Developmental Tuning of Epigenetic Clock

Abstract

Research in the field of gerontology has traditionally focused on later life stages. There is increasing evidence, however, that both the rate of age-related functional decline and the later-life health status can be programmed during early development. The central role of epigenetic mechanisms (methylation of DNA, histone modifications and regulation by non-coding RNAs) in mediating these long-term effects has been elucidated. Both rate and direction of age-associated change of epigenetic patterns ("epigenetic drift") were shown to be largely dependent on early-life environmental conditions. Inter-individual divergences in epigenetic profiles may arise following the stochastic errors in maintaining epigenetic marks, but they may also be adaptively mediated by specific environmental cues. Recent cohort studies indicate that ticking rate of epigenetic clock, estimated by a DNA methylation-based methods, may be developmentally adjusted, and that individual's discrepancies among epigenetic and chronological age would be likely programmed early in development. In this Perspective article, recent findings suggesting the importance of early-life determinants for life-course dynamics of epigenetic drift are summarized and discussed.

Keywords: DNA methylation; age-related disease; aging rate; developmental programming; epigenetic clock; epigenetic drift.

FIGURE 1

Hypothetical modes of life-course dynamics of epigenetic aging. (A) premature epigenetic aging; (B) accelerated epigenetic aging; and (C) slowed epigenetic aging. In all panels, red lines represent subjects exposed to adverse early-life events and black lines represent unexposed subjects.