Aging biomarkers: Potential mediators of association between long-term ozone exposure and risk of atherosclerosis

Background: Long-term exposure to ambient ozone links to aging biomarkers and increased risk for atherosclerotic cardiovascular diseases (ASCVD). However, the roles of aging biomarkers in the association of long-term exposure to ambient ozone with ASCVD are unclear. Methods: A total of 5298 participants completed the questionnaire and physical examination and provided biological specimens. Aging biomarkers (telomere length [TL] and mitochondrial copy number [mtDNA-CN]) were measured by using a real-time polymerase chain reaction method. The concentration of ambient ozone was assessed using a random forest model. Associations of ambient ozone or aging biomarkers with 10-year ASCVD risk were analyzed using logistic regression models. The roles of aging biomarkers in the association of ambient ozone exposure with 10-year ASCVD risk were explored by mediation analysis. Results: The adjusted odds ratios and 95% confidence interval of high 10-year ASCVD risk were 1.16 (1.08, 1.25), 0.71 (0.60, 0.85), and 0.78 (0.64, 0.96) in association with each 1-unit increment in ambient ozone (1 μg/m³) concentration, relative TL, and mtDNA-CN, respectively. The mediated proportion of the association between ambient ozone exposure and high 10-year ASCVD risk by TL or mtDNA-CN was 21.13% or 7.75%, respectively. The total proportion of association between ambient ozone exposure and high 10-year ASCVD risk mediated by TL plus mtDNA-CN was 21.02%. Conclusions: Long-term exposure to ambient ozone was associated with increased 10-year ASCVD risk, and the association was partially mediated by aging biomarkers (shortened TL and decreased mtDNA-CN). This study indicated that ambient ozone pollution–related ASCVD risk might be partially explained by the telomere–mitochondrial axis of aging.