Ambient long-term air pollution exposure and epigenetic aging clocks: A systematic review and meta-analysis

Ambient air pollution may accelerate biological aging, but the extent of its impact remains uncertain. Epigenetic clocks capture aging by comparing biological to chronological age, highlighting whether an individual is aging biologically faster (accelerating) or slower (decelerating) than expected. This systematic review and meta-analysis aimed to evaluate the association between long-term outdoor air pollution exposure [particulate matter (PM_2.5, PM₁₀), nitrogen dioxide (NO₂), or black carbon (BC)] and epigenetic clocks. We systematically searched the databases of PubMed, Scopus, and Google Scholar until April 2025. Random-effects models were used to estimate beta coefficients for the association between air pollutants and epigenetic age acceleration (EAA). The study protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO: CRD42024628148). Our meta-analysis included 18 studies with a combined sample size of 363,381 participants. Using the Horvath EAA, no significant associations were found for all pollutants [per 5 μg/m³ PM_2.5: 0.523 y (95 %CI: -0.136, 1.182, p = 0.12); 5 μg/m³ PM₁₀: 0.043 y (95 %CI: -0.281, 0.366, p = 0.80); 10 μg/m³ NO₂: -0.078 y (95 %CI: -0.201, 0.044, p = 0.21); 0.5 μg/m³ BC: 0.268 y (95 %CI: -0.165, 0.701, p = 0.23)]. In a sensitivity analysis, when only including adult populations, the effect for a 5 µg/m³ increase in PM_2.5 was more pronounced [0.740 y (95 %CI: -0.050, 1.529, p = 0.066)]. For PhenoAge EAA, inconsistent associations between pollutants and epigenetic aging were observed, which were driven by a single study. Finally, for GrimAge EAA, no associations with pollutant exposures were identified. In conclusion, this meta-analysis suggests a potential weak association between ambient particulate air pollution exposure and Horvath epigenetic age acceleration in adults; however, this currently lacks statistical significance. Other epigenetic clocks showed inconsistent or no associations. Additional high-quality longitudinal studies are needed to clarify the nature and strength of the potential link between air pollution exposure and epigenetic aging.