Liver-related biomarkers mediate the potential effect of volatile organic compounds on an anti-aging hormone: a cross-sectional study

Abstract

Volatile Organic Compounds (VOCs) are a class of air pollutants that have adverse metabolic and endocrine effects. α-Klotho, an anti-aging hormone, is susceptible to environmental pollution. This study aimed to explore the association between urinary VOCs and serum α-Klotho levels and the underlying molecular mechanisms. 1680 individuals from the U.S. were included. The association between VOCs and α-Klotho was explored using multivariate linear regression. Weighted quantile sum (WQS) regressions were used to identify the important distribution of VOCs on α-Klotho, and Bayesian kernel machine regressions (BKMR) were implemented to assess the joint and univariate effects of all VOCs on α-Klotho. Mediation analyses of liver-related biomarkers in the effects of mixed and single VOCs on α-Klotho were also performed. The multivariate linear regression model showed that multiple VOCs were negatively associated with α-Klotho. The WQS models ascertained that N-acetyl-S-(2-carboxyethyl)-L-cysteine (CEMA), N-acetyl-S-(2-cyanoethyl)-L-cysteine (CYMA), and 2-aminothiazoline-4-carboxylic acid (ATCA) play dominant roles. In the BKMR model, we found that the joint effects of mixed VOCs were negatively associated with α-Klotho in the general population (40–79 years) and middle-aged population (40–59 years). Finally, mediation analyses showed that liver-related biomarkers exhibited a substantial mediation effect in the single ATCA on α-Klotho, with a proportion as high as 31.6% in the middle-aged population. Our study demonstrated that liver-related biomarkers mediate the influence of VOCs, especially ATCA, on α-Klotho. Our findings suggest that reducing VOC exposure may be a potential strategy to maintain α-Klotho levels.