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.
Highlights
The 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
Age acceleration is associated with a comprehensive frailty measure The potential relationship between epigenetic age acceleration and frailty-related phenotypes apparently has been investigated only in one previous study: in an analysis of the Lothian Birth Cohort 1936 (LBC1936), significant correlation coefficients ranging from −0.05 to −0.07 were found between DNAm age acceleration and cognitive functioning, grip strength, or lung function [10]
Given that the LBC1936 participants were rather strictly 70 years of age when assessed for the study of age acceleration, the present findings extend the prior evidence from the old to middle-aged-old age group, as they were based on study participants aged 50 to 75 years
Summary
The 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, on its association with telomere length and frailty, which can be considered major correlates of age on the genomic and clinical level, respectively. Frailty has received growing attention in recent years, due to pronounced associations with longevity and other aging-related phenotypes and the corresponding perception that frailty measures reflect an individual’s clinically relevant biological age [4, 5]. Telomere length (TL) has been suggested to reflect an individual’s biological age at the genomic DNA level, and associations of measures of TL with various agingand frailty-related phenotypes, such as sarcopenia [8] and bone loss [9], have been reported. In a rare study analyzing both TL and DNAm age, the development of symptoms of posttraumatic stress syndrome was associated with both variables—in plausibly opposite, yet altogether unexpected directions—but their mutual correlation apparently was not investigated [11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
