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Objective: Contemporary research suggests reduced telomere length in schizophrenia spectrum disorders (SZ) compared to age-adjusted non-affected individuals. However, the role of telomere maintenance and telomere repair in SZ is poorly understood as well as the involvement of telomere biology in cognitive abnormalities in SZ., Methods: The study consisted of 758 participants (SZ [n = 357] and healthy controls, HC [n = 401]) collected as part of the Norwegian TOP study. Participants were assessed with standardized neuropsychological tests measuring five cognitive domains. Leucocyte telomere length (TL) was measured via blood and determined by quantitative real-time Polymerase Chain Reaction (qPCR) providing a telomere to single copy ratio (T/S ratio), used to estimate the mean telomere length. Telomerase activity was assessed by the expression levels of the Telomerase Reverse Transcriptase (TERT) and Telomerase RNA Component (TERC) genes. To assess telomere maintenance and telomere repair we calculated the telomerase expression to TL ratio (TERT/TL and TERC/TL respectively)., Results: Patients had reduced TERT (F = 5.03, p = 0.03), but not TERC expression (F = 1.04, p = 0.31), and higher TERT/TL (F = 6.68, p = 0.01) and TERC/TL (F = 6.71, p = 0.01), adjusted for age, sex, and ethnicity. No statistically significant association was observed between any of the telomere biology markers and the cognitive domains (p > 0.05)., Conclusion: Our study shows changes in TERT expression and telomere maintenance and telomere repair in SZ compared HC. However, the role of telomere biology in the mechanism underlying cognitive impairment in psychosis seems limited., Competing Interests: Declaration of competing interest Authors declare no conflict of interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes virus-induced-senescence. There is an association between shorter telomere length (TL) in coronavirus disease 2019 (COVID-19) patients and hospitalization, severity, or even death. However, it remains unknown whether virus-induced-senescence is reversible. We aim to evaluate the dynamics of TL in COVID-19 patients 1 year after recovery from intensive care units (ICU). Longitudinal study enrolling 49 patients admitted to ICU due to COVID-19 (August 2020 to April 2021). Relative telomere length (RTL) quantification was carried out in whole blood by monochromatic multiplex real-time quantitative PCR (MMqPCR) assay at hospitalization (baseline) and 1 year after discharge (1-year visit). The association between RTL and ICU length of stay (LOS), invasive mechanical ventilation (IMV), prone position, and pulmonary fibrosis development at 1-year visit was evaluated. The median age was 60 years, 71.4% were males, median ICU-LOS was 12 days, 73.5% required IMV, and 38.8% required a prone position. Patients with longer ICU-LOS or who required IMV showed greater RTL shortening during follow-up. Patients who required pronation had a greater RTL shortening during follow-up. IMV patients who developed pulmonary fibrosis showed greater RTL reduction and shorter RTL at the 1-year visit. Patients with longer ICU-LOS and those who required IMV had a shorter RTL in peripheral blood, as observed 1 year after hospital discharge. Additionally, patients who required IMV and developed pulmonary fibrosis had greater telomere shortening, showing shorter telomeres at the 1-year visit. These patients may be more prone to develop cellular senescence and lung-related complications; therefore, closer monitoring may be needed., (© 2024. The Author(s).)

Ageing and chronic stress have been linked to reduced telomere length (TL) in mixed-age groups. Whether stress response components are linked to TL during the midlife-to-late adulthood transition remains unclear. Our study aimed to synthesise evidence on the relationship between psychological and biological components of stress response on TL in middle-aged and older adults. We conducted a systematic review of studies obtained from six databases (PubMed, CINAHL, EMBASE, PsycINFO, Web of Science, and Scopus) and evaluated by two independent reviewers. Original research measuring psychological and biological components of stress response and TL in human individuals were included. From an initial pool of 614 studies, 15 were included (n = 9446 participants). Synthesis of evidence showed that higher psychological components of the stress response (i.e., global perceived stress or within a specific life domain and cognitive appraisal to social-evaluative stressors) were linked to shorter TL, specifically in women or under major life stressors. For the biological stress response, cortisol, dehydroepiandrosterone sulphate and IGF-1/cortisol imbalance, IL-6, MCP-1, blood pressure, and heart rate presented a significant association with TL, but this relationship depended on major life stressors and the stress context (manipulated vs. non-manipulated conditions). This comprehensive review showed that psychological and biological components of the stress response are linked to shorter TL, but mainly in women or those under a major life stressor and stress-induced conditions. The interaction between stressor attributes and psychological and biological reactions in the transition from middle to late adulthood still needs to be fully understood, and examining it is a critical step to expanding our understanding of stress's impact on ageing trajectories., (© 2024 The Authors. Stress and Health published by John Wiley & Sons Ltd.)

The biological mechanisms that explain how adverse early life events influence adult disease risk are poorly understood. One proposed mechanism is via the induction of accelerated biological aging, for which telomere length is considered a biomarker. We aimed to determine if maternal depression pre- and post-partum was associated with telomere length in children at 4 years of age (n = 4299). Mothers completed structured questionnaires assessing depression during pregnancy (Edinburgh Depression Scale), at 9 months (Edinburgh Depression Scale), and at 54 months postpartum (Patient Health Questionnaire 9). Regression methods were used to investigate the relationship between telomere length (DNA from saliva) and maternal depression score recorded at each stage. Significant covariates included in the final model were: maternal age at pregnancy; child sex; child ethnicity; gestational age group, and rurality group. Child telomere length was found to be longer if their mother had a higher depression score at both postpartum time points tested (9 months of age; coefficient 0.003, SE = 0.001, P = 0.01, 54 months of age; coefficient 0.003, SE = 0.002, P = 0.02). Although these findings seem paradoxical, increased telomere length may be an adaptive response to early life stressors. We propose several testable hypotheses for these results and to determine if the positive association between depression and telomere length is a developmental adaptation or an indirect consequence of environmental factors., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Telomeres, the safeguarding caps at the tips of chromosomes, are pivotal in the aging process of cells and have been linked to skin ailments and inflammatory conditions. Telomeres undergo a gradual reduction in length and factors such as oxidative stress hasten this diminishing process. Skin diseases including inflammatory conditions can be correlated with the shortening of telomeres and the persistent activation of DNA damage response in skin tissues. Telomere dysfunction could disrupt the balance of the skin, impairs wound healing, and may contribute to abnormal cytokine production. Skin aging and processes related to telomeres may function as one of the triggers for skin diseases. The presence of proinflammatory cytokines and dysfunctional telomeres in conditions such as Dyskeratosis Congenita implies a possible connection between the shortening of telomeres and the onset of chronic inflammatory skin disorders. In autoinflammatory skin diseases, chronic inflammation hinders wound healing thus aggravating the progression of the disease. The NF-ĸB pathway might contribute to the initiation or progression of chronic disorders by influencing mechanisms associated with telomere biology. The intricate connections between telomeres, telomerase, telomere-associated proteins, and skin diseases are still a complex puzzle to be solved. Here, we provide an overview of the impact of telomeres on both health and disease with a specific emphasis on their role in skin, inflammation and autoinflammatory skin disorders.

