related. In responding individuals, the higher incidence of torpor also prevented telomeres shortening. These results indicate that both phenotypes, responding and non-responding to short photoperiod, can overcome the challenges posed by an unpredictably changing environment.},
}

Animals
*Phodopus/physiology/blood/genetics
Seasons
*Hydrocortisone/blood
Photoperiod
Male
*Telomere
Stress, Physiological
*Telomere Shortening
Female

@article {pmid40524536,
year = {2025},
author = {Duque, A and Lin, J and Jeliffe-Pawlowski, L and Coleman-Phox, K and Rand, L and Wojcicki, JM},
title = {Leukocyte telomere length and birth characteristics associated with obesity in infancy in a predominantly Latinx cohort.},
journal = {Pediatric obesity},
volume = {},
number = {},
pages = {e70034},
doi = {10.1111/ijpo.70034},
pmid = {40524536},
issn = {2047-6310},
support = {//Preterm Birth Inititiatve (PTBi)/ ; //Little Giraffe Foundation/ ; },
abstract = {BACKGROUND: Previous studies suggest that in utero exposures may impact future weight gain trajectories in infancy. Leukocyte telomere length (LTL) collected at birth may be an additional variable to test in models for childhood obesity as adult studies suggest that LTL may be predictive of metabolic disease.

METHODS: Using a primarily Latinx mother-child longitudinal cohort design, we assessed the relationship between newborn LTL measured via quantitative PCR and obesity at 12 months (WFA ≥ 95th percentile). Secondary outcomes included weight-for-age (WFA) Z scores at 12 months and covariates included birth anthropometrics and maternal prenatal health. Logistic and linear regression models were used to assess independent predictors for infant obesity and WFA Z scores.

RESULTS: We followed 302 children until 12 months including 65.89% with Latinx ethnicity and 4.97% had obesity at 12 months. Independent predictors of obesity at 12 months included higher birthweight Z scores (OR 2.24, 1.16, 5.05) and WFA Z scores at 6 months (OR 1.56, 1.19, 2.05). Longer LTL at birth and higher Apgar scores at 5 min were protective (OR 0.04, 95%CI 0.002, 0.79 and OR 0.30, 95%CI 0.13-0.72, respectively). LTL at birth was negatively associated with WFA Z scores at 12 months of age in multivariable models (Coeff = -0.58, 95%CI -1.05, -0.12).

CONCLUSIONS: LTL at birth may be a marker, in addition to birthweight, that can be used to assess an infant's risk for subsequent obesity. Future studies are needed to better assess and determine possible maternal exposures associated with shorter newborn LTL.},
}

@article {pmid40523014,
year = {2025},
author = {Kumawat, S and Shametov, A and Valeeva, LR and Ju, Y and Martinez, I and Logeswaran, D and Chen, H and Coughlan, JM and Chen, JJ and Yuan, YW and Sobel, JM and Koo, DH and Shakirov, EV and Choi, JY},
title = {Monkeyflower (Mimulus) uncovers the evolutionary basis of the eukaryote telomere sequence variation.},
journal = {PLoS genetics},
volume = {21},
number = {6},
pages = {e1011738},
pmid = {40523014},
issn = {1553-7404},
mesh = {*Telomere/genetics ; *Evolution, Molecular ; Telomerase/genetics ; Phylogeny ; RNA/genetics ; Genetic Variation ; In Situ Hybridization, Fluorescence ; Transcriptome ; Eukaryota/genetics ; },
abstract = {Telomeres are nucleoprotein complexes with crucial role of protecting chromosome ends. Because of its vital functions, components of the telomere, including its sequence, should be under strong evolutionary constraint. Yet across the tree of life there are numerous examples of telomere sequence variation and the evolutionary mechanism driving this diversification is unclear. Here, we studied the telomeres in Mimulus by investigating the noncoding telomerase RNA (TR), which is a core component of the telomere maintenance complex and determines the telomere sequence in eukaryotes. We conducted de novo transcriptomics and genome analysis of 18 species, and discovered Mimulus has evolved at least three different telomere sequences: (AAACCCT)n, (AAACCCG)n, and (AAACCG)n. We discovered several species with TR duplications, implying functional consequences that could influence telomere evolution. For instance, M. lewisii harbored two sequence-divergent TR paralogs while its sister species the paralog had pseudogenized. Nanopore-sequencing and fluorescence in situ hybridization indicated M. lewisii had a sequence heterogeneous telomere, and Telomeric Repeat Amplification Protocol combined with Terminal Restriction Fragment analysis confirmed the telomerase can use both TR paralogs for telomere synthesis. Interestingly in closely related species M. cardinalis, TR was also duplicated and both paralogs were expressed but its telomere consisted of a single telomere repeat. Evolutionary analysis indicated the TR paralogs arose from an ancient duplication, which also underlies the evolutionary origin of multiple Mimulus species with divergent telomere sequences. We propose sequence variation in eukaryotic telomeres arises from an evolutionary process involving TR duplication, sequence divergence, and loss of TR paralog.},
}

*Telomere/genetics
*Evolution, Molecular
Telomerase/genetics
Phylogeny
RNA/genetics
Genetic Variation
In Situ Hybridization, Fluorescence
Transcriptome
Eukaryota/genetics

@article {pmid40519641,
year = {2025},
author = {Zhang, H and Audry, J and Runge, KW},
title = {A Chromosome End Without Terminal Telomere Repeats is Stable for Multiple Cell Divisions.},
journal = {microPublication biology},
volume = {2025},
number = {},
pages = {},
pmid = {40519641},
issn = {2578-9430},
abstract = {We have formed new short telomeres in Schizosaccharomyces pombe using an inducible nuclease that cuts near telomere repeats in cells that lack, cannot recruit or cannot fully activate telomerase. Sequencing these new telomeres showed that cells can divide at least 4 times with ~30 bp of non-telomeric sequence at the chromosome end in cells lacking telomerase, which contrasts with current models for the roles of terminal single-stranded telomere repeats and the telomere proteins in telomere protection and replication. Cells that cannot recruit or activate telomerase had similar results, with additional terminal truncations or telomere repeat addition.},
}

@article {pmid40515885,
year = {2025},
author = {Jiang, Y and Liu, J and Pan, B and Yu, S and Hu, C and Li, Q and Cheng, H and Chen, L and Jiang, M and Xu, D and Wang, C and Yan, J},
title = {Prediction of lung adenocarcinoma prognosis and clinical treatment efficacy by telomere-associated gene risk model.},
journal = {Discover oncology},
volume = {16},
number = {1},
pages = {1102},
pmid = {40515885},
issn = {2730-6011},
support = {ZYTS-80//Teaching reform project of Southwest Medical University/ ; Q20015//Youth Innovation Research Project of Sichuan Province in 2020/ ; },
abstract = {BACKGROUND: The most prevalent cause of cancer-related death in China and across the globe is lung adenocarcinoma (LUAD). Telomere shortening (TS) has been found to contribute to the development of LUAD. Therefore, our aim is to investigate the impact of telomere-related genes (TRGs) on immunotherapy and clinical prognosis prediction in LUAD.

