Epigenetic drift

Epigenetic drift describes the progressive, largely stochastic divergence of DNA methylation patterns between cells, tissues, and individuals as age advances. The landmark demonstration was Fraga and colleagues' 2005 PNAS study showing that monozygotic twins start life nearly epigenetically identical but accumulate substantial differences in global and locus-specific 5-methylcytosine and histone acetylation with age and environmental exposure. Drift differs conceptually from the clock-like, deterministic methylation changes exploited by Horvath-type epigenetic age estimators: drift adds noise and reduces inter-cell coherence, whereas clock signal is directional. Issa (2014) framed drift as a vicious cycle in which environmental insults degrade the epigenome and predispose to age-related disease and cancer. Drift is now a recognised hallmark of aging.