# Association of serum cotinine with phenotypic age acceleration and oxidative stress markers in US adults: A cross-sectional study

## TL;DR

Higher levels of a tobacco exposure marker in blood are linked to faster biological aging and oxidative stress in US adults.

## Contribution

This study provides population-level evidence that serum cotinine is associated with accelerated biological aging and identifies potential oxidative stress mechanisms.

## Key findings

- Each doubling of serum cotinine was linked to a 0.22-year increase in phenotypic age acceleration.
- Oxidative stress markers like GGT and uric acid partially explained the association between cotinine and aging.
- The association was stronger in women and those with lower socioeconomic status.

## Abstract

Tobacco exposure is a plausible accelerator of biological aging, yet population-level evidence and mechanisms remain insufficiently defined. We examined the association between serum cotinine and phenotypic age acceleration (PhenoAgeAccel), and assessed whether oxidative-stress biomarkers were related to the serum cotinine–PhenoAgeAccel association.

We conducted a cross-sectional, survey-weighted analysis of n=19744 adults from NHANES 2011–2018. PhenoAgeAccel was computed as the residual from regressing PhenoAge on chronological age. Multivariable linear regressions related serum cotinine to PhenoAgeAccel across hierarchical adjustment models. Restricted cubic splines assessed non-linearity. Mediation analysis was conducted to quantify the extent to which oxidative-stress biomarkers contribute to this association.

Higher serum cotinine was associated with accelerated biological aging: each doubling of serum cotinine corresponded to a 0.22-year increase in PhenoAgeAccel (β=0.22; 95% CI: 0.16–0.29). Mediation analyses indicated that γ-glutamyl transferase (GGT) and uric acid (UA) statistically accounted for 9.5% of the association between serum cotinine and PhenoAgeAccel (p<0.001). Interactions were observed for sex and PIR, with stronger associations among women and participants with lower socioeconomic status. There was no evidence of non-linearity in the relationships of the serum cotinine with GGT, PhenoAgeAccel, or UA.

In this nationally representative cross-sectional study of US adults, higher serum cotinine levels were associated with greater phenotypic age acceleration. Oxidative-stress biomarkers were related to the observed association, although causal inferences cannot be drawn.