Per- and poly-fluoroalkyl substances (PFAS) accelerate biological aging mediated by increased C-reactive protein

Unhealthy biological aging is related to higher incidence of varied age-related diseases, even higher all-cause mortality. Previous small sample size study suggested that Per- and poly-fluoroalkyl substances (PFAS) was associated with biological aging, but the evidence of exposure-response relationships, potential effect modifiers, and potential mediators were not investigated. Therefore, we conducted a cross-sectional analysis of national study including 14, 865 adults in the US from 8 survey cycles of NHANES from 2003 to 2018, to investigate the associations of PFAS compounds in body serum, including perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS), with biological aging. Generalized linear models showed that higher human exposure to PFAS was associated with accelerated biological aging. Importantly, human exposure to PFOA, PFOS, PFNA, and PFHxS with detected level (above 0.10 ng/mL) was associated with an average of 3.3 year (95 %CI: 2.7, 3.9, P < 0.001), 14.9 year (95 %CI: 7.2, 22.7, P < 0.001), 10.9 years (95 %CI: 3.9, 17.7, P < 0.001), and 8.8 years (95 %CI: 4.8, 12.9, P < 0.001) of biological aging acceleration. Cubic spline models indicated exposure-response relationships where there was no safe threshold of PFAS level regarding harms to human healthy aging. The weighted sum regression model found the significant associations of PFAS compound mixture with biological aging acceleration, and PFOA was the dominant contributor among 4 PFAS compounds. Mediation analysis suggested that C-reactive protein, one of the inflammation biomarkers, might play as mediator in PFAS-induced accelerated biological aging, but not Triglyceride-glucose index. In summary, our study suggests that the effects of PFAS on biological aging acceleration should be of concern and more action plans to address their negative impact on human health should be launched.