@article {pmid39057072,
year = {2024},
author = {Macamo, ED and Mkhize-Kwitshana, ZL and Mthombeni, J and Naidoo, P},
title = {The Impact of HIV and Parasite Single Infection and Coinfection on Telomere Length: A Systematic Review.},
journal = {Current issues in molecular biology},
volume = {46},
number = {7},
pages = {7258-7290},
doi = {10.3390/cimb46070431},
pmid = {39057072},
issn = {1467-3045},
support = {HDID5149/KR/2021//SAMRC/ ; },
abstract = {HIV and parasite infections accelerate biological aging, resulting in immune senescence, apoptosis and cellular damage. Telomere length is considered to be one of the most effective biomarkers of biological aging. HIV and parasite infection have been reported to shorten telomere length in the host. This systematic review aimed to highlight work that explored the influence of HIV and parasite single infections and coinfection on telomere length. Using specific keywords related to the topic of interest, an electronic search of several online databases (Google Scholar, Web of Science, Scopus, Science Direct and PubMed) was conducted to extract eligible articles. The association between HIV infection or parasite infection and telomere length and the association between HIV and parasite coinfection and telomere length were assessed independently. The studies reported were mostly conducted in the European countries. Of the 42 eligible research articles reviewed, HIV and parasite single infections were independently associated with telomere length shortening. Some studies found no association between antiretroviral therapy (ART) and telomere length shortening, while others found an association between ART and telomere length shortening. No studies reported on the association between HIV and parasite coinfection and telomere length. HIV and parasite infections independently accelerate telomere length shortening and biological aging. It is possible that coinfection with HIV and parasites may further accelerate telomere length shortening; however, this is a neglected field of research with no reported studies to date.},
}

@article {pmid39057051,
year = {2024},
author = {Macamo, ED and Mkhize-Kwitshana, ZL and Duma, Z and Mthombeni, J and Naidoo, P},
title = {Telomere Length in a South African Population Co-Infected with HIV and Helminths.},
journal = {Current issues in molecular biology},
volume = {46},
number = {7},
pages = {6853-6867},
doi = {10.3390/cimb46070409},
pmid = {39057051},
issn = {1467-3045},
support = {HDID5149/KR/202//SAMRC/ ; },
abstract = {Biological ageing refers to the gradual decrease in physiological functions, resulting in immune senescence, cellular damage and apoptosis. Telomere length is a biomarker of biological ageing. Limited studies have associated shorter telomere length with HIV and parasite single infections, with no studies reporting the association of HIV and parasite co-infection with telomere length. The study aimed to investigate whether telomere length shortening is accelerated in a South African population co-infected with HIV and helminths compared to participants singly infected with either HIV or helminths. Additionally, telomere length data were compared with participants' biochemical and full blood count parameters. A total of 200 participants were in groups of uninfected control, HIV single infection, helminth single infection and HIV and helminth co-infection groups. Relative telomere length (RTL) was determined using Real-Time PCR and associated with biochemical and full blood count parameters using multivariate regression analysis models that were adjusted for confounders. The uninfected control group was used as a reference group. The uninfected control group had the highest mean RTL (1.21 ± 0.53) while the HIV-infected (0.96 ± 0.42) and co-infected (0.93 ± 0.41) groups had similar RTLs, and lastly, the helminth-infected group (0.83 ± 0.33) had the lowest RTL (p = 0.0002). When compared to the uninfected control group, a significant association between RTL and biochemical parameters, including blood iron (β = -0.48), ferritin (β = -0.48), transferrin saturation (β = -0.57), transferrin (β = -0.57), phosphate (β = -0.47), vitamin A (β = -0.49) and C-reactive protein (β = -0.52) were noted in the co-infected group (p < 0.05). In addition, a significant association between RTL and full blood count, including (β = -0.47), haematocrit (β = -0.46), mean corpuscular volume (β = -0.47), lymphocytes (β = -0.45), mean corpuscular haemoglobin concentration (β = -0.45), red cell distribution width (β = -0.47), monocytes (β = -0.45), eosinophils (β = -0.45), basophils (β = -0.44) and transferrin saturation (β = -0.57) were also noted in the co-infected group (p < 0.05). Accelerated biological ageing, as indicated by telomere length shortening, is associated with HIV and helminth co-infections.},
}

@article {pmid39055058,
year = {2024},
author = {Chen, X and Liu, B and Zhou, J and Lin, J and Jiang, W and Xie, R},
title = {Association between telomere length and erectile dysfunction: a cross-sectional study.},
journal = {Frontiers in endocrinology},
volume = {15},
number = {},
pages = {1391013},
doi = {10.3389/fendo.2024.1391013},
pmid = {39055058},
issn = {1664-2392},
mesh = {Humans ; Male ; *Erectile Dysfunction ; Cross-Sectional Studies ; Middle Aged ; *Telomere ; Leukocytes/metabolism/pathology ; Aged ; Adult ; Nutrition Surveys ; Telomere Homeostasis ; Telomere Shortening ; Risk Factors ; },
abstract = {BACKGROUND: Leukocyte telomere length (LTL) serves as a significant biomarker of aging. Erectile dysfunction (ED) is a commonly observed condition among middle-aged and older men. The objective of this study is to explore the potential association between LTL and ED.

METHODS: We utilized data from the National Health and Nutrition Examination Survey (NHANES) to examine the association between LTL and ED. Weighted multivariate regression analyses were performed as the primary statistical method. Subgroup analyses were conducted to investigate specific population subsets, and restricted cubic spline (RCS) analyses were employed to assess the non-linear relationship between LTL and ED.

RESULTS: The results of weighted multivariate regression analyses revealed a negative correlation between LTL and the risk of ED. Individuals with ED exhibited shorter LTL compared to those without ED. For each unit increase in LTL, there was a 54% reduction in the risk of ED (odds ratios[OR] 0.46, 95% confidence intervals[CI] 0.25-0.85). When LTL was considered as a categorical variable, the group with the longest LTL (Q5) had a 44% lower risk of ED compared to the group with the shortest LTL(Q1) (OR 0.56, 95% CI 0.39-0.81). A non-linear relationship was observed between TL and ED. Various sensitivity analyses were conducted to validate the stability of the results, and consistent findings were obtained.

CONCLUSION: The negative association between leukocyte LTL and ED suggests that delaying the shortening of LTL may decrease the risk of ED.},
}

Humans
Male
*Erectile Dysfunction
Cross-Sectional Studies
Middle Aged
*Telomere
Leukocytes/metabolism/pathology
Aged
Adult
Nutrition Surveys
Telomere Homeostasis
Telomere Shortening
Risk Factors

@article {pmid39054789,
year = {2024},
author = {Tempaku, PF and D'Almeida, V and Andersen, ML and Tufik, S},
title = {Sleep is associated with telomere shortening: A population-based longitudinal study.},
journal = {Journal of sleep research},
volume = {},
number = {},
pages = {e14274},
doi = {10.1111/jsr.14274},
pmid = {39054789},
issn = {1365-2869},
support = {#23/08657-0 to VDA//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; #20/13467-8 to MLA//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; },
abstract = {As the chronological age increases, there is a decrease in the telomere length (TL). Associations between TL and age-related diseases have been described. Since the major pathophysiological factors related to inadequate sleep (including sleep complaints and sleep disorders) contribute to the exacerbation of inflammation and oxidative stress, an association of sleep and TL has been proposed. The aim of this study was to evaluate the association between sleep-related variables with TL in a longitudinal framework. We used data derived from the EPISONO cohort, which was followed over 8 years. All individuals answered sleep-related questionnaires, underwent a full-night polysomnography (PSG), and had their blood collected for DNA extraction. The TL was measured through a quantitative real time polymerase chain reaction. Age, sex, body mass index (BMI), smoking, physical activity status, and the 10 principal components (ancestry estimate) were considered covariables. Of the 1042 individuals in the EPISONO cohort, 68.3% agreed to participate in the follow-up study (n = 712). Baseline SpO2 (ß = 0.008, p = 0.007), medium SpO2 (ß = 0.013, p = 0.013), and total sleep time <90% (ß = -0.122, p = 0.012) had an effect on TL from the follow-up. The 8 year TL attrition was inversely associated with total sleep time, sleep efficiency, sleep architecture variables, wake after sleep onset, arousal index, oxygen-related variables baseline, and the presence of obstructive sleep apnea (OSA). We conclude that individuals with worse sleep quality, alterations in sleep architecture, and OSA had greater TL attrition over the 8 years. Using a longitudinal approach, these findings confirm previous cross-sectional evidence linking sleep with accelerated biological ageing.},
}

@article {pmid39054004,
year = {2024},
author = {Ng, GYQ and Hande, MP},
title = {Use of peptide nucleic acid probe to determine telomere dynamics in improving chromosome analysis in genetic toxicology studies.},
journal = {Mutation research. Genetic toxicology and environmental mutagenesis},
volume = {897},
number = {},
pages = {503773},
doi = {10.1016/j.mrgentox.2024.503773},
pmid = {39054004},
issn = {1879-3592},
mesh = {*Peptide Nucleic Acids ; *Telomere/drug effects/genetics ; Humans ; *In Situ Hybridization, Fluorescence/methods ; Animals ; Mutagens/toxicity ; Karyotyping/methods ; },
abstract = {Genetic toxicology, strategically located at the intersection of genetics and toxicology, aims to demystify the complex interplay between exogenous agents and our genetic blueprint. Telomeres, the protective termini of chromosomes, play instrumental roles in cellular longevity and genetic stability. Traditionally karyotyping and fluorescence in situ hybridisation (FISH), have been indispensable tools for chromosomal analysis following exposure to genotoxic agents. However, their scope in discerning nuanced molecular dynamics is limited. Peptide Nucleic Acids (PNAs) are synthetic entities that embody characteristics of both proteins and nucleic acids and have emerged as potential game-changers. This perspective report comprehensively examines the vast potential of PNAs in genetic toxicology, with a specific emphasis on telomere research. PNAs' superior resolution and precision make them a favourable choice for genetic toxicological assessments. The integration of PNAs in contemporary analytical workflows heralds a promising evolution in genetic toxicology, potentially revolutionizing diagnostics, prognostics, and therapeutic avenues. In this timely review, we attempted to assess the limitations of current PNA-FISH methodology and recommend refinements.},
}

*Peptide Nucleic Acids
*Telomere/drug effects/genetics
Humans
*In Situ Hybridization, Fluorescence/methods
Animals
Mutagens/toxicity
Karyotyping/methods

@article {pmid39052566,
year = {2024},
author = {Huang, SH and Abrametz, K and McGrath, SL and Kobryn, K},
title = {Design and characterization of hyperactive mutants of the Agrobacterium tumefaciens telomere resolvase, TelA.},
journal = {PloS one},
volume = {19},
number = {7},
pages = {e0307590},
doi = {10.1371/journal.pone.0307590},
pmid = {39052566},
issn = {1932-6203},
mesh = {*Agrobacterium tumefaciens/genetics/enzymology ; *Telomere/metabolism/genetics ; *Bacterial Proteins/genetics/metabolism/chemistry ; Mutation ; Models, Molecular ; },
abstract = {Telomere resolvases are a family of DNA cleavage and rejoining enzymes that produce linear DNAs terminated by hairpin telomeres from replicated intermediates in bacteria that possess linear replicons. The telomere resolvase of Agrobacterium tumefaciens, TelA, has been examined at the structural and biochemical level. The N-terminal domain of TelA, while not required for telomere resolution, has been demonstrated to play an autoinhibitory role in telomere resolution, conferring divalent metal responsiveness on the reaction. The N-terminal domain also inhibits the competing reactions of hp telomere fusion and recombination between replicated telomere junctions. Due to the absence of the N-terminal domain from TelA/DNA co-crystal structures we produced an AlphaFold model of a TelA monomer. The AlphaFold model suggested the presence of two inhibitory interfaces; one between the N-terminal domain and the catalytic domain and a second interface between the C-terminal helix and the N-core domain of the protein. We produced mutant TelA's designed to weaken these putative interfaces to test the validity of the modeled interfaces. While our analysis did not bear out the details of the predicted interfaces the model was, nonetheless, extremely useful in guiding design of mutations that, when combined, demonstrated an additive activation of TelA exceeding 250-fold. For some of these hyperactive mutants stimulation of telomere resolution has also been accompanied by activation of competing reactions. However, we have also characterized hyperactive TelA mutants that retain enough autoinhibition to suppress the competing reactions.},
}

*Agrobacterium tumefaciens/genetics/enzymology
*Telomere/metabolism/genetics
*Bacterial Proteins/genetics/metabolism/chemistry
Mutation
Models, Molecular

@article {pmid39050459,
year = {2024},
author = {Tomasova, K and Seborova, K and Kroupa, M and Horak, J and Kavec, M and Vodickova, L and Rob, L and Hruda, M and Mrhalova, M and Bartakova, A and Bouda, J and Fleischer, T and Kristensen, VN and Vodicka, P and Vaclavikova, R},
title = {Telomere length as a predictor of therapy response and survival in patients diagnosed with ovarian carcinoma.},
journal = {Heliyon},
volume = {10},
number = {13},
pages = {e33525},
pmid = {39050459},
issn = {2405-8440},
abstract = {Impaired telomere length (TL) maintenance in ovarian tissue may play a pivotal role in the onset of epithelial ovarian cancer (OvC). TL in either target or surrogate tissue (blood) is currently being investigated for use as a predictor in anti-OvC therapy or as a biomarker of the disease progression, respectively. There is currently an urgent need for an appropriate approach to chemotherapy response prediction. We performed a monochrome multiplex qPCR measurement of TL in peripheral blood leukocytes (PBL) and tumor tissues of 209 OvC patients. The methylation status and gene expression of the shelterin complex and telomerase catalytic subunit (hTERT) were determined within tumor tissues by High-Throughput DNA methylation profiling and RNA sequencing (RNA-Seq) analysis, respectively. The patients sensitive to cancer treatment (n = 46) had shorter telomeres in PBL compared to treatment-resistant patients (n = 93; P = 0.037). In the patients with a different therapy response, transcriptomic analysis showed alterations in the peroxisome proliferator-activated receptor (PPAR) signaling pathway (q = 0.001). Moreover, tumor TL shorter than the median corresponded to better overall survival (OS) (P = 0.006). TPP1 gene expression was positively associated with TL in tumor tissue (P = 0.026). TL measured in PBL could serve as a marker of platinum therapy response in OvC patients. Additionally, TL determined in tumor tissue provides information on OvC patients' OS.},
}

@article {pmid39048791,
year = {2024},
author = {Garg, V and Bohra, A and Mascher, M and Spannagl, M and Xu, X and Bevan, MW and Bennetzen, JL and Varshney, RK},
title = {Unlocking plant genetics with telomere-to-telomere genome assemblies.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {39048791},
issn = {1546-1718},
abstract = {Contiguous genome sequence assemblies will help us to realize the full potential of crop translational genomics. Recent advances in sequencing technologies, especially long-read sequencing strategies, have made it possible to construct gapless telomere-to-telomere (T2T) assemblies, thus offering novel insights into genome organization and function. Plant genomes pose unique challenges, such as a continuum of ancient to recent polyploidy and abundant highly similar and long repetitive elements. Owing to progress in sequencing approaches, for most crop plants, chromosome-scale reference genome assemblies are available, but T2T assembly construction remains challenging. Here we describe methods for haplotype-resolved, gapless T2T assembly construction in plants, including various crop species. We outline the impact of T2T assemblies in elucidating the roles of repetitive elements in gene regulation, as well as in pangenomics, functional genomics, genome-assisted breeding and targeted genome manipulation. In conjunction with sequence-enriched germplasm repositories, T2T assemblies thus hold great promise for basic and applied plant sciences.},
}

@article {pmid39045889,
year = {2024},
author = {Yang, C and Zhang, Y and Li, J and Liu, X and Qiu, J and Zhang, J and Liu, X and Zhang, Y and Zhao, Y},
title = {Short leukocyte telomere length and high plasma phospholipid fatty acids increase the risk of type 2 diabetes.},
journal = {Endocrine connections},
volume = {},
number = {},
pages = {},
doi = {10.1530/EC-24-0033},
pmid = {39045889},
issn = {2049-3614},
abstract = {In the last forty years, there has been a notable rise in the occurrence of diabetes within China, leading to the country now having the highest number of individuals affected by this condition globally. This prospective observational study examined the effect of different baseline relative leukocyte telomere length (RTL) and the combined effect of baseline RTL and plasma phospholipid fatty acid (PPFA) on the risk of developing diabetes. Adults from Ningxia Province who underwent baseline and follow-up surveys were included in the study. The correlation between the baseline RTL and PPFA was investigated using a multiple linear regression model. The combined effect of baseline RTL and PPFA levels on the risk of developing type 2 diabetes mellitus (T2DM) were investigated using a cox regression model with time as the covariate. A total of 1461 study subjects were included in this study. 141 subjects developed T2DM during the follow-up period. The baseline age was negatively correlated with RTL.Multiple linear regression analysis showed that C16:0 and MUFA concentrations influenced RTL. Subjects with shorter RTL at baseline had a higher risk of developing diabetes than those with longer RTL. Subjects with shorter RTL and higher C16:0 and MUFA concentrations at baseline had a higher risk of developing T2DM than those with longer RTL and lower C16:0 and MUFA concentrations. Our findings indicated that PPFA affects changes in RTL. In addition, RTL and PPFA are associated with the occurrence of T2DM.},
}

@article {pmid39045323,
year = {2024},
author = {Ibraheem Shelash Al-Hawary, S and Ali Alzahrani, A and Ghaleb Maabreh, H and Abed Jawad, M and Alsaadi, SB and Kareem Jabber, N and Alawadi, A and Alsalamy, A and Alizadeh, F},
title = {The association of metabolic syndrome with telomere length as a marker of cellular aging: a systematic review and meta-analysis.},
journal = {Frontiers in genetics},
volume = {15},
number = {},
pages = {1390198},
pmid = {39045323},
issn = {1664-8021},
abstract = {BACKGROUND: It has been suggested that metabolic syndrome (MetS) accelerates the aging process, potentially contributing to the development of age-related complications. Available studies examining the relation of MetS to telomere length (TL), a putative biological marker of aging, have yielded inconclusive findings. This meta-analysis was performed to investigate the association between MetS and TL.

METHODS: A comprehensive systematic search was conducted in PubMed and Scopus databases to identify relevant literature published up to February 2024. Standard mean difference (SMD) and standardized beta coefficient (β) with their 95% confidence intervals (CI) were used as effect sizes to measure the associations using the random effects model.

RESULTS: A total of nine studies, comprising a total sample size of 8,606 participants, were eligible for the meta-analysis. No significant difference in mean TL was found between patients with and without MetS (SMD = -0.03, 95%CI = -0.17 to 0.10), with a significant heterogeneity across the studies (I [2] = 89.7.0%, p ≤ 0.001). In contrast, it was revealed that MetS is negatively related to TL (β = -0.08, 95%CI = -0.15 to -0.004). In the subgroup analysis, this finding was supported by the International Diabetes Federation (IDF) definition of MetS.

CONCLUSION: This meta-analysis highlighted that MetS may be linked to a shorter TL. Additional studies are required to confirm this finding.},
}

@article {pmid39045115,
year = {2022},
author = {Zakharova, N and Bravve, L and Mamedova, G and Kaydan, M and Ershova, E and Martynov, A and Veiko, N and Kostyuk, S},
title = {Telomere Length as a Marker of Suicidal Risk in Schizophrenia.},
journal = {Consortium psychiatricum},
volume = {3},
number = {2},
pages = {37-47},
pmid = {39045115},
issn = {2713-2919},
abstract = {BACKGROUND: Schizophrenia and suicidal behavior are associated with shortening in the length of telomeres. The aim of the study was to compare the content (pg/mcg) of telomeric repeat in DNA isolated from peripheral blood cells in three groups of subjects: patients with schizophrenia and a history of suicide attempts, patients with schizophrenia without suicidal tendencies, and healthy control volunteers.

METHODS: Relapses according to gender and age were examined in 47 patients with schizophrenia with suicidal behavior, 47 patients without self-destructive conditions, and 47 volunteers with healthy control and maintenance for the content of telomeric and the number of copies of mitochondrial DNA (mtDNA) in peripheral blood leukocytes.

RESULTS: Analysis of determining the content of telomeric repeat (TR) in the DNA of massive weight gain in the series: patients with schizophrenia and suicidal attempts - patients with schizophrenia without suicidal observations - healthy controls (225±28.4 (227 [190; 250]) vs. 243±21 (245 [228; 260]) vs. 255±17.9 (255 [242; 266]), p <0.005. The same trend is observed for the number of mtDNA copies (257±101.5 (250 [194; 297])) vs. 262.3±59.3 (254 [217; 312]) vs. 272±79.9 (274 [213; 304]); p=0.012), but no significant differences were recorded.

CONCLUSIONS: For the first time, the phenomenon of telomere shortening was discovered in schizophrenics with suicidal risk. The length of the telomere corresponds to the parameter of a biological marker - an objectively measured indicator of normal or pathological processes, but gaining an idea of its reliability is still necessary for verification with an assessment of its sensitivity, specificity, and positive and negative predictive value. The telomere may be considered a putative predictive indicator of suicidal risk.},
}

@article {pmid39042999,
year = {2024},
author = {L Rocha, J and Lou, RN and Sudmant, PH},
title = {Structural variation in humans and our primate kin in the era of telomere-to-telomere genomes and pangenomics.},
journal = {Current opinion in genetics & development},
volume = {87},
number = {},
pages = {102233},
doi = {10.1016/j.gde.2024.102233},
pmid = {39042999},
issn = {1879-0380},
abstract = {Structural variants (SVs) account for the majority of base pair differences both within and between primate species. However, our understanding of inter- and intra-species SV has been historically hampered by the quality of draft primate genomes and the absence of genome resources for key taxa. Recently, advances in long-read sequencing and genome assembly have begun to radically reshape our understanding of SVs. Two landmark achievements include the publication of a human telomere-to-telomere (T2T) genome as well as the development of the first human pangenome reference. In this review, we first look back to the major works laying the foundation for these projects. We then examine the ways in which T2T genome assemblies and pangenomes are transforming our understanding of and approach to primate SV. Finally, we discuss what the future of primate SV research may look like in the era of T2T genomes and pangenomics.},
}

@article {pmid39043540,
year = {2024},
author = {Goncalves da Silva, D and Graciano da Silva, N and Amato, AA},
title = {Leukocyte telomere length in subjects with metabolic dysfunction-associated steatotic liver disease.},
journal = {Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajg.2024.06.005},
pmid = {39043540},
issn = {2090-2387},
abstract = {BACKGROUND AND STUDY AIMS: This study aimed to examine the association between peripheral leukocyte telomere length and indicators of metabolic abnormalities in subjects with metabolic dysfunction-associated steatotic liver disease (MASLD) assessed by magnetic resonance imaging (MRI).

PATIENTS AND METHODS: This cross-sectional study included adults over 20 years with body mass index (BMI) of over >25 kg/m[2] and sonographic evidence of hepatic steatosis. The subjects were evaluated by clinical and biochemical variables, determination of hepatic fat fraction by MRI and relative peripheral leukocyte telomere length by quantitative real-time polymerase chain reaction.

RESULTS: Thirty-two subjects (22 men and 10 women) with MASLD were included, with a median age of 40 years, median BMI of 33.75 kg/m[2], median HFF 19 %, and median relative T/S ratio of 0.64. Subjects with relative T/S ratio below the median had significantly higher age, lower BMI, higher AST serum levels, higher GGT serum levels, lower serum ferritin levels, and higher FIB4 score. In a multivariable logistic regression model considering relative T/S ratio below or above the median only age was significantly associated with relative T/S ratio. Our findings suggest that age is the most important factor associated with telomere length among subjects with MASLD.

