Search

Lung cancer (LC) constitutes an important cause of death among patients with Chronic Obstructive Pulmonary Disease (COPD). Both diseases may share pathobiological mechanisms related to oxidative damage and cellular senescence. In this study, the potential value of leucocyte telomere length, a hallmark of aging, and 8-OHdG concentrations, indicative of oxidative DNA damage, as risk biomarkers of LC was evaluated in COPD patients three years prior to LC diagnosis. Relative telomere length measured using qPCR and serum levels of 8-OHdG were determined at the baseline in 99 COPD smokers (33 with LC and 66 age-matched COPD without LC as controls). Of these, 21 COPD with LC and 42 controls had the biomarkers measured 3 years before. Single nucleotide variants (SNVs) in TERT, RTEL, and NAF1 genes were also determined. COPD cases were evaluated, which showed greater telomere length (p < 0.001) and increased serum 8-OHdG levels (p = 0.004) three years prior to LC diagnosis compared to the controls. This relationship was confirmed at the time of LC diagnosis. No significant association was found between the studied SNVs in cases vs. controls. In conclusion, this preliminary study shows that longer leucocyte telomere length and increased 8-OHdG serum levels can be useful as early biomarkers of the risk for future lung cancer development among COPD patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Short repeated sequences of DNA at the end of chromosomes are called telomeres; these help to maintain the chromosome structure. During normal cell replication, some of the sequences are lost; therefore, the length of telomeres may be associated with the aging of the overall animal. Longevity in livestock is difficult to measure and improve; however, telomere dynamics may represent an opportunity to monitor or influence longevity. Beginning in the 1990s, livestock clones were studied with respect to the change in telomeres because cloned DNA was often from a mature animal and, therefore, might have shorter telomeres associated with age. However, results differed by the species and cell type used to produce the clones. Telomere dynamics have been best characterized in dairy cows, pigs, and horses. In general, older animals have shorter telomeres, and stress imposed upon animals results in shorter telomeres; however, exceptions have been observed to both generalities. Attrition and other telomeric characteristics have been less well described in beef cattle, goats, and sheep. Longevity is measured uniquely and differs for species and production systems within the same species; therefore, it is appropriate to encourage the telomere-longevity correspondence in each. Telomeres are repeated sequences of nucleotides at the end of chromosomes. They deteriorate across mitotic divisions of a cell. In Homo sapiens this process of lifetime reduction has been shown to correspond with aspects of organismal aging and exposure to stress or other insults. The early impetus to characterize telomere dynamics in livestock related to the concern that aged donor DNA would result in earlier cell senescence and overall aging in cloned animals. Telomere length investigations in dairy cows included breed effects, estimates of additive genetic control (heritability 0.12 to 0.46), and effects of external stressors on telomere degradation across animal life. Evaluation of telomeres with respect to aging has also been conducted in pigs and horses, and there are fewer reports of telomere biology in beef cattle, sheep, and goats. There were minimal associations of telomere length with animal productivity measures. Most, but not all, work in livestock has documented an inverse relationship between peripheral blood cell telomere length and age; that is, a longer telomere length was associated with younger age. Because livestock longevity affects productivity and profitability, the role of tissue-specific telomere attrition in aging may present alternative improvement strategies for genetic improvement while also providing translational biomedical knowledge. [ABSTRACT FROM AUTHOR]

Although previous studies have suggested a relationship between telomere shortening and systemic sclerosis (SSc), the association between these two traits remains poorly understood. The objective of this study was to assess the causal relationship between telomere length in leukocytes (LTL) and SSc using the two-sample Mendelian randomization approach, with the genome-wide association study data for both LTL and SSc. The results of inverse-variance weighted regression (OR = 0.716 [95% CI 0.528–0.970], p = 0.031) and the Mendelian randomization pleiotropy residual sum and outlier method (OR = 0.716 [95% CI 0.563–0.911], p = 0.035) indicate an association between telomere length and SSc. Specifically, longer genetically predicted LTL is associated with a reduced risk of SSc. Sensitivity tests highlight the significant roles of the variants rs10936599 and rs2736100 annotated to the TERC and TERT genes, respectively. Our findings suggest an influence of telomere length in leukocytes on the development of SSc. [ABSTRACT FROM AUTHOR]

Biological aging is a relevant risk factor for chronic diseases, and several indicators for measuring this factor have been proposed, with telomere length (TL) among the most studied. Oxidative stress may regulate telomere shortening, which is implicated in the increased risk. Using a novel estimator for TL, we examined whether adherence to the Mediterranean diet (MedDiet), a highly antioxidant-rich dietary pattern, is associated with longer TL. We determined TL using DNA methylation algorithms (DNAmTL) in 414 subjects at high cardiovascular risk from Spain. Adherence to the MedDiet was assessed by a validated score, and genetic variants in candidate genes and at the genome-wide level were analyzed. We observed several significant associations (p < 0.05) between DNAmTL and candidate genes (TERT, TERF2, RTEL1, and DCAF4), contributing to the validity of DNAmTL as a biomarker in this population. Higher adherence to the MedDiet was associated with lower odds of having a shorter TL in the whole sample (OR = 0.93; 95% CI: 0.85–0.99; p = 0.049 after fully multivariate adjustment). Nevertheless, this association was stronger in women than in men. Likewise, in women, we observed a direct association between adherence to the MedDiet score and DNAmTL as a continuous variable (beta = 0.015; SE: 0.005; p = 0.003), indicating that a one-point increase in adherence was related to an average increase of 0.015 ± 0.005 kb in TL. Upon examination of specific dietary items within the global score, we found that fruits, fish, "sofrito", and whole grains exhibited the strongest associations in women. The novel score combining these items was significantly associated in the whole population. In the genome-wide association study (GWAS), we identified ten polymorphisms at the suggestive level of significance (p < 1 × 10−5) for DNAmTL (intergenics, in the IQSEC1, NCAPG2, and ABI3BP genes) and detected some gene–MedDiet modulations on DNAmTL. As this is the first study analyzing the DNAmTL estimator, genetics, and modulation by the MedDiet, more studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Emerging evidence has shown that leukocyte telomere length (LTL) is associated with various health‐related outcomes, while the causality of these associations remains unclear. We performed a systematic review and meta‐analysis of current evidence from Mendelian randomization (MR) studies on the association between LTL and health‐related outcomes. We searched PubMed, Embase, and Web of Science up to April 2022 to identify eligible MR studies. We graded the evidence level of each MR association based on the results of the main analysis and four sensitive MR methods, MR‐Egger, weighted median, MR‐PRESSO, and multivariate MR. Meta‐analyses of published MR studies were also performed. A total of 62 studies with 310 outcomes and 396 MR associations were included. Robust evidence level was observed for the association between longer LTL and increased risk of 24 neoplasms (the strongest magnitude for osteosarcoma, GBM, glioma, thyroid cancer, and non‐GBM glioma), six genitourinary and digestive system outcomes of excessive or abnormal growth, hypertension, metabolic syndrome, multiple sclerosis, and clonal hematopoiesis of indeterminate potential. Robust inverse association was observed for coronary heart disease, chronic kidney disease, rheumatoid arthritis, juvenile idiopathic arthritis, idiopathic pulmonary fibrosis, and facial aging. Meta‐analyses of MR studies suggested that genetically determined LTL was associated with 12 neoplasms and 9 nonneoplasm outcomes. Evidence from published MR studies supports that LTL plays a causal role in various neoplastic and nonneoplastic diseases. Further research is required to elucidate the underlying mechanisms and to bring insight into the potential prediction, prevention, and therapeutic applications of telomere length. [ABSTRACT FROM AUTHOR]

Age is a major risk factor for neurodegenerative diseases. Shortening of leucocyte telomeres with advancing age, arguably a measure of "biological" age, is a known phenomenon and epidemiologically correlated with age‐related disease. The main mechanism of telomere shortening is cell division, rendering telomere length in post‐mitotic cells presumably stable. Longitudinal measurement of human brain telomere length is not feasible, and cross‐sectional cortical brain samples so far indicated no attrition with age. Hence, age‐related changes in telomere length in the brain and the association between telomere length and neurodegenerative diseases remain unknown. Here, we demonstrate that mean telomere length in the putamen, a part of the basal ganglia, physiologically shortens with age, like leukocyte telomeres. This was achieved by using matched brain and leukocyte‐rich spleen samples from 98 post‐mortem healthy human donors. Using spleen telomeres as a reference, we further found that mean telomere length was brain region‐specific, as telomeres in the putamen were significantly shorter than in the cerebellum. Expression analyses of genes involved in telomere length regulation and oxidative phosphorylation revealed that both region‐ and age‐dependent expression pattern corresponded with region‐dependent telomere length dynamics. Collectively, our results indicate that mean telomere length in the human putamen physiologically shortens with advancing age and that both local and temporal gene expression dynamics correlate with this, pointing at a potential mechanism for the selective, age‐related vulnerability of the nigro‐striatal network. [ABSTRACT FROM AUTHOR]

