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 two 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 (DNAm). Data come from the 2016 Health and Retirement Study DNAm 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 five epigenetic aging measures: Horvath, Hannum, PhenoAge, GrimAge, DunedinPACE. Four categories of joint PM2.5 and heat were analyzed: (1=reference) low PM2.5 (<9.2 𝜇g/m3) and low heat (<80 on heat index); (2) low PM2.5 and high heat; (3) high PM2.5 and low heat; and (4) 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 DNAm aging for Horvath (𝛽=0.74 95%CI:0.04, 1.15), Hannum (𝛽=0.74 95% CI:0.20, 1.28) and PhenoAge (𝛽=0.93 95% CI:0.33, 1.52). High PM2.5 and low heat had weaker associations (Horvath 𝛽=-0.001 95%CI:-0.68, 0.68, Hannum 𝛽=0.36 95%CI:-034, 1.05; PhenoAge 𝛽=0.18 95%CI:-0.56, 0.92), as did joint effects of high PM2.5 and high heat (Horvath 𝛽=0.11 95%CI:-0.68, 0.89, Hannum 𝛽=0.42 95%CI:-0.46, 1.20; PhenoAge 𝛽=0.56 95%CI:-0.30, 1.42). Exposure to short-term high heat and low air pollution may accelerate epigenetic aging.