Whole-body aging mediates the association between exposure to volatile organic compounds and osteoarthritis among U.S. middle-to-old-aged adults

Humans are constantly exposed to various volatile organic compounds (VOCs) because of their widespread sources and characteristic of easy evaporation. Existing evidence regarding the association between VOC exposure and osteoarthritis (OA) risk is limited.This study aimed to investigate the associations between individual urinary VOC metabolites (VOCMs) and the VOCM mixture, representing internal exposure levels of VOCs, with prevalent OA risk and to explore the mediating effect of aging and oxidative stress (OS) in these associations.Data from the National Health and Nutrition Examination Surveys 2005-2020 were analyzed. Weighted generalized linear regression was employed to explore the associations between individual VOCMs and OA risk, as well as aging and OS biomarkers. A five-repeated ten-fold cross-validation elastic net model was used to identify critical VOCMs for the weight quantile sum (WQS) analysis, which was performed to explore the VOCM mixture and OA risk association. Parallel and serial mediation analyses were conducted to identify the potential mediators and mediation pathways.This study included 6578 American adults aged ≥40 years, among whom 1052 (16.0 %) individuals reported prevalent OA. Urinary levels of N-acetyl-S-(benzyl)-L-cysteine, mandelic acid and phenylglyoxylic acid were positively associated with OA risk. Eleven VOCMs with nonzero coefficients were identified and included in the WQS analysis, and results revealed an average increase of 24.4 % in OA risk (OR = 1.244, 95 % CI: 1.041, 1.486) per one-quantile increment in the VOCM mixture. Two aging biomarkers, phenotypic age and biological age, parallelly mediated the association between the VOCM mixture and OA risk, with mediation effect proportions of 9.0 % and 16.4 %, respectively.Exposure to VOCs is associated with an increased OA risk in middle-to-old aged American adults. The mediating effect of aging contributes to the association between co-exposure to VOCs and OA risk. Further prospective studies are required to substantiate these findings.