MATERIALS AND METHODS: TRGs were obtained from TelNet, while RNA-seq and clinical information were retrieved from the GEO and TCGA databases. TelNet preserves a series of genes known to be engaged in telomere maintenance and also provides information on the type of telomere maintenance mechanism in which the gene is involved. Data pertinent to RNA sequencing and clinical parameters were accessed from two widely-accessed electronic repositories- the GEO and TCGA databases, respectively. We conducted univariate Cox regression analysis in order to recognize prognostic TRGs and employed multivariate Cox regression analysis to develop a risk model for these TRGs. The patients were stratified into high-risk and low-risk groups based on the first quartile of the risk score. The predictive ability and stability of the model were subsequently verified through Kaplan-Meier analysis, ROC curve, and C-index. We investigated the immune landscapes of different risk groups and predicted their responses to immunotherapy. Lastly, we evaluated the sensitivity of different groups to commonly used chemotherapeutic and targeted drugs through drug sensitivity analysis.

RESULTS: Univariate Cox analysis identified 12 prognostic TRGs, while a signature consisting of 4 prognostic TRGs was constructed through multivariate Cox analysis. Survival analysis indicated a significantly shorter survival time in the high-risk group. The predictive immunotherapy analysis suggested that patients in the high-risk group may have a more favorable response to immunotherapy. Finally, we identified 28 appropriate chemotherapeutic and 51 targeted drugs for different patient groups.

CONCLUSION: The study has successfully developed a prognostic model for LUAD prediction that takes into account TRGs and predicts both prognosis and response to immunotherapy.},
}

@article {pmid40502707,
year = {2025},
author = {Gong, Y and Wang, Y and Delgado-Peraza, F and Nogueras-Ortiz, C and Noren Hooten, N and Croteau, DL and Temre, M and Molnar, AE and Bodogai, M and Zou, A and Abdelmohsen, K and Zhu, W and Zhang, Y and Gorospe, M and Weng, NP and Evans, MK and Kapogiannis, D and Liu, Y},
title = {Telomere attrition alters extracellular vesicles conferring adverse impacts on neuronal viability and inflammatory response.},
journal = {iScience},
volume = {28},
number = {6},
pages = {112661},
pmid = {40502707},
issn = {2589-0042},
abstract = {Telomere shortening is a hallmark of aging associated with various diseases, yet its impact on extracellular vesicles (EVs) remains poorly understood. We investigated EV abundance, size, cargo content, and functional implications in a human aging cohort and the telomerase reverse transcriptase null (Tert [-/-]) mice. Human plasma EVs showed reduced telomeric DNA cargo with age. In generation 3 (G3) Tert [-/-]mice with shortened telomeres, we observed a significant reduction in plasma EV concentration and tissue-specific changes in EV levels and telomeric DNA content. Proteomic analysis revealed altered protein levels related to inflammation and lipid metabolism in plasma- and tissue-derived EVs. Functionally, EVs from G3 Tert [-/-]mice stimulated a pro-inflammatory response in bone marrow-derived macrophages and exhibited neurotoxic effects on primary cultured neurons. These findings highlight the intricate interplay between telomere shortening and EV biology, underscoring the potential of EVs as intercellular mediators, biomarkers, and therapeutic targets for conditions associated with telomere loss.},
}

@article {pmid40501906,
year = {2025},
author = {Spindler, J and Pandolfo, F and Koch, AE and Piccirillo, P and Bihler, J and Morgenstern, M and Buschbaum, S and Coon, J and Hänsel-Hertsch, R and Mehta, KPM and Panier, S},
title = {SLX4IP acts in parallel to FANCM to limit BLM-dependent replication stress at ALT telomeres.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.05.28.656696},
pmid = {40501906},
issn = {2692-8205},
abstract = {UNLABELLED: Alternative Lengthening of Telomeres (ALT) is a telomerase-independent telomere maintenance mechanism that enables cancer cells to gain unlimited replicative capacity. ALT relies on recombination-mediated telomere elongation and is promoted by telomeric replication stress. However, ALT requires strict regulation, as excessive replication stress or recombination are cytotoxic. Central to ALT is the RecQ helicase BLM, which regulates telomeric replication stress and promotes telomere recombination and DNA synthesis. Despite its key role in the ALT pathway, BLM must be tightly regulated to prevent deleterious outcomes. Here, we identify SLX4IP as a key suppressor of BLM-driven replication stress at ALT telomeres. Loss of SLX4IP in ALT-positive cells leads to BLM-dependent telomeric replication stress and impaired replication fork progression. Mechanistically, SLX4IP limits the unwinding of unligated Okazaki fragments by BLM on the lagging strand during telomere replication. This reduces the formation of toxic 5' DNA flaps and prevents hyperactivation of ATR signalling and deleterious recombination levels. We also uncover a synthetic lethal interaction between SLX4IP and FANCM, an ATPase/translocase that is a known regulator of BLM at telomeric replication forks in ALT cells. We demonstrate that SLX4IP and FANCM act in parallel to restrain BLM activity, thereby maintaining the balance of replication stress and recombination that is necessary for productive ALT. These findings reveal a vulnerability in ALT-positive cancers lacking SLX4IP and establish SLX4IP as a potential biomarker for therapeutic strategies targeting FANCM.