CONCLUSION: Our findings suggest that age is the most important factor associated with telomere length among subjects with MASLD.},
}

@article {pmid39042290,
year = {2024},
author = {Bortoletto, S and Nunes-Souza, E and Marchi, R and Ruthes, MO and Okano, LM and Tofolo, MV and Centa, A and Fonseca, AS and Rosolen, D and Cavalli, LR},
title = {MicroRNAs role in telomere length maintenance and telomerase activity in tumor cells.},
journal = {Journal of molecular medicine (Berlin, Germany)},
volume = {},
number = {},
pages = {},
pmid = {39042290},
issn = {1432-1440},
abstract = {MiRNAs, a class of non-coding RNA molecules, have emerged as critical modulators of telomere length and telomerase activity by finely tuning the expression of target genes (and not gene targets) within signaling pathways involved in telomere homeostasis. The primary objective of this systematic review was to compile and synthesize the existing body of knowledge on the role, association, and involvement of miRNAs in telomere length. Additionally, the review explored the regulation, function, and activation mechanism of the human telomerase reverse transcriptase (hTERT) gene and telomerase activity in tumor cells. A comprehensive analysis of 47 selected articles revealed 40 distinct miRNAs involved in these processes. These miRNAs were shown to exert their function, in both clinical cases and cell line models, either directly or indirectly, regulating hTERT and telomerase activity through distinct molecular mechanisms. The regulatory roles of these miRNAs significantly affected major cancer phenotypes, with outcomes largely dependent on the tissue type and the cellular actions within the tumor cells, whereby they functioned as oncogenes or tumor suppressors. These findings strongly support the pivotal role of miRNAs in modulating telomere length and telomerase activity, thereby contributing to the intricate and complex regulation of telomere homeostasis in tumor cells. Moreover, they emphasize the potential of targeting miRNAs and key regulatory genes as therapeutic strategies to disrupt cancer cell growth and promote senescence, offering promising avenues for novel cancer treatments.},
}

@article {pmid39038850,
year = {2024},
author = {Zhao, R and Xu, M and Yu, X and Wondisford, AR and Lackner, RM and Salsman, J and Dellaire, G and Chenoweth, DM and O'Sullivan, RJ and Zhao, X and Zhang, H},
title = {SUMO promotes DNA repair protein collaboration to support alternative telomere lengthening in the absence of PML.},
journal = {Genes & development},
volume = {},
number = {},
pages = {},
doi = {10.1101/gad.351667.124},
pmid = {39038850},
issn = {1549-5477},
abstract = {The alternative lengthening of telomeres (ALT) pathway maintains telomere length in a significant fraction of cancers that are associated with poor clinical outcomes. A better understanding of ALT mechanisms is therefore necessary for developing new treatment strategies for ALT cancers. SUMO modification of telomere proteins contributes to the formation of ALT telomere-associated PML bodies (APBs), in which telomeres are clustered and DNA repair proteins are enriched to promote homology-directed telomere DNA synthesis in ALT. However, it is still unknown whether-and if so, how-SUMO supports ALT beyond APB formation. Here, we show that SUMO condensates that contain DNA repair proteins enable telomere maintenance in the absence of APBs. In PML knockout ALT cell lines that lack APBs, we found that SUMOylation is required for manifesting ALT features independent of PML and APBs. Chemically induced telomere targeting of SUMO produces condensate formation and ALT features in PML-null cells. This effect requires both SUMOylation and interactions between SUMO and SUMO interaction motifs (SIMs). Mechanistically, SUMO-induced effects are associated with the accumulation of DNA repair proteins, including Rad52, Rad51AP1, RPA, and BLM, at telomeres. Furthermore, Rad52 can undergo phase separation, enrich SUMO at telomeres, and promote telomere DNA synthesis in collaboration with the BLM helicase in a SUMO-dependent manner. Collectively, our findings suggest that SUMO condensate formation promotes collaboration among DNA repair factors to support ALT telomere maintenance without PML. Given the promising effects of SUMOylation inhibitors in cancer treatment, our findings suggest their potential use in perturbing telomere maintenance in ALT cancer cells.},
}

@article {pmid39037376,
year = {2024},
author = {Coukos, A and Saglietti, C and Sempoux, C and Haubitz, M and Greuter, T and Mittaz-Crettol, L and Maurer, F and Mdawar-Bailly, E and Moradpour, D and Alberio, L and Good, JM and Baerlocher, GM and Fraga, M},
title = {High prevalence of short telomeres in idiopathic porto-sinusoidal vascular disorder.},
journal = {Hepatology communications},
volume = {8},
number = {8},
pages = {},
doi = {10.1097/HC9.0000000000000500},
pmid = {39037376},
issn = {2471-254X},
mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; *Telomere Shortening/genetics ; Aged ; Adult ; Prevalence ; Telomere/genetics ; Hypertension, Portal/genetics ; In Situ Hybridization, Fluorescence ; Telomere-Binding Proteins/genetics ; Telomerase/genetics ; },
abstract = {BACKGROUND: Telomeres prevent damage to coding DNA as end-nucleotides are lost during mitosis. Mutations in telomere maintenance genes cause excessive telomere shortening, a condition known as short telomere syndrome (STS). One hepatic manifestation documented in STS is porto-sinusoidal vascular disorder (PSVD).

METHODS: As the etiology of many cases of PSVD remains unknown, this study explored the extent to which short telomeres are present in patients with idiopathic PSVD.

RESULTS: This monocentric cross-sectional study included patients with histologically defined idiopathic PSVD. Telomere length in 6 peripheral blood leukocyte subpopulations was assessed using fluorescent in situ hybridization and flow cytometry. Variants of telomere-related genes were identified using high-throughput exome sequencing. In total, 22 patients were included, of whom 16 (73%) had short (9/22) or very short (7/22) telomeres according to age-adjusted reference ranges. Fourteen patients (64%) had clinically significant portal hypertension. Shorter telomeres were more frequent in males (p = 0.005) and patients with concomitant interstitial lung disease (p < 0.001), chronic kidney disease (p < 0.001), and erythrocyte macrocytosis (p = 0.007). Portal hypertension (p = 0.021), low serum albumin level (p < 0.001), low platelet count (p = 0.007), and hyperbilirubinemia (p = 0.053) were also associated with shorter telomeres. Variants in known STS-related genes were identified in 4 patients with VSTel and 1 with STel.

CONCLUSIONS: Short and very short telomeres were highly prevalent in patients with idiopathic PSVD, with 31% presenting with variants in telomere-related genes. Telomere biology may play an important role in vascular liver disease development. Clinicians should consider measuring telomeres in any patient presenting with PSVD.},
}

Humans
Male
Female
Cross-Sectional Studies
Middle Aged
*Telomere Shortening/genetics
Aged
Adult
Prevalence
Telomere/genetics
Hypertension, Portal/genetics
In Situ Hybridization, Fluorescence
Telomere-Binding Proteins/genetics
Telomerase/genetics

@article {pmid39033276,
year = {2024},
author = {Panelli, DM and Wang, X and Mayo, J and Wong, RJ and Hong, X and Becker, M and Aghaeepour, N and Druzin, ML and Zuckerman, BS and Stevenson, DK and Shaw DrPH, GM and Bianco, K},
title = {Association of pregnancy complications and postpartum maternal leukocyte telomeres in two diverse cohorts: a nested case-control study.},
journal = {BMC pregnancy and childbirth},
volume = {24},
number = {1},
pages = {490},
pmid = {39033276},
issn = {1471-2393},
support = {NIH K12HD103084/NH/NIH HHS/United States ; R35GM138353/GF/NIH HHS/United States ; },
mesh = {Humans ; Female ; Pregnancy ; Case-Control Studies ; Adult ; *Leukocytes ; *Postpartum Period ; *Pre-Eclampsia/blood ; *Premature Birth/epidemiology ; Pilot Projects ; Pregnancy Complications/blood ; Telomere ; Cohort Studies ; Urban Population/statistics & numerical data ; Telomere Shortening ; Young Adult ; },
abstract = {BACKGROUND: Biologic strain such as oxidative stress has been associated with short leukocyte telomere length (LTL), as well as with preeclampsia and spontaneous preterm birth, yet little is known about their relationships with each other. We investigated associations of postpartum maternal LTL with preeclampsia and spontaneous preterm birth.

METHODS: This pilot nested case control study included independent cohorts of pregnant people with singleton gestations from two academic institutions: Cohort 1 (hereafter referred to as Suburban) were enrolled prior to 20 weeks' gestation between 2012 and 2018; and Cohort 2 (hereafter referred to as Urban) were enrolled at delivery between 2000 and 2012. Spontaneous preterm birth or preeclampsia were the selected pregnancy complications and served as cases. Cases were compared with controls from each study cohort of uncomplicated term births. Blood was collected between postpartum day 1 and up to 6 months postpartum and samples were frozen, then simultaneously thawed for analysis. Postpartum LTL was the primary outcome, measured using quantitative polymerase chain reaction (PCR) and compared using linear multivariable regression models adjusting for maternal age. Secondary analyses were done stratified by mode of delivery and self-reported level of stress during pregnancy.

RESULTS: 156 people were included; 66 from the Suburban Cohort and 90 from the Urban Cohort. The Suburban Cohort was predominantly White, Hispanic, higher income and the Urban Cohort was predominantly Black, Haitian, and lower income. We found a trend towards shorter LTLs among people with preeclampsia in the Urban Cohort (6517 versus 6913 bp, p = 0.07), but not in the Suburban Cohort. There were no significant differences in LTLs among people with spontaneous preterm birth compared to term controls in the Suburban Cohort (6044 versus 6144 bp, p = 0.64) or in the Urban Cohort (6717 versus 6913, p = 0.37). No differences were noted by mode of delivery. When stratifying by stress levels in the Urban Cohort, preeclampsia was associated with shorter postpartum LTLs in people with moderate stress levels (p = 0.02).

CONCLUSION: Our exploratory results compare postpartum maternal LTLs between cases with preeclampsia or spontaneous preterm birth and controls in two distinct cohorts. These pilot data contribute to emerging literature on LTLs in pregnancy.},
}

Humans
Female
Pregnancy
Case-Control Studies
Adult
*Leukocytes
*Postpartum Period
*Pre-Eclampsia/blood
*Premature Birth/epidemiology
Pilot Projects
Pregnancy Complications/blood
Telomere
Cohort Studies
Urban Population/statistics & numerical data
Telomere Shortening
Young Adult

@article {pmid39032311,
year = {2024},
author = {Panelli, DM and Mayo, JA and Wong, RJ and Becker, M and Feyaerts, D and Marić, I and Wu, E and Gotlib, IH and Gaudillière, B and Aghaeepour, N and Druzin, ML and Stevenson, DK and Shaw, GM and Bianco, K},
title = {Mode of delivery predicts postpartum maternal leukocyte telomere length.},
journal = {European journal of obstetrics, gynecology, and reproductive biology},
volume = {300},
number = {},
pages = {224-229},
doi = {10.1016/j.ejogrb.2024.07.026},
pmid = {39032311},
issn = {1872-7654},
abstract = {BACKGROUND: Recent studies have suggested that pregnancy accelerates biologic aging, yet little is known about how biomarkers of aging are affected by events during the peripartum period. Given that immune shifts are known to occur following surgery, we explored the relation between mode of delivery and postpartum maternal leukocyte telomere length (LTL), a marker of biologic aging.

STUDY DESIGN: Postpartum maternal blood samples were obtained from a prospective cohort of term, singleton livebirths without hypertensive disorders or peripartum infections between 2012 and 2018. The primary outcome was postpartum LTLs from one blood sample drawn between postpartum week 1 and up to 6 months postpartum, measured from thawed frozen peripheral blood mononuclear cells using quantitative PCR in basepairs (bp). Multivariable linear regression models compared LTLs between vaginal versus cesarean births, adjusting for age, body mass index, and nulliparity as potential confounders. Analyses were conducted in two mutually exclusive groups: those with LTL measured postpartum week 1 and those measured up to 6 months postpartum. Secondarily, we compared multiomics by mode of delivery using machine-learning methods to evaluate whether other biologic changes occurred following cesarean. These included transcriptomics, metabolomics, microbiomics, immunomics, and proteomics (serum and plasma).

RESULTS: Of 67 included people, 50 (74.6 %) had vaginal and 17 (25.4 %) had cesarean births. LTLs were significantly shorter after cesarean in postpartum week 1 (5755.2 bp cesarean versus 6267.8 bp vaginal, p = 0.01) as well as in the later draws (5586.6 versus 5945.6 bp, p = 0.04). After adjusting for confounders, these differences persisted in both week 1 (adjusted beta -496.1, 95 % confidence interval [CI] -891.1, -101.1, p = 0.01) and beyond (adjusted beta -396.8; 95 % CI -727.2, -66.4. p = 0.02). Among the 15 participants who also had complete postpartum multiomics data available, there were predictive signatures of vaginal versus cesarean births in transcriptomics (cell-free [cf]RNA), metabolomics, microbiomics, and proteomics that did not persist after false discovery correction.

CONCLUSION: Maternal LTLs in postpartum week 1 were nearly 500 bp shorter following cesarean. This difference persisted several weeks postpartum, even though other markers of inflammation had normalized. Mode of delivery should be considered in any analyses of postpartum LTLs and further investigation into this phenomenon is warranted.},
}

@article {pmid39031441,
year = {2024},
author = {Djos, A and Svensson, J and Gaarder, J and Umapathy, G and Nilsson, S and Ek, T and Vogt, H and Georgantzi, K and Öra, I and Träger, C and Kogner, P and Martinsson, T and Fransson, S},
title = {Loss of Chromosome Y in Neuroblastoma Is Associated With High-Risk Disease, 11q-Deletion, and Telomere Maintenance.},
journal = {Genes, chromosomes & cancer},
volume = {63},
number = {7},
pages = {e23260},
doi = {10.1002/gcc.23260},
pmid = {39031441},
issn = {1098-2264},
support = {TM 22-156; SF 18-99 18-099//Swedish Childhood Cancer Foundation/ ; PK PR2023-007//Swedish Childhood Cancer Foundation/ ; KP2020-0021//Swedish Childhood Cancer Foundation/ ; PROF2019-0001//Swedish Childhood Cancer Foundation/ ; TM 22-2359//Swedish Cancer Foundation/ ; PK 22-2492 Pj//Swedish Cancer Foundation/ ; ALFGBG-447171//Swedish state under the LUA/ALF agreement/ ; TM 521-2014-3031//Swedish Research Council/ ; TM/PK-RB13-0204//Swedish Foundation for Strategic Research/ ; },
mesh = {Humans ; *Neuroblastoma/genetics/pathology ; Male ; *Chromosomes, Human, Y/genetics ; *Chromosome Deletion ; *Chromosomes, Human, Pair 11/genetics ; Infant ; Child, Preschool ; Female ; Telomere Homeostasis/genetics ; Child ; Histone Demethylases/genetics ; Telomere/genetics ; N-Myc Proto-Oncogene Protein/genetics ; Sweden/epidemiology ; },
abstract = {Neuroblastoma (NB) is a heterogeneous childhood cancer with a slightly higher incidence in boys than girls, with the reason for this gender disparity unknown. Given the growing evidence for the involvement of loss of the Y chromosome (LoY) in male diseases including cancer, we investigated Y chromosome status in NB. Male NB tumor samples from a Swedish cohort, analyzed using Cytoscan HD SNP-microarray, were selected. Seventy NB tumors were analyzed for aneuploidy of the Y chromosome, and these data were correlated with other genetic, biological, and clinical parameters. LoY was found in 21% of the male NB tumors and it was almost exclusively found in those with high-risk genomic profiles. Furthermore, LoY was associated with increased age at diagnosis and enriched in tumors with 11q-deletion and activated telomere maintenance mechanisms. In contrast, tumors with an MYCN-amplified genomic profile retained their Y chromosome. The understanding of LoY in cancer is limited, making it difficult to conclude whether LoY is a driving event in NB or function of increased genomic instability. Gene expression analysis of Y chromosome genes in male NB tumors showed low expression of certain genes correlating with worse overall survival. KDM5D, encoding a histone demethylase stands out as an interesting candidate for further studies. LoY has been shown to impact the epigenomic layer of autosomal loci in nonreproductive tissues, and KDM5D has been reported as downregulated and/or associated with poor survival in different malignancies. Further studies are needed to explore the mechanisms and functional consequences of LoY in NB.},
}

Humans
*Neuroblastoma/genetics/pathology
Male
*Chromosomes, Human, Y/genetics
*Chromosome Deletion
*Chromosomes, Human, Pair 11/genetics
Infant
Child, Preschool
Female
Telomere Homeostasis/genetics
Child
Histone Demethylases/genetics
Telomere/genetics
N-Myc Proto-Oncogene Protein/genetics
Sweden/epidemiology

@article {pmid39030357,
year = {2024},
author = {Jeon, HJ and Levine, MT and Lampson, MA},
title = {Telomere Elongation During Pre-Implantation Embryo Development.},
journal = {Advances in anatomy, embryology, and cell biology},
volume = {238},
number = {},
pages = {121-129},
pmid = {39030357},
issn = {0301-5556},
mesh = {Animals ; *Embryonic Development/genetics ; *Telomere/metabolism ; Humans ; Telomere Homeostasis ; Telomerase/metabolism/genetics ; },
abstract = {The primary mechanism of telomere elongation in mammals is reverse transcription by telomerase. An alternative (ALT) pathway elongates telomeres by homologous recombination in some cancer cells and during pre-implantation embryo development, when telomere length increases rapidly within a few cell cycles. The maternal and paternal telomeres in the zygote are genetically and epigenetically distinct, with differences in telomere length and in chromatin packaging. We discuss models for how these asymmetries may contribute to telomere regulation during the earliest embryonic cell cycles and suggest directions for future research.},
}

Animals
*Embryonic Development/genetics
*Telomere/metabolism
Humans
Telomere Homeostasis
Telomerase/metabolism/genetics

@article {pmid39023108,
year = {2024},
author = {Bem, MMS and Paraizo-Horvath, CMS and Freitas, PS and Brito, TRP},
title = {Is it possible that menopause is associated with telomere length? Findings of an integrative review.},
journal = {Climacteric : the journal of the International Menopause Society},
volume = {},
number = {},
pages = {1-5},
doi = {10.1080/13697137.2024.2376193},
pmid = {39023108},
issn = {1473-0804},
abstract = {OBJECTIVE: Knowing the important repercussions of menopause for women's health and that female longevity can be better understood through studies based on aging biomarkers, studies on the relationship between menopause and telomere shortening may help to better understand this stage of life. This study aimed to analyze what research has been produced regarding the relationship between menopause and telomere length.

METHODS: This integrative literature review included searches in PubMed, CINAHL, LILACS, Web of Science and Scopus databases. Four studies were selected for the final sample.

RESULTS: The findings of these studies indicate that older age for menopause and longer reproductive life (difference between age at menopause and menarche) are associated with longer telomeres, that is, with longevity.

CONCLUSION: The relationship between menopause and telomere length is uncertain. The small number of studies included in this review, and the fact that the results indicate that the relationship between menopause and telomere length may be dependent on the stage of the menopause and race/ethnicity, suggest that additional research focusing on these variables should be carried out.},
}

@article {pmid39021990,
year = {2024},
author = {Nila, NN and Mahmud, Z and Paul, A and Rahman, T and Hossain Howlader, MZ and Hosen, MI},
title = {Investigating the structural and functional consequences of germline single nucleotide polymorphisms located in the genes of the alternative lengthening of telomere (ALT) pathway.},
journal = {Heliyon},
volume = {10},
number = {12},
pages = {e33110},
pmid = {39021990},
issn = {2405-8440},
abstract = {BACKGROUND: The Alternative Lengthening of Telomeres (ALT) pathway represents a non-canonical mechanism of telomere maintenance that operates independently of the conventional telomerase activity. The three biologically significant proteins, designated as SMARCAL1 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1), DAXX (Death domain-associated protein 6) and ATRX (alpha-thalassemia/mental retardation, X-linked) are associated with ALT in certain cancer types. The purpose of this study was to identify the most high-risk nsSNPs (non-synonymous Single Nucleotide Polymorphisms) within these three genes and assess their impacts on the structure and function of the proteins they encode.

METHODS: The reported genetic polymorphisms of SMARCAL1, DAXX and ATRX genes were retrieved from the Ensembl database. Later, various computational tools like PROVEAN, PolyPhen2, SNPs and GO, SNAP2, Predict-SNP, Panther and PMut were used to predict the most deleterious nsSNPs. MutPred was used to understand the underlying molecular reasons of those nsSNPs being deleterious, followed by prediction of Post Translational Modification Sites (PTMs) using ModPred. I-Mutant and MUpro were used to predict the effect of SNP on energy stability. Later, 3D clustering analysis was done using Mutation 3D server. Moreover, ConSurf was utilized to identify the conservation scores of wild-type amino acids. Additionally, the NCBI conserved domain search tool was employed to pinpoint conserved domains within these three proteins. Project-Hope helped for biophysical validation, followed by prediction of these genes' interaction and function by using GeneMANIA.

RESULT: Analysis on SMARCAL1 protein revealed that among 665 nsSNPs, four were identified as the most deleterious: L578S, T581S, P582A, and P582S. Similarly, within the DAXX protein, among a pool of 480 nsSNPs, P284S, R230C, and R230S were found out to be the most deleterious variants. In case of ATRX protein, V178D, R246C, and V277G, from the total of 1009 nsSNPs, were predicted to be the most deleterious. All these nsSNPs were found to occur at residue positions that are 100 % conserved within protein domains and were predicted to be most damaging from both structural and functional perspectives and highly destabilizing to their corresponding proteins.

CONCLUSION: Computational investigation on the 3 proteins-SMARCAL1, DAXX and ATRX through different bioinformatics analysis tools concludes that the identified high risk nsSNPs of these proteins are pathogenic SNPs. These variants potentially exert functional and structural influences, thus making them valuable candidates for future genetic studies.},
}

@article {pmid39019487,
year = {2024},
author = {Salberg, S and Smith, MJ and Lamont, R and Chen, Z and Beauchamp, MH and Craig, W and Doan, Q and Gravel, J and Zemek, R and Lannin, NA and Yeates, KO and Mychasiuk, R},
title = {Shorter Telomere Length Is Associated With Older Age, Poor Sleep Hygiene, and Orthopedic Injury, but Not Mild Traumatic Brain Injury, in a Cohort of Canadian Children.},
journal = {The Journal of head trauma rehabilitation},
volume = {},
number = {},
pages = {},
pmid = {39019487},
issn = {1550-509X},
abstract = {BACKGROUND: Predicting recovery following pediatric mild traumatic brain injury (mTBI) remains challenging. The identification of objective biomarkers for prognostic purposes could improve clinical outcomes. Telomere length (TL) has previously been used as a prognostic marker of cellular health in the context of mTBI and other neurobiological conditions. While psychosocial and environmental factors are associated with recovery outcomes following pediatric mTBI, the relationship between these factors and TL has not been investigated. This study sought to examine the relationships between TL and psychosocial and environmental factors, in a cohort of Canadian children with mTBI or orthopedic injury (OI).

METHODS: Saliva was collected at a postacute (median 7 days) timepoint following injury to assess TL from a prospective longitudinal cohort of children aged 8 to 17 years with either mTBI (n = 202) or OI (n = 90), recruited from 3 Canadian sites. Questionnaires regarding psychosocial and environmental factors were obtained at a postacute follow-up visit and injury outcomes were assessed at a 3-month visit. Univariable associations between TL and psychosocial, environmental, and outcome variables were assessed using Spearman's correlation. Further adjusted analyses of these associations were performed by including injury group, age, sex, and site as covariates in multivariable generalized linear models with a Poisson family, log link function, and robust variance estimates.

RESULTS: After adjusting for age, sex, and site, TL in participants with OI was 7% shorter than those with mTBI (adjusted mean ratio = 0.93; 95% confidence interval, 0.89-0.98; P = .003). As expected, increasing age was negatively associated with TL (Spearman's r = -0.14, P = .016). Sleep hygiene at 3 months was positively associated with TL (adjusted mean ratio = 1.010; 95% confidence interval, 1.001-1.020; P = .039).

CONCLUSION: The relationships between TL and psychosocial and environmental factors in pediatric mTBI and OI are complex. TL may provide information regarding sleep quality in children recovering from mTBI or OI; however, further investigation into TL biomarker validity should employ a noninjured comparison group.},
}

@article {pmid39013662,
year = {2024},
author = {Band, G and Leffler, EM},
title = {Malaria endemicity linked to shorter telomeres in leukocytes.},
journal = {Trends in parasitology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.pt.2024.06.017},
pmid = {39013662},
issn = {1471-5007},
abstract = {Leukocyte telomere length is a highly polygenic trait that has been associated with a complex range of lifestyle factors and disease risk. McQuillan et al.'s results comparing telomere length to malaria incidence rates suggest that infections may be another important factor, possibly through permanent shortening of telomeres in hematopoietic progenitor cells.},
}

@article {pmid39013263,
year = {2024},
author = {Martínez-Ezquerro, JD and Ortiz-Ramírez, M and García-delaTorre, P and González-Covarrubias, V and Sánchez-García, S},
title = {Physical Performance and Telomere Length in Older Adults.},
journal = {Archives of medical research},
volume = {55},
number = {6},
pages = {103046},
doi = {10.1016/j.arcmed.2024.103046},
pmid = {39013263},
issn = {1873-5487},
abstract = {BACKGROUND: The aging population prompts studying risk factors and markers to predict healthy aging. Telomere length is a promising candidate for assessing various age-related traits.

