Research Paper Volume 13, Issue 11 pp 14604—14629

Accelerated DNA methylation age and medication use among African Americans

Minjung Kho1, , Yi Zhe Wang1, , Dima Chaar1, , Wei Zhao1, , Scott M. Ratliff1, , Thomas H. Mosley2, , Patricia A. Peyser1, , Sharon L.R. Kardia1, , Jennifer A. Smith1, ,

  • 1 Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA
  • 2 Memory Impairment and Neurodegenerative Dementia (MIND) Center, University of Mississippi Medical Center, Jackson, MS 39216, USA

Received: January 9, 2021       Accepted: May 14, 2021       Published: June 3, 2021
How to Cite

Copyright: © 2021 Kho et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


DNA methylation age acceleration, the discrepancy between epigenetic age and chronological age, is associated with mortality and chronic diseases, including diabetes, hypertension, and hyperlipidemia. In this study, we investigate whether medications commonly used to treat these diseases in 15 drug categories are associated with four epigenetic age acceleration measures: HorvathAge acceleration (HorvathAA), HannumAge acceleration (HannumAA), PhenoAge acceleration, and GrimAge acceleration (GrimAA) using cross-sectional (Phase 1, N=1,100) and longitudinal (Phases 1 and 2, N=266) data from African Americans in the Genetic Epidemiology Network of Arteriopathy (GENOA) study. In cross-sectional analyses, the use of calcium channel blockers was associated with 1.27 years lower HannumAA after adjusting for covariates including hypertension (p=0.001). Longitudinal analyses showed that, compared to those who never used antihypertensives, those who started to take antihypertensives after Phase 1 had a 0.97-year decrease in GrimAA (p=0.007). In addition, compared to those who never used NSAID analgesics, those who started to take them after Phase 1 had a 2.61-year increase in HorvathAA (p=0.0005). Our study demonstrates that three commonly used medications are associated with DNAm age acceleration in African Americans and sheds light on the potential epigenetic effects of pharmaceuticals on aging at the cellular level.


ADM: adrenomedullin; ADRs: adverse drug reactions; ARB: angiotensin receptor type I blocker; ACEI: Angiotensin-converting enzyme inhibitor; B2M: beta-2 microglobulin; CVD: cardiovascular disease; CystatinC: Cystatin C; DNAm: DNA methylation; GENOA: Genetic Epidemiology Network of Arteriopathy; GrimAA: GrimAge acceleration; GDF15: growth differentiation factor 15; HannumAA: HannumAge acceleration; HS: high school; HDL: high-density lipoproteins; HorvathAA: HorvathAge acceleration; Leptin: leptin; LDL: low-density lipoproteins; MTC: Medi-Span Therapeutic Classification; NSAIDs: nonsteroidal anti-inflammatory drugs; NAS: Normative Aging Study; PhenoAA: PhenoAge acceleration; PAI1: plasminogen activation inhibitor 1; PVCA: principal variance component analysis; RCP: Regression on Correlated Probes; RAAS: renin–angiotensin–aldosterone system; SST: somatostatin; PACKYRS: the amount of cigarettes smoked in pack-years; TIMP1: tissue inhibitor metalloproteinase 1.