Association of Serum Per- and Polyfluoroalkyl Substances Exposure with Leukocyte Telomere Length in Chinese Middle-Aged and Older Adults: Role of Genetic Susceptibility and Healthy Diet

The association between per- and polyfluoroalkyl substances (PFASs) and leukocyte telomere length (LTL) remains unclear, especially with regard to the roles of genetic and dietary factors. The study population was a subsample of the baseline survey from a nested case-control study within the Dongfeng-Tongji cohort study, with a total of 1489 middle-aged and older adults included. We measured serum levels of 10 PFASs, as well as peripheral blood LTL, and constructed a polygenic score (PGS) and a healthy diet score. Associations between PFASs and LTL were analyzed by using general linear regression. Both multiplicative interaction terms and stratified analyses were used for the assessment of the modification effects. Serum perfluorodecanoic acid (PFDA) and perfluoroundecanoic acid (PFUDA) were negatively associated with LTL. A doubling of PFDA or PFUDA levels led to a significant decrease in LTL [percent change (95% CI): -1.55 (-2.82, -0.27); -1.61 (-3.01, -0.19), respectively]. Significant associations of PFAS exposure and PGS with LTL were observed in those with a low healthy diet score. In the low-score group, participants with high PFAS exposure (especially, PFOA, PFNA, PFDA, and PFUDA) and high PGS had the shortest LTL [percent change (95% CI): -16.04 (-22.94, -8.53) for high PFNA and high PGS and -11.96 (-19.10, -4.18) for high PFUDA and high PGS]. This study revealed that PFAS exposure was associated with LTL shortening, and those with low healthy diet scores are vulnerable to the joint effects of PFAS exposure and genetic susceptibility, offering insights for regulatory and public health actions.