Background: Aging-related processes contribute to neurodegeneration and disability in multiple sclerosis (MS). Biomarkers of biological aging such as leukocyte telomere length (LTL) could help personalise prognosis. Pregnancy has been shown to be protective against disability accumulation in women with MS, though it is unclear if this effect relates to aging mechanisms or LTL., Objectives: This study aimed to cross-sectionally characterise LTL in a cohort of individuals with MS, and to correlate LTL with disability severity and pregnancy history., Methods: We extracted DNA from the whole blood of 501 people with MS in Melbourne, Australia. Expanded Disability Status Scale (EDSS) score and demographic data, as well as pregnancy history for 197 females, were obtained at sample collection. Additional data were extracted from the MSBase Registry. LTL was determined in base pairs (bp) using real-time quantitative polymerase chain reaction., Results: A relationship between EDSS score and shorter LTL was robust to multivariable adjustment for demographic and clinical factors including chronological age, with an adjusted LTL reduction per 1.0 increase in EDSS of 97.1 bp (95 % CI = 9.7-184.5 bp, p = 0.030). Adjusted mediation analysis found chronological age accounted for 33.6 % of the relationship between LTL and EDSS score (p = 0.018). In females with pregnancy data, history of pregnancy was associated with older age (median 49.7 vs 33.0 years, p < 0.001). There were no significant relationships between adjusted LTL and any history of pregnancy (LTL increase of 65.3 bp, 95 % CI = -471.0-601.5 bp, p = 0.81) or number of completed pregnancies (LTL increase of 14.6 bp per pregnancy, 95 % CI = -170.3-199.6 bp, p = 0.87)., Conclusions: The correlation between LTL and disability independent of chronological age and other factors points to a link between neurological reserve in MS and biological aging, and a potential research target for pathophysiological and therapeutic mechanisms. Although LTL did not significantly differ by pregnancy history, longitudinal analyses could help identify interactions with prospectively captured pregnancy effects., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M Zhong has received conference travel support from Novartis and Roche, and research support from the Australian Government Research Training Program and MS Research Australia. S Salberg, S Sampangi, A van der Walt, and R Mychasiuk report no disclosures. H Butzkueven has received institutional (Monash University) funding from Biogen, F. Hoffmann-La Roche Ltd, Merck and Novartis; has carried out contracted research for Novartis, Merck, F. Hoffmann-La Roche Ltd and Biogen; has taken part in speakers’ bureau for Biogen, F. Hoffmann-La Roche Ltd, Novartis and Merck; has received personal compensation for steering committee activities from Oxford Health Policy Forum and StatFinn. V Jokubaitis receives research grant support from Roche outside of the submitted work. She receives research support from the Australian National Health and Medical Research Council and MS Australia., (Copyright © 2024. Published by Elsevier B.V.)

Objective: Parental trauma exposure and trauma-related distress can increase the risk of adverse health outcomes in offspring, but the pathways implicated in intergenerational transmission are not fully explicated. Accelerated biological aging may be one mechanism underlying less favorable health in trauma-exposed individuals and their offspring. This study examines the associations of preconception maternal and paternal posttraumatic stress disorder (PTSD) symptoms with child telomere length, and maternal prenatal C-reactive protein (CRP) as a biological mechanism., Methods: Mothers ( n = 127) and a subset of the fathers ( n = 84) reported on PTSD symptoms before conception. Mothers provided blood spots in the second and third trimesters that were assayed for CRP. At age 4 years, children provided buccal cells for measurement of telomere length. Models adjusted for parental age, socioeconomic status, maternal prepregnancy body mass index, child biological sex, and child age., Results: Mothers' PTSD symptoms were significantly associated with shorter child telomere length ( β = -0.22, SE = 0.10, p = .023). Fathers' PTSD symptoms were also inversely associated with child telomere length ( β = -0.21, SE = 0.11), although nonsignificant ( p = .065). There was no significant indirect effect of mothers' PTSD symptoms on child telomere length through CRP in pregnancy, but higher second-trimester CRP was significantly associated with shorter child telomere length ( β = -0.35, SE = 0.18, p = .048)., Conclusions: Maternal symptoms of PTSD before conception and second-trimester inflammation were associated with shorter telomere length in offspring in early childhood, independent of covariates. Findings indicate that intergenerational transmission of parental trauma may occur in part through accelerated biological aging processes and provide further evidence that prenatal proinflammatory processes program child telomere length.Open Science Framework Preregistration:https://osf.io/7c2d5/?view&#95;only=cd0fb81f48db4b8f9c59fc8bb7b0ef97 ., (Copyright © 2023 by the American Psychosomatic Society.)

Hibernation is a widespread metabolic strategy among mammals for surviving periods of food scarcity. During hibernation, animals naturally alternate between metabolically depressed torpor bouts and energetically expensive arousals without ill effects. As a result, hibernators are promising models for investigating mechanisms that buffer against cellular stress, including telomere protection and restoration. In non-hibernators, telomeres, the protective structural ends of chromosomes, shorten with age and metabolic stress. In temperate hibernators, however, telomere shortening and elongation can occur in response to changing environmental conditions and associated metabolic state. We investigate telomere dynamics in a tropical hibernating primate, the fat-tailed dwarf lemur (Cheirogaleus medius). In captivity, these lemurs can hibernate when maintained under cold temperatures (11-15 °C) with limited food provisioning. We study telomere dynamics in eight fat-tailed dwarf lemurs at the Duke Lemur Center, USA, from samples collected before, during, and after the hibernation season and assayed via qPCR. Contrary to our predictions, we found that telomeres were maintained or even lengthened during hibernation, but shortened immediately thereafter. During hibernation, telomere lengthening was negatively correlated with time in euthermia. Although preliminary in scope, our findings suggest that there may be a preemptive, compensatory mechanism to maintain telomere integrity in dwarf lemurs during hibernation. Nevertheless, telomere shortening immediately afterward may broadly result in similar outcomes across seasons. Future studies could profitably investigate the mechanisms that offset telomere shortening within and outside of the hibernation season and whether those mechanisms are modulated by energy surplus or crises., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Although maternal stressor exposure has been associated with shorter telomere length (TL) in offspring, this literature is based largely on White samples. Furthermore, timing of maternal stressors has rarely been examined. Here, we examined how maternal stressors occurring during adolescence, pregnancy, and across the lifespan related to child TL in Black and White mothers., Method: Mothers (112 Black; 110 White; M age = 39) and their youngest offspring ( n = 222; M age = 8) were part of a larger prospective cohort study, wherein mothers reported their stressors during adolescence (assessed twice during adolescence for the past year), pregnancy (assessed in midlife for most recent pregnancy), and across their lifespan (assessed in midlife). Mother and child provided saliva for TL measurement. Multiple linear regression models examined the interaction of maternal stressor exposure and race in relation to child TL, controlling for maternal TL and child gender and age. Race-stratified analyses were also conducted., Results: Neither maternal adolescence nor lifespan stressors interacted with race in relation to child TL. In contrast, greater maternal pregnancy stressors were associated with shorter child TL, but this effect was present for children of White but not Black mothers. Moreover, this effect was significant for financial but not social pregnancy stressors. Race-stratified models revealed that greater financial pregnancy stressors predicted shorter telomeres in offspring of White, but not Black mothers., Conclusions: Race and maternal stressors interact and are related to biological aging across generations, but these effects are specific to certain races, stressors, and exposure time periods.

Aging is a collection of changes that contribute to decline in maximum function and ultimately death of an organism. This process is controlled and initiated by several mechanisms including telomere shortening, oxidative stress, AMP-activated protein kinase and sirt-1. Several therapies have been reported to relieve the process of aging. Among these, diet therapy seems to be the most appropriate approach. Fruits are an important part of regular diet. They contain several compounds which have potential to handle the problem of aging and its related disorders. The present paper provides a comprehensive review on different factors present in various fruits related to the process of aging together with their antiaging mechanisms., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Social epidemiology posits that chronic stress from social determinants will lead to a prolonged inflammatory response that may induce accelerated aging as measured, for example, through telomere length (TL). In this paper, we hypothesize variables across demographic, health-related, and contextual/environmental domains influence the body's stress response, increase inflammation (as measured through high-sensitivity C-reactive protein (hs-CRP)), and thereby lead to shortening of telomeres. This population-based research uses data from the 2008 Health and Retirement Study on participants ages ≤ 54-95 + years, estimating logistic regression and Cox proportional hazards models of variables (with and without confounders) across the domains on shortened TL. A mediation analysis is also conducted. Contrary to expectations, hs-CRP is not associated with risk of shortened TL. Rather, factors related to accessing health care, underlying conditions of frailty, and social inequality appear to predict risk of shorter TL, and models demonstrate considerable confounding. Further, hs-CRP is not a mediator for TL. Therefore, the social determinants of health examined do not appear to follow an inflammatory pathway for shortened TL. The finding of a relationship to social determinants affecting access to health care and medical conditions underscores the need to address social determinants alongside primary care when examining health inequities., (© 2022. The Author(s).)

