We explore the relationship between epigenetic aging and drug metabolism. We review current evidence for changes in drug metabolism in normal aging, followed by a description of how epigenetic modifications associated with age can regulate the expression and functionality of genes. In particular, we focus on the role of epigenome-wide studies of human and mouse liver in understanding these age-related processes with respect to xenobiotic processing. We highlight genes encoding drug metabolizing enzymes and transporters revealed to be affected by epigenetic aging in these studies. We conclude that substantial evidence exists for epigenetic aging impacting drug metabolism and transport genes, but more work is needed. We further highlight the promise of pharmacoepigenetics applied to enhancing drug safety in older adults.
Keywords: DNA methylation; cytochrome P450s; drug metabolism; drug transporters; geriatrics; histone modifications; older adults; pharmacotherapy.