Air pollution, particulate matter composition and methylation-based biologic age

BACKGROUND: Epigenetic age, as defined by DNA methylation, may be influenced by air pollution exposure. OBJECTIVE: To evaluate the relationship between NO(2), particulate matter (PM), PM components and accelerated epigenetic age. METHODS: In a sample of non-Hispanic white women living in the contiguous U.S. (n = 2747), we estimated residential exposure to PM(2.5), PM(10) and NO(2) using a model incorporating land-use regression and kriging. Predictive k-means was used to assign participants to clusters representing different PM(2.5) component profiles. We measured DNA methylation (DNAm) in blood using the Illumina's Infinium HumanMethylation450 BeadChip and calculated DNAm age using the Hannum, Horvath and Levine epigenetic clocks. Age acceleration was defined based on residuals after regressing DNAm age on chronological age. We estimated associations between interquartile range (IQR) increases in pollutants and age acceleration using linear regression. For PM(2.5), we stratified by cluster membership. We examined epigenome-wide associations using robust linear regression models corrected with false discovery rate q-values. RESULTS: NO(2) was inversely associated with age acceleration using the Hannum clock (β = −0.24, 95% Cl: − 0.47, −0.02). No associations were observed for PM(10). For PM(2.5), the association with age acceleration varied by PM(2.5) component cluster. For example, with the Levine clock, an IQR increase in PM(2.5) was associated with an over 6-year age acceleration in a cluster that has relatively high fractions of crustal elements relative to overall PM(2.5) (β = 6.57, 95% CI: 2.68, 10.47), and an almost 2-year acceleration in a cluster characterized by relatively low sulfur fractions (β = 1.88, 95% CI: 0.51, 3.25). In a cluster distinguished by lower relative nitrate concentrations, PM(2.5) was inversely associated with age acceleration (β = −1.33, 95% CI: −2.43, −0.23). Across the epigenome, NO(2) was associated with methylation at 2 CpG sites. CONCLUSION: Air pollution was associated with epigenetic age, a marker of mortality and disease risk, among certain PM(2.5) component profiles.