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Background: Vitamin B 12 is essential for deoxyribonucleic acid synthesis and genome stability. A deficiency of vitamin B 12 is associated with telomere shortening, genomic aging, and increased risk of chronic disease and mortality., Objectives: The study aims to determine the effect of vitamin B 12 supplementation on leukocyte telomere length (LTL) in infants at risk of vitamin B 12 deficiency., Methods: The study was a predefined secondary analysis of a randomized controlled trial enrolling 600 Nepalese infants aged 6 -11 mo, who were supplemented with 2 μg (2-3 recommended daily allowances) vitamin B 12 or placebo daily for 1 y. At the end of the study, LTL was measured in 497 participants. Mean LTL was compared between the treatment arms in the full sample and predefined subgroups based on markers of vitamin B 12 status, hemoglobin, sex, and growth indices., Results: LTL at end-study did not differ between the vitamin B 12 and placebo arm with a standardized mean difference (95% confidence interval) of 0.04 (-0.14, 0.21). There was no effect of vitamin B 12 on LTL in any of the subgroups., Conclusions: Providing daily vitamin B 12 for 1 y during infancy in a population at risk of vitamin B 12 deficiency does not affect LTL. This trial was registered at clinicaltrials.gov as NCT02272842., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Telomere length (TL) is a biomarker of biological aging that may be affected by prenatal exposure to air pollution. The aim of this study was to assess the association between prenatal exposure to air pollution and TL in maternal blood cells (leukocytes), placenta and umbilical cord blood cells, sampled immediately after birth in 296 Danish mother-child pairs from a birth cohort. Exposure data was obtained using the high-resolution and spatial–temporal air pollution modeling system DEHM-UBM-AirGIS for PM2.5, PM10, SO2, NH4+, black carbon (BC), organic carbon (OC), CO, O3, NO2, and NOx at residential and occupational addresses of the participating women for the full duration of the pregnancy. The association between prenatal exposure to air pollutants and TL was investigated using distributed lag models. There were significant and positive associations between TL in umbilical cord blood cells and prenatal exposure to BC, OC, NO2, NOx, CO, and O3 during the second trimester. TL in umbilical cord blood was significantly and inversely associated with prenatal exposure to PM2.5, BC, OC, SO2, NH4+, CO and NO2 during the third trimester. There were similar inverse associations between TL from umbilical cord blood cells and air pollution exposure at the residential and occupational addresses. There were weaker or no associations between air pollution exposure and TL in placenta tissue and maternal blood cells. In conclusion, both the second and third trimesters of pregnancy are shown to be sensitive windows of exposure to air pollution affecting fetal TL.

Polychlorinated biphenyls (PCBs) induce the expression of the proto-oncogene c-myc which has a role in cellular growth and proliferation programs. The c-myc up-regulates the telomerase reverse transcriptase which adds the telomeres repeating sequences to the chromosomal ends to compensate for the progressive loss of telomeric sequence. We performed multivariate linear regression to analyze the association of PCBs, polychlorinated dibenzo-p-dioxins, and 1,2,3,4,6,7,8-heptachlorodibenzofuran with leukocyte telomere length (LTL) in the adult population (n = 2413) of the National Health and Nutrition Examination Survey 1999–2002. LTL was natural log-transformed and the results were re-transformed and presented as percent differences. Individuals in the 3rd and 4th quartiles of the sum of PCBs were associated with 8.33% (95% CI: 4.08–13.88) and 11.63% (95% CI: 6.18–17.35) longer LTLs, respectively, compared with the lowest quartile, with evidence of a dose–response relationship (p-trend

