Epigenetic Regulation of Drug Metabolism in Aging: Utilizing Epigenetics to Optimize Geriatric Pharmacotherapy

Abstract

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.

Tweetable abstract

Evidence is emerging that epigenetic aging affects the regulation of genes involved in drug metabolism and transport. This may stimulate development of new biomarkers for drug safety in older adults.

Keywords: :

• cytochrome P450s
• drug metabolism
• DNA methylation
• drug transporters
• geriatrics
• histone modifications
• older adults
• pharmacotherapy

Author contributions

S Abudahab and JL McClay contributed to the design and conception and review of the manuscript. S Abudahab wrote the first draft of the manuscript. S Abudahab, PW Slattum, ET Price and JL McClay contributed to the conceptualization of the review. S Abudahab, PW Slattum, ET Price and JL McClay reviewed, edited and approved the submitted version.

Financial disclosure

This work was funded by the National Institute on Aging (NIA), US National Institutes of Health, through grant R15AG061649 to JL McClay. S Abudahab was supported by R15AG061649 and a graduate studentship from Virginia Commonwealth University School of Pharmacy. S Abudahab completed this study in partial fulfillment of the doctoral (PhD) requirements in Pharmaceutical Sciences at Virginia Commonwealth University. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.