Associations between long-term exposure to PM_2.5 component species and blood DNA methylation age in the elderlyThe VA normative aging study

Background Long-term PM_2.5 exposure and aging have been implicated in multiple shared diseases; studying their relationship is a promising strategy to further understand the adverse impact of PM_2.5 on human health. Objective We assessed the relationship of major PM_2.5 component species (ammonium, elemental carbon, organic carbon, nitrate, and sulfate) with Horvath and Hannum DNA methylation (DNAm) age, two DNA methylation-based predictors of chronological age. Methods This analysis included 552 participants from the Normative Aging Study with multiple visits between 2000 and 2011 (n = 940 visits). We estimated 1-year PM_2.5 species levels at participants' addresses using the GEOS-chem transport model. Blood DNAm-age was calculated using CpG sites on the Illumina HumanMethylation450 BeadChip. We fit linear mixed-effects models, controlling for PM_2.5 mass and lifestyle/environmental factors as fixed effects, with the adaptive LASSO penalty to identify PM_2.5 species associated with DNAm-age. Results Sulfate and ammonium were selected by the LASSO in the Horvath DNAm-age models. In a fully-adjusted multiple-species model, interquartile range increases in both 1-year sulfate (95%CI0.28, 0.74, P < 0.0001) and ammonium (95%CI0.02, 0.70, P = 0.04) levels were associated with at least a 0.36-year increase in Horvath DNAm-age. No PM_2.5 species were selected by the LASSO in the Hannum DNAm-age models. Our findings persisted in sensitivity analyses including only visits with 1-year PM_2.5 levels within US EPA national ambient air quality standards. Conclusion Our results demonstrate that sulfate and ammonium were most associated with Horvath DNAm-age and suggest that DNAm-age measures differ in their sensitivity to ambient particle exposures and potentially disease.