Background: Omega-3 (n-3) and omega-6 (n-6) fatty acids may contribute to oxidative stress and inflammation, which are related to telomere shortening. Evidence supporting an association between intake of n-3 or n-6 fatty acids and leukocyte telomere length (LTL) in males has been limited., Objectives: We conducted a cross-sectional study to examine the associations of total or individual n-3 or total n-6 fatty acid intake with LTL in US males., Methods: We included 2,494 US males with LTL measurement from 4 nested case-control studies within the Health Professionals Follow-Up Study. Individuals with previous histories of cancers, diabetes, and cardiovascular diseases at or before blood collection were excluded. Blood collection was performed between 1993 and 1995, and relevant information including n-3 and n-6 intake was collected in 1994 by questionnaire. The LTL was log-transformed and Z scores of the LTL were calculated for statistical analyses by standardizing the LTL in comparison with the mean within each selected nested case-control study., Results: We found that consumption of DHA (22:6n-3) was positively associated with LTL. In the multivariable-adjusted model, compared with individuals who had the lowest intake of DHA (i.e., first quartile group), the percentage differences (95% CIs) of LTL were -3.7 (-13.7, 7.5), 7.0 (-4.3, 19.7), and 8.2 (-3.5, 21.3) for individuals in the second, third, and fourth quartiles of consumption, respectively (P-trend = 0.0498). We did not find significant associations between total n-3 or total n-6 fatty acid intakes and LTL. In addition, we found that males who consumed canned tuna had longer LTL than those who did not; in the multivariable-adjusted model, the percentage difference of LTL was 10.5 (95% CI: 1.3, 20.4) (P = 0.02)., Conclusions: Our results suggest that higher intakes of DHA and canned tuna consumption are associated with longer LTL., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Introduction: Telomere shortening, as seen with aging, can cause chromosomal instability and promote cancer progression. We investigated the association between circulating telomere length and overall and disease-free survival in a sub-cohort of patients with colorectal cancer., Methods: Baseline genomic DNA from blood leukocytes was extracted from N = 92 newly diagnosed stage I-IV patients with colorectal cancer enrolled at the ColoCare Study site in Heidelberg, Germany. Detailed information on clinicodemographic (including age) and lifestyle risk factors, and clinical outcomes (including recurrence and survival) was collected. Telomere length was measured in DNA using multiplex quantitative polymerase chain reaction. Kaplan Meier survival curves were generated comparing shorter to longer telomere lengths with log-rank testing., Results: The mean T/S ratio for study patients was 0.5 (range: 0.3-0.9). Shorter telomeres were associated with older age at baseline. Patients with shorter telomeres experienced a worse overall and disease-free survival, although this association did not reach statistical significance. Kaplan-Meier survival curves for those with circulating telomere length below vs. above the median showed poorer overall (log-rank p = 0.31) and disease-free survival (long-rank p = 0.23)., Conclusions: Our results suggest that individuals with shorter telomeres, as seen with aging, may experience a worse overall and disease-free survival after colorectal cancer diagnosis. Larger sample sizes with longer follow-up are needed to further evaluate telomere length as a prognostic biomarker in colorectal cancer progression., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and Aim: Alterations of glucose homeostasis can increase advanced glycation end products (AGEs) that exacerbate vascular inflammatory disease and may increase vascular senescence and aging. This study examined the relationships between carboxymethyl-lysine (CML) and soluble receptor for AGEs (sRAGE) with leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn), as cell aging biomarkers, in patients with established coronary artery disease (CAD)., Methods and Results: We studied 459 patients with CAD further categorized as having normal glucose homeostasis (NG, n = 253), pre-diabetes (preT2D, n = 85), or diabetes (T2D, n = 121). All patients were followed up for the occurrence of major adverse cardiovascular events (MACEs). Plasma concentrations of sRAGE and CML were measured by ELISA. mtDNAcn and LTL were measured by qRT-PCR. CML levels were significantly higher in patients with preT2D (p < 0.007) or T2D (p < 0.003) compared with those with NG. mtDNAcn resulted lower in T2D vs preT2D (p = 0.04). At multivariate Cox proportional hazard analysis, short LTL (HR: 2.89; 95% CI: 1.11-10.1; p = 0.04) and high levels of sRAGE (HR: 2.20; 95% CI: 1.01-5.14; p = 0.04) were associated with an increased risk for MACEs in patients with preT2D and T2D, respectively. T2D patients with both short LTL and high sRAGE levels had the highest risk of MACEs (HR: 3.11; 95% CI: 1.11-9.92; p = 0.04)., Conclusions: High levels of sRAGE and short LTL were associated with an increased risk of MACEs, especially in patients with diabetes, supporting the usefulness of both biomarkers of glycemic impairment and aging in predicting cardiovascular