HIGHLIGHTS: SLX4IP depletion activates the replication stress response at ALT telomeresSLX4IP acts in parallel to FANCM to limit replication stress at ALT telomeresThe synthetic lethal interaction between SLX4IP and FANCM is dependent on BLMSLX4IP depletion causes BLM-dependent lagging-strand replication stress.},
}

@article {pmid40499086,
year = {2025},
author = {Kimball, TN and Prapiadou, S and Tack, RWP and Yong-Qiang Tan, B and Senff, JR and Kourkoulis, C and Singh, S and Rosand, J and Anderson, CD},
title = {Association of Leucocyte Telomere Length With Stroke, Dementia, and Late-Life Depression: The Role of Modifiable Risk Factors.},
journal = {Neurology},
volume = {105},
number = {1},
pages = {e213794},
pmid = {40499086},
issn = {1526-632X},
mesh = {Humans ; Female ; Male ; Risk Factors ; Middle Aged ; *Leukocytes ; *Stroke/epidemiology/genetics ; Aged ; *Dementia/epidemiology/genetics ; *Depression/genetics/epidemiology ; Mendelian Randomization Analysis ; *Telomere ; United Kingdom/epidemiology ; Incidence ; },
abstract = {BACKGROUND AND OBJECTIVES: Stroke, dementia, and late-life depression (LLD) are age-related brain diseases that pose significant public health challenges and costs. Leucocyte telomere length (LTL) is a biological aging marker influenced by both genetic and lifestyle factors. The aim of our study was to determine the association between LTL and these diseases. We further investigated whether modifying risk factors of age-related brain disease, as measured using the Brain Care Score (BCS), mitigates LTL associations.

METHODS: We analyzed participants from the UK Biobank with available LTL and risk factor information. We examined LTL's associations with stroke, dementia, and LLD, individually and as a composite outcome, using continuous measures and tertile stratification. Disease risks were evaluated through cumulative incidence curves, incidence rates per 1,000 person-years, and adjusted Cox models. Risk comparisons across LTL tertiles were stratified by risk factor profiles, with high BCS (≥15) indicating healthier lifestyle choices and low BCS (≤10) reflecting less optimal lifestyle choices. Mendelian randomization (MR) was used to test causal associations.

RESULTS: The study included 356,173 participants (median age 56 years; 53.69% female). Shorter LTL was consistently associated with higher incidence rates across all outcomes. Participants in the shortest LTL tertile had elevated risks of the composite outcome (hazard ratio [HR] 1.11; 95% CI 1.08-1.15), stroke (HR 1.08; 95% CI 1.02-1.15), dementia (HR 1.19; 95% CI 1.12-1.26), and LLD (HR 1.14; 95% CI 1.09-1.18). Individuals with both shorter LTL and lower BCS faced significantly increased risks of age-related brain diseases (HR 1.11; 95% CI 1.07-1.16) and individually for stroke (HR 1.10; 95% CI 1.02-1.19), dementia (HR 1.17; 95% CI 1.08-1.28), and LLD (HR 1.13; 95% CI 1.07-1.19). Conversely, individuals with higher BCS within the shortest LTL group did not show a significant increase in risk of any age-related brain diseases. MR analyses did not identify causal relationships between LTL and these outcomes.

DISCUSSION: Individuals with shorter LTL are at increased risk of stroke, dementia, and LLD. Improved modifiable risk factor profiles seem to mitigate the impact of LTL on these diseases. Future research should explore the effectiveness of lifestyle interventions in mitigating adverse biological aging effects on brain health.},
}

Humans
Female
Male
Risk Factors
Middle Aged
*Leukocytes
*Stroke/epidemiology/genetics
Aged
*Dementia/epidemiology/genetics
*Depression/genetics/epidemiology
Mendelian Randomization Analysis
*Telomere
United Kingdom/epidemiology
Incidence

@article {pmid40498073,
year = {2025},
author = {Couteau, F and Gagné, LM and Boulay, K and Rousseau, P and Carbonneau, M and McQuaid, M and Sharma, J and Sawchyn, C and Fernandez, E and Glatz, D and Rizk, R and Lalonde, ME and Mehrjoo, Y and Chu, TW and Moquin-Beaudry, G and Beauséjour, C and Sergeev, M and Costantino, S and Avizonis, D and Topisirovic, I and Jabado, N and Wurtele, H and Autexier, C and Mallette, FA},
title = {R-2-hydroxyglutarate-mediated inhibition of KDM4A compromises telomere integrity.},
journal = {Nucleic acids research},
volume = {53},
number = {11},
pages = {},
pmid = {40498073},
issn = {1362-4962},
support = {//Fondation de l'Hôpital Maisonneuve-Rosemont/ ; MOP-133442/CAPMC/CIHR/Canada ; GER-163050/CAPMC/CIHR/Canada ; MOP-133449/CAPMC/CIHR/Canada ; PJT-166130/CAPMC/CIHR/Canada ; RGPIN-2019-05082//Natural Sciences and Engineering Research Council of Canada/ ; RGPIN-2017-05227//Natural Sciences and Engineering Research Council of Canada/ ; //Terry Fox New Investigator Award/ ; //Terry Fox New Frontiers Program Project/ ; //Leukemia Lymphoma Society/ ; 18198//Cancer Research Society/ ; 24032//Cancer Research Society/ ; //Canada Foundation of Innovation/ ; //Dr. John R. and Clara M. Fraser Memorial Trust/ ; 116128//Terry Fox Foundation/ ; //McGill University/ ; //Fonds de Recherche du Québec - Santé/ ; //Cole Foundation/ ; //CRC/ ; },
mesh = {Humans ; *Glutarates/pharmacology/metabolism ; Isocitrate Dehydrogenase/genetics/metabolism ; *Jumonji Domain-Containing Histone Demethylases/antagonists & inhibitors/metabolism/genetics ; *Telomere/metabolism/drug effects/genetics ; Cellular Senescence/drug effects/genetics ; Histones/metabolism ; Cell Line, Tumor ; Tumor Suppressor Protein p53/metabolism/genetics ; Mutation ; },
abstract = {Mutation, deletion, or silencing of genes encoding cellular metabolism factors occurs frequently in human malignancies. Neomorphic mutations in isocitrate dehydrogenases 1 and 2 (IDH1/2) promoting the production of R-2-hydroxyglutarate (R-2HG) instead of α-ketoglutarate (αKG) are recurrent in human brain cancers and constitute an early event in low-grade gliomagenesis. Due to its structural similarity with αKG, R-2HG acts as an inhibitor of αKG-dependent enzymes. These include the JUMONJI family of lysine demethylases, among which KDM4A is particularly sensitive to R-2HG-mediated inhibition. However, the precise molecular mechanism through which inhibition of αKG-dependent enzymes by R-2HG promotes gliomagenesis remains poorly understood. Here, we show that treatment with R-2HG induces cellular senescence in a p53-dependent manner. Furthermore, expression of mutated IDH1R132H or exposure to R-2HG, which leads to KDM4A inhibition, causes telomeric dysfunction. We demonstrate that KDM4A localizes to telomeric repeats and regulates abundance of H3K9(me3) at telomeres. We show that R-2HG caused reduced replication fork progression, and that depletion of SMARCAL1, a helicase involved in replication fork reversal, rescues telomeric defects caused by R-2HG or KDM4A depletion. These results establish a model whereby IDH1/2 mutations cause R-2HG-mediated inhibition of KDM4A, leading to telomeric DNA replication defects, telomere dysfunction, and associated genomic instability.},
}

