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 PM_2.5 exposure and aging have been implicated in multiple shared diseases; studying their relationship is a promising strategy to further understand the adverse impact of PM_2.5 on human health.

Objective: We assessed the relationship of major PM_2.5 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 PM_2.5 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 PM_2.5 mass and lifestyle/environmental factors as fixed effects, with the adaptive LASSO penalty to identify PM_2.5 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 PM_2.5 species were selected by the LASSO in the Hannum DNAm-age models. Our findings persisted in sensitivity analyses including only visits with 1-year PM_2.5 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.

Keywords: DNA methylation age; Epigenetics; Long-term exposure; Particulate matter 2.5.

Fig. 1

A) The relationship between BIC, a criterion for model selection and λ (lambda), the adaptive LASSO penalty parameter, for DNAm-age. The vertical line at λ = 11 denotes the penalty parameter with the lowest BIC. B) LASSO coefficient paths: plot of coefficient profiles for PM_2.5 components as a function of λ. At λ = 11, sulfate and ammonium are the only PM_2.5 components with a non-zero coefficient.