AIM OF THE STUDY: To investigate the association between physical performance and telomere length.

METHODS: We enrolled 323 older Mexican adults from the "Cohort of Obesity, Sarcopenia, and Frailty of Older Mexican Adults" affiliated with the Instituto Mexicano del Seguro Social and assessed their physical performance using the Short Physical Performance Battery, dividing participants into low (≤7) and high (>7) groups. Absolute telomere length was determined by qPCR, and individuals were classified into short (≤4.22 kb) and long (>4.22 kb) groups. We calculated the mean and adjusted mean, considering sex and age, among others, with 95% CI. We estimated the effect size between physical performance and telomere length using Cohen's d for unequal group sizes and calculated the odds ratio for physical performance based on telomere length.

RESULTS: Participants with low physical performance had significantly shorter telomeres (mean 4.14.44.7 kb, adjusted mean 3.54.04.5 kb, p <0.001), while those with high physical performance exhibited longer telomeres (mean 5.55.75.9 kb, adjusted mean 4.75.35.8 kb, p <0.001), with a medium-to-high telomere length effect size (d = 0.762). The odds of low physical activity increased 2.13.66.1-fold per kb of telomere attrition (adjOR 1.73.36.3, p <0.001).

CONCLUSION: Decreased physical function is associated with shorter telomere length. Absolute telomere length presents a promising biomarker for distinguishing between healthy and unhealthy aging, warranting further investigation.},
}

@article {pmid39012375,
year = {2024},
author = {Kallingal, A and Krzemieniecki, R and Maciejewska, N and Brankiewicz-Kopcińska, W and Baginski, M},
title = {TRF1 and TRF2: pioneering targets in telomere-based cancer therapy.},
journal = {Journal of cancer research and clinical oncology},
volume = {150},
number = {7},
pages = {353},
pmid = {39012375},
issn = {1432-1335},
mesh = {Humans ; *Neoplasms/genetics/drug therapy/metabolism/therapy ; *Telomeric Repeat Binding Protein 2/metabolism/genetics ; *Telomeric Repeat Binding Protein 1/metabolism/genetics ; *Telomere/metabolism ; Molecular Targeted Therapy/methods ; Antineoplastic Agents/therapeutic use/pharmacology ; Shelterin Complex ; Telomere-Binding Proteins ; },
abstract = {This article presents an in-depth exploration of the roles of Telomere Repeat-binding Factors 1 and 2 (TRF1 and TRF2), and the shelterin complex, in the context of cancer biology. It emphasizes their emerging significance as potential biomarkers and targets for therapeutic intervention. Central to the shelterin complex, TRF1 and TRF2 are crucial in maintaining telomere integrity and genomic stability, their dysregulation often being a hallmark of cancerous cells. The article delves into the diagnostic and prognostic capabilities of TRF1 and TRF2 across various cancer types, highlighting their sensitivity and specificity. Furthermore, it reviews current strides in drug discovery targeting the shelterin complex, detailing specific compounds and their modes of action. The review candidly addresses the challenges in developing therapies aimed at the shelterin complex, including drug resistance, off-target effects, and issues in drug delivery. By synthesizing recent research findings, the article sheds light on the intricate relationship between telomere biology and cancer development. It underscores the urgency for continued research to navigate the existing challenges and fully leverage the therapeutic potential of TRF1, TRF2, and the shelterin complex in the realm of cancer treatment.},
}

Humans
*Neoplasms/genetics/drug therapy/metabolism/therapy
*Telomeric Repeat Binding Protein 2/metabolism/genetics
*Telomeric Repeat Binding Protein 1/metabolism/genetics
*Telomere/metabolism
Molecular Targeted Therapy/methods
Antineoplastic Agents/therapeutic use/pharmacology
Shelterin Complex
Telomere-Binding Proteins

@article {pmid39010148,
year = {2024},
author = {Yang, Q and Zhang, J and Fan, Z},
title = {Causal association between telomere length and female reproductive endocrine diseases: a univariable and multivariable Mendelian randomization analysis.},
journal = {Journal of ovarian research},
volume = {17},
number = {1},
pages = {146},
pmid = {39010148},
issn = {1757-2215},
abstract = {BACKGROUND: The relationship between leukocyte telomere length (LTL) and female reproductive endocrine diseases has gained significant attention and research interest in recent years. However, there is still limited understanding of the exact impacts of LTL on these diseases. Therefore, the primary objective of this study was to investigate the genetic causal association between LTL and female reproductive endocrine diseases by employing Mendelian randomization (MR) analysis.

METHODS: Instruments for assessing genetic variation associated with exposure and outcome were derived from summary data of published genome-wide association studies (GWAS). Inverse-variance weighted (IVW) was utilized as the main analysis method to investigate the causal relationship between LTL and female reproductive endocrine diseases. The exposure data were obtained from the UK Biobanks GWAS dataset, comprising 472,174 participants of European ancestry. The outcome data were acquired from the FinnGen consortium, including abnormal uterine bleeding (menorrhagia and oligomenorrhea), endometriosis (ovarian endometrioma and adenomyosis), infertility, polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI) and premenstrual syndrome (PMS). Furthermore, to account for potential confounding factors such as smoking, alcohol consumption, insomnia, body mass index (BMI) and a history of pelvic inflammatory disease (PID), multivariable MR (MVMR) analysis was also conducted. Lastly, a series of pleiotropy tests and sensitivity analyses were performed to ensure the reliability and robustness of our findings. P < 0.0063 was considered to indicate statistically significant causality following Bonferroni correction.

RESULTS: Our univariable MR analysis demonstrated that longer LTL was causally associated with an increased risk of menorrhagia (IVW: odds ratio [OR]: 1.1803; 95% confidence interval [CI]: 1.0880-1.2804; P = 0.0001) and ovarian endometrioma (IVW: OR: 1.2946; 95%CI: 1.0970-1.5278; P = 0.0022) at the Bonferroni significance level. However, no significant correlation was observed between LTL and oligomenorrhea (IVW: OR: 1.0124; 95%CI: 0.7350-1.3946; P = 0.9398), adenomyosis (IVW: OR: 1.1978; 95%CI: 0.9983-1.4372; P = 0.0522), infertility (IVW: OR: 1.0735; 95%CI: 0.9671-1.1915; P = 0.1828), PCOS (IVW: OR: 1.0633; 95%CI: 0.7919-1.4278; P = 0.6829), POI (IVW: OR: 0.8971; 95%CI: 0.5644-1.4257; P = 0.6459) or PMS (IVW: OR: 0.7749; 95%CI: 0.4137-1.4513; P = 0.4256). Reverse MR analysis indicated that female reproductive endocrine diseases have no causal effect on LTL. MVMR analysis suggested that the causal effect of LTL on menorrhagia and ovarian endometrioma remained significant after accounting for smoking, alcohol consumption, insomnia, BMI and a history of PID. Pleiotropic and sensitivity analyses also showed robustness of our results.

CONCLUSION: The results of our bidirectional two-sample MR analysis revealed that genetically predicted longer LTL significantly increased the risk of menorrhagia and ovarian endometrioma, which is consistent with the findings from MVMR studies. However, we did not notice any significant effects of LTL on oligomenorrhea, adenomyosis, infertility, PCOS, POI or PMS. Additionally, reproductive endocrine disorders were found to have no impact on LTL. To enhance our understanding of the effect and underlying mechanism of LTL on female reproductive endocrine diseases, further large-scale studies are warranted in the future.},
}

@article {pmid39005478,
year = {2024},
author = {Comstock, W and Sanford, E and Navarro, M and Smolka, MB},
title = {Profiling Tel1 Signaling Reveals a Non-Canonical Motif Targeting DNA Repair and Telomere Control Machineries.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.07.03.601872},
pmid = {39005478},
issn = {2692-8205},
abstract = {The stability of the genome relies on Phosphatidyl Inositol 3-Kinase-related Kinases (PIKKs) that sense DNA damage and trigger elaborate downstream signaling responses. In S. cerevisiae , the Tel1 kinase (ortholog of human ATM) is activated at DNA double strand breaks (DSBs) and short telomeres. Despite the well-established roles of Tel1 in the control of telomere maintenance, suppression of chromosomal rearrangements, activation of cell cycle checkpoints, and repair of DSBs, the substrates through which Tel1 controls these processes remain incompletely understood. Here we performed an in depth phosphoproteomic screen for Tel1-dependent phosphorylation events. To achieve maximal coverage of the phosphoproteome, we developed a scaled-up approach that accommodates large amounts of protein extracts and chromatographic fractions. Compared to previous reports, we expanded the number of detected Tel1-dependent phosphorylation events by over 10-fold. Surprisingly, in addition to the identification of phosphorylation sites featuring the canonical motif for Tel1 phosphorylation (S/T-Q), the results revealed a novel motif (D/E-S/T) highly prevalent and enriched in the set of Tel1-dependent events. This motif is unique to Tel1 signaling and not shared with the Mec1 kinase, providing clues to how Tel1 plays specialized roles in DNA repair and telomere length control. Overall, these findings define a Tel1-signaling network targeting numerous proteins involved in DNA repair, chromatin regulation, and telomere maintenance that represents a framework for dissecting the molecular mechanisms of Tel1 action.},
}

@article {pmid39002862,
year = {2024},
author = {Dimitrov, M and Merkle, S and Cao, Q and Tryon, RK and Vercellotti, GM and Holtan, SG and Kao, RL and Srikanthan, M and Terezakis, SA and Tolar, J and Ebens, CL},
title = {Allogeneic hematopoietic cell transplant for bone marrow failure or myelodysplastic syndrome in dyskeratosis congenita/telomere biology disorders: Single-center single-arm open-label trial of reduced intensity conditioning without radiation.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2024.07.007},
pmid = {39002862},
issn = {2666-6367},
abstract = {BACKGROUND: Dyskeratosis congenita/Telomere biology disorders (DC/TBD) often manifest as bone marrow failure (BMF) or myelodysplastic syndrome (MDS). Allogeneic hematopoietic cell transplant (alloHCT) rescues hematologic complications, but radiation and alkylator-based conditioning regimens cause diffuse whole-body toxicity and may expedite DC/TBD-specific non-hematopoietic complications. Optimization of conditioning intensity in DC/TBD to allow for donor hematopoietic cell engraftment with the least amount of toxicity remains a critical goal of the alloHCT field.

OBJECTIVES/STUDY DESIGN: We report prospectively collected standard alloHCT outcomes from a single-center single-arm open-label clinical trial of bone marrow or peripheral blood stem cell alloHCT for DC/TBD-associated BMF or MDS. Conditioning was reduced intensity (RIC) including alemtuzumab 1mg/kg, fludarabine 200 mg/m[2], and cyclophosphamide 50 mg/kg. A previous single-arm open-label phase II clinical trial for the same patient population conducted at the same center, differing only by inclusion of 200 centigray of total body irradiation (TBI), served as a control cohort.

RESULTS: The Non-TBI cohort included 10 patients (ages 1.7-65.9 years, median follow-up of 3.9 years) compared to the control TBI cohort which included 12 patients (ages 2.2-52.2 years, median follow-up of 10.5 years). Baseline characteristics differed only in total CD34+ cells received, with a median of 5.6 (Non-TBI) compared to 2.6 (TBI) x 10[6]/kg (p=0.02; no difference in total nucleated cells). The cumulative incidence of day +100 grade II-IV acute and 4-year chronic graft-versus-host disease (GvHD) were low at 0 and 10% (Non-TBI) and 8 and 17% (TBI), respectively (acute, p=0.36; chronic, p=0.72). Primary graft failure was absent. Secondary non-neutropenic graft failure occurred in one (Non-TBI cohort). The Non-TBI cohort demonstrated delayed achievement of full donor chimerism but superior lymphocyte recovery. There was no difference in 4-year overall survival at 80% (Non-TBI) and 75% (TBI; p=0.78). MDS as an indication for alloHCT was uncommon, but overall associated with poor outcomes. There were 3 MDS patients in the Non-TBI cohort: 1 relapsed and died at day+387; 1 relapsed at day+500 and is alive 5.5 years later following salvage with a 2[nd] alloHCT; 1 relapsed at day+1093 and is alive at day +100 after a 2[nd] alloHCT. There was 1 MDS patient in the TBI cohort who achieved 100% donor myeloid engraftment without relapse but died at day+827 from a bacterial infection in the setting of immune mediated cytopenia.

CONCLUSION: Elimination of TBI from the RIC regimen for DC/TBD was not associated with significant changes in rates of graft failure, GvHD, and overall survival, but was associated with delayed achievement of full donor chimerism and improved lymphocyte reconstitution. For DC/TBD-associated BMF, TBI appears to be dispensable. Optimal approaches to DC/TBD-associated MDS remain unclear. Larger cohorts are needed to better assess the unique contribution of TBI and donor CD34+ cell dose. Longer follow-up is required to assess differences in DC/TBD complications and late effects.},
}

@article {pmid39002254,
year = {2024},
author = {Redon, L and Constant, T and Smith, S and Habold, C and Giroud, S},
title = {Understanding seasonal telomere length dynamics in hibernating species.},
journal = {Journal of thermal biology},
volume = {123},
number = {},
pages = {103913},
doi = {10.1016/j.jtherbio.2024.103913},
pmid = {39002254},
issn = {0306-4565},
abstract = {Oxidative stress is thought to be one of the main causes of ageing as it progressively damages cell components throughout life, eventually causing cellular failure and apoptosis. In many organisms, telomeres shorten throughout life under the effect of, amongst other factors, oxidative stress, and are therefore commonly used as marker of biological ageing. However, hibernators, which are regularly exposed to acute oxidative stress when rewarming from torpor, are unexpectedly long-lived. In this review, we explore the causes of oxidative stress associated with hibernation and its impact on telomere dynamics in different taxa, focussing on hibernating rodents. We then speculate on the adaptive mechanisms of hibernators to compensate for the effects of oxidative stress, which may explain their increased longevity. Because winter hibernation appears to be associated with high oxidative stress, hibernators, particularly rodents, may periodically invest in repair mechanisms and antioxidant defences, resulting in seasonal variations in telomere lengths. This research shows how species with a slow life-history strategy deal with large changes in oxidative stress, unifying evolutionary and physiological theories of ageing. Because of the marked seasonal variation in telomere length, we also draw attention when using telomeres as markers for biological aging in seasonal heterotherms and possibly in other highly seasonal species.},
}

@article {pmid39001954,
year = {2024},
author = {Boccardi, V and Cari, L and Bastiani, P and Scamosci, M and Cecchetti, R and Nocentini, G and Mecocci, P},
title = {Aberrant telomeric structures and serum markers of telomere dysfunction in healthy aging: a preliminary study.},
journal = {Biogerontology},
volume = {},
number = {},
pages = {},
pmid = {39001954},
issn = {1573-6768},
abstract = {Telomeres undergo a progressive shortening process as individuals age, and it has been proposed that severely shortened and dysfunctional telomeres play a role in the aging process and the onset of age-related diseases in human beings. An emerging body of evidence indicates that the shortening of telomeres in cultured human cells is also influenced by other replication defects occurring within telomeric repeats. These abnormalities can be detected on metaphase chromosomes. Recent studies have also identified a set of serological markers for telomere dysfunction and DNA damage (elongation factor 1α [EF-1α], stathmin, and N-acetyl-glucosaminidase). With this study, the correlation between telomere abnormalities (by FISH) and these biomarkers as measured in blood serum (by ELISA) from a cohort of 22 healthy subjects at different ages (range 26-101 years) was analyzed. A strong positive correlation between aging and the presence of aberrant telomere structures, sister telomere loss (STL), and sister telomere chromatid fusions (STCF) was detected. When serum markers of telomere dysfunction were correlated with telomere abnormalities, we found that stathmin correlated with total aberrant telomeres structures (r = 0.431, p = 0.0453) and STCF (r = 0.533, p = 0.0107). These findings suggest that serum stathmin can be considered an easy-to-get marker of telomere dysfunction and may serve as valuable indicators of aging.},
}

@article {pmid39001406,
year = {2024},
author = {Park, M and Lee, DE and Hong, Y and Suh, JK and Lee, JA and Kim, M and Park, HJ},
title = {Telomere Length in Adolescent and Young Adult Survivors of Childhood Cancer.},
journal = {Cancers},
volume = {16},
number = {13},
pages = {},
doi = {10.3390/cancers16132344},
pmid = {39001406},
issn = {2072-6694},
support = {2022-0195//National Cancer Center/Republic of Korea ; },
abstract = {We examined the leukocyte relative telomere length (RTL) in Korean adolescent and young adult (AYA) survivors of childhood cancer and evaluated the association of leukocyte RTL with multiple factors, including malignancy type, cancer treatment, age, and chronic health conditions (CHCs). Eighty-eight AYA survivors of childhood cancer with a median follow-up period of 73 months were recruited. RTL in pediatric cancer survivors was not significantly shorter than the predicted value for age-matched references. Neither age at diagnosis nor duration of therapy influenced the RTL. Among the 43 patients with hematologic malignancies, those who underwent allogeneic hematopoietic stem cell transplantation (HSCT) showed a significant shortening of the RTL compared with those who did not (p = 0.039). Among the 15 patients who underwent allogeneic HSCT, those who developed acute graft-versus-host disease (GVHD) of grade II or higher had significantly shorter RTL than those who did not (p = 0.012). Patients with grade II CHCs had significantly shorter RTL than those without CHCs or with grade I CHCs (p = 0.001). Survivors with ≥2 CHCs also exhibited shorter RTL (p = 0.027). Overall, pediatric cancer survivors had similar telomere lengths compared to age-matched references. HSCT recipients and patients with severe or multiple CHCs had shorter telomeres. GVHD augmented telomere attrition in HSCT recipients.},
}

@article {pmid38993011,
year = {2024},
author = {Chik, HYJ and Mannarelli, ME and Dos Remedios, N and Simons, MJP and Burke, T and Schroeder, J and Dugdale, HL},
title = {Adult telomere length is positively correlated with survival and lifetime reproductive success in a wild passerine.},
journal = {Molecular ecology},
volume = {},
number = {},
pages = {e17455},
doi = {10.1111/mec.17455},
pmid = {38993011},
issn = {1365-294X},
support = {PCIG12-GA-2012-333096/ERC_/European Research Council/International ; NE/J024567/1//Natural Environment Research Council/ ; },
abstract = {Explaining variation in individual fitness is a key goal in evolutionary biology. Recently, telomeres, repeating DNA sequences capping chromosome ends, have gained attention as a biomarker for body state, physiological costs, and senescence. Existing research has provided mixed evidence for whether telomere length correlates with fitness, including survival and reproductive output. Moreover, few studies have examined how the rate of change in telomere length correlates with fitness in wild populations. Here, we intensively monitored an insular population of house sparrows, and collected longitudinal telomere and life history data (16 years, 1225 individuals). We tested whether telomere length and its rate of change predict fitness measures, namely survival, lifespan and annual and lifetime reproductive effort and success. Telomere length positively predicted short-term survival, independent of age, but did not predict lifespan, suggesting either a diminishing telomere length-survival correlation with age or other extrinsic factors of mortality. The positive association of telomere length with survival translated into reproductive benefits, as birds with longer telomeres produced more genetic recruits, hatchlings and reared more fledglings over their lifetime. In contrast, there was no association between telomere dynamics and annual reproductive output, suggesting telomere dynamics might not reflect the costs of reproduction in this population, potentially masked by variation in individual quality. The rate of change of telomere length did not correlate with neither lifespan nor lifetime reproductive success. Our results provide further evidence that telomere length correlates with fitness, and contribute to our understanding of the selection on, and evolution of, telomere dynamics.},
}

@article {pmid38987851,
year = {2024},
author = {Yin, Q and Tang, TT and Lu, XY and Ni, WJ and Yin, D and Zhang, YL and Jiang, W and Zhang, Y and Li, ZL and Wen, Y and Gan, WH and Zhang, AQ and Lv, LL and Wang, B and Liu, BC},
title = {Macrophage-derived exosomes promote telomere fragility and senescence in tubular epithelial cells by delivering miR-155.},
journal = {Cell communication and signaling : CCS},
volume = {22},
number = {1},
pages = {357},
pmid = {38987851},
issn = {1478-811X},
support = {82070735;82030024;81720108007//National Natural Science Foundation of China/ ; 82070735;82030024;81720108007//National Natural Science Foundation of China/ ; 2018YFC130046, 2018YFC1314000//National Key Research Programme of Ministry of Science and Technology/ ; },
abstract = {BACKGROUND: Chronic kidney disease (CKD) is highly prevalent worldwide, and its global burden is substantial and growing. CKD displays a number of features of accelerated senescence. Tubular cell senescence is a common biological process that contributes to CKD progression. Tubulointerstitial inflammation is a driver of tubular cell senescence and a common characteristic of CKD. However, the mechanism by which the interstitial inflammation drives tubular cell senescence remains unclear. This paper aims to explore the role of exosomal miRNAs derived from macrophages in the development of tubular cell senescence.

METHODS: Among the identified inflammation-related miRNAs, miR-155 is considered to be one of the most important miRNAs involved in the inflammatory response. Macrophages, the primary immune cells that mediate inflammatory processes, contain a high abundance of miR-155 in their released exosomes. We assessed the potential role of miR-155 in tubular cell senescence and renal fibrosis. We subjected miR-155[-/-] mice and wild-type controls, as well as tubular epithelial cells (TECs), to angiotensin II (AngII)-induced kidney injury. We assessed kidney function and injury using standard techniques. TECs were evaluated for cell senescence and telomere dysfunction in vivo and in vitro. Telomeres were measured by the fluorescence in situ hybridization.

RESULTS: Compared with normal controls, miR-155 was up-regulated in proximal renal tubule cells in CKD patients and mouse models of CKD. Moreover, the expression of miR-155 was positively correlated with the extent of renal fibrosis, eGFR decline and p16[INK4A] expression. The overexpression of miR-155 exacerbated tubular senescence, evidenced by increased detection of p16[INK4A]/p21expression and senescence-associated β-galactosidase activity. Notably, miR-155 knockout attenuates renal fibrosis and tubule cell senescence in vivo. Interestingly, once released, macrophages-derived exosomal miR-155 was internalized by TECs, leading to telomere shortening and dysfunction through targeting TRF1. A dual-luciferase reporter assay confirmed that TRF1 was the direct target of miR-155. Thus, our study clearly demonstrates that exosomal miR-155 may mediate communication between macrophages and TECs, subsequently inducing telomere dysfunction and senescence in TECs.