Humans
*Glutarates/pharmacology/metabolism
Isocitrate Dehydrogenase/genetics/metabolism
*Jumonji Domain-Containing Histone Demethylases/antagonists & inhibitors/metabolism/genetics
*Telomere/metabolism/drug effects/genetics
Cellular Senescence/drug effects/genetics
Histones/metabolism
Cell Line, Tumor
Tumor Suppressor Protein p53/metabolism/genetics
Mutation

@article {pmid40492114,
year = {2025},
author = {Zhang, Y and Fan, J and Zhao, J and Zhu, H and Xia, Y and Xu, H},
title = {A telomere-associated molecular landscape reveals immunological, microbial, and therapeutic heterogeneity in colorectal cancer.},
journal = {Frontiers in molecular biosciences},
volume = {12},
number = {},
pages = {1615533},
pmid = {40492114},
issn = {2296-889X},
abstract = {BACKGROUND: Colorectal cancer (CRC) ranks among the most prevalent malignancies of the gastrointestinal tract and remains a leading cause of cancer-related mortality worldwide. Although telomere biology has been increasingly implicated in immune modulation and tumor progression, its clinical significance in CRC remains poorly understood.

METHODS: We developed a telomere score, termed TELscore, by integrating transcriptomic and intratumoral microbiome profiles from publicly available colorectal cancer (CRC) cohorts. To comprehensively characterize TELscore subgroups, we performed pathway enrichment analysis, tumor immune microenvironment (TIME) profiling, and microbiome niche assessment. Whole-slide histopathological images (WSIs) and immunohistochemical (IHC) staining were utilized to visualize immune features, including tertiary lymphoid structures (TLSs), across subgroups. Patients were stratified into high and low TELscore categories, and the predictive robustness was validated across multiple independent training and validation cohorts. Chemotherapeutic drug sensitivity was evaluated using pharmacogenomic data from the Genomics of Drug Sensitivity in Cancer (GDSC) database. Furthermore, the predictive capacity of TELscore for immunotherapy response was independently assessed in an external cohort. Finally, single-cell RNA sequencing (scRNA-seq) analysis was conducted to further dissect the cellular landscape and immunological heterogeneity within the TME.

RESULTS: TELscore stratified patients into two biologically and clinically distinct subgroups. The high TELscore group, which exhibited significantly shorter DFS, showed marked enrichment of tumorigenic pathways such as EMT, along with a distinctly immunosuppressive TME. This was reflected by elevated ESTIMATE/TIDE scores and corroborated by CIBERSORT, which revealed increased infiltration of M0 macrophages and upregulation of immunosuppressive signatures. In contrast, the low TELscore group was enriched for cell cycle related pathways, including E2F targets and the G2/M checkpoint, and demonstrated higher infiltration of pro-inflammatory M1 macrophages. 16S rRNA sequencing further revealed a divergent intratumoral microbiome between subgroups, the high TELscore group harbored significantly greater relative abundance of Selenomonas and Lachnoclostridium, two pathogenic genera previously associated with colorectal tumorigenesis. Complementary histopathological assessment via WSI demonstrated a marked absence of intraTLSs in high TELscore tumors. From a therapeutic standpoint, high TELscore tumors exhibited reduced sensitivity to standard chemotherapeutic agents-including Fluorouracil, Irinotecan, Oxaliplatin, and Docetaxel-as reflected by elevated IC50 values. Conversely, these tumors demonstrated increased susceptibility to MAPK pathway inhibitors, such as Selumetinib and Trametinib. Notably, TELscore also served as a robust predictor of immunotherapy response, which was validated in the IMvigor210 cohort. Finally, scRNA analysis highlighted profound cellular and functional divergence between TELscore subgroups. We identified intensified intercellular communication between inflammatory macrophages and fibroblasts, reinforcing the presence of an immunosuppressive niche.

CONCLUSION: TELscore is a robust stratification tool that captures the interplay between tumor biology, immune characteristics, and microbial ecology in colorectal cancer. By identifying clinically relevant subtypes with distinct therapeutic vulnerabilities, TELscore offers a powerful framework to advance personalized treatment and precision oncology.},
}

@article {pmid40487781,
year = {2025},
author = {Mondolin, V and Karlsson, H and Perasto, L and Paunio, T and Vitikainen, E and Martens, DS and Karlsson, L and Tuulari, JJ and Kataja, EL},
title = {Associations of Leukocyte Telomere Length With Trait Resilience, Adverse Childhood Experiences, and Psychological Distress Among Expecting Parents in the FinnBrain Birth Cohort.},
journal = {Biological psychiatry global open science},
volume = {5},
number = {4},
pages = {100498},
pmid = {40487781},
issn = {2667-1743},
abstract = {BACKGROUND: Telomere attrition has previously been associated with mental health problems and adverse childhood experiences (ACEs). Resilience has been shown to protect against mental health problems even in the context of ACEs. In this study, we examined the associations between leukocyte telomere length (LTL), symptoms of psychological distress, ACEs, and trait resilience. We examined whether LTL mediates the negative effects of ACEs and whether trait resilience moderates the association between LTL and distress.

METHODS: The study population was drawn from the ongoing FinnBrain Birth Cohort Study and included 342 mothers and 339 fathers who had provided blood samples and questionnaire data during pregnancy. Questionnaire data included the Connor-Davidson Resilience Scale 10, Edinburgh Postnatal Depression Scale, Symptom Checklist-90, and Trauma and Distress Scale. Data analysis included regression analysis, mixed-methods models, and statistical evaluation.

RESULTS: ACEs were associated with depressive and anxiety symptoms. However, contrary to the initial hypothesis, LTL was not associated with ACEs or distress symptoms and thus did not mediate their association. Furthermore, resilience was not associated with LTL and did not moderate the possible association between LTL and distress symptoms.

