Short-Term Exposure of PM_2.5 and Epigenetic Aging: A Quasi-Experimental Study

Abstract

Epigenetic age (EA) is an emerging DNA methylation-based biomarker of biological aging, but whether EA is causally associated with short-term PM_2.5 exposure remains unknown. We conducted a quasi-experimental study of 26 healthy adults to test whether short-term PM_2.5 exposure accelerates seven EAs with three health examinations performed before, during, and after multiple PM_2.5 pollution waves. Seven EAs were derived from the DNA methylation profiles of the Illumina HumanMethylationEPIC BeadChip from CD4+ T-helper cells. We found that an increase of 10 μg/m³ in the 0-24 h personal PM_2.5 exposure prior to health examinations was associated with a 0.035, 0.035, 0.050, 0.055, 0.052, and 0.037-unit increase in the changes of z-scored DNA methylation age acceleration (AA,Horvath), AA (Hannum), AA (GrimAge), DunedinPoAm, mortality risk score (MS), and epiTOC, respectively (<i>p</i>-values < 0.05). The same increase in the 24-48 h average personal PM_2.5 exposure yielded smaller effects but was still robustly associated with the changes in AA (GrimAge), DunedinPoAm, and MS. Such acute aging effects of PM_2.5 were mediated by the changes in several circulating biomarkers, including EC-SOD and sCD40L, with up to ∼28% mediated proportions. Our findings demonstrated that short-term PM_2.5 exposure could accelerate aging reflected by DNA methylation profiles via blood coagulation, oxidative stress, and systematic inflammation.