Association of Smoking Behavior, Intensity, and Time Since Cessation with Epigenetic Aging Biomarkers: Results from NHANES 1999-2002.
Level 4 - case-series / case-control
Cross-sectional analysis of observational survey data
PubMed 41445615 · doi:10.64898/2025.12.18.25342556
What was done
Researchers conducted a cross-sectional study using data from the NHANES 1999–2002 cycles to evaluate the relationship between smoking behaviors and 12 blood DNA methylation-based epigenetic aging biomarkers. The study analyzed 2,320 U.S. adults aged 50 and older (1,043 never, 903 former, and 374 current smokers; mean age 65.1±9.3 years, 49.1% female). Measured exposures included self-reported smoking status, past-month smoking intensity, years since smoking cessation, and secondhand smoke exposure measured by serum cotinine levels (0.05–10 ng/ml). Survey-weighted linear models adjusted for confounders and multiple comparisons.
What was found
Current and former smokers had higher GrimAge2 acceleration compared to never smokers by 9.1 years (95% CI: 8.0, 10.2) and 2.8 years (95% CI: 2.3, 3.3), respectively. Current smokers had an increased pace of aging of 0.15 additional years per chronological year (95% CI: 0.13, 0.17) and former smokers of 0.04 (95% CI: 0.03, 0.05). Methylation-predicted telomere length was shorter in current (-132±19 bp) and former (-30±15 bp) smokers. Each pack smoked in the past month was associated with 0.1-year increases in GrimAge2 and PhenoAge, and 0.01 aged months/year in aging pace. In former smokers, each year since cessation was associated with decreases of -0.14 years in GrimAge2, -0.06 years in PhenoAge, and -0.03 aged months/year in pace of aging. Secondhand smoke exposure was associated with a 0.8-year increase in GrimAge2.
Why it matters
This study provides population-based evidence that tobacco exposure accelerates biological aging across several epigenetic clocks, while showing that cessation is associated with a steady reduction in epigenetic age acceleration over time.
Limits
The study design is cross-sectional, preventing causal inference or longitudinal observation of individual changes. Active smoking exposure metrics relied on self-report. The cohort was limited to adults aged 50 and older from historical (1999–2002) survey waves, and epigenetic biomarkers were evaluated only in whole blood.
Cited by
- supports Smoking accelerates epigenetic age in epidemiological studies.