CONCLUSIONS: We found no association between TL and ACEs, psychological distress, or trait resilience. The mild distress symptoms, limited exposure to high ACEs, and the predominantly moderate to high socioeconomic status in the sample may be relevant to interpreting these findings. Encouragingly, not all ACEs necessarily lead to telomere attrition.},
}

@article {pmid40484928,
year = {2025},
author = {Bai, J and Wang, M and Luo, Y and Duan, B and Yang, Y and Fu, Y and Li, S and Yang, Z and Zheng, P and Yu, T and Yin, X and Bai, H and Long, Q and Ma, Y},
title = {Tumor microenvironment remodeling with a telomere-targeting agent and its cooperative antitumor effects with a nanovaccine.},
journal = {Journal of nanobiotechnology},
volume = {23},
number = {1},
pages = {429},
pmid = {40484928},
issn = {1477-3155},
support = {82203034//National Natural Science Foundation of China/ ; 82073371//National Natural Science Foundation of China/ ; 202201AT070238//Science and Technology Project of Yunnan Province/ ; 2021-I2M-1-043//Chinese Academy of Medical Sciences Initiative for Innovative Medicine/ ; 202401BC070009//Major Project in Basic Research of Yunnan Province/ ; 202002AA100009//Yunnan Province Major Science and Technology Special Project/ ; },
mesh = {Animals ; *Tumor Microenvironment/drug effects ; Mice ; *Cancer Vaccines/pharmacology ; *Telomere/drug effects/metabolism ; Cell Line, Tumor ; Humans ; *Antineoplastic Agents/pharmacology ; Female ; Mice, Inbred BALB C ; Immunogenic Cell Death/drug effects ; Cell Proliferation/drug effects ; Nanoparticles/chemistry ; Myeloid-Derived Suppressor Cells/drug effects ; Nanovaccines ; },
abstract = {The nucleoside analogue 6-thio-2'-deoxyguanosine (6-thio-dG, also known as THIO) is a telomere-targeting agent with important clinical potency. It can selectively kill telomerase-positive tumor cells. We previously reported that THIO could successfully induce immunogenic cell death (ICD) in multiple mouse tumor cell lines. In this study, we further explored the potential impact of THIO on remodeling the tumor microenvironment, regulating anti-tumor immune responses, and its possible synergistic effects with other therapeutic methods, such as tumor vaccines. Our results showed that THIO could also induce ICD in various human tumor cell lines. The induction of ICD in tumor cells promoted the migration and maturation of antigen-presenting cells. Administration of THIO significantly inhibited the growth of established CT26 and TC-1 tumors in mice. Meanwhile, it enhanced the anti-tumor CTL response and reduced the levels of immunosuppressive myeloid-derived suppressor cells (MDSCs) in both the spleen and tumor tissues. Additionally, THIO had a direct inhibitory effect on the proliferation and differentiation of MDSCs. Moreover, when combined with bacterial biomimetic vesicles or a nanovaccine, such as THIO with BBV or different Q11-tumor antigen peptide nanofibers, it exhibited enhanced anti-tumor effects and immune responses compared to monotherapy in either "immune hot" TC-1 tumors or "immune cold" B16-F10 tumors. In summary, THIO has the ability to remodel the tumor microenvironment, exert a specific killing effect on tumor cells, and effectively cooperate with tumor vaccines. This broadens the anti-tumor mechanisms of THIO and provides a promising strategy for improving anti-tumor immunotherapies.},
}

Animals
*Tumor Microenvironment/drug effects
Mice
*Cancer Vaccines/pharmacology
*Telomere/drug effects/metabolism
Cell Line, Tumor
Humans
*Antineoplastic Agents/pharmacology
Female
Mice, Inbred BALB C
Immunogenic Cell Death/drug effects
Cell Proliferation/drug effects
Nanoparticles/chemistry
Myeloid-Derived Suppressor Cells/drug effects
Nanovaccines

@article {pmid40483557,
year = {2025},
author = {She, H and Liu, Z and Xu, Z and Zhang, H and Wu, J and Cheng, F and Wang, X and Qian, W},
title = {A complete telomere-to-telomere assembly of Spinacia oleracea genome reveals Y chromosome evolution and centromere landscape.},
journal = {Plant communications},
volume = {},
number = {},
pages = {101410},
doi = {10.1016/j.xplc.2025.101410},
pmid = {40483557},
issn = {2590-3462},
}

@article {pmid40481860,
year = {2025},
author = {de Mendonça Nunes, B and Nunes de Oliveira, MB and da Silva Dantas, FJ and de Souza da Fonseca, A},
title = {Low-power red laser and ultraviolet A LED irradiation reduces mRNA levels from telomere maintenance genes in Saccharomyces cerevisiae.},
journal = {Lasers in medical science},
volume = {40},
number = {1},
pages = {260},
pmid = {40481860},
issn = {1435-604X},
mesh = {*Saccharomyces cerevisiae/radiation effects/genetics ; *RNA, Messenger/metabolism/genetics ; *Low-Level Light Therapy ; *Ultraviolet Rays ; *Telomere/radiation effects/genetics ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; },
abstract = {Therapeutic protocols based on photobiomodulation (PBM) have been used for treatment of clinical conditions, such as wounds, pain, and inflammation processes. Existent data indicates that PBM is capable of altering reactive oxygen species (ROS) production. High levels of ROS can cause shortening and dysfunctional telomeres. Therefore, a better understanding of the effects induced by PBM on telomere maintenance is needed. This study aimed to assess the expression of genes related to telomere maintenance in Saccharomyces cerevisiae after irradiation with low-power red laser and ultraviolet A LED. Cultures of S. cerevisiae were exposed to low-power red laser (660 nm, 21.2 J/cm[2], 205 s, 99 mW) and ultraviolet A LED (390 nm, 6 J/cm[2], 205 s, 7 mW), incubated for 1 h in rich medium, total mRNA was extracted, cDNA was synthetized, and RAP1, RIF1, RIF2, STN1 and TEN1 mRNA levels in S. cerevisiae FF18733 cells were evaluated by real-time quantitative polymerase chain reaction. The results indicated that, at the fluences evaluated, exposure to low-power red laser does not induce changes on genes expression but exposure to ultraviolet A LED alone, and to simultaneous ultraviolet A LED and low-power red laser significantly (p < 0.05) reduce STN1 and TEN1 mRNA levels in S. cerevisiae. Exposure to low-power red laser could not affect mRNA telomere maintenance genes but exposure to ultraviolet A LED, and simultaneous low-power red laser and ultraviolet A LED, could decrease gene expression of telomere maintenance genes in S. cerevisiae. Our results could be taken into account for irradiation conditions carried out in current clinical protocols based on low-power lasers and LEDs as well as for developing new clinical protocols targeting telomere maintenance involved in PBM-induced therapeutic effects.},
}