outcomes in patients with CAD., Competing Interests: Declaration of competing interest The authors declare no conflict of interest for this study., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Much research has demonstrated the beneficial effects of mindfulness-based stress reduction (MBSR) on psychological and physical health, but it is not known whether MBSR may impact cellular aging in healthy populations. Further, little research has evaluated MBSR against an active control condition, which precludes strong conclusions regarding the unique effects of mindfulness on psychological functioning. The present study examined the effects of MBSR versus music therapy-based stress reduction (MTSR) on trait mindfulness, self-compassion, and several psychological health outcomes, as well as leukocyte telomere length (LTL). One hundred and fifty eight Singaporean Chinese adults were recruited and randomly assigned to an eight-week MBSR or MTSR course. Participants provided blood samples and completed a battery of self-report measures pre- and post-intervention. Analyses showed that participants in the MBSR condition demonstrated significantly greater improvements in depressive symptoms, trait mindfulness, and self-compassion compared to the control condition. Treatment condition did not predict changes in LTL, anxiety, stress, or happiness, though there was a trend for duration of home mindfulness practice to predict increases in LTL. Overall, the study demonstrated MBSR's unique effects in reducing depressive symptoms. Improvements in trait mindfulness and self-compassion correspond with theorized mechanisms of change underlying mindfulness training. The lack of intervention effect with regards to LTL suggests that a more intensive intervention may be required for mindfulness to exert noticeable impact on aging at the cellular level, or that the effect may only emerge over a longer term., (Copyright © 2020. Published by Elsevier Ltd.)

Telomere length and mitochondrial DNA content are considered biomarkers of cellular aging, oxidative stress, and inflammation, but there is almost no information on their association with tobacco smoke exposure in fetal and early life. The aim of this study was to assess whether prenatal and childhood tobacco exposure were associated with leukocyte telomere length (LTL) and mitochondrial DNA (mtDNA) content in children. As part of a multi-centre European birth cohort study HELIX (Human Early-Life Exposome) (n = 1396) we assessed maternal smoking status during pregnancy through questionnaires, and through urinary cotinine levels that were then used to classify women as not exposed to smoking (<10 µg/L), exposed to secondhand smoke (SHS) (10-50 µg/L) and active smokers (>50 µg/L). When the children were around 8 years of age (range: 5.4-12.0 years), childhood SHS tobacco smoke exposure was assessed through an extensive questionnaire and through measurements of urinary cotinine (<3.03 µg/L non-detected, >3.03 µg/L detected). Leukocyte mtDNA content and LTL were measured in the children at 8 years employing real time polymerase chain reaction (qPCR). Effect estimates were calculated using multivariate linear regression models for prenatal and childhood exposures adjusted for potential confounders. Maternal cotinine levels indicative of SHS exposure during pregnancy were associated with a decrease of 3.90% in LTL in children (95% CI: -6.68, -0.91), compared with non-smoking, whereas the association for maternal cotinine levels indicative of active smoking did not reach statistical significance (-3.24%; 95% CI: -6.59, 0.21). Childhood SHS tobacco exposure was not associated with LTL in children. Global SHS exposure during childhood was associated with an increase of 3.51% (95% CI: 0.78, 6.27) in mtDNA content. Our findings suggest that tobacco smoke exposure during pregnancy, even at SHS levels, may accelerate telomere shortening in children and thus induce biological aging from an early age., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Air pollution exposure is a major global health concern and has been associated with molecular aging. Unfortunately, the situation has not received much attention in the African region. The aim of this study was to investigate whether current personal ambient NO 2 and benzene, toluene, ethyl-benzene and xylenes (ortho (o)-, meta (m)- and para (p)-xylene (BTEX) exposure is associated with leukocyte telomere length (LTL), a marker of molecular ageing, in apparently healthy women (mean ± SD age: 42.5 ± 13.4 years) residing in the Cape Town region of South Africa. The repeated measures study collected