CONCLUSIONS: Our work suggests a new mechanism by which macrophage exosomes are involved in the development of tubule senescence and renal fibrosis, in part by delivering miR-155 to target TRF1 to promote telomere dysfunction. Our study may provide novel strategies for the treatment of AngII-induced kidney injury.},
}

@article {pmid38979576,
year = {2024},
author = {Semper, C and Watanabe, N and Karimullina, E and Patel, DT and Di Leo, R and Castellanos, M and Patel, DH and Chaconas, G and Savchenko, A},
title = {Structure analysis of the telomere resolvase from the Lyme disease spirochete Borrelia garinii reveals functional divergence of its C-terminal domain.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkae580},
pmid = {38979576},
issn = {1362-4962},
support = {//National Institute of Allergy and Infectious Diseases/ ; HHSN272201700060C/NH/NIH HHS/United States ; /HH/HHS/United States ; PJT-153336/CAPMC/CIHR/Canada ; },
abstract = {Borrelia spirochetes are the causative agents of Lyme disease and relapsing fever, two of the most common tick-borne illnesses. A characteristic feature of these spirochetes is their highly segmented genomes which consists of a linear chromosome and a mixture of up to approximately 24 linear and circular extrachromosomal plasmids. The complexity of this genomic arrangement requires multiple strategies for efficient replication and partitioning during cell division, including the generation of hairpin ends found on linear replicons mediated by the essential enzyme ResT, a telomere resolvase. Using an integrative structural biology approach employing advanced modelling, circular dichroism, X-ray crystallography and small-angle X-ray scattering, we have generated high resolution structural data on ResT from B. garinii. Our data provides the first high-resolution structures of ResT from Borrelia spirochetes and revealed active site positioning in the catalytic domain. We also demonstrate that the C-terminal domain of ResT is required for both transesterification steps of telomere resolution, and is a requirement for DNA binding, distinguishing ResT from other telomere resolvases from phage and bacteria. These results advance our understanding of the molecular function of this essential enzyme involved in genome maintenance in Borrelia pathogens.},
}

@article {pmid38977857,
year = {2024},
author = {Zhang, Y and Zhao, M and Tan, J and Huang, M and Chu, X and Li, Y and Han, X and Fang, T and Tian, Y and Jarret, R and Lu, D and Chen, Y and Xue, L and Li, X and Qin, G and Li, B and Sun, Y and Deng, XW and Deng, Y and Zhang, X and He, H},
title = {Telomere-to-telomere Citrullus super-pangenome provides direction for watermelon breeding.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {38977857},
issn = {1546-1718},
abstract = {To decipher the genetic diversity within the cucurbit genus Citrullus, we generated telomere-to-telomere (T2T) assemblies of 27 distinct genotypes, encompassing all seven Citrullus species. This T2T super-pangenome has expanded the previously published reference genome, T2T-G42, by adding 399.2 Mb and 11,225 genes. Comparative analysis has unveiled gene variants and structural variations (SVs), shedding light on watermelon evolution and domestication processes that enhanced attributes such as bitterness and sugar content while compromising disease resistance. Multidisease-resistant loci from Citrullus amarus and Citrullus mucosospermus were successfully introduced into cultivated Citrullus lanatus. The SVs identified in C. lanatus have not only been inherited from cordophanus but also from C. mucosospermus, suggesting additional ancestors beyond cordophanus in the lineage of cultivated watermelon. Our investigation substantially improves the comprehension of watermelon genome diversity, furnishing comprehensive reference genomes for all Citrullus species. This advancement aids in the exploration and genetic enhancement of watermelon using its wild relatives.},
}

@article {pmid38974386,
year = {2024},
author = {Zhang, Z and Zhang, J and Zhang, K and Ge, X and Zhai, X},
title = {Robust evidence supports a causal link between higher birthweight and longer telomere length: a mendelian randomization study.},
journal = {Frontiers in genetics},
volume = {15},
number = {},
pages = {1264028},
pmid = {38974386},
issn = {1664-8021},
abstract = {BACKGROUND: Observational studies have suggested a potential relationship between birthweight and telomere length. However, the causal link between these two parameters remains undefined. In this study, we use Mendelian Randomization (MR). This method employs genetic variants as instrumental variables, to explore the existence of causal associations and elucidate the causal relationship between birth weight and telomere length.

METHODS: We used 35 single nucleotide polymorphisms (SNPs) as instrumental variables for birth weight. These SNPs were identified from a meta-analysis involving 153,781 individuals. Furthermore, we obtained summary statistics for telomere length from a study conducted on 472,174 United Kingdom Biobank participants. To evaluate the causal estimates, we applied the random effect inverse variance weighted method (IVW) and several other MR methods, such as MR-Egger, weighted median, and MR-PRESSO, to verify the reliability of our findings.

RESULTS: Our analysis supports a significant causal relationship between genetically predicted birth weight and telomer3e length. The inverse variance weighted analysis results for birth weight (Beta = 0.048; 95%CI = 0.023 to 0.073; p < 0.001) corroborate this association.

CONCLUSION: Our study provides robust evidence supporting a causal link between higher birth weight and longer telomere length.},
}

@article {pmid38973734,
year = {2024},
author = {Farzan, SF and Niu, Z and Guo, F and Shahriar, M and Kibriya, MG and Jasmine, F and Sarwar, G and Jackson, BP and Ahsan, H and Argos, M},
title = {Exposure to metal mixtures and telomere length in Bangladeshi children.},
journal = {American journal of epidemiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/aje/kwae181},
pmid = {38973734},
issn = {1476-6256},
abstract = {Telomere length is associated with chronic diseases and in younger populations, may represent a biomarker of disease susceptibility. As growing evidence suggests that environmental factors, including metals, may impact telomere length, we investigated the association between 17 metals measured in toenail samples and leukocyte relative telomere length (RTL), among 472 five- to seven-year-old children enrolled in the Bangladesh Environmental Research in Children's Health (BiRCH) cohort. In single exposure linear regression models, a doubling of arsenic (As) and mercury (Hg) (μg/g) were associated with a -0.21 (95%CI: -0.032, -0.010; p=0.0005) and -0.017 (95%CI: -0.029, -0.004; p=0.006) difference in RTL, respectively. In Bayesian Kernel Machine Regression (BKMR) mixture models, the overall metal mixture was inversely associated with RTL (P-for-trend <0.001). Negative associations with RTL were observed with both log2-As and log2-Hg, while an inverted U-shaped association was observed for log2-zinc (Zn) with RTL. We found little evidence of interaction among metals. Sex-stratification identified stronger associations of the overall mixture and log2-As with RTL among females, compared to males. Our study suggests that As and Hg may independently influence RTL in mid-childhood. Further studies are needed to investigate potential long-term impacts of metal-associated telomere shortening in childhood on health outcomes in adult life.},
}

@article {pmid38972874,
year = {2024},
author = {Zhao, H and Zhou, H and Sun, G and Dong, B and Zhu, W and Mu, X and Li, X and Wang, J and Zhao, M and Yang, W and Zhang, G and Ji, R and Geng, T and Gong, D and Meng, H and Wang, J},
title = {Telomere-to-telomere genome assembly of the goose Anser cygnoides.},
journal = {Scientific data},
volume = {11},
number = {1},
pages = {741},
pmid = {38972874},
issn = {2052-4463},
mesh = {Animals ; *Geese/genetics ; *Telomere/genetics ; *Genome ; Molecular Sequence Annotation ; },
abstract = {Our study presents the assembly of a high-quality Taihu goose genome at the Telomere-to-Telomere (T2T) level. By employing advanced sequencing technologies, including Pacific Biosciences HiFi reads, Oxford Nanopore long reads, Illumina short reads, and chromatin conformation capture (Hi-C), we achieved an exceptional assembly. The T2T assembly encompasses a total length of 1,197,991,206 bp, with contigs N50 reaching 33,928,929 bp and scaffold N50 attaining 81,007,908 bp. It consists of 73 scaffolds, including 38 autosomes and one pair of Z/W sex chromosomes. Importantly, 33 autosomes were assembled without any gap, resulting in a contiguous representation. Furthermore, gene annotation efforts identified 34,898 genes, including 436,162 RNA transcripts, encompassing 806,158 exons, 743,910 introns, 651,148 coding sequences (CDS), and 135,622 untranslated regions (UTR). The T2T-level chromosome-scale goose genome assembly provides a vital foundation for future genetic improvement and understanding the genetic mechanisms underlying important traits in geese.},
}

Animals
*Geese/genetics
*Telomere/genetics
*Genome
Molecular Sequence Annotation

@article {pmid38967394,
year = {2024},
author = {Liang, C and Zhao, R and Du, J and Zhao, G and Zhang, Y},
title = {The association between dietary selenium intake and telomere length in hypertension.},
journal = {Journal of clinical hypertension (Greenwich, Conn.)},
volume = {},
number = {},
pages = {},
doi = {10.1111/jch.14861},
pmid = {38967394},
issn = {1751-7176},
support = {82100283//National Natural Science Foundation of China/ ; 82270407//National Natural Science Foundation of China/ ; 232102310181//The Scientific and Technological Project of Henan Province/ ; },
abstract = {Telomere length is closely linked to biological aging, oxidative stress, and the development of cardiovascular diseases. This study aimed to assess the association between dietary selenium intake and telomere length in individuals with hypertension. Data on dietary selenium intake were captured through the National Health and Nutrition Examination Survey (NHANES) computer-assisted dietary interview system (CADI). Telomere length determination entailed selecting blood samples from all participants in the NHANES database. The analysis was performed using Analysis System software, with Empower stats utilized for data analysis. Results showed that there was a significant association between dietary selenium intake and telomere length in hypertension, particularly within the female group. In female hypertension cases, a 1 mcg increase in dietary selenium intake corresponded to a telomere length increase of 1.19 bp, even after adjusting for age, race, BMI, marital status, physical activity, energy intake, and stroke history. The relationship between dietary selenium intake and telomere length exhibited a linear pattern in female hypertension patients. This study identified a positive association between dietary selenium intake and telomere length in hypertension, particularly within the female group.},
}

@article {pmid38966866,
year = {2024},
author = {Yang, T and Cai, Y and Huang, T and Yang, D and Yang, X and Yin, X and Zhang, C and Yang, Y and Yang, Y},
title = {A telomere-to-telomere gap-free reference genome assembly of avocado provides useful resources for identifying genes related to fatty acid biosynthesis and disease resistance.},
journal = {Horticulture research},
volume = {11},
number = {7},
pages = {uhae119},
doi = {10.1093/hr/uhae119},
pmid = {38966866},
issn = {2662-6810},
abstract = {Avocado (Persea americana Mill.) is an economically valuable plant because of the high fatty acid content and unique flavor of its fruits. Its fatty acid content, especially the relatively high unsaturated fatty acid content, provides significant health benefits. We herein present a telomere-to-telomere gapless genome assembly (841.6 Mb) of West Indian avocado. The genome contains 40 629 predicted protein-coding genes. Repeat sequences account for 57.9% of the genome. Notably, all telomeres, centromeres, and a nucleolar organizing region are included in this genome. Fragments from these three regions were observed via fluorescence in situ hybridization. We identified 376 potential disease resistance-related nucleotide-binding leucine-rich repeat genes. These genes, which are typically clustered on chromosomes, may be derived from gene duplication events. Five NLR genes (Pa11g0262, Pa02g4855, Pa07g3139, Pa07g0383, and Pa02g3196) were highly expressed in leaves, stems, and fruits, indicating they may be involved in avocado disease responses in multiple tissues. We also identified 128 genes associated with fatty acid biosynthesis and analyzed their expression patterns in leaves, stems, and fruits. Pa02g0113, which encodes one of 11 stearoyl-acyl carrier protein desaturases mediating C18 unsaturated fatty acid synthesis, was more highly expressed in the leaves than in the stems and fruits. These findings provide valuable insights that enhance our understanding of fatty acid biosynthesis in avocado.},
}

@article {pmid38964064,
year = {2024},
author = {Chang-Chien, J and Kuo, ML and Tseng, YL and Huang, HY and Tsai, HJ and Yao, TC},
title = {Differential effects of long- and short-term exposure to PM2.5 on accelerating telomere shortening: from in vitro to epidemiological studies.},
journal = {Ecotoxicology and environmental safety},
volume = {281},
number = {},
pages = {116650},
doi = {10.1016/j.ecoenv.2024.116650},
pmid = {38964064},
issn = {1090-2414},
abstract = {Exposure to air pollutants has been associated with DNA damage and increases the risks of respiratory diseases, such as asthma and COPD; however short- and long-term effects of air pollutants on telomere dysfunction remain unclear. We investigated the impact of short- and long-term exposure to fine particulate matter with an aerodynamic diameter below 2.5 μm (PM2.5) on telomere length in human bronchial epithelial BEAS-2B cells, and assessed the potential correlation between PM2.5 exposure and telomere length in the LIGHTS childhood cohort study. We observed that long-term, but not short-term, PM2.5 exposure was significantly associated with telomere shortening, along with the downregulation of human telomerase reverse transcriptase (hTERT) mRNA and protein levels. Moreover, long-term exposure to PM2.5 induced proinflammatory cytokine secretion, notably interleukin 6 (IL-6) and IL-8, triggered subG1 cell cycle arrest, and ultimately caused cell death. Long-term exposure to PM2.5 upregulated the LC3-II/ LC3-I ratio but led to p62 protein accumulation in BEAS-2B cells, suggesting a blockade of autophagic flux. Moreover, consistent with our in vitro findings, our epidemiological study found significant association between annual average exposure to higher PM2.5 and shortening of leukocyte telomere length in children. However, no significant association between 7-day short-term exposure to PM2.5 and leukocyte telomere length was observed in children. By combining in vitro experimental and epidemiological studies, our findings provide supportive evidence linking potential regulatory mechanisms to population level with respect to long-term PM2.5 exposure to telomere shortening in humans.},
}

@article {pmid38963484,
year = {2024},
author = {Lim, CJ},
title = {Telomere C-Strand Fill-In Machinery: New Insights into the Human CST-DNA Polymerase Alpha-Primase Structures and Functions.},
journal = {Sub-cellular biochemistry},
volume = {104},
number = {},
pages = {73-100},
pmid = {38963484},
issn = {0306-0225},
mesh = {Humans ; *Telomere/metabolism/genetics ; *DNA Polymerase I/metabolism/genetics/chemistry ; *DNA Primase/metabolism/genetics/chemistry ; *Telomere-Binding Proteins/metabolism/genetics ; *DNA Replication ; Telomerase/metabolism/genetics ; },
abstract = {Telomeres at the end of eukaryotic chromosomes are extended by a specialized set of enzymes and telomere-associated proteins, collectively termed here the telomere "replisome." The telomere replisome acts on a unique replicon at each chromosomal end of the telomeres, the 3' DNA overhang. This telomere replication process is distinct from the replisome mechanism deployed to duplicate the human genome. The G-rich overhang is first extended before the complementary C-strand is filled in. This overhang is extended by telomerase, a specialized ribonucleoprotein and reverse transcriptase. The overhang extension process is terminated when telomerase is displaced by CTC1-STN1-TEN1 (CST), a single-stranded DNA-binding protein complex. CST then recruits DNA polymerase α-primase to complete the telomere replication process by filling in the complementary C-strand. In this chapter, the recent structure-function insights into the human telomere C-strand fill-in machinery (DNA polymerase α-primase and CST) will be discussed.},
}

Humans
*Telomere/metabolism/genetics
*DNA Polymerase I/metabolism/genetics/chemistry
*DNA Primase/metabolism/genetics/chemistry
*Telomere-Binding Proteins/metabolism/genetics
*DNA Replication
Telomerase/metabolism/genetics

@article {pmid38960007,
year = {2024},
author = {Alehagen, U and Aaseth, J and Schomburg, L and Larsson, A and Opstad, T and Alexander, J},
title = {Selenoprotein P increases upon Selenium and Coenzyme Q10 Supplementation and is Associated with Telomere Length, Quality of Life and Reduced Inflammation and Mortality.},
journal = {Free radical biology & medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.freeradbiomed.2024.06.027},
pmid = {38960007},
issn = {1873-4596},
abstract = {BACKGROUND: Selenoprotein P (SELENOP) transports selenium to extrahepatic tissues and is a biomarker of selenium status. Low soil selenium leads to low dietary selenium intake. A consequence is an increased risk of cardiovascular disease.

OBJECTIVE: To investigate clinical aspects associated with SELENOP deficiency, including biomarkers of inflammation, quality of life, and mortality within 12 years, and the effect of dietary selenium and coenzyme Q10 supplementation on SELENOP.

METHODS: SELENOP was determined at inclusion and after four years of supplementation in 403 elderly community-living participants low in selenium receiving selenium yeast (200 μg/day) and coenzyme Q10 (200 mg/ day), or placebo. Pre-intervention, the average serum selenium level was 67μg/L. T-tests, repeated measures of variance, Cox proportional regressions analyses, Kaplan-Meier graphs and ANCOVA analyses were applied. Associations with biomarkers of inflammation, telomere length, quality of life and mortality were investigated. Benchmark modelling was used to determine the serum selenium concentration at which the saturation levels of SELENOP and GPx3 was achieved. Comparison with GPx3 and serum selenium to identify increased mortality risk was performed, and the effect of supplementation on SELENOP levels were evaluated.

RESULTS: Inverse associations were observed between the level of SELENOP at inclusion and biomarkers for inflammation. At follow-up, shorter telomere lengths were seen in those with low levels of SELENOP at inclusion, whereas high levels of SELENOP were associated with better quality of life and decreased mortality. SELENOP had increased prognostic power compared to GPx3 and selenium. Saturation of SELENOP was achieved at a serum selenium level of 146 μg/L, and for GPx3 at 99 μg/L. Supplementation induced higher levels of SELENOP.

CONCLUSION: Significant associations between SELENOP and inflammation, length of telomeres, quality of life, and mortality were observed. Thus, selenium supplementation improved SELENOP expression, thereby facilitating systemic selenium bioavailability and resulting in the observed positive health effects.},
}

@article {pmid38959478,
year = {2024},
author = {Panda, S and Roychowdhury, T and Dutta, A and Chakraborty, S and Das, T and Chatterjee, S},
title = {ALTering Cancer by Triggering Telomere Replication Stress through the Stabilization of Promoter G-Quadruplex in SMARCAL1.},
journal = {ACS chemical biology},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschembio.4c00285},
pmid = {38959478},
issn = {1554-8937},
abstract = {Most of the human cancers are dependent on telomerase to extend the telomeres. But ∼10% of all cancers use a telomerase-independent, homologous recombination mediated pathway called alternative lengthening of telomeres (ALT). Due to the poor prognosis, ALT status is not being considered yet in the diagnosis of cancer. No such specific treatment is available to date for ALT positive cancers. ALT positive cancers are dependent on replication stress to deploy DNA repair pathways to the telomeres to execute homologous recombination mediated telomere extension. SMARCAL1 (SWI/SNF related, matrix-associated, actin-dependent regulator of chromatin, subfamily A-like 1) is associated with the ALT telomeres to resolve replication stress thus providing telomere stability. Thus, the dependency on replication stress regulatory factors like SMARCAL1 made it a suitable therapeutic target for the treatment of ALT positive cancers. In this study, we found a significant downregulation of SMARCAL1 expression by stabilizing the G-quadruplex (G4) motif found in the promoter of SMARCAL1 by potent G4 stabilizers, like TMPyP4 and BRACO-19. SMARCAL1 downregulation led toward the increased localization of PML (promyelocytic leukemia) bodies in ALT telomeres and triggered the formation of APBs (ALT-associated promyelocytic leukemia bodies) in ALT positive cell lines, increasing telomere replication stress and DNA damage at a genomic level. Induction of replication stress and hyper-recombinogenic phenotype in ALT positive cells mediated by G4 stabilizing molecules already highlighted their possible application as a new therapeutic window to target ALT positive tumors. In accordance with this, our study will also provide a valuable insight toward the development of G4-based ALT therapeutics targeting SMARCAL1.},
}

@article {pmid38953168,
year = {2024},
author = {Estrem, B and Davis, RE and Wang, J},
title = {End resection and telomere healing of DNA double-strand breaks during nematode programmed DNA elimination.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkae579},
pmid = {38953168},
issn = {1362-4962},
support = {AI155588/NH/NIH HHS/United States ; //University of Tennessee, Knoxville/ ; },
abstract = {Most DNA double-strand breaks (DSBs) are harmful to genome integrity. However, some forms of DSBs are essential to biological processes, such as meiotic recombination and V(D)J recombination. DSBs are also required for programmed DNA elimination (PDE) in ciliates and nematodes. In nematodes, the DSBs are healed with telomere addition. While telomere addition sites have been well characterized, little is known regarding the DSBs that fragment nematode chromosomes. Here, we used embryos from the human and pig parasitic nematode Ascaris to characterize the DSBs. Using END-seq, we demonstrate that DSBs are introduced before mitosis, followed by extensive end resection. The resection profile is unique for each break site, and the resection generates 3'-overhangs before the addition of neotelomeres. Interestingly, telomere healing occurs much more frequently on retained DSB ends than on eliminated ends. This biased repair of the DSB ends may be due to the sequestration of the eliminated DNA into micronuclei, preventing neotelomere formation at their ends. Additional DNA breaks occur within the eliminated DNA in both Ascaris and Parascaris, ensuring chromosomal breakage and providing a fail-safe mechanism for PDE. Overall, our data indicate that telomere healing of DSBs is specific to the break sites responsible for nematode PDE.},
}

@article {pmid38950694,
year = {2024},
author = {Zhang, D and Eckhardt, CM and McGroder, C and Benesh, S and Porcelli, J and Depender, C and Bogyo, K and Westrich, J and Thomas-Wilson, A and Jobanputra, V and Garcia, CK},
title = {Clinical Impact of Telomere Length Testing for Interstitial Lung Disease.},
journal = {Chest},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.chest.2024.06.006},
pmid = {38950694},
issn = {1931-3543},
abstract = {BACKGROUND: Shortened telomere length (TL) is a genomic risk factor for fibrotic interstitial lung disease (ILD), but its role in clinical management is unknown.

RESEARCH QUESTION: What is the clinical impact of TL testing on the management of ILD?

STUDY DESIGN AND METHODS: Patients were evaluated in the Columbia University ILD clinic and underwent CLIA-certified TL testing by flow cytometry and fluorescence in-situ hybridization (FlowFISH) as part of clinical management. Short TL was defined as below the 10[th] age-adjusted percentile for either granulocytes or lymphocytes by FlowFISH. Patients were offered genetic counseling and testing if they had short TL or a family history of ILD. FlowFISH TL was compared against research qPCR TL measurement.

RESULTS: A total of 108 patients underwent TL testing, including those with clinical features of short telomere syndrome such as familial pulmonary fibrosis (50%) or extrapulmonary manifestations in the patient (25%) or a relative (41%). The overall prevalence of short TL was 46% and was similar across clinical ILD diagnoses. The number of short telomere clinical features was independently associated with detecting short TL (OR 2.00, 95% CI [1.27, 3.32]). TL testing led to clinical management changes for 35 (32%) patients, most commonly resulting in reduction or avoidance of immunosuppression. Of the patients who underwent genetic testing (n=34), a positive or candidate diagnostic finding in telomere-related genes was identified in 10 (29%) patients. Inclusion of TL testing below the 1[st] percentile helped reclassify 8 of 9 variants of uncertain significance (VUS) into actionable findings. The qPCR test correlated with FlowFISH, but age-adjusted percentile cutoffs may not be equivalent between the two assays.

INTERPRETATION: Incorporating TL testing in ILD impacted clinical management and led to the discovery of new actionable genetic variants.},
}

@article {pmid38951712,
year = {2024},
author = {Lechel, A and Ande, S and Ju, Z and Plentz, RR and Schaetzlein, S and Rudolph, C and Wilkens, L and Wiemann, SU and Saretzki, G and Malek, NP and Manns, MP and Buer, J and Rudolph, KL},
title = {Author Correction: The cellular level of telomere dysfunction determines induction of senescence or apoptosis in vivo.},
journal = {EMBO reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s44319-024-00192-9},
pmid = {38951712},
issn = {1469-3178},
}

@article {pmid38946430,
year = {2024},
author = {Longo, M and Greco, E and Listorti, I and Varricchio, MT and Litwicka, K and Arrivi, C and Mencacci, C and Greco, P},
title = {Telomerase activity, telomere length, and the euploidy rate of human embryos.},
journal = {Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology},
volume = {40},
number = {1},
pages = {2373742},
doi = {10.1080/09513590.2024.2373742},
pmid = {38946430},
issn = {1473-0766},
mesh = {Humans ; Female ; Adult ; *Telomerase/genetics/metabolism ; *Telomere ; Prospective Studies ; Pregnancy ; Aneuploidy ; Fertilization in Vitro ; Granulosa Cells/metabolism ; Infertility, Female/genetics/therapy ; Ovulation Induction ; Blastocyst ; Telomere Homeostasis/physiology ; Sperm Injections, Intracytoplasmic ; },
abstract = {BACKGROUND: Telomeres maintain chromosome stability, while telomerase counteracts their progressive shortening. Telomere length varies between cell types, with leukocyte telomere length (LTL) decreasing with age. Reduced telomerase activity has been linked to reproductive issues in females, such as low pregnancy rates and premature ovarian failure, with recent studies indicating correlations between telomere length in granulosa cells and IVF outcomes.

OBJECTIVES: The study aims to explore the relationship between telomere length, telomerase activity, and euploid blastocyst rate in infertile women undergoing IVF/ICSI PGT-A cycles.

METHODS: This prospective study involves 108 patients undergoing controlled ovarian stimulation and PGT-A. Telomere length and telomerase activity were measured in peripheral mononuclear cells and granulosa cells (GC), respectively.

RESULTS: The telomere repeat copy number to single gene copy number ratio (T/S) results respectively 0.6 ± 0.8 in leukocytes and 0.7 ± 0.9 in GC. An inverse relationship was found between LTL and the patient's age (p < .01). A higher aneuploid rate was noticed in patients with short LTL, with no differences in ovarian reserve markers (p = .15), number of oocytes retrieved (p = .33), and number of MII (p = 0.42). No significant association was noticed between telomere length in GC and patients' age (p = 0.95), in ovarian reserve markers (p = 0.32), number of oocytes retrieved (p = .58), number of MII (p = .74) and aneuploidy rate (p = .65).

