The impact of polycyclic aromatic hydrocarbons (PAHs) and metals on aging biomarkers-telomere length (TL) and mitochondrial DNA copy number (mtDNAcn)- has been investigated separately. However, their combined effects, particularly in highly exposed occupational populations, remain unexamined, despite their frequent co-occurrence in environmental settings. This study measured baseline urinary and blood samples from 867 coke oven workers at baseline for 33 chemical pollutants and mtDNAcn, and assessed leukocyte TL at both baseline and follow-up. The combined effect of metals and PAHs on aging biomarkers was evaluated using weighted quantum sum (WQS) regression and Bayesian kernel machine regression (BKMR), and mediation analyses were also conducted. Multiple linear regression incorporating 33 pollutants and least absolute shrinkage and selection operator (LASSO) regression were used to identify individual exposures with significant effects, while restricted cubic splines were applied to explore potential nonlinear dose–response relationships. We observed that both the WQS and BKMR indicated that 33 chemical mixtures exposure was significantly negatively associated with the TL ratio (follow-up/baseline) and positively associated with baseline mtDNAcn. Urinary 1-hydroxypyrene, molybdenum, selenium (Se), and barium were identified as the major contributors. Furthermore, oxidative stress and inflammation mediated the link of major individual pollutants as well as the chemical mixture to biological aging. Network toxicology analysis identified HSP90AA1 and HSP90AB1 as core molecular targets underlying the effect of Se on TL regulation. To our knowledge, this is the first study to investigate the joint effects and underlying mechanisms of co-exposure to PAHs and metals on biomarkers of biological aging.
Mu et al. (Thu,) studied this question.