Long-term ambient particle exposures and blood DNA methylation age: Findings from the VA normative aging study

Background: Ambient particles have been shown to exacerbate measures of biological aging; yet, no studies have examined their relationships with DNA methylation age (DNAm-age), an epigenome-wide DNA methylation based predictor of chronological age. Objective: We examined the relationship of DNAm-age with fine particulate matter (PM2.5), a measure of total inhalable particle mass, and black carbon (BC), a measure of particles from vehicular traffic. Methods: We used validated spatiotemporal models to generate 1-year PM2.5 and BC exposure levels at the addresses of 589 older men participating in the VA Normative Aging Study with 1-3 visits between 2000 and 2011 (n = 1032 observations). Blood DNAm-age was calculated using 353 CpG sites from the Illumina HumanMethylation450 BeadChip. We estimated associations of PM2.5 and BC with DNAm-age using linear mixed effects models adjusted for age, lifestyle/environmental factors, and aging-related diseases. Results: After adjusting for covariates, a 1-μg/m3 increase in PM2.5 (95% CI: 0.30, 0.75, P < 0.0001) was significantly associated with a 0.52-year increase in DNAm-age. Adjusted BC models showed similar patterns of association (β = 3.02, 95% CI: 0.48, 5.57, P = 0.02). Only PM2.5 (β = 0.54, 95% CI: 0.24, 0.84, P = 0.0004) remained significantly associated with DNAm-age in two-particle models. Methylation levels from 20 of the 353 CpGs contributing to DNAm-age were significantly associated with PM2.5 levels in our two-particle models. Several of these CpGs mapped to genes implicated in lung pathologies including LZTFL1, PDLIM5, and ATPAF1. Conclusion: Our results support an association of long-term ambient particle levels with DNAm-age and suggest that DNAm-age is a biomarker of particle-related physiological processes.