data from 61 women. Seven-day median (interquartile range (IQR)) personal NO 2 and BTEX exposure levels were determined via compact passive diffusion samplers carried on the person prior to baseline (NO 2 : 14.2 (9.4-17.2) μg/m³; Benzene: 3.1 (2.1-5.3) μg/m³) and 6-month follow-up (NO 2 : 10.6 (6.6-13.6) μg/m³; Benzene: 2.2 (1.3-4.9) μg/m³) visits. LTL was measured at baseline and follow-up using a real-time PCR method. Multiple linear mixed model analyses (adjusting for age, body mass index, smoking, employment status, level of education and assessment visit) showed that each IQR increment increase in NO 2 (7.0 μg/m³) and benzene (3.3 μg/m³) was associated with -7.30% (95% CI: -10.98 to -3.46%; p < 0.001) and -6.78% (95% CI: -11.88 to -1.39%; p = 0.015) difference in LTL, respectively. The magnitude of these effects of NO 2 and benzene corresponds to the effect of an increase of 10.3- and 6.0-year in chronological age on LTL. Our study shows that personal exposures to NO 2 and benzene are associated with molecular ageing as indicated by LTL in healthy women residing in the Cape Town region., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Telomere length is considered a biomarker of human aging and premature morbidity and mortality which has been associated with chronic stress., Methods: We assessed the relation between perceived racism and telomere length in the Black Women's Health Study, a follow-up study of U.S. black women begun in 1995. Participants were asked about frequency of "everyday racism" (e.g., "people act as if they think you are not intelligent") and "institutional racism" (e.g., "ever treated unfairly due to race by police"). Using quantitative real-time polymerase chain reaction assay, relative telomere lengths (RTL) were measured as the copy number ratio of telomere repeat to a single control gene in 997 participants. Associations of racism variables with log-RTL were estimated by multivariable linear regression, with adjustment for age at blood draw and potential confounders., Results: Participants were aged 40-70 years (mean = 55.6 years), and mean telomere length was 0.77 (range 0.21-1.38). In stratified analyses, there was an inverse association between everyday racism and log-RTL among women who did not discuss their experiences of racism with others (β = -0.1104; 95% CI = -0.2140 to -0.0067; P = .045)., Conclusions: Everyday racism was associated with shorter telomere length among women who reported not discussing those experiences with others., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Aims: Leukocyte telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN), as hallmarks of cellular aging, may be involved in the development of coronary artery disease (CAD) by modulating oxidative stress. This study aimed to investigate the effects of leukocyte TL and mtDNA-CN alone or in combination on CAD risk and severity in the Chinese population., Methods: In this two-stage case-control study with 1511 CAD patients and 1553 controls, leukocyte TL and mtDNA-CN were determined by a quantitative PCR assay. Three oxidative parameters, including leukocyte 8-hydroxy-2'-deoxyguanosine (8-OHdG), plasma malondialdehyde, and plasma reactive oxygen species (ROS), were quantified by ELISA or colorimetric kits in a subset of 129 cases and 129 controls., Results: In the combined cohort, each 1-SD decrease in TL and mtDNA-CN was significantly associated with a 1.17-fold and 1.14-fold increased risk of CAD (p < 0.001 for all), respectively, after adjusting for confounders. The aggregated score, which reflected the cumulative dosage of the tertiles of TL and mtDNA-CN, showed inverse dose-response correlations with CAD risk (p trend  < 0.001), and severity, as determined by the severity of clinical presentations (p trend  = 0.037), the presence of multi-vessel CAD (p trend  = 0.004), and modified Gensini scores (p trend  = 0.009). Similar dose-response relations of the aggregated score to leukocyte 8-OHdG and plasma ROS were also identified., Conclusions: Our data suggested reductions in both TL and mtDNA-CN as independent risk factors for CAD. The combination of TL and mtDNA-CN might jointly contribute to CAD risk, CAD severity, and oxidative stress., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: In utero particulate matter exposure produces oxidative stress that impacts cellular processes that include telomere biology. Newborn telomere length is likely critical to an individual's telomere biology; reduction in this initial telomere setting may signal increased susceptibility to adverse outcomes later in life. We examined associations between prenatal