Associations between long-term exposure to PM2.5 component species and blood DNA methylation age in the elderly: The VA normative aging study.

BACKGROUND Long-term PM2.5 exposure and aging have been implicated in multiple shared diseases; studying their relationship is a promising strategy to further understand the adverse impact of PM2.5 on human health. OBJECTIVE We assessed the relationship of major PM2.5 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 PM2.5 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 PM2.5 mass and lifestyle/environmental factors as fixed effects, with the adaptive LASSO penalty to identify PM2.5 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%CI: 0.28, 0.74, P<0.0001) and ammonium (95%CI: 0.02, 0.70, P=0.04) levels were associated with at least a 0.36-year increase in Horvath DNAm-age. No PM2.5 species were selected by the LASSO in the Hannum DNAm-age models. Our findings persisted in sensitivity analyses including only visits with 1-year PM2.5 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.