The association between per- and polyfluoroalkyl substances and biological aging among middle and older age adults: The moderating effect of caffeine

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are pervasive environmental pollutants associated with aging-related diseases and mortality risks, yet their relationship with biological aging remains underexplored. Notably, dietary antioxidants like caffeine have been shown to alleviate oxidative stress and inflammation, and these pathways are closely related to PFAS-induced toxicity and aging processes. However, whether dietary caffeine intake could mitigate the adverse effect of PFAS on biological aging is still unknown. This study aims to investigate the association between PFAS exposure and biological aging among participants in the National Health and Nutrition Examination Survey 2003-2018, and assess the potential modification effect of dietary caffeine intake. Biological aging indicators were calculated using the Klemera-Doubal method (KDM-BA) and Phenotypic Age (PhenoAge). This study included 6846 participants (3385 men [49.4 %], 3461 women [50.6 %]) with a mean age of 60 ± 11 years. After adjusting for potential covariates, we found significant positive correlations between exposure to PFHS and biological aging (KDM-BA: 0.56 [0.25-0.87]; PhenoAge: 0.46 [0.08-0.83]). Notably, these correlations were more pronounced among participants with lower caffeine intake (KDM-BA: 0.80 [0.41-1.19]; PhenoAge: 0.80 [0.30-1.30]). Furthermore, results from the restricted cubic spline model indicated a nonlinear relationship between PFHS and biological aging. The weighted quantile sum model demonstrates PFAS mixture was positively associated with biological aging (KDM-BA: 1.25 [1.04-1.45]; PhenoAge: 0.79 [0.55-1.03]). Our findings suggested that PFAS were significantly associated with biological aging, whereas higher dietary caffeine intake may mitigate these adverse effects, highlighting the importance of this preventive measure.