particulate matter with diameter ≤2.5 µm (PM 2.5 ) and relative leukocyte telomere length (LTL) measured in cord blood using a data-driven approach to characterize sensitive windows of prenatal PM 2.5 effects and explore sex differences., Methods: Women who were residents of Mexico City and affiliated with the Mexican Social Security System were recruited during pregnancy (n = 423 for analyses). Mothers' prenatal exposure to PM 2.5 was estimated based on residence during pregnancy using a validated satellite-based spatio-temporally resolved prediction model. Leukocyte DNA was extracted from cord blood obtained at delivery. Duplex quantitative polymerase chain reaction was used to compare the relative amplification of the telomere repeat copy number to single gene (albumin) copy number. A distributed lag model incorporating weekly averages for PM 2.5 over gestation was used in order to explore sensitive windows. Sex-specific associations were examined using Bayesian distributed lag interaction models., Results: In models that included child's sex, mother's age at delivery, prenatal environmental tobacco smoke exposure, pre-pregnancy BMI, gestational age, birth season and assay batch, we found significant associations between higher PM 2.5 exposure during early pregnancy (4-9 weeks) and shorter LTL in cord blood. We also identified two more windows at 14-19 and 34-36 weeks in which increased PM 2.5 exposure was associated with longer LTL. In stratified analyses, the mean and cumulative associations between PM 2.5 and shortened LTL were stronger in girls when compared to boys., Conclusions: Increased PM 2.5 during specific prenatal windows was associated with shorter LTL and longer LTL. PM 2.5 was more strongly associated with shortened LTL in girls when compared to boys. Understanding sex and temporal differences in response to air pollution may provide unique insight into mechanisms., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Chronic caregiving stress may accelerate biological aging; however, the ability to integrate the meaning of caregiving through self-awareness, adaptation, and growth can buffer the negative effects of stress. Narrative researchers have shown that people who coherently integrate difficult experiences into their life story tend to have better mental health, but no prior study has examined the prospective association between narrative identity and biological indicators, such as telomere length. We tested whether narrative identity might be prospectively associated with resilience to long-term parenting stress, depressive symptoms, and protection from telomere shortening, especially among caregivers., Methods: We conducted a semi-structured interview about parenting and quantified narrative themes by applying well-validated, standardized coding systems with high inter-rater reliability among 88 mothers: 32 "caregivers" (mothers with a child diagnosed with an autism spectrum disorder), and 56 "controls" (mothers with a neurotypical child). To assess longitudinal changes, we measured mental health (parenting stress [PS], depressive symptoms [DS]) and leukocyte telomere length [LTL], a biomarker of aging, at baseline and again 18 months later. We examined whether narrative identity themes were related to these outcomes and whether associations differed across caregivers versus controls., Results: Caregivers exhibited significantly higher basal levels of PS and DS relative to controls (all p's < .05), but no significant difference in LTL (p > .05). Caregivers rated higher in the narrative theme of integration showed healthier future 18-month trajectories in PS (B = -0.832, 99% CI: [-1.315, -0.155], p < .01) and LTL (B = 1.193, 99% CI: [0.526, 2.130], p < .01), but no differences in depressive symptoms (p > .05), adjusting for age and antidepressant use. Analyses examining affective themes in caregiver narratives did not demonstrate significant associations. Narrative themes did not predict outcomes in controls., Conclusions: The data suggest that narratives reflecting coherent integration, but not necessarily affect, prospectively relate to psychological and biological stress resilience. Maternal caregivers' ability to tell an integrated story of their parenting experiences forecasts lower parenting stress and telomere shortening over time. This study suggests the possibility that helping individuals better integrate the meaning of stressful experiences, but not necessarily to affectively redeem them, may constitute a potential novel target for intervention among chronically stressed populations such as caregivers., (Published by Elsevier Inc.)

