Current and former smoking were associated with accelerated epigenetic aging by 9.1 years (95% CI: 8.0-10.2) and 2.8 years respectively, with deceleration observed after cessation.
Cross-Sectional (n=2,300)
Yes
Does smoking and smoking cessation affect epigenetic age acceleration in adults?
Smoking is associated with accelerated epigenetic aging, but this effect declines with each year since smoking cessation, suggesting reversibility.
Effect estimate: 9.1 years older (95% CI 8.0, 10.2)
Abstract Rationale Smoking is a major risk factor for all-cause mortality, including the development of chronic respiratory diseases. It can induce changes in DNA methylation, but the effects and reversibility of smoking behaviors on different epigenetic clocks are not fully explored. We aimed to examine the association of active and secondhand (SHS) smoking, intensity, and time since cessation with epigenetic age acceleration in whole blood among U.S. adults. Methods We analyzed 2,300 adults representative of the U.S. from the National Health and Nutrition Examination Survey (NHANES) 1999-2002 cycles. Smoking behavior was analyzed for self-reported smoking status (never, former, current), intensity (cigarette packs), years since smoking cessation, and SHS exposure (serum cotinine levels: 0.05-10 ng/ml). We examined the association between 12 validated epigenetic clocks and smoking using survey-weighted regression models adjusted for age, gender, race-ethnicity, education, poverty-to-income ratio, body mass index, and survey cycles. We corrected multiple comparisons using a false discovery rate (FDR)5%, and conducted sensitivity analyses for blood cell counts and analyzed associations with GrimAge2 components. Results Current and former smokers were 9.1 years (95% CI: 8.0, 10.2) and 2.8 years (95% CI: 2.3, 3.3) older in GrimAge2, respectively, compared to never smokers. These exhibited a greater pace of aging (current=15%; former=4%) and reduced telomere length (current=-132 bp, former=-30 bp). Among current smokers, each cigarette pack smoked in the last month was associated with increases of 0.1 years (GrimAge2, PhenoAge) and 0.2% in aging pace (DunedinPoAm) (p5x10-3). However, among former smokers, each year since smoking cessation was associated with a deceleration of -0.14 (GrimAge2) and -0.06 (PhenoAge) years and -0.2% in aging pace. While recent quitters (5 years) were 5.7 years older in GrimAge2 than never smokers, minor differences were observed in long-term quitters (30 years) (Figure 1). Cotinine analysis supported the association of accelerated epigenetic aging with smoking classification and intensity (p4x10-3) and suggested a 0.8-year increase in GrimAge2 for SHS in never and former smokers. All GrimAge2 mortality predictors, except β2 macroglobulin, were associated with smoking, intensity, and/or cessation (p0.05). Conclusions Current and former smoking was associated with accelerated epigenetic aging in clocks reflecting morbidity, mortality, pace of aging, and telomere length shortening, with stronger effects in current smokers. Among current smokers, epigenetic aging proportionately accelerates with smoking intensity. However, among former smokers, it declines with each year since smoking cessation, suggesting a degree of reversibility. This abstract is funded by: Grants R01ES031259, P42ES004705, R01MD011721 (US NIH). Catalina Ruiz Program (ACIISI; JPG)
Perez-Garcia et al. (2026) conducted a cross-sectional in Smoking (n=2,300). Active and secondhand smoking vs. Never smokers was evaluated on Epigenetic age acceleration (GrimAge2) (9.1 years older, 95% CI 8.0, 10.2). Current and former smoking were associated with accelerated epigenetic aging by 9.1 years (95% CI: 8.0-10.2) and 2.8 years respectively, with deceleration observed after cessation.