Mediating role of telomere shortening in dioxin-like polychlorinated biphenyls associated cognitive decline in children

BACKGROUND: Dioxin-like polychlorinated biphenyls (DL-PCBs) are persistent environmental pollutants known to induce oxidative stress and inflammation, which may accelerate telomere(definition) shortening and affect neurodevelopment. We hypothesized that DL-PCB exposure contributes to cognitive deficits in children by accelerating telomere attrition, which in turn impairs brain function. METHODS: We analyzed serum DL-PCB levels, leukocyte telomere length (LTL), and cognitive performance in 1756 primary school children (aged 7-10 years) from Shenyang, China. Twelve DL-PCB congeners were measured, and cognitive outcomes were assessed using a standardized test battery, including the n-back task (Two-Back and Three-Back) and the Attentional Network Test (ANT). LTL was quantified via qRT-PCR. Linear mixed models, mixture analyses (Quartile g-computation analysis (g-comp), Generalized Weighted Quantile Sum regression (gWQS), Bayesian Kernel Machine Regression (BKMR) ), and mediation analysis were applied, adjusting for relevant covariates. RESULTS: Serum concentrations of PCB77, PCB126, and PCB189 were significantly associated with shorter LTL after Bonferroni correction (β = -0.041 for PCB189 per IQR increase, adjusted p = 0.001). PCB81 and PCB189 showed robust negative associations with superior working memory (Three-Back task; adjusted p < 0.05), while basic working memory (Two-Back) exhibited no significant associations. Inattentiveness (HRT-SE) was negatively associated with PCB157, PCB167, PCB169, and PCB189 in crude models, but these associations were attenuated after correction. Mixture analyses confirmed that DL-PCB mixtures were strongly associated with shorter LTL (g-comp β = -0.104, p < 0.001; gWQS β = -0.055, p < 0.001), as well as poorer superior working memory and inattentiveness. Mediation analysis revealed that LTL explained approximately 5-10% of the total effect of PCB77, PCB81, PCB169, and PCB189 on superior working memory and inattentiveness. CONCLUSION: Overall, early-life DL-PCB exposure is associated with telomere shortening and impaired higher-order cognitive function, with LTL acting as a partial mediator.