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by an expanded CAG repeat. Though symptom onset commonly occurs at midlife and inversely correlates with the CAG repeat expansion, age at clinical onset and progression rate are variable. In the present study we investigated the relationship between leukocyte telomere length (LTL) and HD development. LTL was measured by real-time PCR in manifest HD patients (HD, n = 62), pre-manifest HD patients (pre-HD, n = 38), and age-matched controls (n = 76). Significant LTL differences were observed between the three groups (p < .0001), with LTL values in the order: HD < pre-HD < controls. The relationship between LTL and age was different in the three groups. An inverse relationship between mean LTL and CAG repeat number was found in the pre-HD (p = .03). The overall data seem to indicate that after age 30 years, LT begins to shorten markedly in pre-HD patients according to CAG number and increasing age, up to the values observed in HD. This very suggestive picture allowed us to hypothesize that in pre-manifest HD, LTL could be a measure of time to clinical HD onset. The possible use of LTL as a reliable biomarker to track HD development and progression was evaluated and discussed., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Telomeres consist of exanucleotide tandem repeats and proteins complexes at the end of chromosome ends. Telomeres shorten at each cell division, and as such telomere length is a marker of cellular age. Accelerated telomere shortening and cell senescence have been associated with a number of chronic medical conditions, including psychiatric disorders, where increased prevalence of age-related disorders and shorter telomere length have been reported. Shorter telomeres in psychiatric patients are thought to be the consequence of allostatic load, consisting in the overactivation of allostatic systems due to chronic exposure to severe medical conditions and failure to adapt to chronic stressful stimuli. Most of the studies on telomere length in psychiatry have focused on major depressive disorder, but recent findings have shown shorter leukocyte telomere length in bipolar disorder patients and suggested that lithium may counteract telomeres shortening. These findings provided new insights into the pathophysiology of bipolar disorder and the mechanism of action of lithium. In this review we will present findings from the literature on telomere length in bipolar disorder, with a specific focus on lithium. We will also discuss advances and limitations of published work as well as methodological issues and potential confounding factors that should be taken into account when designing research protocols to study telomere length., (Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.)

Background: Vitamin D deficiency has been linked to all-cause mortality and cancer. However, the biological plausibility of these associations is not well established. Leukocyte telomere length (LTL) shortening is associated with aging and is a hallmark of genomic instability and carcinogenesis. Objective: We aimed to investigate the association between serum 25-hydroxyvitamin D [25(OH)D] concentrations and LTL in the general US population. Methods: We analyzed data from the US NHANES 2001-2002. The study population comprised 1542 younger adults (aged 20-39 y), 1336 middle-aged adults (aged 40-59 y), and 1382 older adults (aged ≥60 y). LTL was measured by using quantitative polymerase chain reaction. Serum 25(OH)D concentrations ≥50 nmol/L were considered optimal. Linear regression, adjusted for age, sex, race/ethnicity, body mass index (BMI), total energy and sugar intakes, calcium intake, socioeconomic status, milk and dietary supplement consumption, and physical activity, was applied to investigate the association between serum 25(OH)D and LTL. Results: In the total population, age, sex, BMI, and non-Hispanic black race/ethnicity were significant predictors of LTL. In the participants aged 40-59 y, an increment in serum 25(OH)D of 10 nmol/L was associated with a 0.03- ± 0.01-kbp longer LTL, adjusted for age, sex, race/ethnicity, and other factors ( P = 0.001). In the same age group, 25(OH)D concentrations ≥50 nmol/L were associated with a 0.13- ± 0.04-kbp longer LTL than those for 25(OH)D concentrations <50 nmol/L ( P = 0.01). The association was independent of age, sex, race/ethnicity, BMI, and other factors. Conclusions: In a nationally representative population of adults, serum 25(OH)D was positively associated with LTL in middle-aged participants (aged 40-59 y), independently of other factors. These findings suggest that decreased 25(OH)D concentrations are associated with genomic instability, although the clinical impact of this observation remains unclear., (© 2017 American Society for Nutrition.)