Shorter telomeres mark cellular aging and are linked to chronic stress exposure as well as negative physical and psychological outcomes. However, it is unclear whether telomere length mediates associations between early stress exposure and later externalizing problems, or whether boys and girls differ in pathways to these concerns. We therefore examined associations between telomere length, early stress via negative caregiving, and children's externalizing symptom development over time in 409 three-year-old children and their parents. Telomere length mediated the association between early parental intrusiveness and later rule-breaking behavior; however, this association was moderated by children's biological sex such that parent intrusiveness was related only to boys' rule-breaking. Findings support the notion that children's telomere length may mark individual differences in responses to negative early caregiving, and highlight a potential mechanism contributing to the development of rule-breaking problems in boys. [ABSTRACT FROM AUTHOR]

The prevalence of diabetes is increasing globally, and this trend is predicted to continue for future decades. Research is needed to uncover new ways to manage diabetes and its co-morbidities. A significant secondary complication of diabetes is kidney disease, which can ultimately result in the need for renal replacement therapy, via dialysis or transplantation. Diabetic kidney disease presents a substantial burden to patients, their families and global healthcare services. This review highlights studies that have harnessed genomic, epigenomic and functional prediction tools to uncover novel genes and pathways associated with DKD that are useful for the identification of therapeutic targets or novel biomarkers for risk stratification. Telomere length regulation is a specific pathway gaining attention recently because of its association with DKD. Researchers are employing both observational and genetics-based studies to identify telomere-related genes associated with kidney function decline in diabetes. Studies have also uncovered novel functions for telomere-related genes beyond the immediate regulation of telomere length, such as transcriptional regulation and inflammation. This review summarises studies that have revealed the potential to harness therapeutics that modulate telomere length, or the associated epigenetic modifications, for the treatment of DKD, to potentially slow renal function decline and reduce the global burden of this disease. [ABSTRACT FROM AUTHOR]

Telomeres are dynamic DNA nucleoprotein structures located at the end of chromosomes where they maintain genomic stability. Due to the end replication problem, telomeres shorten with each cell division. Critically short telomeres trigger cellular senescence, which contributes to various degenerative and age-related diseases, including chronic kidney diseases (CKDs). Additionally, other factors such as oxidative stress may also contribute to accelerated telomere shortening. Indeed, telomeres are highly susceptible to oxidative damage due to their high guanine content. Here, we provide a comprehensive review of studies examining telomere length (TL) in CKDs to highlight the association between TL and the development and progression of CKDs in humans. We then focus on studies investigating TL in patients receiving kidney replacement therapy. The mechanisms of the relationship between TL and CKD are not fully understood, but a shorter TL has been associated with decreased kidney function and the progression of nephropathy. Interestingly, telomere lengthening has been observed in some patients in longitudinal studies. Hemodialysis has been shown to accelerate telomere erosion, whereas the uremic milieu is not reversed even in kidney transplantation patients. Overall, this review aims to provide insights into the biological significance of telomere attrition in the pathophysiology of kidney disease, which may contribute to the development of new strategies for the management of patients with CKDs. [ABSTRACT FROM AUTHOR]

Early‐life telomere length (TL) is associated with fitness in a range of organisms. Little is known about the genetic basis of variation in TL in wild animal populations, but to understand the evolutionary and ecological significance of TL it is important to quantify the relative importance of genetic and environmental variation in TL. In this study, we measured TL in 2746 house sparrow nestlings sampled across 20 years and used an animal model to show that there is a small heritable component of early‐life TL (h2 = 0.04). Variation in TL among individuals was mainly driven by environmental (annual) variance, but also brood and parental effects. Parent‐offspring regressions showed a large maternal inheritance component in TL (hmaternal2 = 0.44), but no paternal inheritance. We did not find evidence for a negative genetic correlation underlying the observed negative phenotypic correlation between TL and structural body size. Thus, TL may evolve independently of body size and the negative phenotypic correlation is likely to be caused by nongenetic environmental effects. We further used genome‐wide association analysis to identify genomic regions associated with TL variation. We identified several putative genes underlying TL variation; these have been inferred to be involved in oxidative stress, cellular growth, skeletal development, cell differentiation and tumorigenesis in other species. Together, our results show that TL has a low heritability and is a polygenic trait strongly affected by environmental conditions in a free‐living bird. [ABSTRACT FROM AUTHOR]

Telomere length and telomere shortening predict survival in many organisms. This raises the question of the contribution of genetic and environmental effects to variation in these traits, which is still poorly known, particularly for telomere shortening. We used experimental (cross‐fostering) and statistical (quantitative genetic "animal models") means to disentangle and estimate genetic and environmental contributions to telomere length variation in pedigreed free‐living jackdaws (Corvus monedula). Telomere length was measured twice in nestlings, at ages 4 (n = 715) and 29 days (n = 474), using telomere restriction fragment (TRF) analysis, adapted to exclude interstitial telomeric sequences. Telomere length shortened significantly over the nestling period (10.4 ± 0.3 bp day–1) and was highly phenotypically (rP = 0.95 ± 0.01) and genetically (rG > 0.99 ± 0.01) correlated within individuals. Additive genetic effects explained a major part of telomere length variation among individuals, with its heritability estimated at h2 = 0.74 on average. We note that TRF‐based studies reported higher heritabilities than qPCR‐based studies, and we discuss possible explanations. Parent–offspring regressions yielded similar heritability estimates for mothers and fathers when accounting for changes in paternal telomere length over life. Year effects explained a small but significant part of telomere length variation. Heritable variation for telomere shortening was low (h2 = 0.09 ± 0.11). The difference in heritability between telomere length (high) and telomere shortening (low) agrees with evolutionary theory, in that telomere shortening has stronger fitness consequences in this population. Despite the high heritability of telomere length, its evolvability, which scales the additive genetic variance by mean telomere length, was on average 0.48%. Hence, evolutionary change of telomere length due to selection is likely to be slow. [ABSTRACT FROM AUTHOR]

Over 20% of all living mammals are bats (order Chiroptera). Bats possess extraordinary adaptations including powered flight, laryngeal echolocation and a unique immune system that enables them to tolerate a diversity of viral infections without presenting clinical disease symptoms. They occupy multiple trophic niches and environments globally. Significant physiological and ecological diversity occurs across the order. Bats also exhibit extreme longevity given their body size with many species showing few signs of ageing. The molecular basis of this extended longevity has recently attracted attention. Telomere maintenance potentially underpins bats' extended healthspan, although functional studies are still required to validate the causative mechanisms. In this review, we detail the current knowledge on bat telomeres, telomerase expression, and how these relate to ecology, longevity and life‐history strategies. Patterns of telomere shortening and telomerase expression vary across species, and comparative genomic analyses suggest that alternative telomere maintenance mechanisms evolved in the longest‐lived bats. We discuss the unique challenges faced when working with populations of wild bats and highlight ways to advance the field including expanding long‐term monitoring across species that display contrasting life‐histories and occupy different environmental niches. We further review how new high quality, chromosome‐level genome assemblies can enable us to uncover the molecular mechanisms governing telomere dynamics and how phylogenomic analyses can reveal the adaptive significance of telomere maintenance and variation in bats. [ABSTRACT FROM AUTHOR]

