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

Abstract

Dioxin-like polychlorinated biphenyls (DL-PCBs) are persistent environmental pollutants known to induce oxidative stress and inflammation, which may accelerate telomere 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. 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. 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. Overall, early-life DL-PCB exposure is associated with telomere shortening and impaired higher-order cognitive function, with LTL acting as a partial mediator.