Telomeres are repetitive DNA sequences (TTAGGG) at the end of chromosomes. Cells with critically short telomeres enter replicative senescence and apoptosis. Several in vitro studies report that antimony causes cell apoptosis in human leukocyte cell lines. The goal of this analysis was to investigate whether there is an association between antimony exposure and leukocyte telomere length (LTL) among US adults aged 20 and older based on the National Health and Nutrition Examination Survey (NHANES) 1999-2002. We used multivariate linear regression to analyze the association of urinary antimony with LTL. LTL was log-natural transformed and the results were re-transformed and presented as percent differences. After adjustment for potential confounders, individuals in the 3rd and 4th quartiles of urinary antimony had statistically significantly shorter LTL (-4.78%, 95% CI: -8.42,-0.90; and -6.11%, 95% CI: -11.04,-1.00, respectively) compared to the lowest referent quartile, with evidence of a dose-response relationship (p-value for trend =0.03). Shorter LTL with antimony was driven by middle aged (40-59 years) and older (60-85 years) adult groups. The association may be biologically plausible because of reported oxidative stress and apoptosis effects of antimony on blood cells, effects known to shorten telomere length., (Published by Elsevier Inc.)

Bipolar disorder (BD) has been suggested to be associated with accelerated aging and premature cell senescence. While findings on shorter telomeres in BD are controversial, a recent study showed that long-term lithium treatment correlates with longer telomeres in BD. In our study, we sought to investigate the correlation between leukocyte telomere length (LTL) and long-term lithium treatment in a sample of 200 BD patients characterized for lithium response. We also compared data from two different methods commonly used to measure telomere length, quantitative PCR (qPCR) and quantitative fluorescence in situ hybridization (Q-FISH). We also measured, for the first time, the effect of lithium in vitro on the expression of the telomerase gene in human-derived neural progenitor cells (NPCs). Our findings showed that LTL correlated negatively with age (p=0.0002) and was independent of sex, diagnosis, age at onset, suicidal behavior, number of mood episodes, response to lithium and use of other psychotropic medications. After correcting for age, LTL was positively correlated with lithium treatment duration in patients treated for more than two years (n=150, R=0.17, p=0.037). There was a significant correlation between data measured with qPCR and Q-FISH (p=0.012, R=0.826). Lithium treatment increased telomerase expression in NPCs, though this effect was not statistically significant. Our data support previous findings showing that long-term lithium treatment associates with longer telomeres in BD, though this effect appeared to be independent from clinical response to the treatment. Moreover, we suggested for the first time that lithium increases the expression of telomerase gene in human neural progenitor cells., (Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.)

The association between leukocyte telomere length (LTL) and cardiovascular disease (CVD) has been published in many reports, although almost exclusively in men. In our study we analysed the association between LTL and five selected variants within three candidate genes (TERC rs12696304; TERF2IP rs3784929 and rs8053257; UCP2 rs659366 and rs622064), which are not only involved in telomere-length maintenance but also potentially associated with higher risk of acute coronary syndrome (ACS) in Czech women (505 cases and 642 controls). We detected significantly shorter LTL in women with ACS (P<0.001), but the difference disappeared after multiple adjustments. We did not find any significant associations between analysed variants and LTL, except for rs622064 within the UCP2 gene, in which case AA homozygotes had a higher LTL (P<0.04). Genotype frequencies of the analysed SNPs did not differ between controls and women with ACS. Variants within UCP2 (rs622064; CC vs. A allele carriers OR=1.61; 95% CI: 1.21-2.15, P<0.002) and within TERF2IP (rs8053257; A allele carriers vs. GG, OR=1.78; 95% CI: 1.07-3.18, P<0.03) were associated with increased risk of type 2 diabetes mellitus (T2DM). Analysed polymorphisms were not major determinants of telomere length or ACS risk in Czech females., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Studies of the effects of smoking on leukocyte telomere length (LTL) using cigarettes smoked per day or pack years smoked (PYS) present limitations. Reported high levels of smoking may not