Aging and epigenetic drift: a vicious cycle

Abstract

The term epigenetics refers to stable patterns of gene expression that are seen during differentiation or X chromosome inactivation and are not dependent on dynamic changes in coding DNA. These gene expression states are encoded in the epigenome -a collection of marks on DNA or on histone tails that are established during embryogenesis. Genome-wide studies in aging cells and tissues have uncovered stochastic DNA methylation drift (gradual increases or decreases at specific loci) that reflects imperfect maintenance of epigenetic marks. Drift creates epigenetic mosaicism in aging stem cells that could potentially restrict their plasticity and worsen phenotypes such as stem cell exhaustion and focal proliferative defects that can lead to cancer.

Identification of differentially methylated markers among cytogenetic risk groups of acute myeloid leukemia

“…Recent studies targeting the whole genome demonstrated overall hypomethylation in association with aging as well as increased methylation in specific promoter CGIs. [26][27][28] In this study, we also observed decreased methylation in older patients. However, the methylation difference between "younger" and "older" AML patients was less prominent than the difference between cytogenetic risk groups.…”

Longitudinal epigenetic drift in mice perinatally exposed to lead

“…1 Studies of aging and genetic dysregulation (e.g., cancer) support a decrease in global genomic DNA methylation (hypomethylation) concurrent with locus-specific increases in DNA methylation (hypermethylation). 2,3 Consequently, epigenetic drift has emerged as a biomarker for aging, with increased DNA methylation targeting developmental genes. 1,4 The preponderance of evidence to date, however, has been measured in crosssectional samples, thereby lacking a longitudinal component of evaluating DNA methylation changes in paired samples over time.…”

DNA methylation and chromatin dynamics during postnatal cardiomyocyte maturation

“…This phenomenon is highly reminiscent of previously reported patterns of DNA methylation associated with aging and cancer (Issa, 2014). Specifically, methylation drift occurs during aging and cancer development, with numerous studies identifying an increase in site-specific DNA methylation (e.g.…”