FIGURE 2.

DNA methylation patterns of monozygotic twins diverge during aging. Despite early similarities, stochastic changes occur in the methylome of each twin, A and B during aging. Epigenetic drift results in age-related hypermethylation of CpG-rich sequences such as CGI promoters, typically found in ubiquitously expressed housekeeping genes, which may be switched off as a result of aberrant age-related methylation. In contrast, highly methylated, transcriptionally repressed CpG-poor promoters tend to become hypomethylated during aging, leading to aberrant gene expression. Tandem satellite repeat sequences in the telomere are also heavily methylated which may promote genome stability and inhibit recombination. Hypermethylated interspersed repeats such as LTRs, SINEs, and LINEs tend to undergo generalized hypomethylation during aging. ^⋆A selection of CpGs undergo programed reproducible methylation changes across the population during aging and have been incorporated into epigenetic clock algorithms used to accurately predict epigenetic age. Each lollipop represents an individual CpG, arrows indicate transcription start sites, X indicates transcriptional repression. CGI, CpG island; LINE, long interspersed nuclear element; LTR, long terminal repeat; SINE, short interspersed nuclear element.