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

Clin Epigenetics. 2016 Feb 26;8:21. doi: 10.1186/s13148-016-0186-5. eCollection 2016.


Background: 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, however, on its association with telomere length and frailty, which can be considered major correlates of age on the genomic and clinical level, respectively.

Results: In 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.

Conclusions: The 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.

Keywords: CpG methylation; Cross-sectional study; Epigenetic age acceleration; Frailty index; General population; Telomere length.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / genetics
  • Aging, Premature / genetics
  • Cross-Sectional Studies
  • DNA Methylation
  • Epigenesis, Genetic*
  • Female
  • Frail Elderly* / statistics & numerical data
  • Germany / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Telomere Shortening*