*Saccharomyces cerevisiae/radiation effects/genetics
*RNA, Messenger/metabolism/genetics
*Low-Level Light Therapy
*Ultraviolet Rays
*Telomere/radiation effects/genetics
Saccharomyces cerevisiae Proteins/genetics/metabolism

@article {pmid40481055,
year = {2025},
author = {Han, JN and Li, Y and Li, W and Yan, HH and Yuan, F and Chen, HG and Han, DJ and Kang, ZS and Zeng, QD},
title = {Haplotype-resolved telomere-to-telomere genome assembly of the dikaryotic fungus pathogen Rhizoctonia cerealis.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {951},
pmid = {40481055},
issn = {2052-4463},
mesh = {Haplotypes ; *Telomere/genetics ; *Genome, Fungal ; *Rhizoctonia/genetics ; },
abstract = {Rhizoctonia cerealis, the causal agent of sharp eyespot, is a highly destructive pathogen of wheat. Despite its global importance, the genetic and molecular mechanisms underlying virulence of R. cerealis remain poorly understood. R. cerealis is a dikaryotic organism and the haplotype phase has been isolated. Based on the PacBio HiFi, Oxford Nanopore, and Hi-C platforms, we assembled the first high quality telomere-to-telomere (T2T) haplotype-resolved genome of R. cerealis, with sizes of 41.50 and 41.05 Mb, and N50 sizes of 2.67 and 2.42 Mb, respectively. High consensus quality values of 57.75 and 57.09 for the two haplotypes validated the accuracy of the assembly. The assembly achieved R-AQI and S-AQI scores of 92.5 and 100, respectively, both indicating reference-level quality. A total 25,353 protein coding genes were predicted for the two haplotypes with a BUSCO score of 96.7%. The genome assembly will serve as the foundation for further research on allele-specific expression, genetic variation and evolution of R. cerealis.},
}

Haplotypes
*Telomere/genetics
*Genome, Fungal
*Rhizoctonia/genetics

@article {pmid40480910,
year = {2025},
author = {Marston, K and Lau, CE and Andrusaityte, S and Bhopal, S and Grazuleviciene, R and Gutzkow, KB and Haro, N and Karachaliou, M and Koutra, K and Krog, NH and Lepeule, J and Maitre, L and Martens, DS and Pozo, OJ and Wijnhoven, A and Nawrot, TS and Vrijheid, M and Robinson, O},
title = {Associations of family affluence with cortisol production and telomere length in European children.},
journal = {EBioMedicine},
volume = {},
number = {},
pages = {105793},
doi = {10.1016/j.ebiom.2025.105793},
pmid = {40480910},
issn = {2352-3964},
abstract = {BACKGROUND: Shorter telomere length is associated with environmental stressors and has been proposed to underlie health inequalities in ageing trajectories. However, the relationship between socioeconomic position, psychosocial stress and telomere length is understudied in childhood, when ageing trajectories may be first defined. We aimed to examine the associations between family affluence, cortisol production and telomere length in a large cross-sectional study of European children.

METHODS: 1160 children, aged 5-12 years, participating in the Human Early Life Exposome (HELIX) project, were recruited from cohorts in the UK, France, Spain, Norway, Lithuania, and Greece. Family material wealth was assessed using the international family affluence scale (FAS), psychosocial stress was defined by total urinary cortisol production, and leucocyte telomere length was measured through qPCR. Associations of FAS with cortisol production and telomere length were analysed using sequentially adjusted multivariable linear regression. The mediating role of cortisol production in the association between FAS and telomere length was examined using natural effects models.

FINDINGS: Compared to children of low FAS, children with high FAS had 4.94% (95% CI: 1.2%, 8.8%) longer telomeres after adjustment for sex, age, ethnicity and cohort. Estimates were similar upon further adjustment for perinatal, child health, and other socioeconomic factors. Additionally, children of medium and high FAS had significantly lower levels of cortisol production than children of low FAS (medium FAS: -20.8%, 95% CI: -31%, -8.5%; high FAS: -16.6% SD, 95% CI: -28%, -3.4%). However, cortisol production was not associated with telomere length, and no significant mediation of cortisol production and other tested mediators was found for the relationship between FAS and telomere length.

INTERPRETATION: The impacts of economic disadvantage are biologically observable in children and have implications for understanding health inequalities, both in child development and the onset of later age-related disease. Given the lack of mediation by cortisol production levels, as assessed via spot urine samples, further research should investigate alternative mechanisms underlying the association between affluence and telomere length.

FUNDING: UK Research and Innovation (Grants: MR/S03532X/1, MR/Y02012X/1), European Community (Grants: 874583, 308333).},
}

@article {pmid40475990,
year = {2025},
author = {Wang, L and Pan, R and Yan, N and Luo, Y and Wang, Y},
title = {Association of self-reported sleep duration with leukocyte telomere length in type 2 diabetes mellitus patients.},
journal = {Frontiers in endocrinology},
volume = {16},
number = {},
pages = {1549175},
pmid = {40475990},
issn = {1664-2392},
mesh = {Humans ; *Diabetes Mellitus, Type 2/genetics/physiopathology ; Male ; Female ; *Leukocytes/metabolism ; Middle Aged ; Cross-Sectional Studies ; *Sleep/physiology ; Self Report ; Aged ; *Telomere/genetics ; China/epidemiology ; *Telomere Homeostasis ; Adult ; Sleep Duration ; },
abstract = {BACKGROUND: Leukocyte telomere length (LTL) is a biomarker of aging, and sleep duration is associated with LTL. However, research exploring the relationship between sleep duration and LTL has yielded inconsistent results. This study aimed to investigate the association between sleep duration and LTL in Chinese patients with type 2 diabetes mellitus (T2DM).

METHODS: A cross-sectional study involving 1,027 T2DM patients was conducted in Ningxia Province, China. Sleep duration was assessed through self-reported measures, while leukocyte telomere length (LTL) was determined using a quantitative polymerase chain reaction (q-PCR) method. Restricted cubic splines (RCS) analysis was initially performed to evaluate the potential nonlinear relationship between sleep duration and LTL. Subsequently, a multiple mixed-effect linear regression model was utilized to examine this association.

RESULTS: Binary analysis revealed an inverse association between sleep duration and LTL (β=-0.170, 95%CI: (-0.271, -0.068), p=0.001), indicating that for every 1-hour increase in sleep duration, LTL decreased by 0.17 kb. RCS analysis showed no evidence of a nonlinear relationship between sleep duration and LTL. After controlling for potential covariates, sleep duration remained negatively associated with LTL (β=-0.123, 95% CI: (-0.229, -0.017), p=0.022). When stratified by sleep quality (moderate or good vs. poor) and age (< 60 vs.≥60 years old), a negative association between sleep duration and LTL was particularly observed among individuals with moderate or good sleep quality and who were under 60 years old.