CONCLUSION: LTL shows a significant inverse correlation with patient age and higher aneuploidy rates. Telomere length in GCs does not correlate with patient age or reproductive outcomes, indicating differential telomere dynamics between leukocytes and granulosa cells.},
}

Humans
Female
Adult
*Telomerase/genetics/metabolism
*Telomere
Prospective Studies
Pregnancy
Aneuploidy
Fertilization in Vitro
Granulosa Cells/metabolism
Infertility, Female/genetics/therapy
Ovulation Induction
Blastocyst
Telomere Homeostasis/physiology
Sperm Injections, Intracytoplasmic

@article {pmid38945863,
year = {2024},
author = {Teramoto, N and Okada, Y and Aburada, N and Hayashi, M and Ito, J and Shirasuna, K and Iwata, H},
title = {Resveratrol intake by males increased the mitochondrial DNA copy number and telomere length of blastocysts derived from aged mice.},
journal = {The Journal of reproduction and development},
volume = {},
number = {},
pages = {},
doi = {10.1262/jrd.2024-043},
pmid = {38945863},
issn = {1348-4400},
abstract = {The present study examined whether male resveratrol intake affected mitochondrial DNA copy number (mt-cn) and telomere length (TL) in blastocysts fathered by young and aged male mice. C57BL/6N male mice supplied with water or water containing 0.1 mM resveratrol were used for embryo production at 14-23 and 48-58 weeks of age. Two-cell-stage embryos were collected from the oviducts of superovulated female mice (8-15 weeks old) and cultured for 3 days until the blastocyst stage. Mt-cn and TL levels were measured by real-time polymerase chain reaction. Resveratrol intake did not affect body weight or water consumption. Resveratrol intake increased the expression levels of SIRT1 in the liver, the antioxidative ability of serum, and extended TL in the heart, whereas there was no significant difference in mt-cn in the heart or TL in sperm. The rate of blastocyst development was significantly lower in aged male mice than in younger mice, and resveratrol intake increased the total number of blastocysts derived from both young and aged males. Resveratrol intake did not affect mt-cn or TL in blastomeres of blastocyst-stage embryos derived from young mice, but significantly increased both mt-cn and TL in blastomeres of blastocysts derived from aged fathers. In conclusion, resveratrol intake increased mt-cn and TL levels in blastocysts derived from aged male mice.},
}

@article {pmid38943658,
year = {2024},
author = {Moeckel, C and Gaydosh, L and Schneper, L and Mitchell, C and Notterman, DA},
title = {Material hardship and telomere length in children.},
journal = {Child development},
volume = {},
number = {},
pages = {},
doi = {10.1111/cdev.14126},
pmid = {38943658},
issn = {1467-8624},
support = {P2CHD047879//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; R01HD036916//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; R01HD076592//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; R01HD36916//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; R01HD39135//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; R01HD40421//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; },
abstract = {Telomere length (TL) serves as a biomarker of exposure to stressors, including material hardship. Data from the Future of Families and Child Wellbeing Study (1998-2015) were utilized to determine whether prior material hardship was associated with shorter salivary TL at years 9 and 15. 49% of the year 9 study population were female, 49% were Black, and 25% were Hispanic. At year 9 (N = 1990), regression analyses found a significant association between prior material hardship and shorter TL (β = -.005, p < .01). Additionally, at year 15 (N = 1874), material hardship experienced during infancy and toddlerhood was associated with shorter TL (β = -.009, p < .01), pointing toward infancy and toddlerhood as a sensitive period.},
}

@article {pmid38943263,
year = {2024},
author = {Lee, Y and Jugessur, A and Gjessing, HK and Harris, JR and Susser, E and Magnus, P and Aviv, A},
title = {Effect of polygenic scores of telomere length alleles on telomere length in newborns and parents.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e14241},
doi = {10.1111/acel.14241},
pmid = {38943263},
issn = {1474-9726},
support = {R01 HL134840/NH/NIH HHS/United States ; 223273//Norges Forskningsråd/ ; 229624//Norges Forskningsråd/ ; 262043//Norges Forskningsråd/ ; 262700//Norges Forskningsråd/ ; },
abstract = {In adults, polygenic scores (PGSs) of telomere length (TL) alleles explain about 4.5% of the variance in TL, as measured by quantitative polymerase chain reaction (qPCR). Yet, these PGSs strongly infer a causal role of telomeres in aging-related diseases. To better understand the determinants of TL through the lifespan, it is essential to examine to what extent these PGSs explain TL in newborns. This study investigates the effect of PGSs on TL in both newborns and their parents, with TL measured by Southern blotting and expressed in base-pairs (bp). Additionally, the study explores the impact of PGSs related to transmitted or non-transmitted alleles on TL in newborns. For parents and newborns, the PGS effects on TL were 172 bp (p = 2.03 × 10[-15]) and 161 bp (p = 3.06 × 10[-8]), explaining 6.6% and 5.2% of the TL variance, respectively. The strongest PGS effect was shown for maternally transmitted alleles in newborn girls, amounting to 214 bp (p = 3.77 × 10[-6]) and explaining 7.8% of the TL variance. The PGS effect of non-transmitted alleles was 56 bp (p = 0.0593) and explained 0.6% of the TL variance. Our findings highlight the importance of TL genetics in understanding early-life determinants of TL. They point to the potential utility of PGSs composed of TL alleles in identifying susceptibility to aging-related diseases from birth and reveal the presence of sexual dimorphism in the effect of TL alleles on TL in newborns. Finally, we attribute the higher TL variance explained by PGSs in our study to TL measurement by Southern blotting.},
}

@article {pmid38937972,
year = {2024},
author = {Wang, K and Jin, J and Wang, J and Wang, X and Sun, J and Meng, D and Wang, X and Guo, L},
title = {The complete telomere-to-telomere genome assembly of lettuce.},
journal = {Plant communications},
volume = {},
number = {},
pages = {101011},
doi = {10.1016/j.xplc.2024.101011},
pmid = {38937972},
issn = {2590-3462},
}

@article {pmid38936230,
year = {2024},
author = {Rodríguez-Fernández, B and Sánchez-Benavides, G and Genius, P and Minguillon, C and Fauria, K and De Vivo, I and Navarro, A and Molinuevo, JL and Gispert, JD and Sala-Vila, A and Vilor-Tejedor, N and Crous-Bou, M and , },
title = {Association between telomere length and cognitive function among cognitively unimpaired individuals at risk of Alzheimer's disease.},
journal = {Neurobiology of aging},
volume = {141},
number = {},
pages = {140-150},
doi = {10.1016/j.neurobiolaging.2024.05.015},
pmid = {38936230},
issn = {1558-1497},
abstract = {INTRODUCTION: Leukocyte telomere length (LTL) is an objective biomarker of biological aging, and it is proposed to play a crucial role in Alzheimer's disease (AD) risk. We aimed at evaluating the cross-sectional association between LTL and cognitive performance in middle-aged cognitively unimpaired individuals at increased risk of AD.

METHODS: A total of 1520 participants from the ALFA cohort were included. Relative telomere length was measured in leukocytes through qPCR. LTL was residualized against age and sex, and associations with cognitive performance were assessed in short and long groups based on residualized LTL (rLTL). Interactions with sex and genetic risk of AD were tested.

RESULTS: Non-linear associations were found between LTL and episodic memory (EM). Better EM was associated with longer rLTL among women in the short rLTL group.

DISCUSSION: Results suggest a potential role of telomeres in the cognitive aging process with sex-specific patterns.},
}

@article {pmid38935034,
year = {2024},
author = {Vaghefi, E and An, S and Corbett, R and Squirrell, D},
title = {Association of retinal image-based, deep learning cardiac BioAge with telomere length and cardiovascular biomarkers.},
journal = {Optometry and vision science : official publication of the American Academy of Optometry},
volume = {},
number = {},
pages = {},
doi = {10.1097/OPX.0000000000002158},
pmid = {38935034},
issn = {1538-9235},
abstract = {SIGNIFICANCE: Our retinal image-based deep learning (DL) cardiac biological age (BioAge) model could facilitate fast, accurate, noninvasive screening for cardiovascular disease (CVD) in novel community settings and thus improve outcome with those with limited access to health care services.

PURPOSE: This study aimed to determine whether the results issued by our DL cardiac BioAge model are consistent with the known trends of CVD risk and the biomarker leukocyte telomere length (LTL), in a cohort of individuals from the UK Biobank.

METHODS: A cross-sectional cohort study was conducted using those individuals in the UK Biobank who had LTL data. These individuals were divided by sex, ranked by LTL, and then grouped into deciles. The retinal images were then presented to the DL model, and individual's cardiac BioAge was determined. Individuals within each LTL decile were then ranked by cardiac BioAge, and the mean of the CVD risk biomarkers in the top and bottom quartiles was compared. The relationship between an individual's cardiac BioAge, the CVD biomarkers, and LTL was determined using traditional correlation statistics.

RESULTS: The DL cardiac BioAge model was able to accurately stratify individuals by the traditional CVD risk biomarkers, and for both males and females, those issued with a cardiac BioAge in the top quartile of their chronological peer group had a significantly higher mean systolic blood pressure, hemoglobin A1c, and 10-year Pooled Cohort Equation CVD risk scores compared with those individuals in the bottom quartile (p<0.001). Cardiac BioAge was associated with LTL shortening for both males and females (males: -0.22, r2 = 0.04; females: -0.18, r2 = 0.03).

CONCLUSIONS: In this cross-sectional cohort study, increasing CVD risk whether assessed by traditional biomarkers, CVD risk scoring, or our DL cardiac BioAge, CVD risk model, was inversely related to LTL. At a population level, our data support the growing body of evidence that suggests LTL shortening is a surrogate marker for increasing CVD risk and that this risk can be captured by our novel DL cardiac BioAge model.},
}

@article {pmid38929154,
year = {2024},
author = {Shan, J and Mo, J and An, C and Xiang, L and Qi, J},
title = {β-Cyclocitral from Lavandula angustifolia Mill. Exerts Anti-Aging Effects on Yeasts and Mammalian Cells via Telomere Protection, Antioxidative Stress, and Autophagy Activation.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {13},
number = {6},
pages = {},
doi = {10.3390/antiox13060715},
pmid = {38929154},
issn = {2076-3921},
support = {2022YFE0104000//the National Key R&D Program of China/ ; 22177102//NSFC/ ; },
abstract = {We used a replicative lifespan (RLS) experiment of K6001 yeast to screen for anti-aging compounds within lavender extract (Lavandula angustifolia Mill.), leading to the discovery of β-cyclocitral (CYC) as a potential anti-aging compound. Concurrently, the chronological lifespan (CLS) of YOM36 yeast and mammalian cells confirmed the anti-aging effect of CYC. This molecule extended the yeast lifespan and inhibited etoposide (ETO)-induced cell senescence. To understand the mechanism of CYC, we analyzed its effects on telomeres, oxidative stress, and autophagy. CYC administration resulted in notable increases in the telomerase content, telomere length, and the expression of the telomeric shelterin protein components telomeric-repeat binding factor 2 (TRF2) and repressor activator protein 1 (RAP1). More interestingly, CYC reversed H2O2-induced telomere damage and exhibited strong antioxidant capacity. Moreover, CYC improved the survival rate of BY4741 yeast under oxidative stress induced by 6.2 mM H2O2, increasing the antioxidant enzyme activity while reducing the reactive oxygen species (ROS), reactive nitrogen species (RNS), and malondialdehyde (MDA) levels. Additionally, CYC enhanced autophagic flux and free green fluorescent protein (GFP) expression in the YOM38-GFP-ATG8 yeast strain. However, CYC did not extend the RLS of K6001 yeast mutants, such as Δsod1, Δsod2, Δcat, Δgpx, Δatg2, and Δatg32, which lack antioxidant enzymes or autophagy-related genes. These findings reveal that CYC acts as an anti-aging agent by modifying telomeres, oxidative stress, and autophagy. It is a promising compound with potential anti-aging effects and warrants further study.},
}

@article {pmid38928414,
year = {2024},
author = {Harutyunyan, T and Sargsyan, A and Kalashyan, L and Igityan, H and Grigoryan, B and Davtyan, H and Aroutiounian, R and Liehr, T and Hovhannisyan, G},
title = {Changes in Telomere Length in Leukocytes and Leukemic Cells after Ultrashort Electron Beam Radiation.},
journal = {International journal of molecular sciences},
volume = {25},
number = {12},
pages = {},
doi = {10.3390/ijms25126709},
pmid = {38928414},
issn = {1422-0067},
support = {22SC-BMBF-1C001//RA MESCS Science Committee and German Federal Ministry of Education and Research/ ; 21AG-1F068//RA MESCS Science Committee/ ; 01DK24003//German Aerospace Center (= Deutsches Forschungszentrum für Luft- und Raumfahrt, DLR)/ ; },
mesh = {Humans ; K562 Cells ; *Leukocytes/radiation effects/metabolism ; *Electrons ; *Telomere/radiation effects/genetics/metabolism ; Leukemia/genetics/pathology/radiotherapy ; Telomere Homeostasis/radiation effects ; In Situ Hybridization, Fluorescence ; Telomere Shortening/radiation effects ; DNA Damage/radiation effects ; Dose-Response Relationship, Radiation ; },
abstract = {Application of laser-generated electron beams in radiotherapy is a recent development. Accordingly, mechanisms of biological response to radiation damage need to be investigated. In this study, telomere length (TL) as endpoint of genetic damage was analyzed in human blood cells (leukocytes) and K562 leukemic cells irradiated with laser-generated ultrashort electron beam. Metaphases and interphases were analyzed in quantitative fluorescence in situ hybridization (Q-FISH) to assess TL. TLs were shortened compared to non-irradiated controls in both settings (metaphase and interphase) after irradiation with 0.5, 1.5, and 3.0 Gy in blood leukocytes. Radiation also caused a significant TL shortening detectable in the interphase of K562 cells. Overall, a negative correlation between TL and radiation doses was observed in normal and leukemic cells in a dose-dependent manner. K562 cells were more sensitive than normal blood cells to increasing doses of ultrashort electron beam radiation. As telomere shortening leads to genome instability and cell death, the results obtained confirm the suitability of this biomarker for assessing genotoxic effects of accelerated electrons for their further use in radiation therapy. Observed differences in TL shortening between normal and K562 cells provide an opportunity for further development of optimal radiation parameters to reduce side effects in normal cells during radiotherapy.},
}

Humans
K562 Cells
*Leukocytes/radiation effects/metabolism
*Electrons
*Telomere/radiation effects/genetics/metabolism
Leukemia/genetics/pathology/radiotherapy
Telomere Homeostasis/radiation effects
In Situ Hybridization, Fluorescence
Telomere Shortening/radiation effects
DNA Damage/radiation effects
Dose-Response Relationship, Radiation

@article {pmid38927760,
year = {2024},
author = {Arellano, MYG and VanHeest, M and Emmadi, S and Abdul-Hafez, A and Ibrahim, SA and Thiruvenkataramani, RP and Teleb, RS and Omar, H and Kesaraju, T and Mohamed, T and Madhukar, BV and Omar, SA},
title = {Role of Mesenchymal Stem/Stromal Cells (MSCs) and MSC-Derived Extracellular Vesicles (EVs) in Prevention of Telomere Length Shortening, Cellular Senescence, and Accelerated Biological Aging.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {11},
number = {6},
pages = {},
doi = {10.3390/bioengineering11060524},
pmid = {38927760},
issn = {2306-5354},
abstract = {Biological aging is defined as a progressive decline in tissue function that eventually results in cell death. Accelerated biologic aging results when the telomere length is shortened prematurely secondary to damage from biological or environmental stressors, leading to a defective reparative mechanism. Stem cells therapy may have a potential role in influencing (counteract/ameliorate) biological aging and maintaining the function of the organism. Mesenchymal stem cells, also called mesenchymal stromal cells (MSCs) are multipotent stem cells of mesodermal origin that can differentiate into other types of cells, such as adipocytes, chondrocytes, and osteocytes. MSCs influence resident cells through the secretion of paracrine bioactive components such as cytokines and extracellular vesicles (EVs). This review examines the changes in telomere length, cellular senescence, and normal biological age, as well as the factors contributing to telomere shortening and accelerated biological aging. The role of MSCs-especially those derived from gestational tissues-in prevention of telomere shortening (TS) and accelerated biological aging is explored. In addition, the strategies to prevent MSC senescence and improve the antiaging therapeutic application of MSCs and MSC-derived EVs in influencing telomere length and cellular senescence are reviewed.},
}

@article {pmid38927389,
year = {2024},
author = {Almuraikhy, S and Sellami, M and Naja, K and Al-Amri, HS and Anwardeen, N and Aden, A and Dömling, A and Elrayess, MA},
title = {Joint Effects of Exercise and Ramadan Fasting on Telomere Length: Implications for Cellular Aging.},
journal = {Biomedicines},
volume = {12},
number = {6},
pages = {},
doi = {10.3390/biomedicines12061182},
pmid = {38927389},
issn = {2227-9059},
support = {IRCC-2022-467//Qatar University/ ; },
abstract = {Aging is a fundamental biological process that progressively impairs the functionality of the bodily systems, leading to an increased risk of diseases. Telomere length is one of the most often used biomarkers of aging. Recent research has focused on developing interventions to mitigate the effects of aging and improve the quality of life. The objective of this study was to investigate the combined effect of exercise and Ramadan fasting on telomere length. Twenty-nine young, non-obese, healthy females were randomized into two groups: the control group underwent a 4-week exercise training program, and the second group underwent a 4-week exercise training program while fasting during Ramadan. Blood samples were collected, and measurements of clinical traits, cytokines, oxidative stress, and telomere length were performed before and after intervention. Telomere length increased significantly from baseline in the exercise-while-fasting group, but showed no significant change in the exercise control group. This increase was accompanied by a reduction in TNF-α, among other cytokines. Additionally, a significant positive correlation was observed between the mean change in telomere length and HDL in the exercise-while-fasting group only. This study is the first to report an increase in telomere length after combining Ramadan fasting with training, suggesting that exercising while fasting may be an effective tool for slowing down the aging rate. Further studies using larger and more diverse cohorts are warranted.},
}

@article {pmid38926996,
year = {2024},
author = {Li, DN and Wen, XH},
title = {[Role of Telomere in Clonal Evolution of Acquired Aplastic Anemia--Review].},
journal = {Zhongguo shi yan xue ye xue za zhi},
volume = {32},
number = {3},
pages = {962-964},
doi = {10.19746/j.cnki.issn.1009-2137.2024.03.048},
pmid = {38926996},
issn = {1009-2137},
mesh = {*Anemia, Aplastic/genetics ; Humans ; *Telomere/genetics ; *Clonal Evolution ; *Telomerase/genetics ; Telomere Shortening ; },
abstract = {Studies have found that 1/3 patients with acquired aplastic anemia have shortened telomere length, and the shorter the telomere, the longer the disease course, the more prone to relapse, the lower the overall survival rate, and the higher the probability of clonal evolution. The regulation of telomere length is affected by many factors, including telomerase activity, telomerase-related genes, telomere regulatory proteins and other related factors. Telomere shortening can lead to genetic instability and increases the probability of clonal evolution in patients with acquired aplastic anemia. This article reviews the role of telomere in the clonal evolution of acquired aplastic anemia and factors affecting telomere length.},
}

*Anemia, Aplastic/genetics
Humans
*Telomere/genetics
*Clonal Evolution
*Telomerase/genetics
Telomere Shortening

@article {pmid38933758,
year = {2023},
author = {Zhang, Y and Pang, N and Huang, X and Meng, W and Meng, L and Zhang, B and Jiang, Z and Zhang, J and Yi, Z and Luo, Z and Wang, Z and Niu, L},
title = {Ultrasound deep brain stimulation decelerates telomere shortening in Alzheimer's disease and aging mice.},
journal = {Fundamental research},
volume = {3},
number = {3},
pages = {469-478},
doi = {10.1016/j.fmre.2022.02.010},
pmid = {38933758},
issn = {2667-3258},
abstract = {Telomere length is a reliable biomarker for health and longevity prediction in both humans and animals. The common neuromodulation techniques, including deep brain stimulation (DBS) and optogenetics, have excellent spatial resolution and depth penetration but require implementation of electrodes or optical fibers. Therefore, it is important to develop methods for noninvasive modulation of telomere length. Herein, we reported on a new method for decelerating telomere shortening using noninvasive ultrasound deep brain stimulation (UDBS). Firstly, we found that UDBS could activate the telomerase-associated proteins in normal mice. Then, in the Alzheimer's disease mice, UDBS was observed to decelerate telomere shortening of the cortex and myocardial tissue and to effectively improve spatial learning and memory abilities. Similarly, UDBS was found to significantly slow down telomere shortening of the cortex and peripheral blood, and improve motor and cognitive functions in aging mice. Finally, transcriptome analysis revealed that UDBS upregulated the neuroactive ligand-receptor interaction pathway. Overall, the present findings established the critical role of UDBS in delaying telomere shortening and indicated that ultrasound modulation of telomere length may constitute an effective therapeutic strategy for aging and aging-related diseases.},
}

@article {pmid38926610,
year = {2024},
author = {Wang, Z and Zuo, M and Li, W and Chen, S and Yuan, Y and He, Y and Yang, Y and Mao, Q and Liu, Y},
title = {The impact of telomere length on the risk of idiopathic normal pressure hydrocephalus: a bidirectional Mendelian randomization study.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {14713},
pmid = {38926610},
issn = {2045-2322},
support = {2023YFG0127//the Sichuan Science and Technology Program/ ; 2023YFQ0002//the Sichuan Science and Technology Program/ ; },
abstract = {Idiopathic normal pressure hydrocephalus (iNPH) affects mainly aged populations. The gradual shortening of telomere length (TL) is one of the hallmarks of aging. Whereas the genetic contribution of TL to the iNPH is incompletely understood. We aimed to investigate the causal relationship between TL and iNPH through the Mendelian randomization (MR) analysis. We respectively obtained 186 qualified single nucleotide polymorphisms (SNPs) of TL and 20 eligible SNPs of iNPH for MR analysis. The result of MR analysis showed that genetically predicted longer TL was significantly associated with a reduced odd of iNPH (odds ratio [OR] = 0.634 95% Confidence interval [CI] 0.447-0.899, p = 0.011). The causal association remained consistent in multivariable MR (OR = 0.530 95% CI 0.327-0.860, p = 0.010). However, there was no evidence that the iNPH was causally associated with the TL (OR = 1.000 95% CI 0.996-1.004, p = 0.955). Our study reveals a potential genetic contribution of TL to the etiology of iNPH, that is a genetically predicted increased TL might be associated with a reduced risk of iNPH.},
}

@article {pmid38922965,
year = {2024},
author = {Joo, SY and Sung, K and Lee, H},
title = {Balancing act: BRCA2's elaborate management of telomere replication through control of G-quadruplex dynamicity.},
journal = {BioEssays : news and reviews in molecular, cellular and developmental biology},
volume = {},
number = {},
pages = {e2300229},
doi = {10.1002/bies.202300229},
pmid = {38922965},
issn = {1521-1878},
support = {2020R1A5A1018081//National Research Foundation of Korea (NRF)/ ; 2021R1A2C1006191//National Research Foundation of Korea (NRF)/ ; },
abstract = {In billion years of evolution, eukaryotes preserved the chromosome ends with arrays of guanine repeats surrounded by thymines and adenines, which can form stacks of four-stranded planar structure known as G-quadruplex (G4). The rationale behind the evolutionary conservation of the G4 structure at the telomere remained elusive. Our recent study has shed light on this matter by revealing that telomere G4 undergoes oscillation between at least two distinct folded conformations. Additionally, tumor suppressor BRCA2 exhibits a unique mode of interaction with telomere G4. To elaborate, BRCA2 directly interacts with G-triplex (G3)-derived intermediates that form during the interconversion of the two different G4 states. In doing so, BRCA2 remodels the G4, facilitating the restart of stalled replication forks. In this review, we succinctly summarize the findings regarding the dynamicity of telomeric G4, emphasize its importance in maintaining telomere replication homeostasis, and the physiological consequences of losing G4 dynamicity at the telomere.},
}

