Intratissue DNA Methylation Heterogeneity in Aging

DNA methylation is a critical epigenetic marker involved in development, differentiation, and cell fate diversity. Here we discuss the possible role of adaptive and stochastic changes in DNA methylation in aging. We describe recent progress in studying stochastic changes in DNA methylation, most notably alterations at the level of the single cell. We show that fidelity of individual CpG sites is several orders of magnitude lower than the fidelity of DNA sequence integrity. At this high level of instability, age-related methylation changes could well be a cause of the gradual loss of specific cell fate or differentiation status and, therefore contribute to loss of function and increased disease risk at old age. However, the current lack of a complete understanding of the relationship between DNA methylation patterns and gene expression essentially constrains definite conclusions about the impact of DNA methylation changes on the aging process.