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Human leukocyte telomere length (LTL) decreases with age and shorter LTL has previously been associated with increased prospective mortality. However, it is not clear whether LTL merely marks the health status of an individual by its association with parameters of immune function, for example, or whether telomere shortening also contributes causally to lifespan variation in humans. We measured LTL in 870 nonagenarian siblings (mean age 93 years), 1580 of their offspring and 725 spouses thereof (mean age 59 years) from the Leiden Longevity Study (LLS). We found that shorter LTL is associated with increased prospective mortality in middle (30-80 years; hazard ratio (HR) = 0.75, P = 0.001) and highly advanced age (≥90 years; HR = 0.92, P = 0.028), and show that this association cannot be explained by the association of LTL with the immune-related markers insulin-like growth factor 1 to insulin-like growth factor binding protein 3 molar ratio, C-reactive protein, interleukin 6, cytomegalovirus serostatus or white blood cell counts. We found no difference in LTL between the middle-aged LLS offspring and their spouses (β = 0.006, P = 0.932). Neither did we observe an association of LTL-associated genetic variants with mortality in a prospective meta-analysis of multiple cohorts (n = 8165). We confirm LTL to be a marker of prospective mortality in middle and highly advanced age and additionally show that this association could not be explained by the association of LTL with various immune-related markers. Furthermore, the approaches performed here do not further support the hypothesis that LTL variation contributes to the genetic propensity for longevity.
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... Other recent meta-analyses support the concurrent associations between short telomeres and diabetes ) and several cancers Wentzensen et al. 2011;Zhu et al. 2016). Several studies indicate that short telomeres from varied cellular sources, such as leukocytes and saliva, including a study with >60,000 adults (Rode et al. 2015), are associated with increased morbidity and mortality of various agerelated diseases (Cawthon et al. 2003;Bakaysa et al. 2007;Kimura et al. 2008;Schaefer et al. 2013;Deelen et al. 2014;Glei et al. 2015;Forero et al. 2016;Scheller Madrid et al. 2016). However, null studies also exist (Njajou et al. 2009;Bendix et al. 2014;Duggan et al. 2014;Svensson et al. 2014). ...
... Furthermore, the significance of LTL as a prognostic indicator for death in the general population is conflicting. Two previous cohort reports have revealed that LTL is a biomarker of mortality (13,14), while other prospective studies have failed to demonstrate such association (15, 16). As for diabetes, two studies in European populations with relatively small sample size found that LTL was associated with all-cause death in type 1 diabetes, and LTL combined with clinicopathological characteristics can provide additional prognostic significance on death probability in T2D individuals (17,18). ...
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Objective The joint effect of leukocyte telomere length (LTL) and type 2 diabetes (T2D) on the risk of all-cause death has been sparsely explored. The study designed to examine the joint effect of T2D and LTL on the probability of death in American adults. Methods A cohort of 6862 adults with LTL measurements and with or without T2D from the NHANES 1999-2002 with follow-up information until 2015 was studied. Quantitative PCR was used to measure the length of telomeres relative to standard reference DNA (T/S ratio). Individuals were grouped into three tertiles according to the LTL levels, with the first tertile demonstrating the lowest one and used as the reference group. The effects of LTL and T2D status on death were evaluated using Kaplan–Meier curves along with log-rank test. Three Cox proportional hazards models with adjustment for various confounders were used to examine the links between TL and all-cause death possibility using adjusted hazard ratios (HRs). Results Adults in the sample averaged 45.54 years of age, with 49.51% being male. After a median follow-up period of 14.4 years, 1543 (22.5%) individuals died from all cause. The probability of all-cause mortality was higher among individuals with LTL in the highest tertile than individuals in the lowest tertile (aHR = 0.89; 95%CI: 0.77-1.03); however, the difference did not reach the level of statistical significance ( P = 0.11). Conversely, the individuals with T2D had a higher probability of death than individuals without (aHR = 1.26; 95%CI: 1.06-1.50; P = 0.0092). When LTL and T2D status were investigated jointly, subjects in the highest TLT tertile and with T2D had the highest probability of mortality compared with their counterparts (aHR = 1.34; 95%CI: 1.07-1.68; P = 0.0101). However, there was no independent effect of low TLT on mortality as demonstrated among individuals with diabetes (aHR = 1.14; 95%CI: 0.95-1.38; P = 0.1662). Conclusion The joint effect of TLT and T2D was larger than the sum of the independent effects on the risk of all-cause death. Participants with high TLT and diabetes showed the highest possibility of death compared with other groups.
... A study on a large population (n = 105,539) showed that women have longer telomeres than men and that there are gender-related differences in biological aging [74], which may be due to hormonal differences, such as estrogen levels and the role of the X chromosome [75,76]. There is also a relationship between shorter telomeres and higher mortality [77,78]. Decreased age-related immune surveillance and increased inflammation are associated with the shortening of telomeres and decreased telomerase activity [79]. ...
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Aging is closely related to the occurrence of human diseases; however, its exact biological mechanism is unclear. Advancements in high-throughput technology provide new opportunities for omics research to understand the pathological process of various complex human diseases. However, single-omics technologies only provide limited insights into the biological mechanisms of diseases. DNA, RNA, protein, metabolites, and microorganisms usually play complementary roles and perform certain biological functions together. In this review, we summarize multi-omics methods based on the most relevant biomarkers in single-omics to better understand molecular functions and disease causes. The integration of multi-omics technologies can systematically reveal the interactions among aging molecules from a multidimensional perspective. Our review provides new insights regarding the discovery of aging biomarkers, mechanism of aging, and identification of novel antiaging targets. Overall, data from genomics, transcriptomics, proteomics, metabolomics, integromics, microbiomics, and systems biology contribute to the identification of new candidate biomarkers for aging and novel targets for antiaging interventions.
... Cortisol, a key glucocorticoid, regulates the immune system, growth factors, and neurodevelopment. [6][7][8][9][10][11][12][13] Cortisol production follows a circadian rhythm that is developed during the first year of life. 14 Chronic stress disrupts the tight regulation of this circadian rhythm. ...
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... 289,290 Age-adjusted, inverse associations between mean LTL and all-cause mortality have been established in a range of studies. 286,[291][292][293][294][295][296][297][298][299][300][301][302][303][304] However, the association diminishes with age 305 and fails to predict mortality in cohorts of the very old. 306,307 Early childhood LTL most accurately predicts life expectancy. ...
Chapter
This chapter introduces the epigenetic processes that govern how exercise affects the aging processes. We begin with an introduction to the molecular changes that occur with aging including methylation and histone and noncoding RNA modifications. We then present the evidence for changes in these processes by exercise and physical activity, Lastly, we present evidence for and against a role for exercise on changes in telomere length and aging.
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