Exposure to polycyclic aromatic hydrocarbons and accelerated DNA methylation aging

Abstract

BACKGROUND: Aging is related to an increased risk of morbidity and mortality and is affected by environmental factors. Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse health outcomes; but the association of such exposure with DNA methylation aging, a novel aging marker, is unclear. OBJECTIVES: Our aim was to investigate the association of PAH exposure with methylation aging. METHODS: We trained and validated a methylation age predictor suitable for Chinese populations using whole blood methylation data in 989 Chinese and 160 Caucasians. We defined two aging indicators: Dage, as methylation age minus chronological age; and aging rate, the ratio of methylation to chronological age. The association of PAH exposure with aging indicators was evaluated using linear regressions in three panels of healthy Chinese participants (N = 539, among the aforementioned 989 Chinese participants) whose exposure levels were assessed by 10 urinary monohydroxy-PAH metabolites. RESULTS: We developed a methylation age predictor providing accurate predictions in both Chinese individuals and Caucasian persons (R = 0:94–0:96, RMSE = 3:8–4:3). Among the 10 urinary metabolites that we measured, 1-hydroxypyrene and 9-hydroxyphenanthrene were associated with methylation aging independently of other OH-PAHs and risk factors; 1-unit increase in 1-hydroxypyrene was associated with a 0.53-y increase in Dage [95% confidence interval (CI): 0.18, 0.88; false discovery rate (FDR) FDR =0:004] and 1.17% increase in aging rate (95% CI: 0.36, 1.98; FDR =0:02), whereas for 9-hydroxyphenanthrene, the increase was 0.54-y for Dage (95% CI: 0.17, 0.91; FDR =0:004), and 1.15% for aging rate (95% CI: 0.31, 1.99; FDR =0:02). The association direction was consistent across the three Chinese panels with the association magnitude correlating with the panels’ exposure levels; the association was validated by methylation data of purified leukocytes. Several cytosine-phosphoguanines, including those located on FHL2 and ELOVL2, were found associated with both aging indicators and monohydroxy-PAH levels. CONCLUSIONS: We developed a methylation age predictor specific for Chinese populations but also accurate for Caucasian populations. Our findings suggest that exposure to PAHs may be associated with an adverse impact on human aging and epigenetic alterations in Chinese populations.