Frailty is associated with the epigenetic clock but not with telomere length in a German cohort

Abstract

BackgroundThe epigenetic clock, in particular epigenetic pre-aging quantified by the so-called DNA methylation age acceleration, has recently been suggested to closely correlate with a variety of disease phenotypes. There remains a dearth of data, however, on its association with telomere length and frailty, which can be considered major correlates of age on the genomic and clinical level, respectively.ResultsIn this cross-sectional observational study on altogether 1820 subjects from two subsets (n = 969 and n = 851; mean ± standard deviation age 62.1 ± 6.5 and 63.0 ± 6.7 years, respectively) of the ESTHER cohort study of the elderly general population in Germany, DNA methylation age was calculated based on a 353 loci predictor previously developed in a large meta-study, and the difference-based epigenetic age acceleration was calculated as predicted methylation age minus chronological age. No correlation of epigenetic age acceleration with telomere length was found in our study (p = 0.63). However, there was an association of DNA methylation age acceleration with a comprehensive frailty measure, such that the accumulated deficits significantly increased with increasing age acceleration. Quantitatively, about half an additional deficit was added per 6 years of methylation age acceleration (p = 0.0004). This association was independent from age, sex, and estimated leukocyte distribution, as well as from a variety of other confounding variables considered.ConclusionsThe results of the present study suggest that epigenetic age acceleration is correlated with clinically relevant aging-related phenotypes through pathways unrelated to cellular senescence as assessed by telomere length. Innovative approaches like Mendelian randomization will be needed to elucidate whether epigenetic age acceleration indeed plays a causal role for the development of clinical phenotypes.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0186-5) contains supplementary material, which is available to authorized users.

Tobacco smoking and smoking-related DNA methylation are associated with the development of frailty among older adults

“…42 Previous studies have evaluated its relationships with 2 other aging estimators, telomere length, 43,44 and age-related DNA methylation changes ("epigenetic clock"). 45,46 Telomere length was not associated with frailty, neither in Asian nor in Caucasian populations. 43,44 In contrast, the epigenetic clock was found to be significantly associated with frailty-related phenotypes and the FI.…”

“…46 In addition, Breitling et al showed that the epigenetic clock was correlated with the FI and further confirmed the robustness of this association across diverse domains of health deficits. 45 Our previous study on the relationship between smoking-induced DNA methylation and the epigenetic clock intriguingly found 7 out of the 9 now identified loci to be associated with the epigenetic clock as well, 47 including cg01127300, cg02657160 (CPOX), cg05673882 (POLK), cg07826859 (MYO1G), cg14753356, cg19589396 and cg23667432 (ALPP). The associations of smoking-related methylation with the FI and the epigenetic clock consequently share some pronounced commonalities, though the underlying causality certainly requires further investigation.…”

DNA methylome analysis identifies accelerated epigenetic ageing associated with postmenopausal breast cancer susceptibility

“…This composite biomarker of ageing, which is defined as a weighted average across 353 specific CpG sites, produces an estimate of age (in units of years), referred to as ‘epigenetic age’ or ‘DNA methylation age (DNAm age)’. Recent studies demonstrate that DNAm age is at least a passive biomarker of biological age: the epigenetic age of blood has been found to be predictive of all-cause mortality [5–9], frailty [10], cognitive and physical functioning [5]. Further, the utility of the epigenetic clock method using various tissues and organs has been demonstrated in applications surrounding Alzheimer disease [11], centenarian status [8], pre-natal and early life influences [12], Down syndrome [13], HIV infection [14], Huntington disease [15], obesity [16], lifetime stress [17], menopause [18], and Parkinson disease [19].…”

Epigenetic clock analysis in long-term meditators

“…The deviation between the DNAm age and the chronological age of an individual provides information regarding his epigenetic aging rate (Chen et al, 2016). Faster-running epigenetic clocks have been negatively associated with longevity (Horvath et al, 2015), and positively associated with chronic diseases (Horvath et al, 2014; Horvath and Ritz, 2015; Levine et al, 2015a, 2015b; Perna et al, 2016), frailty (Breitling et al, 2016), cognitive and physical fitness in the elderly (Marioni et al, 2015b) and all cause mortality even after adjusting for chronological age and a variety of known risk factors (Christiansen et al, 2016; Marioni et al, 2015a; Perna et al, 2016). The epigenetic clock therefore may represent an accurate tool to measure the effectiveness of lifestyle-based interventions for the prevention of age-related diseases.…”