Short-term Exposure to PM2.5 and Epigenetic Aging: A Quasi-Experimental Study

Abstract

BACKGROUND AND AIM: Fine particulate matter 2.5μm in aerodynamic diameter (PM2.5), has been considered a global threat to accelerated biological aging. DNA methylation age (DNAmAge) is one of the most studied forms of biological age, its discrepancy with chronological age (i.e. age acceleration, AA) was associated with multiple aging-related health outcomes and had positive associations with long-term PM2.5 exposure. However, the associations of the AAs with short-term PM2.5 exposure are still partly understood. In order to elucidate the causal associations between short-term PM2.5 and DNAmAge, we performed a quasi-experiment with a social experiment design in 26 healthy adults. We aimed to understand whether short-term PM2.5 exposure via PM2.5 pollution waves (PPWs, ambient PM2.5 concentration 75 μg/m3 for 2 or more days) could accelerate the AAs. METHODS: We conducted three visits of the participants: pre-PPW (baseline), during-PPW (1st follow-up), and post-PPW (2nd follow-up). DNA isolated from collected peripheral CD4+ T-helper cells was used to detect DNA methylation levels. Seven forms of AAs including Horvath’s, Hannums’, PhenoAge, GrimAge, DunedinPoAm, mortality risk score, and epiTOC were estimated. RESULTS:Comparing to the baseline, we first observed that all AAs increased during the PPWs and considerably declined after the PPWs, albeit not statistically significant. We further tested the associations of the change in AAs between the two follow-ups with the average personal PM2.5 exposure 0-24h and 24-48h prior to the blood collection. We found that the z-scored AAs of GrimAge and DunedinPoAm were significantly elevated by 0.097 and 0.081-unit with a 5 μg/m3 increase in 0-24h personal PM2.5 exposure. Such acute effects were mediated by several oxidative and inflammation biomarkers with up to 18% mediated proportions. CONCLUSIONS:This quasi-experiment exhibited that short-term exposures to high levels of PM2.5 could moderately accelerate biological aging, which could be captured by the GrimAge and DunedinPoAm, and mediated by the inflammation responses and oxidative stress. KEYWORDS: Air pollution, PM2.5, DNA methylation age, biological aging