Early-life smoking, cardiovascular disease risk, and the mediating role of DNA methylation biomarkers of aging

作者：Chang Sheng, Rui Zhou, Hongcai Wang, Guo‐Qiang Lin, Zhou Cai, Wei Wang · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-025-06492-5 · 被引用次数：7 · 研究领域：Epigenetics and DNA Methylation、Genetic Associations and Epidemiology、Health, Environment, Cognitive Aging

BACKGROUND: Early-life smoking is linked to biological aging and chronic diseases, yet its specific relationship with cardiovascular disease (CVD) risk and the role of DNA methylation biomarkers of aging as potential mediators of that relationship remain underexplored. METHODS: In this study, we analyzed data from 2345 participants in the National Health and Nutrition Examination Survey (NHANES; 1999-2002). Early-life smoking status was assessed on the basis of the age of smoking initiation (ASI) and categorized into three smoking initiation periods (SIPs): childhood (5-14 years), adolescence/adulthood (> 14 years), and never smoked. DNA methylation biomarkers of aging (DNAm PhenoAge, DunedinPoAm, HorvathTelo) were measured, and CVD outcomes were determined via self-reported, physician-confirmed diagnoses. Multivariate logistic regression and causal mediation analyses were performed to assess the associations between SIP and CVD outcomes and explore the mediating effects of DNA methylation biomarkers on those associations. RESULTS: Earlier smoking initiation was more strongly associated with an increased risk of developing CVD, with childhood smoking showing the highest risk (OR = 1.95, 95% CI: 1.15-3.29; P = 0.013). Furthermore, DNA methylation biomarkers of aging were independently associated with increased CVD risk (1-year increase in DNAm PhenoAge: OR = 1.03, 95% CI: 1.01-1.05, P < 0.001; 0.1-unit increase in DunedinPoAm: OR = 1.19, 95% CI: 1.00-1.40, P < 0.05; 1-kb incre...