@article {pmid38922089,
year = {2024},
author = {Ouyang, C and Yang, Y and Pan, J and Liu, H and Wang, X and Zhou, S and Shi, X and Zhang, Y and Wang, D and Hu, X},
title = {Leukocyte Telomere Length Mediates the Associations between Blood Lead and Cadmium with Hypertension among Adults in the United States: A Cross-Sectional Study.},
journal = {Toxics},
volume = {12},
number = {6},
pages = {},
doi = {10.3390/toxics12060409},
pmid = {38922089},
issn = {2305-6304},
support = {No. 23JRRA0969//Gansu Provincial Natural Science Foundation/ ; },
abstract = {There is evidence to support the links between lead and cadmium exposure with hypertension and also with leukocyte telomere length (LTL). The objective of this study is to investigate the role that LTL may play in the relationship between lead and cadmium exposure and hypertension. This study consisted of 3718 participants from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. Logistic regression was used to analyze the relationship between blood metals with hypertension, and the mediating model was used to evaluate the mediating effect of LTL. In the fully adjusted model, both blood lead and cadmium ln-transformed concentrations were significantly positively associated with hypertension risk, as were all quartiles of blood lead. Additionally, we observed positive linear dose-response relationships with hypertension by restricted cubic spline analysis (both p overall < 0.001, p non-linear = 0.3008 for lead and p non-linear = 0.7611 for cadmium). The ln-transformed blood lead and cadmium concentrations were associated with shorter LTL. LTL was inversely related to hypertension and the OR was 0.65 (95% CI: 0.47 to 0.89). Furthermore, LTL had mediating effects on the associations of blood lead and cadmium with hypertension risk, and the mediation proportions were 2.25% and 4.20%, respectively. Our findings suggested that exposure to lead and cadmium raised the risk of hypertension, while LTL played as a mediating factor.},
}

@article {pmid38919841,
year = {2024},
author = {Croons, H and Martens, DS and Vanderstukken, C and Sleurs, H and Rasking, L and Peusens, M and Renaers, E and Plusquin, M and Nawrot, TS},
title = {Telomere length in early childhood and its association with attention: a study in 4-6 year old children.},
journal = {Frontiers in pediatrics},
volume = {12},
number = {},
pages = {1358272},
pmid = {38919841},
issn = {2296-2360},
abstract = {Telomere length (TL), a marker of cellular aging, has been studied in adults with regard to its connection to cognitive function. However, little is known about the association between TL and cognitive development in children. This study investigated the interplay between TL and cognitive functioning in 283 Belgian children aged four to six years of the Environmental Influence on Aging in Early Life (ENVIRONAGE) birth cohort. Child leukocyte TL was measured using qPCR, while cognitive functioning, including attention and memory, was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Linear regression models were employed to examine the association between TL and cognitive outcomes, adjusting for potential confounders. We found an inverse association between TL and the spatial errors made during the Motor Screening task (p = 0.017), indicating a higher motor accuracy in children with longer telomeres. No significant associations were found between TL and other cognitive outcomes. Our results suggest a specific link between TL and motor accuracy but not with the other cognitive domains.},
}

@article {pmid38917803,
year = {2024},
author = {Tan, KT and Slevin, MK and Leibowitz, ML and Garrity-Janger, M and Shan, J and Li, H and Meyerson, M},
title = {Neotelomeres and telomere-spanning chromosomal arm fusions in cancer genomes revealed by long-read sequencing.},
journal = {Cell genomics},
volume = {},
number = {},
pages = {100588},
doi = {10.1016/j.xgen.2024.100588},
pmid = {38917803},
issn = {2666-979X},
abstract = {Alterations in the structure and location of telomeres are pivotal in cancer genome evolution. Here, we applied both long-read and short-read genome sequencing to assess telomere repeat-containing structures in cancers and cancer cell lines. Using long-read genome sequences that span telomeric repeats, we defined four types of telomere repeat variations in cancer cells: neotelomeres where telomere addition heals chromosome breaks, chromosomal arm fusions spanning telomere repeats, fusions of neotelomeres, and peri-centromeric fusions with adjoined telomere and centromere repeats. These results provide a framework for the systematic study of telomeric repeats in cancer genomes, which could serve as a model for understanding the somatic evolution of other repetitive genomic elements.},
}

@article {pmid38916238,
year = {2024},
author = {Zhang, J and Yang, XY and Chen, J and Zhou, Q and Pan, G and Wang, Y and Luo, W and Hou, J and Bao, H and Xu, G and Tang, G and Bai, H and Yu, R},
title = {A Poly(amino acid)-Based Nanomedicine Strategy: Telomere-Telomerase Axis Targeting and Magnetic Resonance Imaging in Hepatocellular Carcinoma Treatment.},
journal = {Nano letters},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.nanolett.4c01767},
pmid = {38916238},
issn = {1530-6992},
abstract = {Targeting telomere maintenance has emerged as a promising strategy for hepatocellular carcinoma (HCC) treatment. However, given the duality of the telomere-telomerase axis in telomere maintenance, a comprehensive strategy is urgently needed. Herein, we develop a poly(amino acid) (D-PAAs)-based strategy for spatiotemporal codelivery of telomerase inhibitor, BIBR1523, and AKT inhibitor, isobavachalcone. By leveraging D-PAAs' modifiability, we synthesize polymer-inhibitor conjugates (PB and PI) and a folic acid-decorated tumor-targeting vector (PF). These building blocks undergo micellization to fabricate a codelivery nanomedicine (P-BI@P-FA) by exploiting D-PAAs' noncovalent assembly. P-BI@P-FA improves the pharmacokinetics, tumor selectivity, and bioavailability of small molecule inhibitors and initiates a dual telomere-specific inhibition by combining telomerase deactivation with telomere disruption. Furthermore, a hybrid tumor-targeting magnetic nanosystem is designed using D-PAAs and manganese dioxide to showcase magnetic resonance imaging capacities. Our D-PAAs-based strategy addresses the pressing need for telomere-specific HCC treatment while allowing for diagnostic application, presenting a promising avenue for nanomedicine design.},
}

@article {pmid38915611,
year = {2024},
author = {Teplitz, GM and Pasquier, E and Bonnell, E and Laurentiis, E and Bartle, L and Lucier, JF and Sholes, S and Greider, CW and Wellinger, RJ},
title = {A mechanism for telomere-specific telomere length regulation.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.06.12.598646},
pmid = {38915611},
abstract = {Telomeric DNA, composed of short, direct repeats, is of crucial importance for chromosome stability. Due to intrinsic problems with replicating this DNA, the repeat tracts shorten at each cell division. Once repeat tracts become critically short, a telomeric stress signal induces cellular senescence and division arrest, which eventually may lead to devastating age-related degenerative diseases associated with dysfunctional telomers. Conversely, maintenance of telomere length by telomerase upregulation is a hallmark of cancer. Therefore, telomere length is a critical determinant of telomere function. How telomere length is established and molecular mechanisms for telomere-specific length regulation remained unknown. Here we show that subtelomeric chromatin is a determinant for how telomere equilibrium set-length is established in cis . The results demonstrate that telomerase recruitment mediated by the telomere-associated Sir4 protein is modulated on chromosome 3L in a telomere-specific way. Increased Sir4 abundance on subtelomeric heterochromatin of this specific telomere leads to telomere lengthening of only that telomere in cis , but not at other telomeres. Therefore, this work describes a mechanism for a how telomere-specific repeat tract length can be established. Further, our results will force the evaluation of telomere length away from a generalized view to a more telomere-specific consideration.},
}

@article {pmid38914514,
year = {2024},
author = {Yang, SH and Liu, HT and Wang, TF and Liou, YS and Sun, DS and Wang, JH and Chen, LY},
title = {Shorter donor leukocyte telomere length is associated with poor peripheral blood stem cell mobilization induced by granulocyte colony-stimulating factor.},
journal = {Journal of the Formosan Medical Association = Taiwan yi zhi},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jfma.2024.06.017},
pmid = {38914514},
issn = {0929-6646},
abstract = {BACKGROUND/PURPOSE: Insufficient numbers of peripheral blood stem cells (PBSC) after granulocyte colony-stimulating factor (G-CSF) mobilization occurs in a significant proportion of PBSC collections, often from older age donors. Telomere length (TL) is often used as an indicator of an individual's biological age. This study aimed to investigate the relationship between donors' leukocyte TL and the outcome of G-CSF-induced PBSC mobilization in healthy unrelated donors.

METHODS: Donors' leukocyte TLs and the outcome of G-CSF-induced PBSC mobilization, as assessed by pre-harvest CD34[+] cell counts, were analyzed in 39 healthy PBSC donors. TL in a non-mobilized general population (n = 90) was included as a control group. G-CSF mobilization effect was categorized into three groups according to pre-harvest CD34[+] cell count: poor (≤25/μL, PMD), intermediate (between 25 and 180/μL), and good (≥180/μl, GMD).

RESULTS: Leukocyte TL of PBSC donors correlated well with pre-harvest CD34[+] cell counts (r = 0.645, p < 0.001). Leukocyte TLs of PMDs (n = 8) were significantly shorter than those of GMDs (n = 9) and non-mobilization controls (p < 0.05). Moreover, all PMD TLs were below the 50th percentile, and 62.5% of PMDs had TLs below the 10th percentile of age-matched control participants. In contrast, no GMD TLs were below the 10th percentile; in fact, 33.3% (3/9) of them were above the 90th percentile.

CONCLUSION: Our results indicate that shorter donor leukocyte TL is associated with poor G-CSF-induced PBSC mobilization. TL, which represents a donor's biological age, could be a potential predictor for mobilization outcome.},
}

@article {pmid38910895,
year = {2024},
author = {Gu, L and Liu, M and Zhang, Y and Zhou, H and Wang, Y and Xu, ZX},
title = {Telomere-related DNA damage response pathways in cancer therapy: prospective targets.},
journal = {Frontiers in pharmacology},
volume = {15},
number = {},
pages = {1379166},
pmid = {38910895},
issn = {1663-9812},
abstract = {Maintaining the structural integrity of genomic chromosomal DNA is an essential role of cellular life and requires two important biological mechanisms: the DNA damage response (DDR) mechanism and telomere protection mechanism at chromosome ends. Because abnormalities in telomeres and cellular DDR regulation are strongly associated with human aging and cancer, there is a reciprocal regulation of telomeres and cellular DDR. Moreover, several drug treatments for DDR are currently available. This paper reviews the progress in research on the interaction between telomeres and cellular DNA damage repair pathways. The research on the crosstalk between telomere damage and DDR is important for improving the efficacy of tumor treatment. However, further studies are required to confirm this hypothesis.},
}

@article {pmid38902824,
year = {2024},
author = {Zhao, S and Li, J and Duan, S and Liu, C and Wang, H and Lu, J and Zhao, N and Sheng, X and Wu, Y and Li, Y and Sun, B and Liu, L},
title = {UBQLN1 links proteostasis and mitochondria function to telomere maintenance in human embryonic stem cells.},
journal = {Stem cell research & therapy},
volume = {15},
number = {1},
pages = {180},
pmid = {38902824},
issn = {1757-6512},
support = {32030033//National Natural Science Foundation of China/ ; 82230052//National Natural Science Foundation of China/ ; 32261160571//National Natural Science Foundation of China/ ; 20JCZDJC00550//Tianjin Science and Technology Plan Key Project/ ; },
abstract = {BACKGROUND: Telomeres consist of repetitive DNA sequences at the chromosome ends to protect chromosomal stability, and primarily maintained by telomerase or occasionally by alternative telomere lengthening of telomeres (ALT) through recombination-based mechanisms. Additional mechanisms that may regulate telomere maintenance remain to be explored. Simultaneous measurement of telomere length and transcriptome in the same human embryonic stem cell (hESC) revealed that mRNA expression levels of UBQLN1 exhibit linear relationship with telomere length.

METHODS: In this study, we first generated UBQLN1-deficient hESCs and compared with the wild-type (WT) hESCs the telomere length and molecular change at RNA and protein level by RNA-seq and proteomics. Then we identified the potential interacting proteins with UBQLN1 using immunoprecipitation-mass spectrometry (IP-MS). Furthermore, the potential mechanisms underlying the shortened telomeres in UBQLN1-deficient hESCs were analyzed.

RESULTS: We show that Ubiquilin1 (UBQLN1) is critical for telomere maintenance in human embryonic stem cells (hESCs) via promoting mitochondrial function. UBQLN1 deficiency leads to oxidative stress, loss of proteostasis, mitochondria dysfunction, DNA damage, and telomere attrition. Reducing oxidative damage and promoting mitochondria function by culture under hypoxia condition or supplementation with N-acetylcysteine partly attenuate the telomere attrition induced by UBQLN1 deficiency. Moreover, UBQLN1 deficiency/telomere shortening downregulates genes for neuro-ectoderm lineage differentiation.

CONCLUSIONS: Altogether, UBQLN1 functions to scavenge ubiquitinated proteins, preventing their overloading mitochondria and elevated mitophagy. UBQLN1 maintains mitochondria and telomeres by regulating proteostasis and plays critical role in neuro-ectoderm differentiation.},
}

@article {pmid38900410,
year = {2024},
author = {Alarabi, M and Pan, Z and Romero-Gómez, M and George, J and Eslam, M},
title = {Telomere length and mortality in lean MAFLD: the other face of metabolic adaptation.},
journal = {Hepatology international},
volume = {},
number = {},
pages = {},
pmid = {38900410},
issn = {1936-0541},
support = {APP1053206//National Health and Medical Research Council/ ; APP2001692//National Health and Medical Research Council/ ; APP1107178//National Health and Medical Research Council/ ; APP1108422//National Health and Medical Research Council/ ; },
abstract = {BACKGROUND AND AIMS: Healthy weight (lean) patients with metabolic dysfunction-associated fatty liver disease (MAFLD) have a more favorable metabolic and histological profile in cross-sectional studies compared with their non-lean counterparts. Paradoxically, they also have higher overall mortality. The underpinning pathophysiology of this paradox is not understood. Telomere attrition is associated with increased mortality in various diseases.

METHODS: We investigated the role of telomere length in the pathogenesis of lean MAFLD in cohorts with biopsy-proven MAFLD (n = 303). We measured serum malondialdehyde (MDA) levels and hepatic 8-hydroxydeoxyguanosine (8-OHdG) and 4-hydroxy-2-nonenal (4-HNE) expression (reactive oxygen species (ROS) markers), growth/differentiation factor-15 (GDF-15) and tested the effect of H2O2 on telomere length and activity in hepatocyte cell lines. The association between leukocyte telomere length and mortality was examined.

RESULTS: Telomere length was significantly lower in patients with lean MAFLD (p < 0.001). They also demonstrated an increase in ROS levels and decreases in GDF-15. H2O2 induced telomere shortening and reducing telomere activity in hepatocyte cell lines. We subsequently confirmed that telomere length shortening at baseline is associated with increased hazards of all-cause mortality; the deleterious effect was more profound in lean people.

CONCLUSION: Differences in telomere length in part explain the increased mortality of lean compared to non-lean patients with MAFLD. The effect is in part mediated through ROS activation and provide opportunities for therapy.},
}

@article {pmid38899963,
year = {2024},
author = {Sheng, Y and Liang, S and Wu, S and Shao, Y and Qiu, X and Liu, S and Huang, D and Pan, D and Wang, L and Juan, JTH and Zeng, X},
title = {Sex-specific effects of maternal blood pressure on newborn telomere length: A prospective study.},
journal = {International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics},
volume = {},
number = {},
pages = {},
doi = {10.1002/ijgo.15721},
pmid = {38899963},
issn = {1879-3479},
support = {AB17195012//Guangxi Science and Technology Program/ ; 81860587//National Natural Science Foundation of China/ ; GXMUYSF202203//Youth Science Foundation of Guangxi Medical University/ ; },
abstract = {OBJECTIVE: To investigate the relationship between maternal blood pressure (BP) and neonatal cord blood telomere length (TL) during pregnancy, and to clarify the sensitive period.

METHODS: We conducted a prospective cohort study with 621 mother-newborn pairs from the Guangxi Zhuang Birth Cohort (GZBC) in China. Multiple informant models, restricted cubic spline regression (RCS) models, and quantile regression models were conducted to analyze the correlation between maternal BP and neonatal TL.

RESULTS: Maternal diastolic blood pressure (DBP) was inversely related to neonatal cord blood TL in the second trimester (P = 0.015) and the third trimester (P = 0.011). There was a male-specific relationship between maternal BP and neonatal TL. A 1 mmHg increment in maternal systolic blood pressure (SBP) and DBP during the second trimester was related with 0.42% (95% CI: -0.80%, -0.04%) and 0.61% (95% CI: -1.13%, -0.09%) shorter TL in male newborns, respectively. Per unit increase of maternal DBP during the third trimester was related with 0.54% (95% CI: -1.03%, -0.05%) shorter TL in male newborns. Pregnant women with hypertensive disease of pregnancy (HDP) had male offspring with shorter TL (P = 0.003). However, no significant relationships were found in female newborns (P = 0.570).

CONCLUSION: Maternal BP during pregnancy is inversely correlated with male neonatal TL and the second and third trimesters are sensitive windows.},
}

@article {pmid38896081,
year = {2024},
author = {Wang, YM and Kaj-Carbaidwala, B and Lane, A and Agarwal, S and Beier, F and Bertuch, A and Borovsky, KA and Brennan, SK and Calado, RT and Catto, LFB and Dufour, C and Ebens, CL and Fioredda, F and Giri, N and Gloude, N and Goldman, F and Hertel, PM and Himes, R and Keel, SB and Koura, DT and Kratz, CP and Kulkarni, S and Liou, I and Nakano, TA and Nastasio, S and Niewisch, MR and Penrice, DD and Sasa, GS and Savage, SA and Simonetto, DA and Ziegler, DS and Miethke, AG and Myers, KC and , },
title = {Liver disease and transplantation in telomere biology disorders: An international multicenter cohort.},
journal = {Hepatology communications},
volume = {8},
number = {7},
pages = {},
doi = {10.1097/HC9.0000000000000462},
pmid = {38896081},
issn = {2471-254X},
mesh = {Humans ; *Liver Transplantation ; Female ; Male ; Retrospective Studies ; Adult ; Middle Aged ; Telomere ; Adolescent ; Liver Diseases/surgery/genetics ; Young Adult ; Child ; Treatment Outcome ; Child, Preschool ; },
abstract = {BACKGROUND: Patients with telomere biology disorders (TBD) develop hepatic disease, including hepatitis, cirrhosis, and hepatopulmonary syndrome. No specific treatment exists for TBD-related liver disease, and the role of liver transplantation (LT) remains controversial. Our study objectives were to describe the clinical characteristics, management, and outcomes in patients with TBD-related liver disease, and their LT outcomes.

METHODS: Data from 83 patients with TBD-associated liver disease were obtained from 17 participating centers in the Clinical Care Consortium of Telomere-Associated Ailments and by self-report for our retrospective, multicenter, international cohort study.

RESULTS: Group A ("Advanced") included 40 patients with advanced liver disease. Of these, 20 underwent LT (Group AT). Group M ("Mild") included 43 patients not warranting LT evaluation, none of whom were felt to be medically unfit for liver transplantation. Supplemental oxygen requirement, pulmonary arteriovenous malformation, hepatopulmonary syndrome, and higher bilirubin and international normalized ratio values were associated with Group A. Other demographics, clinical manifestations, and laboratory findings were similar between groups. Six group A patients were declined for LT; 3 died on the waitlist. Median follow-up post-LT was 2.9 years (range 0.6-13.2 y). One-year survival post-LT was 73%. Median survival post-LT has not been reached. Group AT patients had improved survival by age compared to all nontransplant patients (log-rank test p = 0.02). Of 14 patients with pretransplant hypoxemia, 8 (57%) had improved oxygenation after transplant.

CONCLUSIONS: LT recipients with TBD do not exhibit excessive posttransplant mortality, and LT improved respiratory status in 57%. A TBD diagnosis should not exclude LT consideration.},
}

Humans
*Liver Transplantation
Female
Male
Retrospective Studies
Adult
Middle Aged
Telomere
Adolescent
Liver Diseases/surgery/genetics
Young Adult
Child
Treatment Outcome
Child, Preschool

@article {pmid38896046,
year = {2024},
author = {Cianciosi, D and Forbes-Hernandez, T and Armas Diaz, Y and Elexpuru-Zabaleta, M and Quiles, JL and Battino, M and Giampieri, F},
title = {Manuka honey's anti-metastatic impact on colon cancer stem-like cells: unveiling its effects on epithelial-mesenchymal transition, angiogenesis and telomere length.},
journal = {Food & function},
volume = {},
number = {},
pages = {},
doi = {10.1039/d4fo00943f},
pmid = {38896046},
issn = {2042-650X},
abstract = {Colorectal cancer often leads to metastasis, with cancer stem cells (CSCs) playing a pivotal role in this process. Two closely linked mechanisms, epithelial-mesenchymal transition and angiogenesis, contribute to metastasis and recent research has also highlighted the impact of telomere replication on this harmful tumor progression. Standard chemotherapy alone can inadvertently promote drug-resistant CSCs, posing a challenge. Combining chemotherapy with other compounds, including natural ones, shows promise in enhancing effectiveness while minimizing side effects. This study investigated the anti-metastatic potential of Manuka honey, both alone and in combination with 5-fluorouracil, using a 3D model of colonospheres enriched with CSC-like cells. In summary, it was observed that the treatment reduced migration ability by downregulating the transcription factors Slug, Snail, and Twist, which are key players in epithelial-mesenchymal transition. Additionally, Manuka honey downregulated pro-angiogenic factors and shortened CSC telomeres by downregulating c-Myc - demonstrating an effective anti-metastatic potential. This study suggests new research opportunities for studying the impact of natural compounds when combined with pharmaceuticals, with the potential to enhance effectiveness and reduce side effects.},
}

@article {pmid38895181,
year = {2024},
author = {Mori, JO and Platz, EA and Lu, J and Brame, A and Han, M and Joshu, CE and De Marzo, AM and Meeker, AK and Heaphy, CM},
title = {Longer prostate stromal cell telomere length is associated with increased risk of death from other cancers.},
journal = {Frontiers in medicine},
volume = {11},
number = {},
pages = {1390769},
pmid = {38895181},
issn = {2296-858X},
abstract = {BACKGROUND: Telomeres are located at chromosomal termini and function to maintain genomic integrity. Telomere dysfunction is a well-recognized contributor to aging and age-related diseases, such as prostate cancer. Since telomere length is highly heritable, we postulate that stromal cell telomere length in the tissue of a particular solid organ may generally reflect constitutive stromal cell telomere length in other solid organs throughout the body. Even with telomere loss occurring with each round of cell replication, in general, telomere length in prostate stromal cells in mid-life would still be correlated with the telomere length in stromal cells in other organs. Thus, we hypothesize that prostate stromal cell telomere length and/or telomere length variability is a potential indicator of the likelihood of developing future solid cancers, beyond prostate cancer, and especially lethal cancer.

METHODS: To explore this hypothesis, we conducted a cohort study analysis of 1,175 men who were surgically treated for prostate cancer and were followed for death, including from causes other than their prostate cancer.

RESULTS: In this cohort study with a median follow-up of 19 years, we observed that longer prostate stromal cell telomere length measured in tissue microarray spots containing prostate cancer was associated with an increased risk of death from other solid cancers. Variability in telomere length among these prostate stromal cells was possibly positively associated with risk of death from other solid cancers.