Introduction: Telomeres are specialized DNA-protein complexes located at the ends of all chromosomes and act as a "molecular clock" to determine the replicative lifespan of the cells. Recent studies indicate that life-long exposure to stress, starting from the prenatal period, causes many diseases to emerge at an early age, and telomeres may be possible mediators in this process. This article aims to review the relationship between the stress-telomere-disease triad and the potential role of telomere dysfunction in psychopathologies in the light of current literature. Methods: A literature search was conducted along the lines of a narrative review. PubMed and Web of Science databases were used to identify all types of articles published from inception to January 2022. After the title/ abstract search, articles available in full text and English were selected based on key findings, the applicability of the method used to test the hypothesis, limitations, interpretation of the results, and impact of the results in the field. A total of 73 records were included in this narrative review. Results: The fact that some age-related chronic diseases, such as cardiovascular diseases and type 2 diabetes, are seen more frequently and at an earlier age in certain psychopathologies including depression, bipolar disorder, and schizophrenia suggests that these disorders are premature ageing syndromes. Although there are some conflicting results in the literature, in line with this hypothesis, the presence of shortened telomeres reported in these psychopathologies and the impact of lifelong exposure to stress on this process are remarkable. Conclusion: Many of the studies point to an association and do not tell much about the causality. Hence, the elucidation of the biological processes underlying the relationship between psychological stress, dysfunctional telomeres and complex, common age-related diseases, as well as psychiatric disorders is important and further studies are needed at the cellular level. [ABSTRACT FROM AUTHOR]

Background: Type 1 diabetes is associated with accelerated vascular aging and advanced atherosclerosis resulting in increased rates of cardiovascular disease and premature death. We evaluated associations between Leukocyte telomere length (LTL), allelic variations (SNPs) in LTL-related genes and the incidence of coronary heart disease (CHD) in adults with long-standing type 1 diabetes. Methods: We assessed associations of LTL, measured at baseline by RT–PCR, and of SNPs in 11 LTL-related genes with the risk of coronary heart disease (CHD: myocardial infarction or coronary revascularization) and all-cause death during follow-up in two multicenter French-Belgian prospective cohorts of people with long-standing type 1 diabetes. Results: In logistic and Cox analyses, the lowest tertile of LTL distribution (short telomeres) at baseline was associated with the prevalence of myocardial infarction at baseline and with increased risk of CHD (Hazard ratio 3.14 (1.39–7.70), p = 0.005, for shorter vs longer tertile of LTL) and all-cause death (Hazard ratio 1.63 (95% CI 1.04–2.55), p = 0.03, for shorter vs combined intermediate and longer tertiles of LTL) during follow-up. Allelic variations in six genes related to telomere biology (TERC, NAF1, TERT, TNKS, MEN1 and BICD1) were also associated with the incidence of CHD during follow-up. The associations were independent of sex, age, duration of diabetes, and a range of relevant confounding factors at baseline. Conclusions: Our results suggest that short LTL is an independent risk factor for CHD in people with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Purpose: The study aimed to investigate the effect of metformin treatment on leukocyte telomere length (LTL) and the relationship of LTL with C-reactive protein (CRP), homocysteine, albumin, complete blood count, and HOMA-IR values in patients with polycystic ovary syndrome (PCOS). Material and method: A prospective case–control study consisting of 30 women with PCOS and 30 healthy women without PCOS was performed. The relationship between clinical and laboratory parameters and LTL was analyzed. PCOS patients were treated with metformin (850 mg/day) for three months. Before treatment (BT) and after treatment (AT), each patient's LTL was evaluated and compared with the control group. Results: In the comparison between PCOS and control groups, the difference was significant for LTL, age, body mass index (BMI), and CRP (p = 0.002; p < 0.001; p = 0.001; p = 0.01, respectively). In PCOS patients, the difference between BT and AT, LTL was not statistically significant (BT: 6.06 ± 2.12; AT: 6.30 ± 1.93; p = 0.623; 95% C.I: − 1.22–0.74); however, the difference for weight was significant (BT: 83.78 ± 15.31; AT: 80.62 ± 15.40; p = 0.02; 95% CI: 1.34–4.99). The logistic regression model established by BMI (group 1: 21–24, group 2: 24–29, group 3: 29–34, group 4: > 34), age, and RDW, which predicted the PCOS group by affecting the LTL level, was statistically significant (p < 0.001/PPV = 96.3%; NPV = 88.5%). Each unit reduction in telomere length increased women's probability of PCOS by 0.4 times (p = 0.013; OR = 0.419, 95% CI: 0.211–0.835). Conclusion: Although statistically insignificant, LTL increased after metformin use in PCOS patients, and the mean weight loss reduction was statistically significant. Telomere shortening increased the likelihood of PCOS 0.4 times. [ABSTRACT FROM AUTHOR]

Much research on children in high-risk environments has focused on the biological consequences of maltreatment, adversity, and trauma. Whether other early-life stress sources such as family financial hardship are implicated in the cellular mechanism of disease development remains unclear. This study investigated the long-term effect of childhood exposure to family financial pressure on telomere length. It involved two waves of data collection occurring when participants reached Grade 3 (W1) and 7 (W2), respectively. In W1, parents reported family demographics and perceived financial stressors and pressure. In W2, participants provided buccal swab samples for measurement of their telomere length. Data from 92 participants (Mage in W2 = 13.2 years; 56.5% male) were analyzed. The main type of stressors reported by parents who perceived high family financial pressure in W1 were child-level stressors including affordability of their medical and educational expenses. Participants exposed to high parent-perceived family financial pressure in W1 had shorter telomeres in W2 when compared to those exposed to low parent-perceived family financial pressure (β = −0.61, p = 0.042). Subgroup analyses revealed stronger associations in girls than boys. These findings reveal an important spillover effect between parental financial perceptions and stress and children's health at the cellular level. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is one of the most prevalent and debilitating psychiatric disorders, with a large number of patients not showing an effective therapeutic response to available treatments. Several biopsychosocial factors, such as stress in childhood and throughout life, and factors related to biological aging, may increase the susceptibility to MDD development. Included in critical biological processes related to aging and underlying biological mechanisms associated with MDD is the shortening of telomeres and changes in telomerase activity. This comprehensive review discusses studies that assessed the length of telomeres or telomerase activity and function in peripheral blood cells and brain tissues of MDD individuals. Also, results from in vitro protocols and animal models of stress and depressive-like behaviors were included. We also expand our discussion to include the role of telomere biology as it relates to other relevant biological mechanisms, such as the hypothalamic-pituitary-adrenal (HPA) axis, oxidative stress, inflammation, genetics, and epigenetic changes. In the text and the discussion, conflicting results in the literature were observed, especially considering the size of telomeres in the central nervous system, on which there are different protocols with divergent results in the literature. Finally, the context of this review is considering cell signaling, transcription factors, and neurotransmission, which are involved in MDD and can be underlying to senescence, telomere shortening, and telomerase functions. [ABSTRACT FROM AUTHOR]

Summary: Telomere length has been implicated in the organismal response to stress, but the underlying mechanisms are unknown.Here we examine the impact of telomere length changes on the responses to three contrasting abiotic environments in Arabidopsis, and measure 32 fitness, developmental, physiological and leaf‐level anatomical traits.We report that telomere length in wild‐type and short‐telomere mutants is resistant to abiotic stress, while the elongated telomeres in ku70 mutants are more plastic. We detected significant pleiotropic effects of telomere length on flowering time and key leaf physiological and anatomical traits. Furthermore, our data reveal a significant genotype by environment (G × E) interaction for reproductive fitness, with the benefits and costs to performance depending on the growth conditions.These results imply that life‐history trade‐offs between flowering time and reproductive fitness are impacted by telomere length variation. We postulate that telomere length in plants is subject to natural selection imposed by different environments. [ABSTRACT FROM AUTHOR]

Background: Telomere length (TL) and its attrition are important indicators of physiological stress and biological aging and hence may vary among individuals of the same age. This variation is apparent even in newborns, suggesting potential effects of parental factors and the intrauterine environment on TL of the growing fetus.Methods: Average relative TLs of newborns (cord tissue, N = 950) and mothers (buffy coat collected at 26-28 weeks of gestation, N = 892) were measured in a birth cohort. This study provides a comprehensive analysis of the effects of heritable factors, socioeconomic status, and in utero exposures linked with maternal nutrition, cardiometabolic health, and mental well-being on the newborn TL. The association between maternal TL and antenatal maternal health was also studied.Results: Longer maternal TL (β = 0.14, P = 1.99E-05) and higher paternal age (β = 0.10, P = 3.73E-03) were positively associated with newborn TL. Genome-wide association studies on newborn and maternal TLs identified 6 genetic variants in a strong linkage disequilibrium on chromosome 3q26.2 (Tag SNP-LRRC34-rs10936600: Pmeta = 5.95E-08). Mothers with higher anxiety scores, elevated fasting blood glucose, lower plasma insulin-like growth factor-binding protein 3 and vitamin B12 levels, and active smoking status during pregnancy showed a higher risk of giving birth to offspring with shorter TL. There were sex-related differences in the factors explaining newborn TL variation. Variation in female newborn TL was best explained by maternal TL, mental health, and plasma vitamin B12 levels, while that in male newborn TL was best explained by paternal age, maternal education, and metabolic health. Mother's TL was associated with her own metabolic health and nutrient status, which may have transgenerational effects on offspring TL.Conclusions: Our findings provide a comprehensive understanding of the heritable and environmental factors and their relative contributions to the initial setting of TL and programing of longevity in early life. This study provides valuable insights for preventing in utero telomere attrition by improving the antenatal health of mothers via targeting the modifiable factors.Trial Registration: ClinicalTrials.gov , NCT01174875. Registered on 1 July 2010. [ABSTRACT FROM AUTHOR]

