Genome instability and aging: Cause or effect?

Genome instability, i.e., the tendency of the genome to undergo alterations in DNA information content through mutation, is considered a hallmark of aging. While mutations can be analyzed in clonal lineages, such as tumors, normal tissues have thus far not been amenable to mutation analysis except for the largest type of mutations: chromosomal aberrations. This is because mutations are random events and, therefore, unique to a single cell. New, single-cell sequencing-based methods are now emerging and may soon provide quantitative assays for estimating the possible functional effects of mutations accumulating during aging in various tissues and organs. Here we briefly review the mechanisms of genome instability in normal cells, the accumulation of various types of genome instability with age and their possible physiological consequences.