CONCLUSION: Studying the link between stromal cell telomere length and cancer mortality may be important for guiding the development of cancer interception and prevention strategies.},
}

@article {pmid38892366,
year = {2024},
author = {Lohberger, B and Barna, S and Glänzer, D and Eck, N and Leithner, A and Georg, D},
title = {DNA-PKcs Inhibition Sensitizes Human Chondrosarcoma Cells to Carbon Ion Irradiation via Cell Cycle Arrest and Telomere Capping Disruption.},
journal = {International journal of molecular sciences},
volume = {25},
number = {11},
pages = {},
pmid = {38892366},
issn = {1422-0067},
support = {P32103-B//Austrian Science Foundation/ ; },
mesh = {Humans ; *DNA-Activated Protein Kinase/antagonists & inhibitors/metabolism/genetics ; Cell Line, Tumor ; *Chondrosarcoma/metabolism/genetics/radiotherapy/drug therapy ; *Heavy Ion Radiotherapy ; *Telomere/drug effects/metabolism ; Cell Cycle Checkpoints/drug effects/radiation effects ; DNA Repair/drug effects ; Radiation Tolerance/drug effects ; Pyrazoles/pharmacology ; Cell Proliferation/drug effects ; Bone Neoplasms/metabolism/genetics/pathology/drug therapy ; G2 Phase Cell Cycle Checkpoints/drug effects/radiation effects ; },
abstract = {In order to overcome the resistance to radiotherapy in human chondrosarcoma cells, the prevention from efficient DNA repair with a combined treatment with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) inhibitor AZD7648 was explored for carbon ion (C-ion) as well as reference photon (X-ray) irradiation (IR) using gene expression analysis, flow cytometry, protein phosphorylation, and telomere length shortening. Proliferation markers and cell cycle distribution changed significantly after combined treatment, revealing a prominent G2/M arrest. The expression of the G2/M checkpoint genes cyclin B, CDK1, and WEE1 was significantly reduced by IR alone and the combined treatment. While IR alone showed no effects, additional AZD7648 treatment resulted in a dose-dependent reduction in AKT phosphorylation and an increase in Chk2 phosphorylation. Twenty-four hours after IR, the key genes of DNA repair mechanisms were reduced by the combined treatment, which led to impaired DNA repair and increased radiosensitivity. A time-dependent shortening of telomere length was observed in both cell lines after combined treatment with AZD7648 and 8 Gy X-ray/C-ion IR. Our data suggest that the inhibition of DNA-PKcs may increase sensitivity to X-rays and C-ion IR by impairing its functional role in DNA repair mechanisms and telomere end protection.},
}

Humans
*DNA-Activated Protein Kinase/antagonists & inhibitors/metabolism/genetics
Cell Line, Tumor
*Chondrosarcoma/metabolism/genetics/radiotherapy/drug therapy
*Heavy Ion Radiotherapy
*Telomere/drug effects/metabolism
Cell Cycle Checkpoints/drug effects/radiation effects
DNA Repair/drug effects
Radiation Tolerance/drug effects
Pyrazoles/pharmacology
Cell Proliferation/drug effects
Bone Neoplasms/metabolism/genetics/pathology/drug therapy
G2 Phase Cell Cycle Checkpoints/drug effects/radiation effects

@article {pmid38891017,
year = {2024},
author = {Deb, S and Berei, J and Miliavski, E and Khan, MJ and Broder, TJ and Akurugo, TA and Lund, C and Fleming, SE and Hillwig, R and Ross, J and Puri, N},
title = {The Effects of Smoking on Telomere Length, Induction of Oncogenic Stress, and Chronic Inflammatory Responses Leading to Aging.},
journal = {Cells},
volume = {13},
number = {11},
pages = {},
pmid = {38891017},
issn = {2073-4409},
support = {Bridge Grant//University of Illinois Chicago, Rockford campus/ ; },
mesh = {Humans ; *Inflammation/genetics/pathology ; *Aging/genetics ; *Telomeric Repeat Binding Protein 2/metabolism/genetics ; *Shelterin Complex ; *Cytokines/metabolism ; *Telomere/metabolism ; *Telomerase/metabolism/genetics ; *Smoking/adverse effects ; Ubiquitins/metabolism/genetics ; Telomere-Binding Proteins/metabolism/genetics ; Interferon-gamma/metabolism ; Telomere Homeostasis ; Male ; Telomere Shortening ; Female ; Middle Aged ; },
abstract = {Telomeres, potential biomarkers of aging, are known to shorten with continued cigarette smoke exposure. In order to further investigate this process and its impact on cellular stress and inflammation, we used an in vitro model with cigarette smoke extract (CSE) and observed the downregulation of telomere stabilizing TRF2 and POT1 genes after CSE treatment. hTERT is a subunit of telomerase and a well-known oncogenic marker, which is overexpressed in over 85% of cancers and may contribute to lung cancer development in smokers. We also observed an increase in hTERT and ISG15 expression levels after CSE treatment, as well as increased protein levels revealed by immunohistochemical staining in smokers' lung tissue samples compared to non-smokers. The effects of ISG15 overexpression were further studied by quantifying IFN-γ, an inflammatory protein induced by ISG15, which showed greater upregulation in smokers compared to non-smokers. Similar changes in gene expression patterns for TRF2, POT1, hTERT, and ISG15 were observed in blood and buccal swab samples from smokers compared to non-smokers. The results from this study provide insight into the mechanisms behind smoking causing telomere shortening and how this may contribute to the induction of inflammation and/or tumorigenesis, which may lead to comorbidities in smokers.},
}

Humans
*Inflammation/genetics/pathology
*Aging/genetics
*Telomeric Repeat Binding Protein 2/metabolism/genetics
*Shelterin Complex
*Cytokines/metabolism
*Telomere/metabolism
*Telomerase/metabolism/genetics
*Smoking/adverse effects
Ubiquitins/metabolism/genetics
Telomere-Binding Proteins/metabolism/genetics
Interferon-gamma/metabolism
Telomere Homeostasis
Male
Telomere Shortening
Female
Middle Aged

@article {pmid38890299,
year = {2024},
author = {Schmidt, TT and Tyer, C and Rughani, P and Haggblom, C and Jones, JR and Dai, X and Frazer, KA and Gage, FH and Juul, S and Hickey, S and Karlseder, J},
title = {High resolution long-read telomere sequencing reveals dynamic mechanisms in aging and cancer.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {5149},
pmid = {38890299},
issn = {2041-1723},
support = {CA227934//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P30CA014195//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; CA234047//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; GM142173//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; AG0773424//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; 19PABH134610000//American Heart Association (American Heart Association, Inc.)/ ; ALTF 668-2019//European Molecular Biology Organization (EMBO)/ ; },
mesh = {Humans ; *Telomere/genetics/metabolism ; *Neoplasms/genetics/metabolism ; *Aging/genetics ; Telomerase/genetics/metabolism ; Cell Line, Tumor ; Telomere Shortening/genetics ; Sequence Analysis, DNA/methods ; High-Throughput Nucleotide Sequencing/methods ; Alleles ; },
abstract = {Telomeres are the protective nucleoprotein structures at the end of linear eukaryotic chromosomes. Telomeres' repetitive nature and length have traditionally challenged the precise assessment of the composition and length of individual human telomeres. Here, we present Telo-seq to resolve bulk, chromosome arm-specific and allele-specific human telomere lengths using Oxford Nanopore Technologies' native long-read sequencing. Telo-seq resolves telomere shortening in five population doubling increments and reveals intrasample, chromosome arm-specific, allele-specific telomere length heterogeneity. Telo-seq can reliably discriminate between telomerase- and ALT-positive cancer cell lines. Thus, Telo-seq is a tool to study telomere biology during development, aging, and cancer at unprecedented resolution.},
}

Humans
*Telomere/genetics/metabolism
*Neoplasms/genetics/metabolism
*Aging/genetics
Telomerase/genetics/metabolism
Cell Line, Tumor
Telomere Shortening/genetics
Sequence Analysis, DNA/methods
High-Throughput Nucleotide Sequencing/methods
Alleles

@article {pmid38890274,
year = {2024},
author = {Sanchez, SE and Gu, Y and Wang, Y and Golla, A and Martin, A and Shomali, W and Hockemeyer, D and Savage, SA and Artandi, SE},
title = {Digital telomere measurement by long-read sequencing distinguishes healthy aging from disease.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {5148},
pmid = {38890274},
issn = {2041-1723},
mesh = {Humans ; *Telomere/genetics/metabolism ; *Telomere Homeostasis/genetics ; *Machine Learning ; Adult ; Healthy Aging/genetics ; Middle Aged ; Male ; Aged ; Female ; Telomere Shortening/genetics ; Aging/genetics ; Nanopore Sequencing/methods ; Young Adult ; },
abstract = {Telomere length is an important biomarker of organismal aging and cellular replicative potential, but existing measurement methods are limited in resolution and accuracy. Here, we deploy digital telomere measurement (DTM) by nanopore sequencing to understand how distributions of human telomere length change with age and disease. We measure telomere attrition and de novo elongation with up to 30 bp resolution in genetically defined populations of human cells, in blood cells from healthy donors and in blood cells from patients with genetic defects in telomere maintenance. We find that human aging is accompanied by a progressive loss of long telomeres and an accumulation of shorter telomeres. In patients with defects in telomere maintenance, the accumulation of short telomeres is more pronounced and correlates with phenotypic severity. We apply machine learning to train a binary classification model that distinguishes healthy individuals from those with telomere biology disorders. This sequencing and bioinformatic pipeline will advance our understanding of telomere maintenance mechanisms and the use of telomere length as a clinical biomarker of aging and disease.},
}

Humans
*Telomere/genetics/metabolism
*Telomere Homeostasis/genetics
*Machine Learning
Adult
Healthy Aging/genetics
Middle Aged
Male
Aged
Female
Telomere Shortening/genetics
Aging/genetics
Nanopore Sequencing/methods
Young Adult

@article {pmid38886520,
year = {2024},
author = {Chung, HG and Yang, PS and Cho, S and Jang, E and Kim, D and Yu, HT and Kim, TH and Uhm, JS and Sung, JH and Pak, HN and Lee, MH and Joung, B},
title = {The associations of leukocyte telomere length and intermediary cardiovascular phenotype with adverse cardiovascular outcomes in the white population.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {13975},
pmid = {38886520},
issn = {2045-2322},
abstract = {The evidence about the associations of leukocyte telomere length (LTL) and intermediary cardiovascular phenotypes with adverse cardiovascular outcomes is inconclusive. This study assessed these relationships with cardiovascular imaging, electrocardiography, and the risks of sudden cardiac death (SCD), coronary events, and heart failure (HF) admission. We conducted a cross-sectional analysis of UK Biobank participants enrolled between 2006 and 2010. LTL was measured using quantitative polymerase chain reactions. Electronic health records were used to determine the incidence of SCD, coronary events, and HF admission. Cardiovascular measurements were made using cardiovascular magnetic resonance imaging and machine learning. The associations of LTL with SCD, coronary events, and HF admission and cardiac magnetic resonance imaging, electrocardiogram parameters of 33,043 and 19,554 participants were evaluated by multivariate regression. The median (interquartile range) follow-up period was 11.9 (11.2-12.6) years. Data was analyzed from January to May 2023. Among the 403,382 white participants without coronary artery disease or HF, 181,637 (45.0%) were male with a mean age of 57.1 years old. LTL was independently negatively associated with a risk of SCD (LTL third quartile vs first quartile: hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.72-0.92), coronary events (LTL third quartile vs first quartile: HR: 0.88, 95% CI: 0.84-0.92), and HF admission (LTL fourth quartile vs first quartile: HR: 0.84, 95% CI: 0.74-0.95). LTL was also independently positively associated with cardiac remodeling, specifically left ventricular mass index, left-ventricular-end systolic and diastolic volumes, mean left ventricular myocardial wall thickness, left ventricular stroke volume, and with electrocardiogram changes along the negative degree of T-axis. Cross-sectional study results showed that LTL was positively associated with heart size and cardiac function in middle age, but electrocardiography results did not show these associations, which could explain the negative association between LTL and risk of SCD, coronary events, and HF admission in UK Biobank participants.},
}

@article {pmid38886039,
year = {2024},
author = {Alcock, LJ and Sudhakar, HK and Young, R and Lau, YH},
title = {Fluorescence polarization assay for screening FANCM-RMI inhibitors to target the alternative lengthening of telomeres.},
journal = {Methods in enzymology},
volume = {698},
number = {},
pages = {361-378},
doi = {10.1016/bs.mie.2024.04.014},
pmid = {38886039},
issn = {1557-7988},
mesh = {Humans ; *Fluorescence Polarization/methods ; *Telomere Homeostasis/drug effects ; Protein Binding ; Telomere/metabolism/genetics ; DNA Helicases ; },
abstract = {Alternative Lengthening of Telomeres (ALT) is a mechanism used by 10-15% of all cancers to achieve replicative immortality, bypassing the DNA damage checkpoint associated with short telomeres that leads to cellular senescence or apoptosis. ALT does not occur in non-cancerous cells, presenting a potential therapeutic window for cancers where this mechanism is active. Disrupting the FANCM-RMI interaction has emerged as a promising therapeutic strategy that induces synthetic ALT lethality in genetic studies on cancer cell lines. There are currently no chemical inhibitors reported in the literature, in part due to the lack of reliable biophysical or biochemical assays to screen for FANCM-RMI disruption. Here we describe the development of a robust competitive fluorescence polarization (FP) assay that quantifies target binding at the FANCM-RMI interface. The assay employs a labeled peptide tracer TMR-RaMM2 derived from the native MM2 binding motif, which binds to recombinant RMI1-RMI2 and can be displaced by competitive inhibitors. We report the methods for recombinant production of RMI1-RMI2, design and evaluation of the tracer TMR-RaMM2, along with unlabeled peptide inhibitor controls to enable ALT-targeted drug discovery.},
}

Humans
*Fluorescence Polarization/methods
*Telomere Homeostasis/drug effects
Protein Binding
Telomere/metabolism/genetics
DNA Helicases

@article {pmid38884214,
year = {2024},
author = {Khayat, F and Alshmery, M and Pal, M and Oliver, AW and Bianchi, A},
title = {Binding of the TRF2 iDDR motif to RAD50 highlights a convergent evolutionary strategy to inactivate MRN at telomeres.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkae509},
pmid = {38884214},
issn = {1362-4962},
support = {C302/A24386/CRUK_/Cancer Research UK/United Kingdom ; //University of Sussex/ ; },
abstract = {Telomeres protect chromosome ends from unscheduled DNA repair, including from the MRN (MRE11, RAD50, NBS1) complex, which processes double-stranded DNA breaks (DSBs) via activation of the ATM kinase, promotes DNA end-tethering aiding the non-homologous end-joining (NHEJ) pathway, and initiates DSB resection through the MRE11 nuclease. A protein motif (MIN, for MRN inhibitor) inhibits MRN at budding yeast telomeres by binding to RAD50 and evolved at least twice, in unrelated telomeric proteins Rif2 and Taz1. We identify the iDDR motif of human shelterin protein TRF2 as a third example of convergent evolution for this telomeric mechanism for binding MRN, despite the iDDR lacking sequence homology to the MIN motif. CtIP is required for activation of MRE11 nuclease action, and we provide evidence for binding of a short C-terminal region of CtIP to a RAD50 interface that partly overlaps with the iDDR binding site, indicating that the interaction is mutually exclusive. In addition, we show that the iDDR impairs the DNA binding activity of RAD50. These results highlight direct inhibition of MRN action as a crucial role of telomeric proteins across organisms and point to multiple mechanisms enforced by the iDDR to disable the many activities of the MRN complex.},
}

@article {pmid38883734,
year = {2024},
author = {Skåra, KH and Lee, Y and Jugessur, A and Gjessing, HK and Aviv, A and Brumpton, B and Naess, Ø and Hernáez, Á and Hanevik, HI and Magnus, P and Magnus, MC},
title = {Telomere length in relation to fecundability and use of assisted reproductive technologies: the Norwegian Mother, Father, and Child Cohort Study.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-4430021/v1},
pmid = {38883734},
abstract = {In women, shorter telomeres have been reported to be associated with conditions such as endometriosis and polycystic ovary syndrome, whereas other studies have reported the opposite. In men, studies mostly report associations between shorter telomeres and sperm quality. To our knowledge, no studies have thus far investigated the associations between TL and fecundability or the use of ART. This study is based on the Norwegian Mother, Father, and Child Cohort (MoBa) Study and uses data from the Medical Birth Registry of Norway (MBRN). We included women (24,645 with genotype data and 1,054 with TL measurements) and men (18,339 with genotype data and 965 with TL measurements) participating between 1998 and 2008. We investigated the associations between leukocyte TL and fecundability, infertility, and the use of ART. We also repeated the analyses using instrumental variables for TL, including genetic risk scores for TL and genetically predicted TL. Approximately 11% of couples had experienced infertility and 4% had used ART. TL was not associated with fecundability among women (fecundability ratio [FR], 0.98; 95% confidence interval [CI], 0.92-1.04) or men (FR, 0.99; CI, 0.93-1.06), nor with infertility among women (odds ratio [OR], 1.03; CI, 0.85-1.24) or men (OR, 1.05; CI, 0.87-1.28). We observed an increased likelihood of using ART with increasing TL among men (OR, 1.22; CI, 1.03-1.46), but not among women (OR, 1.10; CI, 0.92-1.31). No significant associations were observed using the instrumental variables. Our results indicate that TL is a poor biomarker of fecundability, infertility and use of ART in MoBa. Additional studies are required to replicate the association observed between TL and ART in men.},
}

@article {pmid38883396,
year = {2024},
author = {Castro, A and Lardone, MC and Giraudo, F and López, P and Ortiz, E and Iñiguez, G and Cassorla, F and Codner, E},
title = {Differential Effect of 2 Hormonal Contraceptives on the Relative Telomere Length of Youth With Type 1 Diabetes.},
journal = {Journal of the Endocrine Society},
volume = {8},
number = {7},
pages = {bvae091},
pmid = {38883396},
issn = {2472-1972},
abstract = {CONTEXT: Adolescents and young women (AYA) with type 1 diabetes (T1D) may require hormonal contraception for an extended period. However, it is unclear what effect hormonal contraception has on telomere length, a marker of the risk for complications.

OBJECTIVE: To investigate the relative telomere length (RTL) in AYA with T1D (AYA-T1D) and healthy young women (AYA-C) after 18 months of combined oral contraception use (COC) with ethinyl estradiol/desogestrel, or a subdermal etonogestrel implant (IM).

METHODS: A nonrandomized prospective study was performed in which 39 AYA-T1D and 40 AYA-C chose the COC or the IM. RTL was measured by monochrome multiplex-quantitative PCR in DNA from peripheral blood mononuclear cells (PBMC). The impact of contraceptives and clinical variables on RTL was assessed using lineal regression analysis.

RESULTS: Longer RTL compared to baseline was observed in AYA-T1D (P < .05) and AYA-C (P  < .01) after using the IM. However, the total of AYA and the AYA-C group treated with COC decreased RTL after 18 months of treatment compared to baseline (P < .05). The type of contraceptive used was determinant for the changes in RTL compared to baseline in all subjects and controls (P ≤ .006). For AYA-T1D, HbA1c levels were not associated with RTL, but the high-sensitivity C-reactive protein was negatively related with the changes in RTL at 18 months compared to baseline (standardized R[2] : 0.230, P  = .003).

CONCLUSION: IM was associated with longer RTL in AYA-T1D and AYA-C. In contrast, a shortening of telomere length in PBMC was observed after using COC.},
}

@article {pmid38883331,
year = {2024},
author = {Song, Y and Zhang, Y and Wang, X and Yu, X and Liao, Y and Zhang, H and Li, L and Wang, Y and Liu, B and Li, W},
title = {Telomere-to-telomere reference genome for Panax ginseng highlights the evolution of saponin biosynthesis.},
journal = {Horticulture research},
volume = {11},
number = {6},
pages = {uhae107},
pmid = {38883331},
issn = {2662-6810},
abstract = {Ginseng (Panax ginseng) is a representative of Chinese traditional medicine, also used worldwide, while the triterpene saponin ginsenoside is the most important effective compound within it. Ginseng is an allotetraploid, with complex genetic background, making the study of its metabolic evolution challenging. In this study, we assembled a telomere-to-telomere ginseng reference genome, constructed of 3.45 Gb with 24 chromosomes and 77 266 protein-coding genes. Additionally, the reference genome was divided into two subgenomes, designated as subgenome A and B. Subgenome A contains a larger number of genes, whereas subgenome B has a general expression advantage, suggesting that ginseng subgenomes experienced asymmetric gene loss with biased gene expression. The two subgenomes separated approximately 6.07 million years ago, and subgenome B shows the closest relation to Panax vietnamensis var. fuscidiscus. Comparative genomics revealed an expansion of gene families associated with ginsenoside biosynthesis in both ginseng subgenomes. Furthermore, both tandem duplications and proximal duplications play crucial roles in ginsenoside biosynthesis. We also screened functional genes identified in previous research and found that some of these genes located in colinear regions between subgenomes have divergence functions, revealing an unbalanced evolution in both subgenomes and the saponin biosynthesis pathway in ginseng. Our work provides important resources for future genetic studies and breeding programs of ginseng, as well as the biosynthesis of ginsenosides.},
}

@article {pmid38882679,
year = {2024},
author = {Zhang, J and Wen, J and Dai, Z and Zhang, H and Zhang, N and Lei, R and Liu, Z and Peng, L and Cheng, Q},
title = {Causal association and shared genetics between telomere length and COVID-19 outcomes: New evidence from the latest large-scale summary statistics.},
journal = {Computational and structural biotechnology journal},
volume = {23},
number = {},
pages = {2429-2441},
pmid = {38882679},
issn = {2001-0370},
abstract = {BACKGROUND: Observational studies suggested that leukocyte telomere length (LTL) is shortened in COVID-19 patients. However, the genetic association and causality remained unknown.

METHODS: Based on the genome-wide association of LTL (N = 472,174) and COVID-19 phenotypes (N = 1086,211-2597,856), LDSC and SUPERGNOVA were used to estimate the genetic correlation. Cross-trait GWAS meta-analysis, colocalization, fine-mapping analysis, and transcriptome-wide association study were conducted to explore the shared genetic etiology. Mendelian randomization (MR) was utilized to infer the causality. Upstream and downstream two-step MR was performed to investigate the potential mediating effects.

RESULTS: LDSC identified a significant genetic association between LTL and all COVID-19 phenotypes (rG < 0, p < 0.05). Six significant regions were observed for LTL and COVID-19 susceptibility and hospitalization, respectively. Colocalization analysis found rs144204502, rs34517439, and rs56255908 were shared causal variants between LTL and COVID-19 phenotypes. Numerous biological pathways associated with LTL and COVID-19 outcomes were identified, mainly involved in -immune-related pathways. MR showed that longer LTL was significantly associated with a lower risk of COVID-19 severity (OR [95% CI] = 0.81 [0.71-0.92], p = 1.24 ×10[-3]) and suggestively associated with lower risks of COVID-19 susceptibility (OR [95% CI] = 0.96 [0.92-1.00], p = 3.44 ×10[-2]) and COVID-19 hospitalization (OR [95% CI] = 0.89 [0.80-0.98], p = 1.89 ×10[-2]). LTL partially mediated the effects of BMI, smoking, and education on COVID-19 outcomes. Furthermore, six proteins partially mediated the causality of LTL on COVID-19 outcomes, including BNDF, QPCT, FAS, MPO, SFTPB, and APOF.

CONCLUSIONS: Our findings suggested that shorter LTL was genetically associated with a higher risk of COVID-19 phenotypes, with shared genetic etiology and potential causality.},
}

@article {pmid38882488,
year = {2024},
author = {Wei, C and Gao, L and Xiao, R and Wang, Y and Chen, B and Zou, W and Li, J and Mace, E and Jordan, D and Tao, Y},
title = {Complete telomere-to-telomere assemblies of two sorghum genomes to guide biological discovery.},
journal = {iMeta},
volume = {3},
number = {2},
pages = {e193},
pmid = {38882488},
issn = {2770-596X},
abstract = {The assembly of two sorghum T2T genomes corrected the assembly errors in the current reference, uncovered centromere variation, boosted functional genomics research, and accelerated sorghum improvement.},
}

@article {pmid38879916,
year = {2024},
author = {Li, X and Li, M and Cheng, J and Guan, S and Hou, L and Zu, S and Yang, L and Wu, H and Li, H and Fan, Y and Zhang, B},
title = {Association of healthy and unhealthy plant-based diets with telomere length.},
journal = {Clinical nutrition (Edinburgh, Scotland)},
volume = {43},
number = {8},
pages = {1694-1701},
doi = {10.1016/j.clnu.2024.06.004},
pmid = {38879916},
issn = {1532-1983},
abstract = {BACKGROUND & AIMS: Previous studies have shown that plant-rich dietary patterns, such as the Mediterranean diet, are associated with longer telomeres. However, no association has been found between vegetarian diet and telomere length. We hypothesized that the quality of plant-based diets plays an important role in telomere length.

METHODS: Data were obtained from the National Health and Nutrition Examination Survey 1999-2002. Diet was assessed using a 24-h recall method. Plant-based diet quality was assessed using the overall plant-based diet index (PDI), healthy PDI (hPDI), and unhealthy PDI (uPDI). Telomere length was measured using quantitative PCR. Linear and ordinal logistic regression models were used to assess the association of PDIs with log-transformed telomere length and ordinal quintiles of telomere length in descending order, respectively.

RESULTS: In both regression models, the overall PDI was not associated with telomere length. The hPDI was associated with longer telomere length [percentage change = 2.34%, 95% confidence interval (CI): 0.42%, 4.31%, Ptrend = 0.016; odds ratio (OR) = 0.81, 95% CI: 0.69, 0.95, Ptrend = 0.013]. However, uPDI was associated with shorter telomere length (percentage change = -3.17%, 95% CI: -5.65%, -0.62%, Ptrend = 0.017; OR = 1.25, 95% CI:1.03, 1.53, Ptrend = 0.014) and this inverse association was stronger in the non-Hispanic white population (Pinteraction = 0.001 in both regression models).