Background and Objectives: Telomeric zinc finger-associated protein (TZAP) is a telomere regulation protein, previously known as ZBTB48. It binds preferentially to elongated telomeres, competing with telomeric repeat factors 1 and 2. TZAP expression may be associated with carcinogenesis, however; this study has not yet been performed in lung cancer. In this study, we examined the clinicopathological and prognostic values of TZAP expression in non-small cell lung cancer (NSCLC). Materials and Methods: Data were collected from The Cancer Genome Atlas. The clinical and prognostic values of TZAP for NSCLC were examined in adenocarcinoma (AD) and squamous cell carcinoma (SCC). Results: TZAP expression significantly increased in NSCLC tissues compared with normal tissues. In AD, TZAP expression was lower in patients with higher T stage (p = 0.005), and was associated with lymph node stage in SCC (p = 0.005). Survival analysis showed shorter disease-free survival in AD patients with lower TZAP expression (p = 0.047). TZAP expression did not have other clinical or prognostic value for AD and SCC. Conclusions: TZAP expression is a potential prognostic marker for NSCLC, especially in patients with AD. [ABSTRACT FROM AUTHOR]

Observational studies have revealed associations between short leucocyte telomere length (LTL), a TL marker in somatic tissues and multiple Metabolic Syndrome (MetS) traits. Animal studies have supported these findings by showing that increased telomere attrition leads to adipose tissue dysfunction and insulin resistance. We investigated the associations between genetically instrumented LTL and MetS traits using Mendelian Randomisation (MR). Fifty‐two independent variants identified at FDR<0.05 from a genome‐wide association study (GWAS) including 78,592 Europeans and collectively accounting for 2.93% of LTL variance were selected as genetic instruments for LTL. Summary‐level data for MetS traits and for the MetS as a binary phenotype were obtained from the largest publicly available GWAS and two‐sample MR analyses were used to estimate the associations of LTL with these traits. The combined effect of the genetic instruments was modelled using inverse variance weighted regression and sensitivity analyses with MR‐Egger, weighted‐median and MR‐PRESSO were performed to test for and correct horizonal pleiotropy. Genetically instrumented longer LTL was associated with higher waist‐to‐hip ratio adjusted for body mass index (β = 0.045 SD, SE = 0.018, p = 0.01), raised systolic (β = 1.529 mmHg, SE = 0.332, p = 4x10−6) and diastolic (β = 0.633 mmHg, SE = 0.222, p = 0.004) blood pressure, and increased MetS risk (OR = 1.133, 95% CI 1.057–1.215). Consistent results were obtained in sensitivity analyses, which provided no evidence of unbalanced horizontal pleiotropy. Telomere shortening might not be a major driver of cellular senescence and dysfunction in human adipose tissue. Future experimental studies should examine the mechanistic bases for the links between longer LTL and increased upper‐body fat distribution and raised blood pressure. [ABSTRACT FROM AUTHOR]

Background: Shorter leukocyte telomere length (LTL) is associated with aging and dementia. Impact of lifestyle changes on LTL, and relation to cognition and genetic susceptibility for dementia, has not been investigated in randomized controlled trials (RCTs).Methods: Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability is a 2-year RCT enrolling 1260 participants at risk for dementia from the general population, aged 60-77 years, randomly assigned (1:1) to multidomain lifestyle intervention or control group. The primary outcome was cognitive change (Neuropsychological Test Battery z-score). Relative LTL was measured using quantitative real-time polymerase chain reaction (trial registration: NCT01041989).Results: This exploratory LTL substudy included 756 participants (377 intervention, 379 control) with baseline and 24-month LTL measurements. The mean annual LTL change (SD) was -0.016 (0.19) in the intervention group and -0.023 (0.17) in the control group. Between-group difference was nonsignificant (unstandardized β-coefficient 0.007, 95% CI -0.015 to 0.030). Interaction analyses indicated better LTL maintenance among apolipoprotein E (APOE)-ε4 carriers versus noncarriers: 0.054 (95% CI 0.007 to 0.102); younger versus older participants: -0.005 (95% CI -0.010 to -0.001); and those with more versus less healthy lifestyle changes: 0.047 (95% CI 0.005 to 0.089). Cognitive intervention benefits were more pronounced among participants with better LTL maintenance for executive functioning (0.227, 95% CI 0.057 to 0.396) and long-term memory (0.257, 95% CI 0.024 to 0.489), with a similar trend for Neuropsychological Test Battery total score (0.127, 95% CI -0.011 to 0.264).Conclusions: This is the first large RCT showing that a multidomain lifestyle intervention facilitated LTL maintenance among subgroups of older people at risk for dementia, including APOE-ε4 carriers. LTL maintenance was associated with more pronounced cognitive intervention benefits.Clinical Trials Registration Number: NCT01041989. [ABSTRACT FROM AUTHOR]

Background: Internalizing mental disorders (IMDs) (depression, anxiety and post-traumatic stress disorder) have been associated with accelerated telomere length (TL) attrition; however, this association has not been investigated in the context of genetic variation that has been found to influence TL. We have previously reported an association between IMDs and accelerated TL attrition among Ugandan HIV+ children and adolescents. This study investigated the moderating effects of selected single nucleotide polymorphisms in the telomerase reverse transcriptase gene (TERT) (rs2736100, rs7726159, rs10069690 and rs2853669) and the telomerase RNA component gene (TERC) (rs12696304, rs16847897 and rs10936599) on the association between IMDs and TL, among Ugandan HIV+ children (aged 5–11 years) and adolescents (aged 12–17 years). Results: We found no significant interaction between IMDs as a group and any of the selected SNPs on TL at baseline. We observed significant interactions of IMDs with TERT rs2736100 (p = 0.007) and TERC rs16847897 (p = 0.012), respectively, on TL at 12 months. Conclusions: TERT rs2736100 and TERC rs16847897 moderate the association between IMDs and TL among Ugandan HIV+ children and adolescents at 12 months. Understanding the nature of this association may shed light on the pathophysiological mechanisms underlying advanced cellular aging in IMDs. [ABSTRACT FROM AUTHOR]

Background: Survival rates for breast cancer (BC) have improved, but quality of life post-diagnosis/treatment can be adversely affected, with survivors reporting a constellation of psychoneurological symptoms (PNS) including stress, anxiety, depression, pain, fatigue, sleep disturbance, and cognitive dysfunction.Methods: To assess a potential relationship between telomere length (TL) and the development/persistence of PNS, we longitudinally studied 70 women (ages 23-71) with early stage BC (I-IIIA) at 5 time-points: prior to treatment (baseline), the mid-point of their chemotherapy cycle, 6 months, 1 year, and 2 years following the initiation of chemotherapy. Measures quantified included assessments of each of the PNS noted above and TL [using both a multiplex qPCR assay and a chromosome-specific fluorescence in situ hybridization (FISH) assay].Results: Variables associated with qPCR mean TLs were age (p = 0.004) and race (T/S ratios higher in Blacks than Whites; p = 0.019). Significant differences (mostly decreases) in chromosome-specific TLs were identified for 32 of the 46 chromosomal arms at the mid-chemo time-point (p = 0.004 to 0.049). Unexpectedly, the sequential administration of doxorubicin [Adriamycin], cyclophosphamide [Cytoxan], and docetaxel [Taxotere] (TAC regimen) was consistently associated with higher TLs, when compared to TLs in women receiving a docetaxel [Taxotere], Carboplatin [Paraplatin], and trastuzumab [Herceptin] [TCH] chemotherapy regimen [association was shown with both the qPCR and FISH assays (p = 0.036)]. Of the PNS, pain was significantly negatively associated with TL (higher pain; shorter telomeres) for a subset of chromosomal arms (5q, 8p, 13p, 20p, 22p, Xp, Xq) (p = 0.014-0.047). Chromosomal TLs were also associated with 7 of the 8 cognitive domains evaluated, with the strongest relationship being noted for chromosome 17 and the visual memory domain (shorter telomeres; lower scores).Conclusions: We showed that race and age were significantly associated with telomere length in women treated for early stage BC and that acquired telomere alterations differed based on the woman's treatment regimen. Our study also demonstrated that pain and cognitive domain measures were significantly related to telomere values in this study cohort. Expanding upon the knowledge gained from this longitudinal study could provide insight about the biological cascade of events that contribute to PNS related to BC and/or its treatment. [ABSTRACT FROM AUTHOR]