Sarcopenic obesity (SO) is characterised by the concurrent presence of sarcopenia and excess adiposity. Telomere shortening has been associated with sarcopenia and obesity alone but the association between SO and telomere length (TL) has not been investigated. This study aimed to investigate SO and TL in an adult population. Data were from 5397 individuals (mean age = 44.7 years, 51.3% male) enrolled in the National Health and Nutrition Examination Survey. Body composition (BC) was assessed by Dual Energy X-Ray Absorptiometry. Two models were used to assess SO: a BC model including four phenotypes derived from the combination of high or low adiposity and muscle mass; and, a truncal fat mass to appendicular skeletal mass ratio (TrFM/ASM). TL was assessed using quantitative polymerase chain reaction and expressed as base pairs. The mean TL, relative to the reference DNA, was calculated and expressed as the mean T/S ratio. A General Linear Model was applied to determine associations between TL for SO. In adjusted analysis, only individuals with SO, defined as the presence of high adiposity-low muscle mass (four-phenotype model), had significantly shorter telomeres (p = 0.05) than the reference group (i.e. low adiposity-high muscle mass), with a mean T/S ratio of 1.02 (95%CI: 0.98-1.05) compared to 1.05 (95%CI: 1.01-1.09), respectively. TrFM/ASM was not associated with TL. Preliminary findings suggest that sarcopenia and obesity may act synergistically to shorten telomeres., (© 2021. The Author(s).)

Aims/hypothesis: Few large-scale prospective studies have investigated associations between relative leucocyte telomere length (rLTL) and kidney dysfunction in individuals with type 2 diabetes. We examined relationships between rLTL and incident end-stage kidney disease (ESKD) and the slope of eGFR decline in Chinese individuals with type 2 diabetes., Methods: We studied 4085 Chinese individuals with type 2 diabetes observed between 1995 and 2007 in the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data. rLTL was measured using quantitative PCR. ESKD was diagnosed based on the ICD-9 code and eGFR., Results: In this cohort (mean ± SD age 54.3 ± 12.6 years) followed up for 14.1 ± 5.3 years, 564 individuals developed incident ESKD and had shorter rLTL at baseline (4.2 ± 1.2 vs 4.7 ± 1.2, p < 0.001) than the non-progressors (n = 3521). On Cox regression analysis, each ∆∆C t decrease in rLTL was associated with an increased risk of incident ESKD (HR 1.21 [95% CI 1.13, 1.30], p < 0.001); the association remained significant after adjusting for baseline age, sex, HbA 1c , lipids, renal function and other risk factors (HR 1.11 [95% CI 1.03, 1.19], p = 0.007). Shorter rLTL at baseline was associated with rapid decline in eGFR (>4% per year) during follow-up (unadjusted OR 1.22 [95% CI 1.15, 1.30], p < 0.001; adjusted OR 1.09 [95% CI 1.01, 1.17], p = 0.024)., Conclusions/interpretation: rLTL is independently associated with incident ESKD and rapid eGFR loss in individuals with type 2 diabetes. Telomere length may be a useful biomarker for the progression of kidney function and ESKD in type 2 diabetes., (© 2021. The Author(s).)

Mesenchymal stem cells (MSCs) experience functional decline with systemic aging, resulting in reduced proliferation, increased senescence, and lower differentiation potential. The placenta represents a valuable source of MSCs, but the possible effect of donor age on the properties of placenta-derived mesenchymal stem cells (PDMSCs) has not been thoroughly studied. Thus, the aim of this study was to underscore the effect of maternal age on the biological characteristics and stemness properties of PDMSCs. PDMSCs were isolated from 5 donor age groups (A: 18-21, B: 22-25, C: 26-30, D:31-35 and E: ≥36 years) for comparison of morphological, proliferative and differentiation properties. The pluripotency markers NANOG, OCT4, and SSEA4, as well as multipotency and differentiation markers, showed higher expression in PDMSCs from mothers aged 22-35 years, with up to a 7-fold increase in adipogenesis. Cumulative population doubling, cell growth curves, and colony-forming unit-fibroblast assays revealed higher self-renewal ability in donors 26-30 years old. An increase in the proliferative characteristics of PDMSCs correlated with increased telomere shortening, suggesting that shorter telomere lengths could be related to cellular division rather than aging. A clear understanding of the effect of maternal age on MSC regenerative potential will assist in increasing the effectiveness of future cell therapies.

The molecular mechanisms that drive hematopoietic stem cell functional decline under conditions of telomere shortening are not completely understood. In light of recent advances in single-cell technologies, we sought to redefine the transcriptional and epigenetic landscape of mouse and human hematopoietic stem cells under telomere attrition, as induced by pathogenic germline variants in telomerase complex genes. Here, we show that telomere attrition maintains hematopoietic stem cells under persistent metabolic activation and differentiation towards the megakaryocytic lineage through the cell-intrinsic upregulation of the innate immune signaling response, which directly compromises hematopoietic stem cells' self-renewal capabilities and eventually leads to their exhaustion. Mechanistically, we demonstrate that targeting members of the Ifi20x/IFI16 family of cytosolic DNA sensors using the oligodeoxynucleotide A151, which comprises four repeats of the TTAGGG motif of the telomeric DNA, overcomes interferon signaling activation in telomere-dysfunctional hematopoietic stem cells and these cells' skewed differentiation towards the megakaryocytic lineage. This study challenges the historical hypothesis that telomere attrition limits the proliferative potential of hematopoietic stem cells by inducing apoptosis, autophagy, or senescence, and suggests that targeting IFI16 signaling axis might prevent hematopoietic stem cell functional decline in conditions affecting telomere maintenance., (© 2021. The Author(s).)