increase toxin exposure levels proportionally. Nicotine metabolism ratio (NMR) predicts total cigarette puff volume and overall exposure based on total N-nitrosamines, is highly reproducible and independent of time since the last cigarette. We hypothesized that smokers with higher NMRs will exhibit increased total puff volume, reflecting efforts to extract more nicotine from their cigarettes and increasing toxin exposure. In addition, higher levels of smoking could cause a gross damage in LTL. The urinary cotinine, 3-OH cotinine and nicotine levels of 147 smokers were analyzed using a LC/MS system Triple-Q6410. LTL and CYP2A6 genotype was determined by PCR in blood samples. We found a significant association between NMR and CYP2A6 genotype. Reduction in LTL was seen in relation to accumulated tobacco consumption and years smoking when we adjusted for age and gender. However, there were no significant differences between NMR values and LTL. In our study the higher exposure was associated with lower number of PYS. Smokers with reduced cigarette consumption may exhibit compensatory smoking behavior that results in no reduced tobacco toxin exposure. Our results suggest that lifetime accumulated smoking exposure could cause a gross damage in LTL rather than NMR or PYS. Nevertheless, a combination of smoking topography (NMR) and consumption (PYS) measures may provide useful information about smoking effects on health outcomes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Leukocyte telomere length (LTL) has been regarded as a potential marker of biologic aging because it usually shortens in a predictable way with age. Recently, a growing interest in cardiovascular aging has led to a number of new epidemiologic studies investigating LTL in various disease conditions. Some methodological problems exist because there are different methods available to determine LTL, and standardization is much needed. For example, in the majority of studies, patients with early-onset coronary heart disease have been shown to have shorter LTL. In addition, patients with diabetes mellitus complications tend to have shorter LTL than control subjects. On the other hand, increased left ventricular hypertrophy or mass is associated with longer LTL, and studies investigating hypertension have reported both shorter and longer LTL than found in normotensive control subjects. There is, therefore, a need for longitudinal studies to elucidate these complicated relationships further, to provide estimations of telomere attrition rates, and to overcome analytical problems when only cross-sectional studies are used. The understanding of cardiovascular aging and telomere biology may open up new avenues for interventions, such as stem cell therapy or agents that could retard this aging process over and beyond conventional risk factor control., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: Shorter leukocyte telomere length (LTL) is associated with higher incidence of coronary heart disease (CHD) and increased mortality. We examined the association of LTL with coronary artery calcification (CAC), which reflects the cumulative burden of coronary atherosclerosis, in an urban Arab sample of Palestinians, a population at high risk of CHD., Methods: Using a cross-sectional design, a random sample of East Jerusalem residents, comprising 250 men aged 45-77 and women aged 55-76 and free of CHD or past stroke, was drawn from the Israel national population register. LTL was measured by Southern blots. CAC was determined by 16-slice multidetector helical CT scanning using Agatston scoring. We applied multivariable logistic modeling to examine the association between sex-specific tertiles of LTL and CAC (comparing scores >100 vs. <100, and the upper third vs. the lower 2 thirds), controlling for age, sex, education and coronary risk factors., Results: CAC, evident in 65% of men and 52% of women, was strongly associated with age (sex-adjusted Spearman's rho 0.495). The multivariable-adjusted odds ratios for CAC >100 (found in 30% of men and 29% of women) were 2.92 (95% CI 1.28-6.68) and 2.29 (0.99-5.30) for the lower and mid-tertiles of LTL vs. the upper tertile, respectively (Ptrend = 0.008). Findings were similar for CAC scores in the upper tertile (Ptrend = 0.006), and persisted after the exclusion of patients with diabetes or receiving statins., Conclusions: Shorter LTL was associated with a greater prevalence of asymptomatic coronary atherosclerosis in an urban Arab population-based sample. Mechanisms underlying this association should be sought., (Copyright © 2013 [Author/Employing Institution]. Published by Elsevier Ireland Ltd.. All rights reserved.)