The epigenome of aging

Abstract

Two major theories have been described to explain aging: the DNA damage theory of aging and the heterochromatin loss model of aging. The DNA damage theory of aging states that increasing accumulation of DNA damage accelerates aging while the heterochromatin loss model hypothesizes that the decay of heterochromatin formation is a hallmark of aging. The DNA damage response pathway as well as the heterochromatin formation requires epigenetic modulators, and thus both these theories encompass changes in the epigenome of a cell which is interplay between histone modifying enzymes, histone variants, ATP-dependent chromatin remodeling proteins, DNA methylation, and non-coding. It is also well documented that the epigenome changes through the life of an organism, a process termed epigenetic drift. Experimental data have shown that the epigenetic modulators perform an important role in defining the lifespan and changes in the epigenome are linked to aging as well as age-related disorders. These epigenetic alterations are one of the nine defining hallmarks of aging. In this review, I will focus on the role of epigenetic modulators in DNA damage response pathway as well as heterochromatin formation and the alterations effected by these modulators on the epigenome during aging.