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

Abstract

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_2.5), 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 PM_2.5 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 PM_2.5 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 PM_2.5 (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 PM_2.5 (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 PM_2.5 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-termambient particle levels with DNAm-age and suggest that DNAm-age is a biomarker of particle-related physiological processes.

Keywords: DNA methylation age; Epigenetics; black carbon; particulate matter 2.5.

Figure 1:

volcano plot of regression coefficients for difference in DNA methylation beta values from 353 DNAm-age CpGs analyzed for association with 1-year PM_2.5 levels in a two-particle model. Linear mixed effects models were used to explore the associations between 1-Year PM_2.5 exposure levels and DNA methylation values for the 353 CpG sites used to calculate DNAm-age. The regression coefficient for the difference in DNA methylation beta values given by a 1 µg/m³ increase in 1-year PM_2.5 exposure level is plotted on the x-axis, and the corresponding significance is plotted on the y-axis. CpG probes meeting statistical significance following FDR adjustment are depicted as hollow circles. DNA methylation beta values range from 0 (completely unmethylated) to 1 (completely methylated).