An exposome-wide association study on association between environmental toxicants and accelerated aging

BACKGROUND: Accelerated aging is linked to a higher risk of chronic diseases. Some emerging environmental toxicants have also been reported to be associated with chronic diseases. However, the relationship between accelerated aging and environmental toxicants remains unclear. OBJECTIVE: Our study seeks to investigate the association between accelerated aging and environmental toxicants via exposome-wide association study and further evaluated whether systemic inflammation may partially explain the association. METHODS: Accelerated aging was calculated by the Klemera-Doubal method (KDM) biological age. Exposome-wide association study (ExWAS), the deletion-substitution-addition (DSA) algorithm, and exposure-class risk scores (ERS) were used to investigate these associations. In addition, we applied a mediation analysis framework to examine whether systemic inflammation statistically accounted for part of these associations. Finally, we also attempted to conduct a mixed-effects analysis on the selected chemicals. RESULTS: ExWAS analysis identified 27 environmental toxicants as risk factors for accelerated aging, with copper (OR = 2.56, 95%CI:1.82-3.59), tungsten (OR = 2.37, 95%CI:1.30-4.31), and N-Acetyl-S-(phenyl)-l-cysteine (OR = 1.47,95%CI:1.25-1.72) being particularly notable. Stratified analyses suggested that sex and BMI may modify the effect of environmental toxicants on accelerated aging, with more nominally significant associations observed in males than in females. Formal interaction testing of the 8 core chemicals confirmed statistically significant effect modification by sex or BMI for key exposures including copper and total cotinine, with the exception of MHBMA3. Mediation analysis showed that SII was statistically associated with the exposure-outcome relationship and may partially explain these associations of several environmental toxicants on accelerated aging, including metals, nicotine metabolites, and polycyclic aromatic hydrocarbons. The ERS analysis showed that three categories yielded statistically significant indirect effects, including acrylamide & glycidamide, nicotine metabolites and metals. Additionally, a positive correlation was observed between the mixture and accelerated aging in the WQS model, with copper showing the greatest contribution. The results of the subsequent Qgcomp and BKMR analyses also corroborated this finding. IMPACT: Our study systematically investigated the associations between environmental toxicants and accelerated aging, identifying multiple environmental toxicants as risk factors. Our findings demonstrate that males and individuals with overweight status exhibit heightened susceptibility to key environmental pollutants. These findings highlight the importance of targeted strategies to reduce environmental exposures in susceptible populations.