The Joint Effects of Exposure to Ambient Long-term Air Pollution and Short-term Heat on Epigenetic Aging in the Health and Retirement Study

Prior research has examined associations of exposure to air pollution and heat with epigenetic alterations separately; however, these 2 exposures commonly used to measure climate change typically co-occur. We examine joint effects of exposure to elevated PM2.5 and heat on DNA methylation.Data come from the 2016 Health and Retirement Study DNA Methylation Sample (N = 3 947) and census tract level annual ambient PM2.5 concentrations and daily heat index data averaged 7 days before blood collection. We used 5 epigenetic aging measures: Horvath, Hannum, PhenoAge, GrimAge, and DunedinPACE. Four categories of joint PM2.5 and heat were analyzed: (a = reference) low PM2.5 (<9.2 <mu>g/m3) and low heat (<80 on heat index); (b) low PM2.5 and high heat; (c) high PM2.5 and low heat; and (d) high PM2.5 and high heat. Linear regression models were adjusted for age, gender, race/ethnicity, education, neighborhood poverty, and cell type.Compared to the reference of low PM2.5 and heat, we found associations of short-term (7-day) high heat and long-term (annual) low PM2.5 with accelerated DNA methylation aging for Horvath (beta = 0.74, 95% CI: 0.04, 1.15), Hannum (beta = 0.74, 95% CI: 0.20, 1.28), and PhenoAge (beta = 0.93, 95% CI: 0.33, 1.52). High PM2.5 and low heat had weaker associations (Horvath beta = -0.001, 95% CI: -0.68, 0.68, Hannum beta = 0.36, 95% CI: -034, 1.05; PhenoAge beta = 0.18, 95% CI: -0.56, 0.92), as did joint effects of high PM2.5 and high heat (Horvath beta = 0.11, 95% CI: -0.68, 0.89; Hannum beta = 0.42, 95% CI: -0.46, 1.20; PhenoAge beta = 0.56, 95% CI: -0.30, 1.42).Exposure to short-term high heat and low air pollution may accelerate epigenetic aging.