ORIGINAL RESEARCH article
Front. Aging
Sec. Genetics, Genomics and Epigenomics of Aging
Emerging PFAS Contaminants PFNA and PFSA Amplify Epigenetic Aging: Sex-and Age-Stratified Risks in an Aging Population
Provisionally accepted
- 1Shanghai Jiao Tong University School of Medicine, Shanghai, China
- 2Shanghai Jiao Tong University, Shanghai, China
- 3Yangtze Delta Region Institute of Tsinghua University, Jiaxing, China
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ABSTRACT: Emerging perfluoroalkyl substances (PFAS), such as perfluorononanoic acid (PFNA) and perfluorosulfonic acid (PFSA), are pervasive environmental contaminants that may influence human health. Their effects on aging, particularly through recently developed robust DNA methylation (DNAm) aging algorithms, remain largely unexplored. Using data from 326 U.S. adults aged ≥50 years (NHANES 1999-2000), we quantified serum PFAS via isotope-dilution tandem mass spectrometry and computed 12 DNAm aging algorithms. Weighted multivariable linear regression models assessed PFAS-DNAm aging associations, stratified by sex and age. PFNA exposure was significantly associated with DNAm algorithms via GrimAgeMortacc (β=2.74, 95% CI:1.04-4.44) and GrimAge2Mortacc (β=2.45, 0.60-4.31), with stronger magnitudes in males (P-interaction=0.0050) and adults aged 50-64 (P-interaction = 0.0270). PFSA was associated with LinAgeacc (β=4.17, 0.60-7.74). Sex-stratified analyses revealed male-specific PFNA-HorvathAgeacc associations (β=4.11, 0.71-7.52). These findings suggest that PFNA and PFSA may drive epigenetic aging disparities in aging populations, with males and middle-aged individuals at heightened risk. These findings underscore the need to regulate emerging PFAS and integrate epigenetic biomarkers into environmental health risk assessments.
Keywords: PFAS, DNA methylation aging, GrimAge, Sex disparities, NHANES
Received: 11 Oct 2025; Accepted: 21 Nov 2025.
Copyright: © 2025 Xu, Ding, Zhang, Gong, Hao, Zhao and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ya-Qian Xu, xuyq1113@sjtu.edu.cn
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