Short-Term Exposure of PM 2.5 and Epigenetic Aging: A Quasi-Experimental Study.

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/m 3 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 ( p -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.