The variable associations between PFASs and biological aging by sex and reproductive stage in NHANES 1999–2018

Per- and polyfluoroalkyl substances (PFASs) are endocrine disrupting chemicals that have myriad effects on human physiology. Estrogenic PFASs may influence biological aging by mimicking the activity of endogenous estrogens, which can decrease inflammation and oxidative stress and enhance telomerase activity. We hypothesized that PFAS exposure would be differentially associated with measures of biological aging based on biological sex and reproductive stage. We analyzed associations between serum PFAS levels and measures of biological aging for pre- and postmenopausal women and men (n = 3193) using data from the 2003 to 2018 waves of the National Health and Nutrition Examination Survey. Examining PFASs both individually and in mixture models, we investigated four measures of clinical aging (Homeostatic Dysregulation, the Klemera-Doubal Method, Phenotypic Age Acceleration, and Allostatic Load), oxidative stress, and telomere length. PFOA and PFOS were negatively associated with Phenotypic Age Acceleration (e.g. decelerated aging) for men B = −0.22, 95% CI: −0.32, −0.12; B = −0.04, 95% CI: −0.06, −0.03) , premenopausal women (B = −0.58, 95% CI: −0.83, −0.32; B = −0.15, 95% CI: −0.20, −0.09), and postmenopausal women (B= −0.22, 95% CI: −0.43, −0.01; B = −0.05, 95% CI: −0.08, −0.02). In mixture models, we found net negative effects for Phenotypic Age Acceleration and Allostatic Load for men, premenopausal women, and postmenopausal women. We also found significant mixture effects for the antioxidants bilirubin and albumin among the three sample groups. We found no evidence to support effects on telomere length. Our findings suggest that PFAS exposure may be inversely associated with some measures of biological aging at the relatively low levels of exposure in this sample, regardless of reproductive stage and sex, which does not support our hypothesis. This research provides insights into how PFAS exposure may variably influence aging measures depending on the physiological process investigated.