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 17 volunteers, we examined the effect of randomized 2-h controlled air pollution exposures on respiratory tissue epigenetic aging. Bronchial epithelial cell DNA methylation 24 h post-exposure was measured using the HumanMethylation450K BeadChip, and there was a minimum 2-week washout period between exposures. All 17 volunteers were exposed to ozone, but only 13 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 0.11 kb, Fisher's exact P-value = .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.