Critically short telomeres indicate cellular senescence. Leukocyte telomere length (LTL) is regarded as an aging predictor. Osteoporosis is an age-related disease. The purpose of our study is to examine the association between LTL, and BMD and osteoporosis among an elderly Chinese population. A total of 1017 participants (584 postmenopausal women) with a mean age of 66.4 years were recruited from April 2016 to August 2017. Dual-energy X-ray absorptiometry was used for BMD measurement at skeleton sites of lumbar spine (LS), femoral neck (FN), and total hip (TH). LTL was measured using quantitative real-time polymerase chain reaction. Among women, age significantly modified the effect of LTL on BMD at FN. Additionally, significant age modification was observed for the association between LTL and LS BMD category (indicative of control or osteopenia or osteoporosis), and the number of osteoporotic sites at LS or TH. The corresponding estimates (95% CI) for the relative excess risk due to interaction (RERI) were - 0.07 (- 0.11, - 0.01) and - 0.11 (- 0.16, - 0.03) sequentially in ordinal logistic regression models. The estimated RERIs (95% CI) were - 0.11 (- 0.25, - 0.02) and - 0.23 (- 0.39, - 0.10) in multinomial logistic regression models for LS/FN/TH BMD category, and - 0.20 (- 0.31, - 0.09) and - 0.34 (- 0.49, - 0.21) for FN BMD category. However, similar findings did not show in men. The effect of LTL on BMD and osteoporosis risk is modified by age in elderly women but not in men, suggesting that the predictive role of LTL in bone loss differs by sex. [ABSTRACT FROM AUTHOR]

Major psychiatric disorders are linked to early mortality and patients afflicted with these ailments demonstrate an increased risk of developing physical diseases that are characteristically seen in the elderly. Psychiatric conditions like major depressive disorder, bipolar disorder and schizophrenia may be associated with accelerated cellular aging, indicated by shortened leukocyte telomere length (LTL), which could underlie this connection. Telomere shortening occurs with repeated cell division and is reflective of a cell’s mitotic history. It is also influenced by cumulative exposure to inflammation and oxidative stress as well as the availability of telomerase, the telomere-lengthening enzyme. Precariously short telomeres can cause cells to undergo senescence, apoptosis or genomic instability; shorter LTL correlates with compromised general health and foretells mortality. Important data specify that LTL may be reduced in principal psychiatric illnesses, possibly in proportion to exposure to the ailment. Telomerase, as measured in peripheral blood monocytes, has been less well characterized in psychiatric illnesses, but a role in mood disorder has been suggested by preclinical and clinical studies. In this manuscript, the most recent studies on LTL and telomerase activity in mood disorders are comprehensively reviewed, potential mediators are discussed, and future directions are suggested. An enhanced comprehension of cellular aging in psychiatric illnesses could lead to their re-conceptualizing as systemic ailments with manifestations both inside and outside the brain. At the same time this paradigm shift could identify new treatment targets, helpful in bringing about lasting cures to innumerable sufferers across the globe. [ABSTRACT FROM AUTHOR]

Background: Although shorter telomeres have been associated with Alzheimer's disease (AD), it is unclear whether longitudinal change in telomere length is associated with AD progression.Objective: To investigate the association of telomere length change with AD diagnosis and progression.Methods: In 653 individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, T/S ratio (telomere versus single copy gene), a proxy of telomere length, was measured for up to five visits per participant (N = 1918 samples post-QC) using quantitative PCR (qPCR). T/S ratio was adjusted for batch effects and DNA storage time. A mixed effects model was used to evaluate association of telomere length with AD diagnostic group and interaction of age and diagnosis. Another mixed effects model was used to compare T/S ratio changes pre- to post-conversion to MCI or AD to telomere change in participants with stable diagnoses.Results: Shorter telomeres were associated with older age (Effect Size (ES) = -0.23) and male sex (ES = -0.26). Neither baseline T/S ratio (ES = -0.036) nor T/S ratio change (ES = 0.046) differed significantly between AD diagnostic groups. MCI/AD converters showed greater, but non-significant, telomere shortening compared to non-converters (ES = -0.186).Conclusions: Although AD compared to controls showed small, non-significant effects for baseline T/S ratio and T/S ratio shortening, we did observe a larger, though still non-significant effect for greater telomere shortening in converters compared to non-converters. Although our results do not support telomere shortening as a robust biomarker of AD progression, further investigation in larger samples and for subgroups of participants may be informative. [ABSTRACT FROM AUTHOR]

Background: Adverse childhood experiences (ACEs) have been associated with poor mental and somatic health. Accumulating evidence indicates that accelerated biological aging—indexed by altered telomere-related markers—may contribute to associations between ACEs and negative long-term health outcomes. Telomeres are repeated, non-coding deoxyribonucleic acid (DNA) sequences at the end of chromosomes. Telomeres shorten during repeated cell divisions over time and are being used as a marker of biological aging. Objectives: The aim of the current paper is to review the literature on the relationship between ACEs and telomere length (TL), with a specific focus on how the heterogeneity of sample and ACEs characteristics lead to varying associations between ACEs and TL. Methods: Multiple databases were searched for relevant English peer-reviewed articles. Thirty-eight papers were found to be eligible for inclusion in the current review. Results: Overall, the studies indicated a negative association between ACEs and TL, although many papers presented mixed findings and about a quarter of eligible studies found no association. Studies with smaller sample sizes more often reported significant associations than studies with larger samples. Also, studies reporting on non-clinical and younger samples more often found associations between ACEs and TL compared to studies with clinical and older samples. Reviewing the included studies based on the "Stressor Exposure Characteristics" recently proposed by Epel et al. (2018) revealed a lack of detailed information regarding ACEs characteristics in many studies. Conclusion: Overall, it is difficult to achieve firm conclusions about associations of ACEs with TL due to the heterogeneity of study and ACE characteristics and the heterogeneity in reported findings. The field would benefit from more detailed descriptions of study samples and measurement of ACEs. [ABSTRACT FROM AUTHOR]

Background: Several observational studies have found leukocyte telomere length (TL) to be associated with Alzheimer's diseases (AD) or dementia. However, these findings were based on small sample sizes and cannot clarify whether this relationship was causal. Genome-wide association studies (GWAS) have identified common variants associated with TL, providing a valuable resource for examining the causal effect of TL on AD using Mendelian Randomization (MR) methods.Objective: To examine if TL was causally associated with AD using GWAS summary statistics.Methods: Using a genetic risk score comprised of seven variants associated with leukocyte TL as an instrumental variable, we tested whether shorter TL was associated with a higher risk of AD by applying an MR approach to the summarized genome-wide association study data.Results: The genetic risk score for TL was associated with higher risk of AD [log-odds ratio (OR) = 0.003 for per TL-decreasing allele; 95% confidence interval (CI): 0.001, 0.005, p = 0.005]. Moreover, the MR analysis provided support for shorter TL to be causally associated with a higher risk of AD (log-OR = 0.04 per SD-decrease of TL; 95% CI: 0.01, 0.08, p = 0.01).Conclusion: We suggest that TL has a causal effect on the risk of AD. [ABSTRACT FROM AUTHOR]