The effects of stress exposure are likely to vary depending on life-stage and stressor. While it has been postulated that mild stress exposure may have beneficial effects, the duration of such effects and the underlying mechanisms are unclear. While the long-term effects of early-life stress are relatively well studied, we know much less about the effects of exposure in adulthood since the early- and adult-life environments are often similar. We previously reported that repeated experimental exposure to a relatively mild stressor in female zebra finches, first experienced in young adulthood, initially had no effect on mortality risk, reduced mortality in middle age, but the apparently beneficial effects disappeared in old age. We show here that this is underpinned by differences between the control and stress-exposed group in the pattern of telomere change, with stress-exposed birds showing reduced telomere loss in middle adulthood. We thereby provide novel experimental evidence that telomere dynamics play a key role linking stress resilience and aging., (© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Profound T-cell lymphopenia is the hallmark of severe coronavirus disease 2019 (COVID-19). T-cell proliferation is telomere length (TL) dependent and telomeres shorten with age. Older COVID-19 patients, we hypothesize, are, therefore, at a higher risk of having TL-dependent lymphopenia. We measured TL by the novel Telomere Shortest Length Assay (TeSLA), and by Southern blotting (SB) of the terminal restriction fragments in peripheral blood mononuclear cells of 17 COVID-19 and 21 non-COVID-19 patients, aged 87 ± 8 (mean ± SD) and 87 ± 9 years, respectively. TeSLA tallies and measures single telomeres, including short telomeres undetected by SB. Such telomeres are relevant to TL-mediated biological processes, including cell viability and senescence. TeSLA yields 2 key metrics: the proportions of telomeres with different lengths (expressed in %) and their mean (TeSLA mTL), (expressed in kb). Lymphocyte count (109/L) was 0.91 ± 0.42 in COVID-19 patients and 1.50 ± 0.50 in non-COVID-19 patients (p < .001). In COVID-19 patients, but not in non-COVID-19 patients, lymphocyte count was inversely correlated with the proportion of telomeres shorter than 2 kb (p = .005) and positively correlated with TeSLA mTL (p = .03). Lymphocyte count was not significantly correlated with SB mTL in either COVID-19 or non-COVID-19 patients. We propose that compromised TL-dependent T-cell proliferative response, driven by short telomere in the TL distribution, contributes to COVID-19 lymphopenia among old adults. We infer that infection with SARS-CoV-2 uncovers the limits of the TL reserves of older persons. Clinical Trials Registration Number: NCT04325646., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Background: Over the life course, African American (AA) women have faster telomere attrition, a biological indicator of accelerated aging, than White women. Race, sex, age, and composite socioeconomic status (SES) modify associations of institutional racial discrimination and telomere length. However, interactions with everyday racial discrimination have not been detected in AA women, nor have interactions with individual socioeconomic predictors., Purpose: We estimated statistical interaction of institutional and everyday racial discrimination with age, education, employment, poverty, and composite SES on telomere length among midlife AA women., Methods: Data are from a cross-section of 140 AA women aged 30-50 years residing in the San Francisco Bay Area. Participants completed questionnaires, computer-assisted self-interviews, physical examinations, and blood draws. Adjusted linear regression estimated bootstrapped racial discrimination-relative telomere length associations with interaction terms., Results: Racial discrimination did not interact with age, poverty, or composite SES measures to modify associations with telomere length. Interactions between independent SES variables were nonsignificant for everyday discrimination whereas institutional discrimination interacted with educational attainment and employment status to modify telomere length. After adjusting for covariates, we found that higher institutional discrimination was associated with shorter telomeres among employed women with lower education (β = -0.020; 95% confidence interval = -0.036, -0.003). Among unemployed women with higher education, higher institutional discrimination was associated with longer telomeres (β = 0.017; 95% confidence interval = 0.003, 0.032). Factors related to having a post-high school education may be protective against the negative effects of institutional racism on cellular aging for AA women., (© Society of Behavioral Medicine 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Abstract: This study aimed to assess the role of leukocyte telomere length (LTL) in the development of atrial fibrillation (AF) among Chinese patients.This is a cross-sectional study. A total of 350 patients from June 2016 to December 2017 were retrospectively analyzed. These included 219 AF patients and 131 with sinus rhythm in the control group. Quantitative real-time PCR was used to measure relative LTL.The relative LTLs of all subjects (n = 350) ranged from 0.4 to 2.41 (0.98 ± 0.29), showing a significant negative correlation (P < .001) with age. The AF-group had significantly shorter LTLs (0.93 ± 0.26 vs 1.07 ± 0.33, P < .001) and were older (61.50 ± 6.49 vs 59.95 ± 6.17, P = .028) than controls. LTLs among patients with persistent AF (PsAF), paroxysmal AF (PAF), and controls were significantly different (P < .001), with LTLs of PsAF patients being the shortest and controls being the longest. After adjusting for possible confounding factors, the PsAF group still showed significantly shorter LTLs than the PAF and control groups (P = .013 and P = .001, respectively). After an 18-month follow-up, 20 out of 119 PAF patients had progressed into PsAF and a relative LTL of ≤0.73 was an independent predictor for progression of PAF into PsAF.LTL was found to be shorter in patients with AF than in age-matched individuals with sinus rhythm and positively correlated with severity of AF. LTL shortening could be an independent risk factor for progression from paroxysmal AF to persistent AF in the short term., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Increased oxidative stress, leukocyte telomere length (LTL) shortening, endothelial dysfunction, and lower insulin-like growth factor (IGF)-1 concentrations reflect key molecular mechanisms of aging. We hypothesized that biomarkers representing these pathways are associated with measures of subclinical atherosclerosis and all-cause mortality., Methods and Results: We evaluated up to 2,314 Framingham Offspring Study participants (mean age 61 years, 55% women) with available biomarkers of aging: LTL, circulating concentrations of IGF-1, asymmetrical dimethylarginine (ADMA), and urinary F2-Isoprostanes indexed to urinary creatinine. We evaluated the association of each biomarker with coronary artery calcium [ln (CAC+1)] and carotid intima-media thickness (IMT). In multivariable-adjusted linear regression models, higher ADMA levels were associated with higher CAC values (βADMA per 1-SD increase 0.25; 95% confidence interval [CI] [0.11, 0.39]). Additionally, shorter LTL and lower IGF-1 values were associated with higher IMT values (βLTL -0.08, 95%CI -0.14, -0.02, and βIGF-1 -0.04, 95%CI -0.08, -0.01, respectively). During a median follow-up of 15.5 years, 593 subjects died. In multivariable-adjusted Cox regression models, LTL and IGF-1 values were inversely associated with all-cause mortality (hazard ratios [HR] per SD increase in biomarker, 0.85, 95% CI 0.74-0.99, and 0.90, 95% CI 0.82-0.98 for LTL and IGF-1, respectively). F2-Isoprostanes and ADMA values were positively associated with all-cause mortality (HR per SD increase in biomarker, 1.15, 95% CI, 1.10-1.22, and 1.10, 95% CI, 1.02-1.20, respectively)., Conclusion: In our prospective community-based study, aging-related biomarkers were associated with measures of subclinical atherosclerosis cross-sectionally and with all-cause mortality prospectively, supporting the concept that these biomarkers may reflect the aging process in community-dwelling adults., Competing Interests: The authors have declared that no competing interests exist.

The field of research on cellular senescence experienced a rapid expansion from being primarily focused on in vitro aspects of aging to the vast territories of animal and clinical research. Cellular senescence is defined by a set of markers, many of which are present and accumulate in a gradual manner prior to senescence induction or are found outside of the context of cellular senescence. These markers are now used to measure the impact of cellular senescence on aging and disease as well as outcomes of anti-senescence interventions, many of which are at the stage of clinical trials. It is thus of primary importance to discuss their specificity as well as their role in the establishment of senescence. Here, the presence and role of senescence markers are described in cells prior to cell cycle arrest, especially in the context of replicative aging and in vivo conditions. Specifically, this review article seeks to describe the process of "cellular aging": the progression of internal changes occurring in primary cells leading to the induction of cellular senescence and culminating in cell death. Phenotypic changes associated with aging prior to senescence induction will be characterized, as well as their effect on the induction of cell senescence and the final fate of cells reviewed. Using published datasets on assessments of senescence markers in vivo, it will be described how disparities between quantifications can be explained by the concept of cellular aging. Finally, throughout the article the applicational value of broadening cellular senescence paradigm will be discussed., (© 2021 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Childhood adversity is linked to shortened telomere length (TL), but behavioral indicators of telomere attrition remain unclear. This study examined the association between adverse childhood experiences (ACEs) and child TL, and if ACEs were indirectly associated with TL through children's self-regulatory abilities (i.e., effortful control and self-control). Hypotheses were tested using national data from teachers, parents, and their children (N = 2,527; M age  = 9.35, SD = .36 years). More ACEs were uniquely associated with short TL, and low self-control mediated the association between more ACEs and short TL. While longitudinal studies are needed to strengthen claims of causation, this study identifies a pathway from ACEs to TL that should be explored further., (© 2020 Society for Research in Child Development.)

Shortened telomeres have been linked to numerous chronic diseases, most importantly coronary artery disease, but the underlying mechanisms remain ill defined. Loss-of-function mutations and deletions in telomerase both accelerate telomere shortening but do not necessarily lead to a clinical phenotype associated with atherosclerosis, questioning the causal role of telomere length in cardiac pathology. The differential extranuclear functions of the 2 main components of telomerase, telomerase reverse transcriptase and telomerase RNA component, offer important clues about the complex relationship between telomere length and cardiovascular pathology. In this review, we critically discuss relevant preclinical models, genetic disorders, and clinical studies to elucidate the impact of telomerase in cardiovascular disease and its potential role as a therapeutic target. We suggest that the antioxidative function of mitochondrial telomerase reverse transcriptase might be atheroprotective, making it a potential target for clinical trials. Graphic Abstract: A graphic abstract is available for this article.

