Person:

Trevisi, Letizia

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-termambient particle levels with DNAm-age and suggest that DNAm-age is a biomarker of particle-related physiological processes.

Background: The mitochondrion is the primary target of oxidative stress in response to exogenous environments. Mitochondrial DNA (mtDNA) is independent from nuclear DNA and uses separate epigenetic machinery to regulate mtDNA methylation. The mtDNA damage induced by oxidative stress can cause mitochondrial dysfunction and is implicated in human diseases; however, mtDNA methylation has been largely overlooked in environmental studies relating to human disease. The purpose of this study was to examine the association between exposure to fine metal‐rich particulates (particulate matter <2.5 µm in diameter [PM2.5]) from welding in a boilermaker union and blood mtDNA methylation in relation to heart rate variability. Methods and Results: Forty‐eight healthy men were recruited on multiple sampling cycles at the Boilermaker Union Local 29, located in Quincy, Massachusetts. We measured personal PM2.5 in the background ambient environment. We measured blood mtDNA methylation in the mtDNA promoter (D‐loop) and genes essential for ATP synthesis (MT‐TF and MT‐RNR1) by bisulfite pyrosequencing. All analyses were adjusted for demographics, type of job, season, welding‐work day, and mtDNA methylation experimental batch effect. The participants’ PM2.5 exposure was significantly higher after a welding‐work day (mean 0.38 mg/m3) than the background personal level (mean 0.15 mg/m3, P<0.001). Blood mtDNA methylation in the D‐loop promoter was associated with PM2.5 levels (β=−0.99%, SE=0.41, P=0.02). MT‐TF and MT‐RNR1 methylation was not associated with PM2.5 exposure (β=0.10%, SE=0.45, P=0.82). Interaction of PM2.5 exposure levels and D‐loop promoter methylation was significantly associated with markers of heart rate variability. Conclusions: Blood mtDNA methylation levels were negatively associated with PM2.5 exposure and modified the adverse relationships between PM2.5 exposure and heart rate variability outcomes.