Leukocyte telomere length (LTL) is a biomarker of cellular aging. African Americans report more stress than other groups; however, the association of psychosocial stressors with biological aging among African Americans remains unclear. The current study evaluated the association of psychosocial factors (negative affect and stressors) with LTL in a large sample of African American men and women (n = 2,516) from the Jackson Heart Study. Using multivariable linear regression, we examined the sex‐specific associations of psychosocial factors (cynical distrust, anger in and out, depressive symptoms, negative affect summary scores, global stress, weekly stress, major life events, and stress summary scores) with LTL. Model 1 adjusted for demographics and education. Model 2 adjusted for model 1, smoking, alcohol intake, physical activity, diabetes, hypertension, and high‐sensitivity C‐reactive protein. Among women, high (vs. low) cynical distrust was associated with shorter mean LTL in model 1 (b = −0.12; p = 0.039). Additionally, high (vs. low) anger out and expressed negative affect summary scores were associated with shorter LTL among women after full adjustment (b = −0.13; p = 0.011; b = −0.12, p = 0.031, respectively). High levels of cynical distrust, anger out, and negative affect summary scores may be risk factors for shorter LTL, particularly among African‐American women. [ABSTRACT FROM AUTHOR]

Leukocyte telomere length (LTL) is a heritable trait with two potential sources of heritability (h2): inherited variation in non-telomeric regions (e.g., SNPs that influence telomere maintenance) and variability in the lengths of telomeres in gametes that produce offspring zygotes (i.e., "direct" inheritance). Prior studies of LTL h2 have not attempted to disentangle these two sources. Here, we use a novel approach for detecting the direct inheritance of telomeres by studying the association between identity-by-descent (IBD) sharing at chromosome ends and phenotypic similarity in LTL. We measured genome-wide SNPs and LTL for a sample of 5069 Bangladeshi adults with substantial relatedness. For each of the 6318 relative pairs identified, we used SNPs near the telomeres to estimate the number of chromosome ends shared IBD, a proxy for the number of telomeres shared IBD (Tshared). We then estimated the association between Tshared and the squared pairwise difference in LTL ((ΔLTL)2) within various classes of relatives (siblings, avuncular, cousins, and distant), adjusting for overall genetic relatedness (ϕ). The association between Tshared and (ΔLTL)2 was inverse among all relative pair types. In a meta-analysis including all relative pairs (ϕ > 0.05), the association between Tshared and (ΔLTL)2 (P = 0.01) was stronger than the association between ϕ and (ΔLTL)2 (P = 0.43). Our results provide strong evidence that telomere length (TL) in parental germ cells impacts TL in offspring cells and contributes to LTL h2 despite telomere "reprogramming" during embryonic development. Applying our method to larger studies will enable robust estimation of LTL h2 attributable to direct transmission of telomeres. [ABSTRACT FROM AUTHOR]

Exposure to childhood adversity has been linked to accelerated telomere shortening, a marker of cellular aging and an indicator of physical health risk. In the current study, we examined whether adult attachment representation moderated the association between childhood adversity and telomere length. Participants included 78 young adults (M age = 20.46, SD = 1.57), who reported on their exposure to adverse childhood experiences (ACE) and were administered the Adult Attachment Interview, which was coded for attachment state of mind. Relative telomere length was assayed from buccal cells. Multiple regression analyses revealed a significant interaction between attachment state of mind and ACE in predicting telomere length. Whereas the association between number of ACE and telomere length was nonsignificant for secure–autonomous, r (50) = –.15, p =.31, and insecure–preoccupied young adults, r (9) = –.15, p =.71, there was a strong negative association between number of ACE and telomere length for insecure–dismissing young adults, r (19) = –.59, p =.007. This study is novel in demonstrating that attachment may affect biological resilience following childhood adversity, contributing to the growing literature about the role of the quality of early caregiving experiences and their representations in shaping biological processes and physical health. [ABSTRACT FROM AUTHOR]

Background: The goal of this systematic review and meta-analysis is to determine the effect of diet on telomere length. Methods: We searched the following databases: MEDLINE, Embase, LILACS, CINAHL, ISI Web of Science, and Scopus, as well as the Cochrane Central Register of Controlled Trials and the National Institutes of Health, from inception to December 2016. Articles that assessed effects of diet on telomere length were included. Results: A total of 2,128 studies were identified, 30 were read in full, and 7 were systematically reviewed. Five RCTs were included in the meta-analysis, covering 9 diets; a total of 533 participants were included. Study heterogeneity (I2) was 89%, and differences were not identified regarding average telomere lengths (mean difference 1.06; 95% CI –1.53 to 3.65). Conclusion: The available evidence suggests that there is no effect of diet on telomere length, but the strong heterogeneity in the type and duration of dietary interventions does not allow any final statement on the absence of an effect of diet on telomere length. [ABSTRACT FROM AUTHOR]

Research on mechanisms underlying fetal programming of health and disease risk has focused primarily on processes that are specific to cell types, organs or phenotypes of interest. However, the observation that developmental conditions concomitantly influence a diverse set of phenotypes, the majority of which are implicated in age-related disorders, raises the possibility that such developmental conditions may additionally exert effects via a common underlying mechanism that involves cellular/molecular ageing-related processes. In this context,we submit that telomere biology represents a process of particular interest in humans because, firstly, this system represents among the most salient antecedent cellular phenotypes for common age-related disorders; secondly, its initial (newborn) setting appears to be particularly important for its long-term effects; and thirdly, its initial setting appears to be plastic and under developmental regulation. We propose that the effects of suboptimal intrauterine conditions on the initial setting of telomere length and telomerase expression/activity capacity may be mediated by the programming actions of stress-related maternal-placental-fetal oxidative, immune, endocrine and metabolic pathways in a manner that may ultimately accelerate cellular dysfunction, ageing and disease susceptibility over the lifespan. This perspectives paper provides an overviewof each of the elements underlying this hypothesis, with an emphasis on recent developments, findings and future directions. This article is part of the theme issue 'Understanding diversity in telomere dynamics'. [ABSTRACT FROM AUTHOR]

Objectives: Psychiatric and substance-use disorders have been associated with premature biological ageing. Telomere length (TL), considered an ageing marker, has been analysed in psychiatric disorders, and to a lesser extent in substance-use disorders, with recent findings suggesting TL may be related to disease pathology. Methods: We conducted a critical and non-systematic literature search of TL studies published up to June 2016 in psychiatric and substance-use disorders, focussing on studies describing mechanisms, including studies linking telomere biology with genetic factors, stress and mitochondrial alterations (104 studies selected). Results: Patients with major depressive disorder and anxiety appear to have shorter leukocyte telomeres compared to controls. Inconclusive results are found for other psychiatric disorders and for substance-use disorders. This may be due in part to differences in medication treatment and response, as studies suggest that some psychotropic medications may modulate TL. Importantly, some studies establish a relationship between telomere machinery, stress and mitochondria function in psychiatric and substance-use disorders. Conclusions: While further longitudinal studies considering telomere genetics are needed to clarify the cause-effect link between telomeres and mitochondria function in psychiatric and substance-use disorders, the recent findings linking these biological processes suggest that telomeres may be more than ageing markers. [ABSTRACT FROM AUTHOR]

Telomeres are repetitive tandem DNA sequences that cap chromosomal ends protecting genomic DNA from enzymatic degradation. Telomeres progressively shorten with cellular replication and are therefore assumed to correlate with biological and chronological age. An expanding body of evidence suggests (i) a predictable inverse association between telomere length, aging and age-related diseases and (ii) a positive association between physical activity and telomere length. Both hypotheses have garnered tremendous research attention and broad consensus; however, the evidence for each proposition is inconsistent and equivocal at best. Telomere length does not meet the basic criteria for an aging biomarker and at least 50% of key studies fail to find associations with physical activity. In this review, we address the evidence in support and refutation of the putative associations between telomere length, aging and physical activity. We finish with a brief review of plausible mechanisms and potential future research directions. [ABSTRACT FROM AUTHOR]

The molecular, neurobiological, and physical health impacts of child maltreatment are well established, yet mechanistic pathways remain inadequately defined. Telomere length (TL) decline is an emerging molecular indicator of stress exposure with definitive links to negative health outcomes in maltreated individuals. The multiple confounders endemic to human maltreatment research impede the identification of causal pathways. This study leverages a unique randomized, cross-foster, study design in a naturalistic translational nonhuman primate model of infant maltreatment. At birth, newborn macaques were randomly assigned to either a maltreating or a competent control mother, balancing for sex, biological mother parenting history, and social rank. Offspring TL was measured longitudinally across the first 6 months of life (infancy) from peripheral blood. Hair cortisol accumulation was also determined at 6, 12, and 18 months of age. TL decline was greater in animals randomized to maltreatment, but also interacted with biological mother group. Shorter TL at 6 months was associated with higher mean cortisol levels through 18 months (juvenile period) when controlling for relevant covariates. These results suggest that even under the equivalent social, nutritional, and environmental conditions feasible in naturalistic translational nonhuman primate models, early adverse caregiving results in lasting molecular scars that foreshadow elevated health risk and physiologic dysregulation. [ABSTRACT FROM AUTHOR]