Chronic pain induces a multitude of harmful effects; recently it has been suggested that chronic pain is also associated with premature aging, manifested in shortened telomere length (TL). However, evidence for this hypothesis is scarce and inconsistent. The aim was twofold: 1) Investigate whether chronic pain is associated with premature aging, and 2) Determine whether physical exercise (PE) moderates this association if it exists. Participants were 116 male subjects, with (n = 67) and without chronic pain (n = 49). Blood samples for TL analysis were collected and participants were interviewed and completed questionnaires. As a part of the cohort, we included people with physical disability; this variable was controlled in the analysis. The TL of individuals with chronic pain was significantly shorter than that of pain-free individuals. Regression analysis revealed a significant moderating effect of PE on chronic pain and TL, above and beyond the effects of disability, age, and weight. Whereas chronic pain was associated with shorter telomeres in participants who did not exercise, this association was nonsignificant among participants who did exercise. The results suggest that chronic pain is associated with premature ageing; however, PE may mitigate this association and may protect individuals against the harmful effects of chronic pain. PERSPECTIVE: The study suggests that it is important to monitor signs of premature ageing among chronic pain patients as they are at risk. However, chronic pain patients may benefit from regular PE in this respect as it may moderate premature ageing., (Copyright © 2020 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Severe therapy-resistant asthma (STRA) is closely associated with distinct clinical and inflammatory pheno-endotypes, which may contribute to the development of age-related comorbidities. Evidence has demonstrated a contribution of accelerated telomere shortening on the poor prognosis of respiratory diseases in adults. Eotaxin-1 (CCL11) is an important chemokine for eosinophilic recruitment and the progression of asthma. In the last years has also been proposed as an age-promoting factor. This study aimed to investigate the association of relative telomere length (rTL) and eotaxin-1 in asthmatic children. Children aged 8-14 years (n=267) were classified as healthy control (HC, n=126), mild asthma (MA, n=124) or severe therapy-resistant asthma (STRA, n=17). rTL was performed by qPCR from peripheral blood. Eotaxin-1 was quantified by ELISA from fresh-frozen plasma. STRA had shorter telomeres compared to HC ( p =0.02) and MA ( p =0.006). Eotaxin-1 levels were up-regulated in STRA [median; IQR25-75)] [(1,190 pg/mL; 108-2,510)] compared to MA [(638 pg/mL; 134-1,460)] ( p =0.03) or HC [(627 pg/mL; 108-1,750)] ( p <0.01). Additionally, shorter telomeres were inversely correlated with eotaxin-1 levels in STRA (r=-0.6, p =0.013). Our results suggest that short telomeres and up-regulated eotaxin-1, features of accelerated aging, could prematurely contribute to a senescent phenotype increasing the risk for early development of age-related diseases in asthma.

Objective: To test the hypothesis that telomere shortening and/or loss are risk factors for infertility., Design: Retrospective analysis of the telomere status in patients with infertility using conventional cytogenetic data collected prospectively., Setting: Academic centers., Patient(s): Cytogenetic slides with cultured peripheral lymphocytes from 50 patients undergoing fertility treatment and 150 healthy donors, including 100 donors matched for age., Intervention(s): Cytogenetic slides were used to detect chromosomal and telomere aberrations., Main Outcome Measure(s): Telomere length and telomere aberrations were analyzed after telomere and centromere staining., Result(s): The mean telomere length of patients consulting for infertility was significantly less than that of healthy donors of similar age. Moreover, patients with infertility showed significantly more extreme telomere loss and telomere doublet formation than healthy controls. Telomere shortening and/or telomere aberrations were more pronounced in patients with structural chromosomal aberrations. Dicentric chromosomes were identified in 6/13 patients, with constitutional chromosomal aberrations leading to chromosomal instability that correlated with chromosomal end-to-end fusions., Conclusion(s): Our findings demonstrate the feasibility of analyzing telomere aberrations in addition to chromosomal aberrations, using cytogenetic slides. Telomere attrition and/or dysfunction represent the main common cytogenetic characteristic of patients with infertility, leading to potential implications for fertility assessment. Pending further studies, these techniques that correlate the outcome of assisted reproduction and telomere integrity status may represent a novel and useful diagnostic and/or prognostic tool for medical care in this field., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The landmark National Aeronautics and Space Administration Twins Study represented an integrated effort to launch human space life science research into the modern age of molecular- and "omics"-based studies. As part of the first One-Year Mission aboard the International Space Station, identical twin astronauts Scott and Mark Kelly were the subjects of this "out of this world" research opportunity. Telomeres, the natural ends of chromosomes that shorten with cell division and a host of lifestyle factors and stresses, are key molecular determinants of aging and aging trajectories., Methods: We proposed that telomere length dynamics (changes over time) represent a particularly relevant and integrative biomarker for astronauts, as they reflect the combined experiences and environmental exposures encountered during spaceflight. Telomere length (quantitative polymerase chain reaction and telomere fluorescence in situ hybridization) and telomerase activity (quantitative polymerase chain reaction -telomere repeat amplification protocol) were longitudinally assessed in the space- and earth-bound twins. Chromosome aberrations (directional genomic hybridization), signatures of radiation exposure, were also evaluated., Results: The twins had relatively similar telomere lengths before spaceflight, and the earth-bound twins' telomeres remained relatively stable over the course of the study. Surprisingly, the space twins' telomeres were longer during spaceflight, and upon return to Earth shortened rapidly, resulting in many more short telomeres after spaceflight than before. Chromosomal signatures of space radiation exposure were also elevated during spaceflight, and increased inversion frequencies persisted after spaceflight, suggestive of ongoing genome instability., Conclusion: Although the definitive mechanisms underlying such dramatic spaceflight-associated shifts in telomere length remain unclear, improved maintenance of telomere length has important implications for aging science and improving healthspan for those on Earth, as well., (Copyright © 2020 by the American Society of Plastic Surgeons.)

Background and Objective: IPF is an ageing-related lung disorder featuring progressive lung scarring. IPF patients are frequently identified with short telomeres but coding mutations in telomerase can only explain a minority of cases. Sex hormones regulate telomerase activity in vitro and levels of sex hormones are related to LTL. The objective of this study was to explore whether sex hormones were associated with LTL, whether they interacted with genetic variants in telomerase and whether polymorphisms in the exon of androgen metabolism genes were associated with plasma testosterone concentrations in male IPF patients., Methods: A case-control study was performed on 101 male IPF subjects and 51 age-matched healthy controls. Early morning plasma sex hormones were quantified, and whole-exome sequencing was used to identify rare protein-altering variants of telomerase and SNP in the exon of androgen metabolism genes. LTL was analysed by PCR and expressed as a T/S ratio., Results: LTL, testosterone and DHT were decreased significantly in the IPF group. After adjustments for age and variant status in telomerase-related genes, only testosterone was positively associated with LTL (P = 0.001). No significant interaction (P = 0.661) was observed between rare protein-altering variants of telomerase and testosterone. No coding SNP in androgen metabolism genes were significantly associated with testosterone concentrations., Conclusion: Plasma testosterone is associated with LTL independent of age or rare protein-altering variants of telomerase. No genetic variations of androgen-related pathway genes are associated with androgen concentrations. Further studies are warranted to examine whether hormonal interventions might retard telomere loss in male IPF patients., (© 2020 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Prenatal exposure to stress increases risk for suboptimal child and adult mental and physical health outcomes, hypothesized to occur via fetal exposure to maternal stress hormones that alter growth and development. One proposed pathway through which stress exposure in utero could affect the offspring is by accelerating cellular aging in the form of telomere attrition. We tested this hypothesis in a cohort of 111 mother-child dyads, where mothers were assessed over 6 or more years, beginning prior to conception, and later during pregnancy, postpartum, and when the children were 3-5 years old. Adjusting for child age and concurrent maternal stress, we found that higher maternal perceived stress in the 3rd trimesters of pregnancy was predictive of shorter child buccal telomere length (bTL) (β = -0.24, p < .05), while maternal preconception and postpartum maternal stress were not associated with bTL (all p's > 0.42). These findings suggest a vulnerable time period in pregnancy when maternal stress influences offspring telomere length, suggesting the early embedding of adult disease might occur through biological aging pathways., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Epilepsy affects about 1 % of the world population. Mesial temporal lobe epilepsy (mTLE) presents with seizures initiated in hippocampus and is the most frequent form of epilepsy. About 30 % of individuals with mTLE do not respond to conventional medications maintaining seizures and consequently new lesions on a daily basis. Treatment-resistant epilepsy has a huge social and individual burden due to impaired quality of life and increased mortality rate. There are many reasons for telomere shortening in individuals with mTLE, such as a chronic mitochondrial oxidative stress and increased levels of pro-inflammatory mediators. In the past 10 years, there was a boom of studies establishing association between telomere length and chronic/complex disorders. Telomeres are essential for the maintenance of genomic integrity. Telomere length has been assumed as a biological marker for stress and cellular ageing. Here we hypothesized that individuals affected with treatment-resistant mTLE would course with a shorter telomere than controls. So, we measured leucocytes telomere length in a sample of 89 individuals, 48 treatment-resistant mTLE compared to 41 healthy controls. As expected, we observed a significant shorter telomere in the peripheral cell leukocytes of treatment-resitant mTLE group. Telomere length was not associated with sex, side of hippocampal sclerosis, family history, etiology of seizures, duration of disease or the Engel score. Our results points towards the need of further investigation to shed light on the relation of telomeres shortening and the outcomes and impacts of epilepsy., (Copyright © 2020. Published by Elsevier B.V.)

