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 (PM), 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 PM 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 ( = 1032 observations). Blood DNAm-age was calculated using 353 CpG sites from the Illumina HumanMethylation450 BeadChip. We estimated associations of PM 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/m increase in PM (95% CI: 0.30, 0.75, <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, = 0.02). Only PM (β = 0.54, 95% CI: 0.24, 0.84, = 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 PM levels in our two-particle models. Several of these CpGs mapped to genes implicated in lung pathologies including , and .

CONCLUSION

Our results support an association of long-termambient particle levels with DNAm-age and suggest that DNAm-age is a biomarker of particle-related physiological processes.