The association between secondhand smoke exposure and accelerated biological aging: A population-based study and Mendelian randomization analysis.

Abstract

Introduction: Aging is an irreversible biological process significantly influenced by oxidative stress, which smoking exacerbates. While the impact of direct smoking on aging is well-documented, the association between secondhand smoke (SHS) exposure and biological aging remains less explored. This study examines the connection between SHS exposure in populations and biological aging, highlighting diabetes as a potential mediator due to its established links to both SHS exposure and accelerated aging through mechanisms such as oxidative stress and chronic inflammation. It further employs genetic tools to establish a causal relationship between SHS exposure and biological aging.

Methods: This study combines secondary dataset analyses and Mendelian randomization analyses. Data from the NHANES 1999-2010 cycles were used, with serum cotinine levels indicating SHS exposure and phenotypic age, derived from age and clinical biomarkers reflecting inflammation, metabolism, and hematologic function, as the measure of biological aging. Multifactorial linear regression assessed associations, with restricted cubic splines used to explore nonlinear trends. Subgroup and mediation analyses were conducted to explore population-specific effects and the mediating role of diabetes. Two-sample Mendelian randomization (MR) using GWAS summary statistics on workplace SHS exposure (N=90168) and phenotypic age acceleration (N=6148) assessed causality.

Results: In the NHANES analysis, low SHS exposure was associated with a 0.37-year increase in biological aging (β=0.37; 95% CI: 0.04-0.70), while high exposure showed a 0.76-year increase (β=0.76; 95% CI: 0.23-1.29). A U-shaped association was found between log-transformed serum cotinine and biological aging (p<0.001), with a threshold at -1.53. Diabetes mediated 31.25% of this association. In the MR analysis, workplace SHS exposure was causally linked to a 3.05-year acceleration in aging (β=3.05; 95% CI: 0.24-5.85).

Conclusions: SHS exposure accelerates biological aging, partly via diabetes. Genetic evidence supports a causal effect, emphasizing the need to minimize SHS exposure.