Discrimination is unfair treatment against a certain group based on race, age, gender, sexual orientation, or other social identities. Discrimination is pervasive in society, elevates psychosocial stress, and is associated with negative mental and physical health outcomes. However, more research is needed to understand the biological mechanisms underlying discrimination-related health disparities. Telomere science may contribute to elucidate some of these aspects. Telomeres are protein-DNA complexes that shorten after cell division and are valuable markers of cellular aging. Short telomeres have been associated with the onset of age-related diseases. Evidence shows that chronic psychological stress may accelerate telomere shortening. Since discrimination can lead to psychological strain with cumulative impact on general health, we hypothesized that groups that report more discrimination show reduced telomere length (TL) as a consequence of psychosocial stress elevation. Through a systematic review of the literature we found 12 articles that met our criteria. Eligible studies measured racial, gender, unfair policing, and multiple forms of discrimination in association with TL. Our review showed mixed results, suggesting that there is weak evidence of a main association between discrimination and TL. However, discrimination may interact with several variables (such as depressive symptoms, acculturation, higher socioeconomic status, internalization of negative racial bias, and not discussing discrimination experiences with others) and contribute to shorten telomeres. Discrimination is a complex social construct composed of a vast sum of experiences, impressions, and contexts that in combination with other sources of stress may have an impact on TL. Telomeres may be a plausible pathway to investigate health discrepancies in discriminated groups in society, but more evidence is needed to investigate the potential harm of discrimination on cells., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Electroconvulsive therapy (ECT) is the most acutely effective treatment for severe treatment-resistant depression. However, there are concerns about its cognitive side-effects and we cannot yet confidently predict who will experience these. Telomeres are DNA-protein complexes that maintain genomic integrity. In somatic cells, telomeres shorten with each cell division. Telomere length (TL) can thus provide a measure of 'biological' aging. TL appears to be reduced in depression, though results are mixed. We sought to test the following hypotheses: (1) that TL would be shorter in patients with depression compared to controls; (2) that TL would be a predictor of response to ECT; and (3) that shorter TL would predict cognitive side-effects following ECT., Method: We assessed TL in whole blood DNA collected from severely depressed patients (n = 100) recruited as part of the EFFECT-Dep Trial and healthy controls (n = 80) using quantitative real-time polymerase chain reaction. Mood and selected cognitive measures, including global cognition, re-orientation time, and autobiographical memory, were obtained pre-/post-ECT and from controls., Results: Our results indicate that TL does not differ between patients with depression compared to controls. TL itself was not associated with mood ratings and did not predict the therapeutic response to ECT. Furthermore, shorter baseline TL is not a predictor of cognitive side-effects post-ECT., Conclusions: Overall, TL assessed by PCR does not represent a useful biomarker for predicting the therapeutic outcomes or risk for selected cognitive deficits following ECT.

Objective: Several studies support potential links between relative leukocyte telomere length (rLTL), a biomarker of biological aging, and type 2 diabetes. This study investigates relationships between rLTL and incident cardiovascular disease (CVD) in patients with type 2 diabetes., Research Design and Methods: Consecutive Chinese patients with type 2 diabetes ( N = 5,349) from the Hong Kong Diabetes Register for whom DNA obtained at baseline was stored and follow-up data were available were studied. rLTL was measured by using quantitative PCR. CVD was diagnosed on the basis of ICD-9 code., Results: Mean follow-up was 13.4 years (SD 5.5 years). rLTL was correlated inversely with age, diabetes duration, blood pressure, HbA 1c , and urine albumin-to-creatinine ratio (ACR), and positively with estimated glomerular filtration rate (eGFR) (all P < 0.001). Subjects with CVD at baseline had a shorter rLTL (4.3 ± 1.2 ΔΔCt) than did subjects without CVD (4.6 ± 1.2 ΔΔCt) ( P < 0.001). Of the 4,541 CVD-free subjects at baseline, the 1,140 who developed CVD during follow-up had a shorter rLTL (4.3 ± 1.2 ΔΔCt) than those who remained CVD-free after adjusting for age, sex, smoking, and albuminuria status (4.7 ± 1.2 ΔΔCt) ( P < 0.001). In Cox regression models, shorter rLTL was associated with higher risk of incident CVD (for each unit decrease, hazard ratio 1.252 [95% CI 1.195-1.311], P < 0.001), which remained significant after adjusting for age, sex, BMI, systolic blood pressure, LDL cholesterol, HbA 1c , eGFR, and ACR (hazard ratio 1.141 [95% CI 1.084-1.200], P < 0.001)., Conclusions: rLTL is significantly shorter in patients with type 2 diabetes and CVD, is associated with cardiometabolic risk factors, and is independently associated with incident CVD. Telomere length may be a useful biomarker for CVD risk in patients with type 2 diabetes., (© 2020 by the American Diabetes Association.)

Background: Conventional observational studies have suggested that 25-hydroxyvitamin D (25(OH)D) is inversely associated with telomere shortening. We aimed to apply two-sample Mendelian randomization (MR) to assess the causal association between serum 25(OH) D and telomere length (TL)., Methods: MR was implemented by using summary-level data from the largest genome-wide association studies (GWAS) on vitamin D (n = 73 699) and TL (n = 37 684). Inverse variance weighted method (IVW) was used to estimate the causal estimates. Weighted median (WM)-based method, and MR-Egger, leave-one-out were applied as sensitivity analysis., Results: The results of MR demonstrated no effect of 25(OH)D on TL (IVW = β:-0.104, p = 0.219, WM = β:-0.109, p = 0.188; MR Egger = β:-0.127, p = 0.506). None of the 25(OH)D-related single nucleotide polymorphisms (SNPs) were significantly associated with TL. Heterogeneity tests did not detect heterogeneity. Furthermore, MR pleiotropy residual sum and outlier (MR-PRESSO) did not highlight any outliers (p = 0.424). Results of leave-one-out method demonstrated that the links are not driven because of the single SNPs., Conclusions: Our study does not support any causal effect of 25(OH) D on TL., Competing Interests: Declaration of interest All authors have no conflict of interest to declare., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

This study aimed to systematically review the association between cardiorespiratory fitness and telomere length (TL). Studies were identified from searches in Cochrane Central, PubMed, Scopus, Sportdiscus, and Web of Science databases through July 2019. Eligibility criteria included: cross-sectional, prospective, and experimental study design; outcomes included TL; results expressed the relationship between cardiorespiratory fitness and TL; studies published in English, Portuguese, or Spanish. A total of 20 articles met the inclusion criteria. Sixteen studies (80%) reported a significant relationship between cardiorespiratory fitness, or training load, and TL. Better cardiorespiratory fitness or a large cardiorespiratory training load are associated with an increase in TL. Although, TL was related to regular moderate-to-vigorous aerobic exercise and cardiorespiratory fitness in older healthy humans, it was not related to cardiorespiratory fitness among young subjects. There seems to be a positive and significant relationship between cardiorespiratory fitness and TL, mainly among middle age and older people, which emphasizes the importance of cardiorespiratory fitness for healthy ageing. Therefore, endurance exercise and better cardiorespiratory fitness may regulate the TL in middle age and older adults, slowing the cellular ageing process.

