Current cigarette smoking and decreased serum levels of α-Klotho, an anti-aging hormone, among US adult participants.

Background and aims: Cigarette smoking is a well-established risk factor for cardiovascular disease and other aging-related disorders; yet the pathogenesis of these diseases induced by smoking remains relatively underexplored. This study was to assess the association between cigarette smoking and serum α-Klotho levels, an anti-aging protein, in US adults.

Methods and results: Data on 4196 participants aged 40-79 years from the 2013-2016 National Health and Nutrition Examination Survey was analyzed for the association using multiple general linear models. Smoking was assessed using both questionnaire data and serum cotinine measurements. Both past and current smokers exhibited significantly lower levels of α-Klotho, with the light smokers exhibiting the lowest levels [geometric mean: 720.85 pg/mL; 95% CI: 662.53, 784.31], compared with non-smokers [806.75 (790.69, 823.13)]. A significantly inverse association between current smoking and α-Klotho levels was revealed. This relationship extended across smoking intensities, with even light smokers displaying the strongest association. After adjusting for potential confounders, light (smoked <5 pack-years), moderate (5-19 pack-years), and heavy smoking (≥20 pack-years) were associated with reductions of 10.81% (-16.91, -4.28), 6.43% (-10.24, -2.47), and 3.38% (-6.83, 0.19) of Klotho levels, respectively, when compared to non-smoking. Active smoking, defined as serum cotinine levels ≥10 ng/mL, was associated with a 4.59% decrease (-6.91, -2.23) in α-Klotho levels.

Conclusion: The study demonstrates an inverse relationship between current smoking and serum α-Klotho levels among middle-aged and older adults. Our findings suggest that Klotho may play an important role in smoking-induced diseases. Further investigations are warranted to explore these interactions.