CONCLUSION: This study adds to the growing literature relating sleep duration with biomarkers of aging and suggests that the shortening of LTL may reflect potential mechanisms through which longer sleep duration contributes to pathological conditions in T2DM patients. It is recommended that healthcare providers, health promoters, and patients pay greater attention to sleep habits, avoiding excessively long sleep durations, to potentially slow cellular aging.},
}

Humans
*Diabetes Mellitus, Type 2/genetics/physiopathology
Male
Female
*Leukocytes/metabolism
Middle Aged
Cross-Sectional Studies
*Sleep/physiology
Self Report
Aged
*Telomere/genetics
China/epidemiology
*Telomere Homeostasis
Adult
Sleep Duration

@article {pmid40475761,
year = {2025},
author = {Feng, L and Bai, K and He, L and Wang, H and Zhang, W},
title = {Transcriptomic insights into the mechanism of action of telomere-related biomarkers in rheumatoid arthritis.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1585895},
pmid = {40475761},
issn = {1664-3224},
mesh = {Humans ; *Arthritis, Rheumatoid/genetics/diagnosis/immunology/metabolism ; Biomarkers/metabolism ; *Transcriptome ; *Telomere/genetics/metabolism ; Gene Expression Profiling ; Computational Biology/methods ; Gene Regulatory Networks ; Nomograms ; },
abstract = {BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune inflammatory disease. The mechanism by which telomeres are involved in the development of RA remains unclear. This study aimed to investigate the relationship between RA and telomeres.

METHODS: In this study, we identified differentially expressed genes (DEGs) between RA and control samples by analyzing transcriptome data from a public database. Candidate genes were determined through the intersection of DEGs and telomere-related genes. Biomarkers were subsequently identified using machine learning algorithms, receiver operating characteristic analysis, and expression level comparisons between RA and control samples. Additionally, a nomogram model was employed to predict the diagnostic ability of biomarkers for RA. Subsequently, the potential mechanisms of these biomarkers in RA were further explored using gene set enrichment analysis (GSEA), subcellular localization, chromosome localization, immune infiltration, functional analysis, molecular regulatory networks, drug prediction, and molecular docking. Furthermore, the expression of biomarkers between RA and control samples was validated through in vitro experiments.

RESULTS: ABCC4, S100A8, VAMP2, PIM2, and ISG20 were identified as biomarkers. These biomarkers demonstrated excellent diagnostic ability for RA through a nomogram. Most of the biomarkers were found to be enriched in processes related to allograft rejection and the cell cycle. Subcellular and chromosomal localization analyses indicated that ABCC4 is localized to the plasma membrane, ISG20 to the mitochondria, PIM2 and S100A8 to the cytoplasm, and VAMP2 to the nucleus. Additionally, nine differential immune cells were identified between RA and control samples, with a strong correlation observed between the biomarkers and activated CD4 memory T cells. S100A8, PIM2, and VAMP2 exhibited high similarity to other biomarkers. Furthermore, three transcription factors (TFs), 121 microRNAs (miRNAs), and six long non-coding RNAs (lncRNAs) were identified as targeted biomarkers. Five drugs-methotrexate, adefovir, furosemide, azathioprine, and cefmetazole-were also identified as targeted biomarkers. Notably, ABCC4 interacted with all five drugs and exhibited the strongest binding energy with methotrexate. The results of the in vitro experiments were consistent with those obtained from the bioinformatics analysis.

CONCLUSION: This study identified five biomarkers-ABCC4, S100A8, VAMP2, PIM2, and ISG20-and offered new insights into potential therapeutic strategies for RA.},
}

Humans
*Arthritis, Rheumatoid/genetics/diagnosis/immunology/metabolism
Biomarkers/metabolism
*Transcriptome
*Telomere/genetics/metabolism
Gene Expression Profiling
Computational Biology/methods
Gene Regulatory Networks
Nomograms

@article {pmid40475582,
year = {2025},
author = {Ragupathi, A and Abid, HZ and Chen, Y and Zhao, R and Kosiyatrakul, ST and Yetil, DI and Neiswander, J and Feltman, R and Thomas, S and Yusupov, B and Singh, M and Zheng, L and Shen, B and Zhang, H and Chu, HC and Schildkraut, CL and Xiao, M and Zhang, D},
title = {DNA2 and FANCM function in two distinctive pathways in disrupting TERRA R-loops and suppressing replication stress at ALT telomeres.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.05.22.655602},
pmid = {40475582},
issn = {2692-8205},
abstract = {Cancers maintain their telomeres through two main telomere maintenance mechanisms (TMMs): 85-90% of cancers rely on telomerase, while 10-15% of cancers adopt the Alternative Lengthening of Telomere (ALT) pathway. Previously, we and others reported that FANCM, one of the Fanconi Anemia proteins, plays a critical role in suppressing replication stress and DNA damage at ALT telomeres by actively disrupting TERRA R-loops [1-4]. Here, we showed that inactivation of DNA2 in ALT-positive (ALT+) cells, but not in telomerase-positive (TEL+) cells, induces a robust increase of replication stress and DNA damage at telomeres, which leads to a pronounced increase of many ALT properties, including telomere dysfunction-induced foci (TIFs), ALT-associated PML bodies (APBs), and C-circles. We further demonstrated that depletion of DNA2 induces a pronounced increase of TERRA R-loops and a decrease in replication efficiency at ALT telomeres. Most importantly, we uncovered a strong additive genetic interaction between DNA2 and FANCM in the ALT pathway. Furthermore, co-depletion of DNA2 and FANCM causes synthetic lethality in ALT+ cells, but not in TEL+ cells, suggesting that targeting DNA2 and FANCM could be a viable strategy to treat ALT+ cancers. Finally, utilizing the single-molecule telomere assay via optical mapping (SMTA-OM) technology, we thoroughly characterized genome-wide changes in DNA2 deficient cells and FANCM deficient cells and found that most chromosome arms manifested increased telomere length. Unexpectedly, we uncovered many chromosome arm-specific telomere changes in those cells, suggesting that telomeres at different chromosome arms may regulate and respond to replication stress differently. Collectively, our study not only shed new light on the molecular mechanisms of the ALT pathway, but also discovered a new strategy for targeting ALT+ cancer.},
}