Aims: Several studies have reported the role of biomarkers either in diabetes or depression. The present study is aimed at profiling the circulating levels of miR-128, brain-derived neurotrophic factor (BDNF), cortisol and telomere length in patients with type 2 diabetes with and without depression compared to individuals with normal glucose tolerance., Methods: Study subjects (n = 160) were recruited from an ongoing epidemiological study in southern India. Non-diabetic and diabetic individuals were diagnosed as per the World Health Organization criteria. Depression score was derived using PHQ-12 questionnaire. Real-time quantitative PCR and ELISA methodologies were used to quantify the biomarkers., Results: Circulatory levels of miR-128 and cortisol were significantly (p < 0.05) increased with decreased BDNF levels and shortened telomeres in T2DM patients with or without depression compared to NGT individuals. T2DM patients with depression had the highest levels of miR-128 and cortisol and lowest levels of BDNF and telomere length compared to other groups. Pearson correlation analysis showed miR-128 levels were negatively associated with BDNF, telomere length and HDL cholesterol and positively correlated with cortisol, depression score, poor glycemic control and insulin resistance. Regression analysis confirmed that miR-128 was significantly associated with depression score even after adjusted for several confounding factors. However, this association was lost when adjusted for cortisol or telomere length., Conclusions: Patients with type 2 diabetes and depression exhibited increased circulatory levels of miR-128 and serum cortisol and decreased levels of BDNF and shortened telomeres. These neuroendocrine signatures were more markedly altered in those with combined diabetes and depression.

Aim: To assess the role of lithium treatment in the relationship between bipolar disorder (BD) and leukocyte telomere length (LTL). Materials & methods: We compared LTL between 131 patients with BD, with or without a history of lithium treatment, and 336 controls. We tested the association between genetically determined LTL and BD in two large genome-wide association datasets. Results: Patients with BD with a history lithium treatment showed longer LTL compared with never-treated patients (p = 0.015), and similar LTL compared with controls. Patients never treated with lithium showed shorter LTL compared with controls (p = 0.029). Mendelian randomization analysis showed no association between BD and genetically determined LTL. Conclusion: Our data support previous findings showing that long-term lithium treatment might protect against telomere shortening.

Major depressive disorder (MDD) is a chronic, severe psychiatric illness with an incidence of 3% worldwide. MDD patients have a significantly impaired quality of life and reduced life expectancy compared to unaffected individuals, the latter being largely accounted for by an increased incidence of suicide and cardiovascular disorders. The premature mortality observed in MDD has been considered a signature of accelerated aging, a hypothesis supported by data showing altered functioning and morphology of several brain regions that are typically present in the aging population. Telomere shortening is a hallmark of cellular aging, and as such several studies explored the involvement of disrupted telomere dynamics in MDD, reporting contrasting findings. In the current study, we measured leukocyte telomere length (LTL) in a sample of 54 MDD patients and 47 non-psychiatric controls characterized for response to antidepressant treatment. After correcting for age, sex, and body mass index, we showed significantly reduced LTL in affected individuals compared to controls (beta = -.22, p = .02). There was no difference in LTL between treatment resistant or responsive MDD patients. Moreover, we observed no correlation between lifetime exposure to antidepressants and LTL. Our study showed that MDD patients have shorter telomeres compared to controls, supporting the hypothesis of accelerated aging in this disorder. However, LTL seemed not to be influenced by antidepressant treatment or to correlate with clinical response to these antidepressants. Further investigations in larger samples and possibly with longitudinal design are warranted to elucidate the role of altered telomere dynamics in MDD., (© 2019 Wiley Periodicals, Inc.)

The length of telomeres is an objective measure of biologic ageing. This study evaluated the extent minutes of walking per week are associated with leukocyte telomere length (LTL) in a random sample of 5,823 U.S. adults. The investigation was cross-sectional and data were obtained from the National Health and Nutrition Examination Survey (NHANES). LTL was measured by the quantitative polymerase chain reaction method. Walking minutes was calculated from walking frequency and duration measures. Results showed that for each year of chronological age, telomeres were 15.6 base pairs shorter (P < 0.0001). With walking minutes and LTL treated as continuous variables, the relationship was quadratic, not linear (F = 11.2, P = 0.0023). With walking time divided into three categories, adults who performed ≥ 150 minutes of walking per week had longer telomeres than those who did no regular walking, and those who did some, but less than the recommendation (F = 5.0, P = 0.0137). Regular walkers were estimated to have a biologic ageing advantage associated with 6.5-7.6 years less biologic ageing compared to non-walkers, after adjusting for covariates. Additional investigations designed to study causality and the mechanisms associated with the walking and LTL relationship are needed.

Aging is associated with increased oxidative stress, chronic inflammation, and decreased telomere length (TL). However, the lifestyle of master athletes can lead to a reduced risk of these conditions, and thus attenuates aging and performance deterioration. We aimed to analyze the relationships between TL and relative performance (RP), and their relation to adiposity, oxidative stress, and inflammation in endurance (END) and sprint/power (SPW) master athletes (MAs). Twenty-two world-class MAs visited the laboratory for anamnesis, anthropometrics, and blood sampling. Inflammatory and oxidative stress parameters were assessed using commercial kits. Relative TL was determined in leukocytes through qPCR analyses. A positive association was observed between RP and TL in both groups (SPW: r= 0.641; END: r= 0.685) and the whole sample ( r= 0.594). The IL6/IL10 ratio presented an inverse correlation with RP in the whole sample ( r= -0.580). Body mass index also demonstrated a negative correlation with TL for the END group ( r= -0.690) and the whole sample analysis ( r= -0.455). Moreover, the IL6/IL10 ratio was negatively associated with strength/power training hours ( r =-0.464), whereas the CAT/TBARS ratio was negatively associated with aerobic training hours ( r= -0.482). In conclusion, TL of MAs was associated with RP regardless of the training model (endurance or sprint/power), and inflammation and adiposity were associated with shorter telomeres., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Bipolar disorder (BD) has been associated with clinical signs of accelerated aging, which potentially underlies its association with several age-related medical conditions, such as hypertension, metabolic imbalances, dementia, and cancer. This paper aims to comprehensively review evidence of biological aging in BD and explore findings and controversies related to common biological clocks in patients, including telomere length, DNA methylation, mitochondrial DNA copy number, inflammation, and oxidative stress. Our results suggest a complex interplay between biological markers and a potential key role of environmental factors, such as childhood trauma and psychological stress, in determining premature aging in patients. Moreover, given its multifactorial nature, our summary evidences the need for further studies incorporating clinical evidence with biomarkers of accelerated aging in BD. Results of this review strongly suggest BD as an accelerated aging disease seen in both clinical and molecular aspects. Understanding the pathophysiology of aging in BD may ultimately lead to identification of pathways that can be targeted for prevention of premature aging in patients and early onset of aging-related conditions., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

There is growing interest in the use of telomere length as a biomarker of health and a predictor of later morbidity and mortality. However, little is known about developmentally expected telomere erosion over the first years of life. This gap hinders our ability to interpret the meaning of relative telomere length and rate of attrition in relation to risk factors and health outcomes. The overall goal of this study was to examine the rate of relative telomere length attrition in a large, normative sample of healthy children (N = 630) followed from infancy to three years of age. A secondary goal was to explore associations between sociodemographic characteristics and telomere erosion over this time period. Relative telomere length was assessed from DNA in saliva samples collected in infancy (M = 8.6 months), age 2 years (M = 25.2 months), and age 3 years (M = 38.3 months). In the sample as a whole, relative telomere length decreased from infancy to 2 years but remained stable from 2 years to 3 years. Notably, increases in relative telomere length were observed in 29 % of children between infancy and 2 years of age and in 46 % of children between 2 and 3 years of age; 62 % of children showed both increases and decreases in relative telomere length across the study period. Females showed longer relative telomere length than males, regardless of timepoint. There was some evidence that parental age and family finances were associated with changes in child relative telomere length across time. Overall, the findings suggest that telomere length attrition is not uniform across the early years of life, with the most rapid attrition occurring during the first two years, and that increases as well as decreases in telomere length during this period are commonly observed., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A growing literature suggests that exposure to adverse social conditions may accelerate biological aging, offering one mechanism through which adversity may increase risk for age-related disease. As one of the most extensively studied biological markers of aging, telomere length (TL) provides a valuable tool to understand potential influences of social adversity on the aging process. Indeed, a sizeable literature now links a wide range of stressors to TL across the life span. The aim of this article is to review and evaluate this extant literature with a focus on studies that investigate psychosocial stress exposures and experiences in early life and adulthood. We conclude by outlining potential biological and behavioral mechanisms through which psychosocial stress may influence TL, and we discuss directions for future research in this area.

