Psychological stress and epigenetic aging in older men: The VA normative aging study

• Type of Material: Article
• Authors: Jamaji Nwanaji-Enwerem, Emory University; Andres Cardenas, Stanford University; Xu Gao, Peking University; Cuicui Wang, Harvard T.H. Chan School of Public Health; Pantel Vokonas, Boston University; Avron Spiro, VA Boston Healthcare System; Anwar Osborne, Emory University; Anna Kosheleva, Harvard T.H. Chan School of Public Health; Lifang Hou, Northwestern University; Andrea A. Baccarelli, Mailman School of Public Health; Joel Schwartz, Harvard T.H. Chan School of Public Health
• Language: English
• Date: 2023-01-01
• Publisher: Elsevier: ScienceDirect
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.tma.2023.06.003
• Title of Journal or Parent Work: Translational Medicine of Aging
• Volume: 7
• Start Page: 66
• End Page: 74
• Grant/Funding Information: This work was supported by National Institutes of Health (R01ES025225, R01ES021733, R01ES027747, P30ES009089, R03AG067064, R01AG018436, and R01ES031259); The VA Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Centers of the U.S. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center, Boston, Massachusetts.
• Keywords: biological age; DNA methylation; trauma; epigenetic clock; DNAm Age; perceived stress
• Research Categories: Biology, Genetics

Abstract

Psychological stress remains an important risk factor for morbidity and mortality throughout the life course. However, there have been counterintuitive findings reported in previous studies of older persons that examine the relationships of perceived psychological stress with DNA methylation-based markers of aging, which also serve as predictors of morbidity and mortality (epigenetic age/clocks). We aimed to replicate and expand findings from existing work by examining relationships of self-reported stress with nine epigenetic clocks: Hannum, Horvath, Intrinsic, Extrinsic, SkinBloodClock, PhenoAge, GrimAge, DNAm Telomere Length, and Pace of Aging. We analyzed data from 607 male participants (mean age 73.2 years) of the VA Normative Aging Study with one to two study visits from 1999 to 2007 (observations = 956). Stress was assessed via the 14-item Perceived Stress Scale (PSS). Epigenetic age was calculated from DNA methylation measured in leukocytes with the HumanMethylation450 BeadChip. In linear mixed effects models adjusted for demographic/lifestyle/health factors, a standard deviation (sd) increase in PSS was associated with Horvath (β = −0.35-years, 95%CI: −0.61, −0.09, P = 0.008) and Intrinsic (β = −0.40-years, 95%CI: −0.67, −0.13, P = 0.004) epigenetic age deceleration. However, in models limited to participants with the highest levels of stress (≥75th-percentile), Horvath (β = 2.29-years, 95%CI: 0.16, 4.41, P = 0.04) and Intrinsic (β = 2.06-years, 95%CI: −0.17, 4.28, P = 0.07) age acceleration associations were observed. Our results reinforce the complexity of psychological stress and epigenetic aging relationships and lay a foundation for future studies that explore longitudinal relationships with other adult stress metrics and factors that can influence stress such as resilience measures.