Background: The purpose of the study was to estimate the heritability of leukocyte telomere length (LTL) and lung function and to examine whether LTL and lung function share genetic or environmental effects in common.Methods: 386 monozygotic and dizygotic Finnish twin sisters (age 68.4±3.4 years) were included. Relative LTL was determined from peripheral blood DNA by qPCR. Lung function measures of FEV1, FVC, FEV1/FVC, and PEF were derived from spirometry. Genetic modeling was performed with MPlus statistical software.Results: Univariate analysis revealed that in LTL, 62% (95% confidence interval 50-72) of the variance was explained by additive genetic and 38% (28-50) by unique environmental factors. For FEV1, FVC, and PEF, the corresponding estimates were 65%-67% for additive genetic and 33%-35% for unique environmental factors. Across the sample, the phenotypic correlation between LTL and FEV1 was modest (r = .104, p = .041). Bivariate correlated factors model revealed that the genetic correlation between LTL and FEV1 was .18 (-0.19 to 0.64) and environmental correlation was -.10 (-0.84 to 0.55).Conclusions: Both LTL and lung function variables are moderately to highly genetically determined. The associations between LTL and the lung function variables were weak. However, the positive genetic correlation point estimate gave minor suggestions that, in a larger sample, genetic factors in common might play a role in the phenotypic correlation between LTL and FEV1. Future studies with larger samples are needed to confirm these preliminary findings. [ABSTRACT FROM AUTHOR]

Objective: To investigate pathological conditions that act as sources of pro-inflammatory cytokines and cytotoxic substances to examine telomere length (TL) in patients with either early (duration of illness [DI] ≤5 years) or chronic (DI >5 years) psychosis using T lymphocytes. Methods: Based on these factors and the important role that T lymphocytes play in inflammation, the present study measured the TL of T lymphocytes in patients with either early or chronic psychosis. Additionally, smoking, metabolic syndrome, depression, and cognitive functioning were assessed to control for confounding effects. Results: TL was significantly longer in patients with early and chronic psychosis than in healthy control subjects and, moreover, the significance of these findings remained after controlling for age, smoking, metabolic syndrome, DI, chlorpromazine-equivalent dose, and cognitive functioning (F=9.57, degree of freedom=2, p<0.001). Additionally, the DI, chlorpromazine-equivalent doses, and the five-factor scores of the Positive and Negative Syndrome Scale were not significantly correlated with the TL of T lymphocytes in either all patients or each psychosis group. Conclusion: Possible mechanisms underlying the effects of antipsychotic medications on telomerase are discussed in the present study, but further studies measuring both telomerase activity and TL using a prospective design will be required. [ABSTRACT FROM AUTHOR]

Background and Objectives: Telomeres are protective caps at the ends of chromosomes, and shorter telomeres are associated with poor physical health. The present study set out to consolidate the varying effect sizes found so far in studies of anxiety and telomere length.Design and Methods: A meta-analytic investigation of the relationship between anxiety and telomere length used information from 17 different samples comprising a total of 19,424 participants.Results: The results showed a small but significant association, r = -.06, between higher anxiety and shorter telomeres. Studies comparing individuals diagnosed with an anxiety disorder with other individuals had a significant effect size, and studies that did not use this comparison threshold did not have a significant effect size.Conclusions: Anxiety is associated with an important biomarker related to health. Future experimental studies that examine the impact of interventions intended to reduce anxiety in conjunction with measurement of telomere length can further clarify the impact of anxiety on telomere length. [ABSTRACT FROM AUTHOR]

Estrogen-based hormone replacement therapy (HRT) may be associated with deceleration of cellular aging. We investigated whether long-term HRT has effects on leukocyte (LTL) or mean and minimum skeletal muscle telomere length (SMTL) in a design that controls for genotype and childhood environment. Associations between telomeres, body composition, and physical performance were also examined. Eleven monozygotic twin pairs (age 57.6 ± 1.8 years) discordant for HRT were studied. Mean duration of HRT use was 7.3 ± 3.7 years in the user sister, while their co-twins had never used HRT. LTL was measured by qPCR and SMTLs by southern blot. Body and muscle composition were estimated by bioimpedance and computed tomography, respectively. Physical performance was measured by jumping height and grip strength. HRT users and non-users did not differ in LTL or mean or minimum SMTL. Within-pair correlations were high in LTL (r = 0.69, p = .020) and in mean (r = 0.74, p = .014) and minimum SMTL (r = 0.88, p = .001). Body composition and performance were better in users than non-users. In analyses of individuals, LTL was associated with BMI (r 2 = 0.30, p = .030), percentage total body (r 2 = 0.43, p = .014), and thigh (r 2 = 0.55, p = .004) fat, while minimum SMTL was associated with fat-free mass (r 2 = 0.27, p = .020) and thigh muscle area (r 2 = 0.42, p = .016). We found no associations between HRT use and telomere length. Longer LTLs were associated with lower total and regional fat, while longer minimum SMTLs were associated with higher fat-free mass and greater thigh muscle area. This suggests that telomeres measured from different tissues may have different associations with measures of body composition. [ABSTRACT FROM AUTHOR]

Background: Shorter telomere length (TL) may signal premature cellular aging and increased risk for disease. While depression and psychosocial stress have been associated with shorter telomeres, other psychological risk factors for cardiovascular disease have received less attention. Purpose: To evaluate the association between TL and psychological risk factors (symptoms of anxiety and depression, hostility and defensiveness traits) for heart disease, and to examine whether chronological age and sex moderate the associations observed. Methods: 132 healthy men and women (Mage = 45.34 years) completed the Marlowe-Crowne Social Desirability Scale, the Beck Depression Inventory II, The Beck Anxiety Inventory and the Cook-Medley Hostility Scale. Relative TL was measured by quantitative polymerase chain reaction (PCR) of total genomic DNA samples. A series of hierarchical linear regressions were performed controlling for pertinent covariates. Results: Shorter TL was observed among individuals high in defensiveness (β = -.221) and depressive symptoms (β = -.213), as well as in those with less hostility (β =.256) and anxiety (β =.220)(all Ps<.05). Psychological variables explained 19% of the variance over and above that explained by covariates (age, sex, exercise, alcohol consumption, systemic inflammation, and 24-hr mean arterial pressure). Age moderated the relation between TL and defensiveness (β =.179, p =.03). Sex did not influence any of the relations. Conclusions: Telomere length is associated with psychological burden though the direction of effect differs depending on the psychological variables under study. Further research is needed to determine the reasons for and implications of these seemingly contradictory findings. [ABSTRACT FROM AUTHOR]

Telomeres are tandem repeat DNA sequences present at the ends of each eukaryotic chromosome to stabilize the genome structure integrity. Telomere lengths progressively shorten with each cell division. Inflammation and oxidative stress, which are implicated as major mechanisms underlying cardiovascular diseases, increase the rate of telomere shortening and lead to cellular senescence. In clinical studies, cardiovascular risk factors such as smoking, obesity, sedentary lifestyle, and hypertension have been associated with short leukocyte telomere length. In addition, low telomerase activity and short leukocyte telomere length have been observed in atherosclerotic plaque and associated with plaque instability, thus stroke or acute myocardial infarction. The aging myocardium with telomere shortening and accumulation of senescent cells limits the tissue regenerative capacity, contributing to systolic or diastolic heart failure. In addition, patients with ion-channel defects might have genetic imbalance caused by oxidative stress-related accelerated telomere shortening, which may subsequently cause sudden cardiac death. Telomere length can serve as a marker for the biological status of previous cell divisions and DNA damage with inflammation and oxidative stress. It can be integrated into current risk prediction and stratification models for cardiovascular diseases and can be used in precise personalized treatments. In this review, we summarize the current understanding of telomeres and telomerase in the aging process and their association with cardiovascular diseases. In addition, we discuss therapeutic interventions targeting the telomere system in cardiovascular disease treatments. [ABSTRACT FROM AUTHOR]

