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

Abstract

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.

Accelerated Epigenetic Ageing in Major Depressive Disorder

“…Further, each method involves almost entirely non-overlapping CpG sites. Although both methods perform similarly in their prediction of mortality (14,36), previous studies have also reported differences in their associations between other traits of interest, for example exposure to environmental particulate matter (37), with neural integrity in post-traumatic stress disorder (36), and with longevity (38). These studies, together with the current findings, therefore suggest that the two DNAm age biomarkers of biological ageing may reflect subtly different aspects of the ageing process.…”

Impacts of the Mitochondrial Genome on the Relationship of Long-Term Ambient Fine Particle Exposure with Blood DNA Methylation Age

“…The number of studies examining relationships of ambient PM2.5 with DNAm-age are limited, but our results are consistent with what they report 8, 10, 52 . Here, we observed comparable, significant positive associations of PM2.5, sulfate, and ammonium with DNAm-age.…”

“…We began with a total of 552 participants with 940 observations between the years 2000 and 2011. This was the study sample that was used in reporting the significant associations between PM2.5 component species and DNAm-age in our previous publication 10 . Of these 552 participants, 249 (45%) had one visit, 218 (40%) had two visits, and 85 (15%) had three or more visits.…”

“…We used the simulation outputs from GEOS-chem, a chemical transport model 35 , fused with land-use variables to generate one-year exposure estimates for PM2.5 as well as sulfate and ammonium, the major PM2.5 component species demonstrated to be most important in predicting DNAm-age 10 . Ten-fold cross-validation demonstrated that the model performed well for PM2.5 mass and its component species with R 2 s ranging from 0.70 to 0.88 36 .…”

Environmentally Induced Epigenetic Plasticity in Development: Epigenetic Toxicity and Epigenetic Adaptation

“…DNA methylation age is a novel epigenome-wide DNA methylation-based measure of individual biological aging predicting the chronological age [58] as well as capturing the interpersonal differences in the risk of many functional alterations, diseases and mortality [59]. In adults, increased PM 2.5 exposure has been linked to accelerated DNA methylation age [60–62], which provides an improved understanding of the role of PM 2.5 as a contributor to accelerated aging and aging-related diseases [63–67], such as cardiopulmonary disease, cognitive decline. Other perturbation-related DNA methylation age modification are also documented.…”