@article {pmid40469570,
year = {2025},
author = {Guzonjić, A and Jovanović, D and Simić, I and Ćeriman Krstić, V and Samardzić, N and Ostanek, B and Marc, J and Sopić, M and Kotur Stevuljević, J},
title = {Telomere length and oxidative stress in small cell lung cancer patients: changes through chemotherapy cycles compared to healthy controls.},
journal = {Biochemia medica},
volume = {35},
number = {2},
pages = {020705},
pmid = {40469570},
issn = {1846-7482},
mesh = {Humans ; Male ; Female ; *Oxidative Stress/drug effects ; *Lung Neoplasms/drug therapy/genetics/metabolism/mortality ; *Small Cell Lung Carcinoma/drug therapy/genetics/metabolism/mortality ; Middle Aged ; Aged ; Aryldialkylphosphatase/metabolism ; *Telomere/metabolism ; Longitudinal Studies ; Leukocytes/metabolism ; Case-Control Studies ; Adult ; Oxidation-Reduction ; Prognosis ; *Telomere Homeostasis ; },
abstract = {INTRODUCTION: Small cell lung cancer (SCLC) is an aggressive malignant disease with poor survival outcomes. The aim of this study was to investigate leukocyte telomere length (LTL) and redox status parameters during chemotherapy and evaluate their prognostic potential based on the hypothesis that shorter LTL and oxidative stress burden correlate with poorer survival.

MATERIALS AND METHODS: This longitudinal study included 60 SCLC patients and 73 healthy controls. Leukocyte telomere length was measured by quantitative PCR (qPCR) method, while redox status parameters (MDA - malondialdehyde, IMA - ischemia-modified albumin, PON1 - paraoxonase 1, redox index) were determined by spectrophotometric methods before, after two and after four cycles of chemotherapy.

RESULTS: All measured parameters showed significant differences between patients and controls, except the oxy-score (P < 0.001). Significant differences in IMA, PON1 and redox index were observed between SCLC patient groups at different time points (P < 0.001). Significant differences in IMA and PON1 were observed between SCLC survival groups, with higher values found in survivors after two chemotherapy cycles (P < 0.001). Redox index was the highest in the pre-chemo group (P = 0.019). Among patients who died, PON1 activity differed significantly between those who died within 2 months and after 4 months (P = 0.028). Kaplan-Meier analysis showed that LTL and PON1 were significant predictors of survival, with values below the 25th percentile associated with a higher risk of death.

CONCLUSIONS: Leukocyte telomere length and PON1 are potential prognostic biomarkers for SCLC survival, suggesting their potential use in non-invasive biomarker panels for improved patient stratification.},
}

Humans
Male
Female
*Oxidative Stress/drug effects
*Lung Neoplasms/drug therapy/genetics/metabolism/mortality
*Small Cell Lung Carcinoma/drug therapy/genetics/metabolism/mortality
Middle Aged
Aged
Aryldialkylphosphatase/metabolism
*Telomere/metabolism
Longitudinal Studies
Leukocytes/metabolism
Case-Control Studies
Adult
Oxidation-Reduction
Prognosis
*Telomere Homeostasis

@article {pmid40463079,
year = {2025},
author = {Garbouchian, A and Cestari Moreno, N and Dey, A and Opresko, P and Barnes, R},
title = {Oxidative Base Damage to Telomeres Sensitizes Cancer Cells to ATR Inhibition.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.05.10.653274},
pmid = {40463079},
issn = {2692-8205},
abstract = {Targeted inhibition of DNA damage response proteins has received significant clinical attention owing to the success of PARP inhibitors. Due to the loss of the G1/S checkpoint, cancer cells are reliant on the G2/M checkpoint to cope with elevated DNA replication stress. We previously demonstrated a single induction of 8-oxo-guanine at telomeres in cancer cells was sufficient to induce replication stress, but was well tolerated at the cellular level. Here, we found inhibition of ATR, Chk1, or Wee1 after induction of telomere oxidative stress significantly induced genome instability and reduced cell viability. This occurred at doses markedly less than those required to increase instability in non-cancer cells. We determined the mechanism of this instability is due to cells progressing through S-phase with telomere damage and exiting G2-phase prematurely, prolonging their mitosis. This study demonstrates targeted oxidative base damage at telomeres can enhance the therapeutic efficacy of ATR inhibition in cancer.},
}

@article {pmid40459934,
year = {2025},
author = {Poeschla, M and Arora, UP and Walne, A and McReynolds, LJ and Niewisch, MR and Giri, N and Zeigler, LP and Gusev, A and Machiela, MJ and Tummala, H and Savage, SA and Sankaran, VG},
title = {Polygenic modifiers impact penetrance and expressivity in telomere biology disorders.},
journal = {The Journal of clinical investigation},
volume = {},
number = {},
pages = {},
doi = {10.1172/JCI191107},
pmid = {40459934},
issn = {1558-8238},
abstract = {BACKGROUND: Telomere biology disorders (TBDs) exhibit incomplete penetrance and variable expressivity, even among individuals harboring the same pathogenic variant. We assessed whether common genetic variants associated with telomere length combine with large-effect variants to impact penetrance and expressivity in TBDs.

METHODS: We constructed polygenic scores (PGS) for telomere length in the UK Biobank to quantify common variant burden, and assessed the PGS distribution across patient cohorts and biobanks to determine whether individuals with severe TBD presentations have increased polygenic burden causing short telomeres. We also characterized rare TBD variant carriers in the UK Biobank.

RESULTS: Individuals with TBDs in cohorts enriched for severe pediatric presentations have polygenic scores predictive of short telomeres. In the UK Biobank, we identify carriers of pathogenic TBD variants who are enriched for adult-onset manifestations of TBDs. Unlike individuals in disease cohorts, the PGS of adult carriers do not show a common variant burden for shorter telomeres, consistent with the absence of childhood-onset disease. Notably, TBD variant carriers are enriched for idiopathic pulmonary fibrosis diagnoses, and telomere length PGS stratifies pulmonary fibrosis risk. Finally, common variants affecting telomere length were enriched in enhancers regulating known TBD genes.

CONCLUSION: Common genetic variants combine with large-effect causal variants to impact clinical manifestations in rare TBDs. These findings offer a framework for understanding phenotypic variability in other presumed monogenic disorders.

FUNDING: This work was supported by National Institutes of Health grants R01DK103794, R01HL146500, R01CA265726, R01CA292941, and the Howard Hughes Medical Institute.},
}

@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.},
}