We investigated whether telomere length (TL) reflecting physical rather than chronological aging is associated with disease progression in the different cognitive stages of Alzheimer's disease (AD). Study participants included 89 subjects with amyloid pathology (A+), determined through amyloid PET or cerebrospinal fluid analysis, including 26 cognitively unimpaired (CU A+) individuals, 28 subjects with mild cognitive impairment (MCI A+), and 35 subjects with AD dementia (ADD A+). As controls, 104 CU A- individuals were selected. The participants were evaluated annually over two years from baseline. Compared to the highest TL quartile group of MCI A+ participants, the lowest TL quartile group yielded 2-year differences of -9.438 (95% confidence interval [CI] = -14.567 ~ -4.309), -26.708 (-41.576 ~ -11.839), 3.198 (1.323 ~ 5.056), and 2.549 (0.527 ~ 4.571) on the Mini-Mental State Examination, Consortium to Establish a Registry for AD, Clinical Dementia Rating-Sum of Boxes, and Blessed Dementia Scale-Activities of Daily Living, respectively. With this group, the lowest TL quartile group had a significantly greater probability of progressing to ADD than the highest TL quartile group (hazard ratio = 13.16, 95% CI = 1.11 ~ 156.61). Telomere shortening may be associated with rapid cognitive decline and conversion to dementia in MCI A+.

Individuals who poorly regulate emotion exhibit premature aging and worse general health. Telomere shortening, a prognostic biomarker of physical health, is related to aging, poor immunocompetence and autonomic nervous system functioning. Cognitive reappraisal is one type of emotion regulation strategy, which involves changing one's appraisal of an aversive situation to modify its emotional impact. Heart rate variability (HRV; i.e., oscillations in heart rate) relates to emotion regulatory processes, such that higher HRV typically reflects greater regulatory capacity. Previous research has identified a positive association between HRV and telomere length. Importantly, the association between HRV and telomere length may change depending on how often an individual uses cognitive reappraisal. One hundred and thirty-seven healthy participants completed measures of cognitive reappraisal frequency, HRV, and underwent blood draws to measure telomere length (computed with the relative ratio of telomere repeat copy number to single copy gene number) in the T cell effector population, CD8 + CD28 - . Cognitive reappraisal moderated the relationship between telomere length and HRV such that individuals with high cognitive reappraisal frequency had a significant positive association between HRV and telomere length, while individuals with average and less than average frequency did not exhibit this relationship. The results suggest that frequent usage of cognitive reappraisal enhances the already positive influence of HRV on chromosomal integrity in CD8 + CD28 - T lymphocytes. Although future research is needed to test these effects causally, these findings suggest that regularly using emotion regulation techniques may buffer the relationship between autonomic nervous system functioning and chromosomal integrity in immune cells., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Telomere length (TL) and shortening is increasingly shown to predict variation in survival and lifespan, raising the question of what causes variation in these traits. Oxidative stress is well known to accelerate telomere attrition in vitro , but its importance in vivo is largely hypothetical. We tested this hypothesis experimentally by supplementing white stork ( Ciconia ciconia ) chicks with antioxidants. Individuals received either a control treatment, or a supply of tocopherol (vitamin E) and selenium, which both have antioxidant properties. The antioxidant treatment increased the concentration of tocopherol for up to two weeks after treatment but did not affect growth. Using the telomere restriction fragment technique, we evaluated erythrocyte TL and its dynamics. Telomeres shortened significantly over the 21 days between the baseline and final sample, independent of sex, mass, size and hatching order. The antioxidant treatment significantly mitigated shortening rate of average TL (-31% in shorter telomeres; percentiles 10th, 20th and 30th). Thus, our results support the hypothesis that oxidative stress shortens telomeres in vivo .

We introduce a novel hypothesis which states that the therapeutic utilisation of psilocybin has beneficial effects on genetic aging. Ex hypothesi, we predict a priori that controlled psilocybin interventions exert quantifiable positive impact on leucocyte telomere length (telomeres are a robust predictor of mortality and multifarious aging-related diseases). Our hypothesising follows the Popperian logic of scientific discovery, viz., bold (and refutable) conjectures form the very foundation of scientific progress. The 'psilocybin-telomere hypothesis' is formalised as a logically valid deductive (syllogistic) argument and we provide substantial evidence to support the underlying premises. Impetus for our theorising derives from a plurality of converging empirical sources indicating that psilocybin has persistent beneficial effects on various aspects of mental health (e.g., in the context of depression, anxiety, PTSD, OCD, addiction, etc.). Additional support is based on a large corpus of studies that establish reliable correlations between mental health and telomere attrition (improved mental health is generally correlated with longer telomeres). Another pertinent component of our argument is based on recent studies which demonstrate that "meditative states of consciousness" provide beneficial effects on genetic aging. Similarly, psilocybin can induce states of consciousness that are neurophysiologically and phenomenologically significantly congruent with meditative states. Furthermore, prior research has demonstrated that a single dose of psilocybin can occasion life-changing transformative experiences (≈ 70% of healthy volunteers rate their experience with psilocybin amongst the five personally most meaningful lifetime events, viz., ranked next to giving birth to a child or losing a loved one). We postulate that these profound psychological events leave quantifiable marks at the molecular genetic/epigenetic level. Given the ubiquitous availability and cost effectiveness of telomere length assays, we suggest that quantitative telomere analysis should be regularly included in future psilocybin studies as an adjunctive biological marker (i.e., to facilitate scientific consilience via methodological triangulation). In order to substantiate the 'psilocybin-telomere hypothesis' potential neuropsychopharmacological, endocrinological, and genetic mechanisms of action are discussed (e.g., HPA-axis reactivity, hippocampal neurogenesis, neurotropic growth factors such as BDNF, 5-HT 2A receptor agonism, neuroplasticity/synaptoplasticity, brain-wide alterations in neuronal functional connectivity density, involvement of the SLC6A4 serotonin transporter gene, inter alia). The proposed research agenda is thus intrinsically highly interdisciplinary, and it has deep ramifications from a philosophy of science perspective as it connects the epistemic level (qualitative experiential phenomenology) with the ontic level (quantitative molecular genetics) of analysis. In the long term, multidisciplinary and innovative investigations of the 'psilocybin-telomere hypothesis' could contribute to the improvement of senotherapeutic psychological interventions and the identification of novel geroprotective and neuroprotective/restorative pharmaceutical targets to decelerate genetic aging and improve well-being and quality of life during the aging process., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background and Objectives: Sex hormone concentrations and telomere length are age related responses of human body, while whether there is a direct relation between sex hormone and telomere length is uncertain. Therefore, we used the data of National Health and Nutrition Examination Survey (NHANES) to quantify their direct association., Research Design and Methods: A total of 710 women aged 35-60 years and 539 men aged 20-85 years were included from two cycles of the NHANES (1999-2002). Telomere length relative to standard reference DNA (T/S ratio) was measured using quantitative polymerase chain reaction method. Seven hormones in serum (5 in men and 2 in women) were assayed. Logistic regressions were used to calculate the odds ratios to evaluate the telomere length-sex hormones association., Results: Men with vigorous physical activity (71.1%) and without history of cardiovascular diseases, diabetes, and lipid-lowering drugs using tended to have a longer telomere length (all P-values < 0.05); while women with longer sedentary time, smaller pregnant or live birth, and with older ages of firth/last birth were likely with longer telomere length (all P-values < 0.05). After adjusted for potential confounders, only anti-Mullerian hormone was positively and stably associated with short leukocytes telomere length in men (OR: 1.098; 95% CI: 1.034, 1.165). We did not detect any significant association of short telomere length with sex hormones in men and women. Discussion and Implications: Serum anti-Mullerian hormone in men was positively and stably associated with telomere length. More large-scaled and well-designed prospective studies are warranted to reconfirm our conclusions., Competing Interests: The authors have no conflict of interest to report.