DNA methylation and healthy human aging

Abstract

The process of aging results in a host of changes at the cellular and molecular levels, which include senescence, telomere shortening, and changes in gene expression. Epigenetic patterns also change over the lifespan, suggesting that epigenetic changes may constitute an important component of the aging process. The epigenetic mark that has been most highly studied is DNA methylation, the presence of methyl groups at CpG dinucleotides. These dinucleotides are often located near gene promoters and associate with gene expression levels. Early studies indicated that global levels of DNA methylation increase over the first few years of life and then decrease beginning in late adulthood. Recently, with the advent of microarray and next-generation sequencing technologies, increases in variability of DNA methylation with age have been observed, and a number of site-specific patterns have been identified. It has also been shown that certain CpG sites are highly associated with age, to the extent that prediction models using a small number of these sites can accurately predict the chronological age of the donor. Together, these observations point to the existence of two phenomena that both contribute to age-related DNA methylation changes: epigenetic drift and the epigenetic clock. In this review, we focus on healthy human aging throughout the lifetime and discuss the dynamics of DNA methylation as well as how interactions between the genome, environment, and the epigenome influence aging rates. We also discuss the impact of determining 'epigenetic age' for human health and outline some important caveats to existing and future studies.

Keywords: DNA methylation; aging; epigenetics; human; review.

Figure 1

Schematic representation of epigenetic drift versus the epigenetic clock. If a specific CpG site is associated with age (top) within an individual, it may be undergoing either epigenetic drift (left) or an epigenetic clock site (right). Both phenomena have different characteristics when examined across a population or within a twin set.

Figure 2

The concordance or discordance between epigenetic age and chronological age may be an indicator of future health. (A) Across a population, people can be categorized as epigenetically old, where their epigenetic age is higher than their chronological age, epigenetically young where the reverse is true, or concordant, where neither is true. (B) It is interesting to speculate whether these groups would show divergent trajectories of health as they age.