Bronchial Cell Epigenetic Aging in a Human Experimental Study of Short-term Diesel and Ozone Exposures.

Blood-based, observational, and cross-sectional epidemiological studies suggest that air pollutant exposures alter biological aging. In a single-blinded randomized crossover human experiment of seventeen volunteers, we examined the effect of randomized 2-hour controlled air pollution exposures on respiratory tissue epigenetic aging. Bronchial epithelial cell DNA methylation (DNAm) 24-hours post-exposure was measured using the HumanMethylation450K BeadChip, and there was a minimum 2-week washout period between exposures. All seventeen volunteers were exposed to ozone, but only thirteen were exposed to diesel exhaust. Horvath DNAmAge (Pearson coefficient [r]=0.64; Median Absolute Error [MAE]=2.7-years), GrimAge (r=0.81; MAE=13-years), and DNAm Telomere Length (DNAmTL) (r=-0.65) were strongly correlated with chronological age in this tissue. Compared to clean air, ozone exposure was associated with longer DNAmTL (median difference 0.11kb, Fisher-exact p-value=0.036). This randomized trial suggests a weak relationship of ozone exposure with DNAmTL in target respiratory cells. Still, causal relationships with long-term exposures need to be evaluated.