CONCLUSIONS: A plant-based dietary pattern rich in healthy plant foods is associated with longer telomeres. However, plant-based dietary patterns rich in unhealthy plant-based foods are associated with shorter telomere lengths, especially in non-Hispanic white populations.},
}

@article {pmid38875394,
year = {2024},
author = {Fu, Y and Lou, H and Chen, Q and Wu, S and Chen, H and Liang, K and Ge, Y and Zhao, C},
title = {Objective assessment of the association between telomere length, a biomarker of aging, and health screening indicators: A cross-sectional study.},
journal = {Medicine},
volume = {103},
number = {24},
pages = {e38533},
doi = {10.1097/MD.0000000000038533},
pmid = {38875394},
issn = {1536-5964},
mesh = {Humans ; Cross-Sectional Studies ; Male ; Female ; Middle Aged ; *Aging/genetics/physiology ; Adult ; Aged ; *Telomere ; *Biomarkers/blood ; Young Adult ; Physical Examination/methods ; Aged, 80 and over ; Health Status ; Health Status Indicators ; },
abstract = {Physical examination data are used to indicate individual health status and organ health, and understanding which physical examination data are indicative of physiological aging is critical for health management and early intervention. There is a lack of research on physical examination data and telomere length. Therefore, the present study analyzed the association between blood telomere length and physical examination indices in healthy people of different ages to investigate the role and association of various organs/systems with physiological aging in the human body. The present study was a cross-sectional study. Sixteen physical examination indicators of different tissue and organ health status were selected and analyzed for trends in relation to actual age and telomere length (TL). The study included 632 individuals with a total of 11,766 data for 16 physical examination indicators. Age was linearly correlated with 11 indicators. Interestingly, telomere length was strongly correlated only with the renal indicators eGFR (P < .001), CYS-C (P < .001), and SCR (P < .001). The study established that renal aging or injury is a risk factor for Physical aging of the human body. Early identification and management are essential to healthcare.},
}

Humans
Cross-Sectional Studies
Male
Female
Middle Aged
*Aging/genetics/physiology
Adult
Aged
*Telomere
*Biomarkers/blood
Young Adult
Physical Examination/methods
Aged, 80 and over
Health Status
Health Status Indicators

@article {pmid38875139,
year = {2024},
author = {Gillooly, JF and Khazan, ES},
title = {Telomeres and the Rate of Living: Linking Biological Clocks of Senescence.},
journal = {Ecological and evolutionary physiology},
volume = {97},
number = {3},
pages = {157-163},
doi = {10.1086/730588},
pmid = {38875139},
issn = {2993-7973},
mesh = {Animals ; *Telomere/metabolism ; *Aging/genetics/physiology ; *Biological Clocks/physiology/genetics ; Telomere Shortening ; Longevity/genetics/physiology ; Energy Metabolism/physiology ; Vertebrates/genetics/physiology ; },
abstract = {AbstractTwo prominent theories of aging, one based on telomere dynamics and the other on mass-specific energy flux, propose biological time clocks of senescence. The relationship between these two theories, and the biological clocks proposed by each, remains unclear. Here, we examine the relationships between telomere shortening rate, mass-specific metabolic rate, and lifespan among vertebrates (mammals, birds, fishes). Results show that telomere shortening rate increases linearly with mass-specific metabolic rate and decreases nonlinearly with increasing body mass in the same way as mass-specific metabolic rate. Results also show that both telomere shortening rate and mass-specific metabolic rate are similarly related to lifespan and that both strongly predict differences in lifespan, although the slopes of the relationships are less than linear. On average, then, telomeres shorten a fixed amount per unit of mass-specific energy flux. So the mitotic clock of telomere shortening and the energetics-based clock described by metabolic rate can be viewed as alternative measures of the same biological clock. These two processes may be linked, we speculate, through the process of cell division.},
}

Animals
*Telomere/metabolism
*Aging/genetics/physiology
*Biological Clocks/physiology/genetics
Telomere Shortening
Longevity/genetics/physiology
Energy Metabolism/physiology
Vertebrates/genetics/physiology

@article {pmid38869742,
year = {2024},
author = {Wang, Q and Xi, L and Yang, N and Song, J and Taiwaikul, D and Zhang, X and Bo, Y and Tang, B and Zhou, X},
title = {Association of leukocyte telomere length with risk of all-cause and cardiovascular mortality in middle-aged and older individuals without cardiovascular disease: a prospective cohort study of NHANES 1999-2002.},
journal = {Aging clinical and experimental research},
volume = {36},
number = {1},
pages = {131},
pmid = {38869742},
issn = {1720-8319},
support = {82060069//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Cardiovascular Diseases/mortality/genetics ; Male ; Middle Aged ; *Leukocytes/metabolism ; Female ; *Nutrition Surveys ; Prospective Studies ; *Telomere/genetics ; Aged ; Risk Factors ; },
abstract = {BACKGROUND: Leukocyte telomere length (LTL) shorting was significantly associated with mortality. This study aimed to investigate the potential association between LTL and all-cause mortality as well as cardiovascular disease (CVD) mortality in middle-aged or older individuals without a history of CVD.

METHODS: A total of 4174 participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2002 were included in this analysis. Cox proportional hazards regression models were utilized to estimate the association between LTL and mortality outcomes. Restricted cubic spline (RCS) curves were employed to evaluate the potential non-linear association.

RESULTS: Over a median follow-up period of 217 months, the weighted rates of all-cause mortality and CVD mortality were 28.58% and 8.32% respectively. Participants in the highest LTL group exhibited a significantly decreased risk of both all-cause mortality (HR: 0.65, 95% CI: 0.54-0.78, P < 0.001) and CVD mortality (HR: 0.64, 95% CI: 0.45-0.93, P < 0.001) compared to those in the lowest group. Kaplan-Meier survival curves further supported a significant association between shorter telomere length and increased risks of both all-cause and CVD mortality (log-rank test P < 0.001). RCS curves demonstrated a linear dose-response relationship between LTL and all-cause mortality as well as CVD mortality. Subgroup and sensitivity analyses confirmed the robustness of the results.

CONCLUSION: Shorter leukocyte telomere length could serve as a potential biomarker for risk stratification of all-cause and CVD mortality among middle-aged and older individuals without a history of CVD.},
}

Humans
*Cardiovascular Diseases/mortality/genetics
Male
Middle Aged
*Leukocytes/metabolism
Female
*Nutrition Surveys
Prospective Studies
*Telomere/genetics
Aged
Risk Factors

@article {pmid38865824,
year = {2024},
author = {Du, B and Liu, B and Fang, YK and Zheng, JZ and Wu, J and Tao, FZ and Zhang, MY and Zhang, TJ},
title = {Shugan Tongluo Qiangjing recipe protects against varicocele of EVC rats through modulating sperm DNA damage, telomere expression and oxidative stress.},
journal = {Tissue & cell},
volume = {89},
number = {},
pages = {102414},
doi = {10.1016/j.tice.2024.102414},
pmid = {38865824},
issn = {1532-3072},
abstract = {Varicocele (VC) refers to expansion and tortuosity of spreading venous plexus in spermatic cord due to poor blood flow. This study aimed to investigate effects of Shugan Tongluo Qiangjing recipe (SGTL) on sperm DNA damage and oxidative stress in experimental VC (EVC) rats. EVC model was established by partial ligation of left renal vein. Spermatic vein diameter, testicular weight, sperm DNA fragmentation index (DFI) were evaluated. Telomere reverse transcriptase (TERT) expression, telomere gene transcription, and testicular tissue morphology were determined·H2O2, catalase, SOD, T-AOC were measured with colorimetry. SGTL significantly decreased spermatic vein diameter (P=0.000) and increased testicular weight (P=0.013) of rats compared those of EVC rats. SGTL maintained testicular tissue morphology in EVC rats. SGTL markedly reduced sperm DFI value in sperm of rats compared to EVC rats (P=0.000). SGTL significantly enhanced TERT expression and telomere gene transcription (P=0.028) in testis of rats compared to EVC rats. SGTL reduced H2O2 levels (P=0.001) and promoted CAT activity (P=0.016), SOD activity (P=0.049), and T-AOC activity (P=0.047) of rats, compared to EVC rats. In conclusion, SGTL could reduce pathogenic process of EVC by reducing sperm DNA damage and regulating telomere length in EVC rats, which may be related to oxidative stress regulation.},
}

@article {pmid38865460,
year = {2024},
author = {Bettin, N and Querido, E and Gialdini, I and Grupelli, GP and Goretti, E and Cantarelli, M and Andolfato, M and Soror, E and Sontacchi, A and Jurikova, K and Chartrand, P and Cusanelli, E},
title = {TERRA transcripts localize at long telomeres to regulate telomerase access to chromosome ends.},
journal = {Science advances},
volume = {10},
number = {24},
pages = {eadk4387},
doi = {10.1126/sciadv.adk4387},
pmid = {38865460},
issn = {2375-2548},
mesh = {*Telomerase/metabolism/genetics ; Humans ; *Telomere/metabolism/genetics ; Telomere Homeostasis ; HeLa Cells ; RNA/metabolism/genetics ; Transcription, Genetic ; Telomere-Binding Proteins/metabolism/genetics ; Cell Cycle/genetics ; Chromosomes, Human/metabolism/genetics ; DNA-Binding Proteins ; Transcription Factors ; },
abstract = {The function of TERRA in the regulation of telomerase in human cells is still debated. While TERRA interacts with telomerase, how it regulates telomerase function remains unknown. Here, we show that TERRA colocalizes with the telomerase RNA subunit hTR in the nucleoplasm and at telomeres during different phases of the cell cycle. We report that TERRA transcripts relocate away from chromosome ends during telomere lengthening, leading to a reduced number of telomeric TERRA-hTR molecules and consequent increase in "TERRA-free" telomerase molecules at telomeres. Using live-cell imaging and super-resolution microscopy, we show that upon transcription, TERRA relocates from its telomere of origin to long chromosome ends. Furthermore, TERRA depletion by antisense oligonucleotides promoted hTR localization to telomeres, leading to increased residence time and extended half-life of hTR molecules at telomeres. Overall, our findings indicate that telomeric TERRA transcripts inhibit telomere elongation by telomerase acting in trans, impairing telomerase access to telomeres that are different from their chromosome end of origin.},
}

*Telomerase/metabolism/genetics
Humans
*Telomere/metabolism/genetics
Telomere Homeostasis
HeLa Cells
RNA/metabolism/genetics
Transcription, Genetic
Telomere-Binding Proteins/metabolism/genetics
Cell Cycle/genetics
Chromosomes, Human/metabolism/genetics
DNA-Binding Proteins
Transcription Factors

@article {pmid38863926,
year = {2024},
author = {Yang, S and Wang, X and Li, Y and Zhou, L and Guo, G and Wu, M},
title = {The association between telomere length and blood lipids: a bidirectional two-sample Mendelian randomization study.},
journal = {Frontiers in endocrinology},
volume = {15},
number = {},
pages = {1338698},
pmid = {38863926},
issn = {1664-2392},
mesh = {Humans ; *Mendelian Randomization Analysis ; *Genome-Wide Association Study ; *Lipids/blood ; Cholesterol, LDL/blood ; Triglycerides/blood ; Telomere/genetics ; Cholesterol, HDL/blood ; Polymorphism, Single Nucleotide ; Telomere Homeostasis ; Apolipoprotein A-I/blood/genetics ; },
abstract = {BACKGROUND: Observational studies suggest an association between telomere length (TL) and blood lipid (BL) levels. Nevertheless, the causal connections between these two traits remain unclear. We aimed to elucidate whether genetically predicted TL is associated with BL levels via Mendelian randomization (MR) and vice versa.

METHODS: We obtained genetic instruments associated with TL, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-1 (ApoA-1) and apolipoprotein B (ApoB) from large-scale genome-wide association studies (GWASs). The causal relationships between TL and BL were investigated via bidirectional MR, multivariable MR and mediation analysis methods. The inverse variance weighted (IVW) method was employed as the principal methodology, complemented by several other estimators to enhance the robustness of the analysis.

RESULTS: In the forward MR analyses, we identified significant positive correlation between genetically predicted TL and the levels of TG (β=0.04, 95% confidence interval [CI]: 0.01 to 0.06, p = 0.003). In the reverse MR analysis, TG (β=0.02, 95% CI: 0.01 to 0.03, p = 0.004), LDL-C (β=0.03, 95% CI: 0.01 to 0.04, p = 0.001) and ApoB (β=0.03, 95% CI: 0.01 to 0.04, p = 9.71×10[-5]) were significantly positively associated with TL, although this relationship was not observed in the multivariate MR analysis. The mediation analysis via two-step MR showed no significant mediation effects acting through obesity-related phenotypes in analysis of TL with TG, while the effect of LDL-C on TL was partially mediated by body mass index (BMI) in the reverse direction, with mediated proportion of 12.83% (95% CI: 0.62% to 25.04%).

CONCLUSIONS: Our study indicated that longer TL were associated with higher TG levels, while conversely, higher TG, LDL-C, and ApoB levels predicted longer TL, with BMI partially mediating these effects. Our findings present valuable insights into the development of preventive strategies and interventions that specifically target TL-related aging and age-related diseases.},
}

Humans
*Mendelian Randomization Analysis
*Genome-Wide Association Study
*Lipids/blood
Cholesterol, LDL/blood
Triglycerides/blood
Telomere/genetics
Cholesterol, HDL/blood
Polymorphism, Single Nucleotide
Telomere Homeostasis
Apolipoprotein A-I/blood/genetics

@article {pmid38857178,
year = {2024},
author = {Asim Javed, M and Mukhopadhyay, S and Normandeau, E and Brochu, AS and Pérez-López, E},
title = {Telomere-to-telomere genome assembly of the clubroot pathogen Plasmodiophora brassicae.},
journal = {Genome biology and evolution},
volume = {},
number = {},
pages = {},
doi = {10.1093/gbe/evae122},
pmid = {38857178},
issn = {1759-6653},
abstract = {Plasmodiophora brassicae (Woronin, 1877), a biotrophic, obligate parasite, is the causal agent of clubroot disease in brassicas. The clubroot pathogen has been reported in more than 80 countries worldwide, causing economic losses of hundreds of millions every year. Despite its widespread impact, very little is known about the molecular strategies it employs to induce the characteristic clubs in the roots of susceptible hosts during infection, nor about the mechanisms it uses to overcome genetic resistance. Here, we provide the first telomere-to-telomere complete genome of Plasmodiophora brassicae. We generated ∼ 27 Gb of Illumina, Oxford Nanopore, and PacBio HiFi data from resting spores of strain Pb3A and produced a 25.3 Mb assembly comprising 20 chromosomes, with an N50 of 1.37 Mb. The BUSCO score, the highest reported for any member of the group Rhizaria (Eukaryota: 88.2%), highlights the limitations within the Eukaryota database for members of this lineage. Using available transcriptomic data and protein evidence, we annotated the Pb3A genome, identifying 10,521 protein-coding gene models. This high-quality, complete genome of Plasmodiophora brassicae will serve as a crucial resource for the plant pathology community to advance the much-needed understanding of the evolution of the clubroot pathogen.},
}

@article {pmid38856709,
year = {2024},
author = {Vieira, RA and Nunes, DP and Lima, DB and Rocha, GDS and Corona, LP and Santos-Orlandi, AAD and Sampaio, ES and Rodrigues, PCOG and de Brito, TRP},
title = {Association between telomere length and anorexia of ageing: a cross-sectional study conducted with community-dwelling older people.},
journal = {Journal of human nutrition and dietetics : the official journal of the British Dietetic Association},
volume = {},
number = {},
pages = {},
doi = {10.1111/jhn.13338},
pmid = {38856709},
issn = {1365-277X},
support = {//Fundação de Amparo à Pesquisa do Estado de Minas Gerais - FAPEMIG/ ; //Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; },
abstract = {BACKGROUND: To verify whether shorter telomere length is associated with anorexia of ageing in community-dwelling older people.

METHODS: Conducted as a cross-sectional investigation, the study enrolled 448 participants residing in an urban area of a municipality in Brazil. Relative telomere length in blood samples was measured using quantitative polymerase chain reaction (qPCR), whereas the presence of anorexia of ageing was determined using the Simplified Appetite Nutritional Questionnaire. Data analysis employed multiple logistic regression.

RESULTS: Among the 448 older individuals surveyed, 70.69% were female, and the predominant age bracket ranged from 60 to 69 years (45.08%). Approximately 25% exhibited the shortest telomeric length, with a corresponding anorexia of ageing prevalence of 41.16%. Older individuals with diminished telomere lengths displayed an increased likelihood of experiencing anorexia of ageing (odds ratio [OR] = 1.92; 95% confidence interval [CI] = 1.12-3.29), independent of factors such as gender, age group, depressive symptoms, pain and performance in basic daily life activities.

CONCLUSIONS: The observed association between anorexia of ageing and a telomeric biomarker underscores the imperative to meticulously evaluate the nutritional dimensions of older people, with a view to implementing interventions that may enhance their overall health status.},
}

@article {pmid38851349,
year = {2024},
author = {Colominas-Ciuró, R and Gray, FE and Arikan, K and Zahn, S and Meier, C and Criscuolo, F and Bize, P},
title = {Effects of persistent organic pollutants on telomere dynamics are sex and age-specific in a wild long-lived bird.},
journal = {The Science of the total environment},
volume = {},
number = {},
pages = {173785},
doi = {10.1016/j.scitotenv.2024.173785},
pmid = {38851349},
issn = {1879-1026},
abstract = {Chemical pollution is a major man-made environmental threat to ecosystems and natural animal populations. Of concern are persistent organic pollutants (POPs), which can persist in the environment for many years. While bioaccumulating throughout the lives of wild animals, POPs can affect their health, reproduction, and survival. However, measuring long-term effects of POPs in wild populations is challenging, and therefore appropriate biomarkers are required in wildlife ecotoxicology. One potential target is telomere length, since telomere preservation has been associated to survival and longevity, and stressors as chemical pollution can disrupt its maintenance. Here, we investigated the effects of different classes of POPs on relative telomere length (RTL) and its rate of change (TROC) in wild long-lived Alpine swifts (Tachymarptis melba). As both RTL and TROC are often reported to differ between sexes and with chronological age, we tested for sex- and age-specific (pre-senescent vs. senescent, ≥ 9 age of years, individuals) effects of POPs. Our results showed that senescent females presented longer RTL and elongated telomeres over time compared to pre-senescent females and males. These sex- and age-related differences in RTL and TROC were influenced by POPs, but differently depending on whether they were organochlorine pesticides (OCPs) or industrial polychlorinated biphenyls (PCBs). OCPs (particularly drins) were negatively associated with RTL, with the strongest negative effects being found in senescent females. Conversely, PCBs led to slower rates of telomere shortening, especially in females. Our study indicates diametrically opposed effects of OCPs on RTL and PCBs on TROC, and these effects were more pronounced in females and senescent individuals. The mechanisms behind these effects (e.g., increased oxidative stress by OCPs; upregulation of telomerase activity by PCBs) remain unknown. Our results highlight the importance in wildlife ecotoxicology to account for sex- and age-related effects when investigating the health effects of pollutants on biomarkers such as telomeres.},
}

@article {pmid38849401,
year = {2024},
author = {Sánchez-Ortí, JV and Correa-Ghisays, P and Balanzá-Martínez, V and Macías Saint-Gerons, D and Berenguer-Pascual, E and Romá-Mateo, C and Victor, VM and Forés-Martos, J and San-Martin, C and Selva-Vera, G and Tabarés-Seisdedos, R},
title = {Systemic inflammation, oxidative damage and neurocognition predict telomere length in a transdiagnostic sample stratified by global DNA methylation levels.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {13159},
pmid = {38849401},
issn = {2045-2322},
support = {UGP-14-184 Project//Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana/ ; PI22/1009//Instituto de Salud Carlos III/ ; PI22/00424//Instituto de Salud Carlos III/ ; PROMETEO/2019/027//European Regional Development Fund/ ; CIPROM/2022/32//European Regional Development Fund/ ; CB06/04/0071//Ministerio de Ciencia e Innovación/ ; 0456-03-40//Grand Challenges Canada/ ; },
mesh = {Humans ; *DNA Methylation ; Male ; Female ; *Oxidative Stress ; *Inflammation/blood/genetics ; Adult ; Middle Aged ; *Telomere/genetics/metabolism ; *Schizophrenia/genetics/blood ; Diabetes Mellitus, Type 2/genetics ; Biomarkers/blood ; Bipolar Disorder/genetics/blood ; Depressive Disorder, Major/genetics/blood ; Leukocytes/metabolism ; Epigenesis, Genetic ; Telomere Homeostasis ; Cognition ; Case-Control Studies ; },
abstract = {Epigenetic mechanisms contribute to the maintenance of both type 2 diabetes mellitus (T2DM) and psychiatric disorders. Emerging evidence suggests that molecular pathways and neurocognitive performance regulate epigenetic dynamics in these disorders. The current combined and transdiagnostic study investigated whether inflammatory, oxidative stress, adhesion molecule, neurocognitive and functional performance are significant predictors of telomere dynamics in a sample stratified by global DNA methylation levels. Peripheral blood inflammation, oxidative stress and adhesion molecule biomarkers and neurocognitive function were assessed twice over a 1-year period in 80 individuals, including 16 with schizophrenia (SZ), 16 with bipolar disorder (BD), 16 with major depressive disorder (MDD), 15 with T2DM, and 17 healthy controls (HCs). Leukocyte telomere length (LTL) was measured by qRT-PCR using deoxyribonucleic acid (DNA) extracted from peripheral blood samples. A posteriori, individuals were classified based on their global methylation score (GMS) at baseline into two groups: the below-average methylation (BM) and above-average methylation (AM) groups. Hierarchical and k-means clustering methods, mixed one-way analysis of variance and linear regression analyses were performed. Overall, the BM group showed a significantly higher leukocyte telomere length (LTL) than the AM group at both time points (p = 0.02; η[2]p = 0.06). Moreover, the BM group had significantly lower levels of tumor necrosis factor alpha (TNF-α) (p = 0.03; η[2]p = 0.06) and C-reactive protein (CRP) (p = 0.03; η[2]p = 0.06) than the AM group at the 1-year follow-up. Across all participants, the regression models showed that oxidative stress (reactive oxygen species [ROS]) (p = 0.04) and global cognitive score [GCS] (p = 0.02) were significantly negatively associated with LTL, whereas inflammatory (TNF-α) (p = 0.04), adhesion molecule biomarkers (inter cellular adhesion molecule [ICAM]) (p = 0.009), and intelligence quotient [IQ] (p = 0.03) were significantly positively associated with LTL. Moreover, the model predictive power was increased when tested in both groups separately, explaining 15.8% and 28.1% of the LTL variance at the 1-year follow-up for the AM and BM groups, respectively. Heterogeneous DNA methylation in individuals with T2DM and severe mental disorders seems to support the hypothesis that epigenetic dysregulation occurs in a transdiagnostic manner. Our results may help to elucidate the interplay between epigenetics, molecular processes and neurocognitive function in these disorders. DNA methylation and LTL are potential therapeutic targets for transdiagnostic interventions to decrease the risk of comorbidities.},
}

Humans
*DNA Methylation
Male
Female
*Oxidative Stress
*Inflammation/blood/genetics
Adult
Middle Aged
*Telomere/genetics/metabolism
*Schizophrenia/genetics/blood
Diabetes Mellitus, Type 2/genetics
Biomarkers/blood
Bipolar Disorder/genetics/blood
Depressive Disorder, Major/genetics/blood
Leukocytes/metabolism
Epigenesis, Genetic
Telomere Homeostasis
Cognition
Case-Control Studies

@article {pmid38849156,
year = {2024},
author = {Murphy, WJ and Harris, AJ},
title = {Toward telomere-to-telomere cat genomes for precision medicine and conservation biology.},
journal = {Genome research},
volume = {},
number = {},
pages = {},
doi = {10.1101/gr.278546.123},
pmid = {38849156},
issn = {1549-5469},
abstract = {Genomic data from species of the cat family Felidae promise to stimulate veterinary and human medical advances, and clarify the coherence of genome organization. We describe how interspecies hybrids have been instrumental in the genetic analysis of cats, from the first genetic maps to propelling cat genomes toward the T2T standard set by the human genome project. Genotype-to-phenotype mapping in cat models has revealed dozens of health-related genetic variants, the molecular basis for mammalian pigmentation and patterning, and species-specific adaptations. Improved genomic surveillance of natural and captive populations across the cat family tree will increase our understanding of the genetic architecture of traits, population dynamics, and guide a future of genome-enabled biodiversity conservation.},
}