Objective: Several cross-sectional studies have related depressive and anxiety disorders to shorter leukocyte telomere length (LTL) as an indicator of cellular aging. However, these studies have left many unresolved questions about underlying causality and ordering of associations. The objective of the present large, longitudinal study was to examine the relationship between depressive and anxiety disorders and LTL over a 6-year time period.Method: Data are from the Netherlands Study of Depression and Anxiety, including 2,292 patients with remitted and current diagnoses of depressive or anxiety disorders and 644 healthy control subjects. LTL was assessed using quantitative PCR and measured at baseline and after 6 years; depressive and anxiety disorder diagnoses and characteristics (course, duration, and severity) were determined at baseline and after 2, 4, and 6 years.Results: Results showed that persons with remitted (B=-52.6) and current (B=-60.8) depressive or anxiety disorder had consistently shorter LTL compared with healthy control subjects across baseline and at the 6-year follow-up, remaining significant when controlling for lifestyle and somatic health variables. Changes in the course of depressive or anxiety disorder characteristics over 6 years, however, were not associated with different LTL attrition rates.Conclusions: This study confirmed robust associations of depressive and anxiety disorders with shorter telomeres, but interestingly, it did not demonstrate that depressive and anxiety disorders and LTL change together over time, suggesting the absence of a direct within-person relationship. Short LTL is suggested to be either a long-term consequence or an underlying vulnerability factor for depressive or anxiety disorders. [ABSTRACT FROM AUTHOR]

Telomeres are the protective complexes at the end of chromosomes, required for genomic stability. Little is known about predictors of attrition in young children or the relationship between parental and child patterns of telomere change. Telomere length was assessed twice over one year, at 4 and at 5 years of age, in Latino preschool children ( n = 77) and their mothers ( n = 70) in whole blood leukocytes. Maternal and child rates of attrition during the same time period were compared in 70 mother-child pairs. More children showed lengthened telomeres over one year compared to their mothers and very few children showed attrition (2.6 %). Approximately 31 % of children and 16 % of mothers displayed lengthening over one year while 66 % of children showed maintenance in contrast with 74 % of mothers. The strongest predictor for child telomere length change was child's baseline telomere length ( r = −0.61, p < 0.01). Maternal rate of change was associated with child rate of change ( r = 0.33, p < 0.01). After controlling for child baseline telomere length, the relationship between child and maternal rate of change trended towards significance (Coeff = 0.20, 95 % CI −0.03 to 0.43; p = 0.08). We found primarily maintenance and lengthening from 4 to 5 years of age in children, with minimal telomere attrition, indicating that most of the telomere loss happens in the first 4 years, plateauing by age 4. Lastly, we found close to 10 % of the variance in rate of change in children shared by mothers. While some of this shared variance is genetic, there are likely environmental factors that need to be further identified that impact rate of telomere length change. [ABSTRACT FROM AUTHOR]

Objective Elevated homocysteine (HC) levels and/or shortened telomere length (TL) are associated with adverse medical conditions. Our objective is to investigate the relationship between HC and TL in cord blood leukocytes of newborns. Study Design This is a nested study from a prospective cohort from 2011 to 2012 in pregnant women admitted for delivery at a university-affiliated hospital. Cord blood was collected at delivery and genomic DNA was analyzed using quantitative PCR. The telomere-to-single copy gene ratio method was employed to quantify TL. Newborn HC levels were measured. generalized linear regression modeling (GLM) and bootstrap statistical analyses were performed. Results Seventy-seven maternal-fetal dyads with a mean gestational age of 39 weeks were included. The distribution of the coefficient of homocysteine showed most values greater than zero demonstrating that homocysteine had a positive relationship with TL. In 915 of 10,000 (9.15%) iterations, the p-value was < 0.05 demonstrating a positive effect. Conclusion Increasing newborn concentrations of HC are not associated with decreasing TL. Larger, prospective studies are needed to confirm these findings and long-term implications. [ABSTRACT FROM AUTHOR]

Aim The aim of the study was to examine the association between telomere erosion and periodontitis in a long-standing prospective cohort study of New Zealand adults. Specific hypotheses tested were as follows: (i) that exposure to periodontitis at ages 26 and 38 was associated with accelerated leucocyte telomere erosion and (ii) that accelerated leucocyte telomere erosion was associated with higher rates of periodontitis by ages 26 and 38. Materials and Methods Periodontal attachment loss data were collected at ages 26 and 38. Blood samples taken at the same ages were analysed to obtain estimates of leucocyte telomere length and erosion over a 12-year period. Results Overall, the mean telomere length was reduced by 0.15 T/S ratio (adjusted) from age 26 to 38 among the 661 participants reported on here. During the same period, the mean attachment loss increased by 10%, after adjusting for sex, socio-economic status and smoking. Regression models showed that attachment loss did not predict telomere length, and that telomere erosion did not predict attachment loss. Conclusions Although both periodontitis and telomere length are age-dependent, they do not appear to be linked, suggesting that determination of leucocyte telomere length may not be a promising clinical approach at this age for identifying people who are at risk for periodontitis. [ABSTRACT FROM AUTHOR]

Short telomeres are associated with increased risk of cardiovascular disease. Here we studied cardiomyocyte telomere length at key ages during the ontogeny of cardiac hypertrophy and failure in the hypertrophic heart rat (HHR) and compared these with the normal heart rat (NHR) control strain. Key ages corresponded with the pathophysiological sequence beginning with fewer cardiomyocytes (2 days), leading to left ventricular hypertrophy (LVH) (13 wk) and subsequently progression to heart failure (38 wk). We measured telomere length, tissue activity of telomerase, mRNA levels of telomerase reverse transcriptase (Tert) and telomerase RNA component (Terc), and expression of the telomeric regulator microRNA miR-34a. Cardiac telomere length was longer in the HHR compared with the control strain at 2 days and 38 wk, but shorter at 13 wk. Neonatal HHR had higher cardiac telomerase activity and expression of Tertand miR-34a. Telomerase activity was not different at 13 or 38 wk. TertmRNA and TercRNA were overexpressed at 38 wk, while miR-34a was overexpressed at 13 wk but downregulated at 38 wk. Circulating leukocytes were strongly correlated with cardiac telomere length in the HHR only. The longer neonatal telomeres in HHR are likely to reflect fewer fetal and early postnatal cardiomyocyte cell divisions and explain the reduced total cardiomyocyte complement that predisposes to later hypertrophy and failure. Although shorter telomeres were a feature of cardiac hypertrophy at 13 wk, they were not present at the progression to heart failure at 38 wk. [ABSTRACT FROM AUTHOR]

Telomere length shortens with aging, and short telomeres have been linked to a wide variety of pathologies. Previous studies suggested a discrepancy in age-associated telomere shortening rate estimated by cross-sectional studies versus the rate measured in longitudinal studies, indicating a potential bias in cross-sectional estimates. Intergenerational changes in initial telomere length, such as that predicted by the previously described effect of a father's age at birth of his offspring ( FAB), could explain the discrepancy in shortening rate measurements. We evaluated whether changes occur in initial telomere length over multiple generations in three large datasets and identified paternal birth year ( PBY) as a variable that reconciles the difference between longitudinal and cross-sectional measurements. We also clarify the association between FAB and offspring telomere length, demonstrating that this effect is substantially larger than reported in the past. These results indicate the presence of a downward secular trend in telomere length at birth over generational time with potential public health implications. [ABSTRACT FROM AUTHOR]

Leukocyte telomere length (LTL) shortens with age, and is a prospective marker of mortality related to cardiovascular disease. Many health behaviors and social environmental factors have been found to be associated with LTL. Several of these are also associated with conscientiousness, a dispositional personality trait. Conscientiousness is a propensity to be planful, adhere to social norms, and inhibit pre-potent responses. Like LTL, conscientiousness is prospectively related to mortality, possibly through cumulative effects on health over the life course via multiple pathways. As a result, we hypothesized that childhood levels of conscientiousness would predict LTL prospectively in adulthood. We selected a sample of 60 women in the Hawaii Personality and Health Cohort; 30 described by their teachers as high on conscientiousness in childhood and 30 described as low on the trait. Dried blood spot samples collected in adulthood 40 years later were used as sources of DNA for the LTL assay. Conscientiousness was associated with longer LTL (p = .02). Controlling for age did not account for this association. Controlling for education and physiological dysregulation partially attenuated the association, and the effect remained significant when accounting for differences in LTL across cultural groups. These results represent the first evidence that childhood personality prospectively predicts LTL 40 years later in adulthood. Our findings would be consistent with a mediation hypothesis whereby conscientiousness predicts life paths and trajectories of health that are reflected in rates of LTL erosion across the lifespan. [ABSTRACT FROM AUTHOR]