Two lesser-studied PFAS compounds commonly detected in human blood have been linked to faster epigenetic aging in US adults, with the strongest associations seen in men and in people aged 50 to 64.
Much of the attention around PFAS has focused on older compounds such as PFOA and PFOS. In the study, however, the clearest associations emerged for PFNA and perfluorooctane sulfonamide, listed in the NHANES data under the older abbreviation PFSA.
The researchers analyzed archived data from 326 adults aged 50 years and older in the 1999–2000 NHANES cycle. Serum PFAS concentrations were measured using isotope-dilution tandem mass spectrometry, while whole-blood DNA methylation profiles were used to calculate 12 epigenetic aging algorithms, including GrimAge-related metrics, HorvathAge, and DunedinPACE.
Rather than relying on a single aging metric, the researchers compared PFAS exposure across 12 DNA methylation algorithms spanning first-, second-, and third-generation epigenetic clocks. The clearest PFNA associations emerged in GrimAge-related measures, suggesting that some PFAS may track more closely with mortality-linked aging pathways than others.
Among the compounds measured, PFNA and PFSA were detected in about 95 percent of participants. PFNA was most strongly associated with accelerated epigenetic aging, with the clearest signals seen in men and in adults aged 50 to 64. Other commonly detected PFAS, including PFOA and PFOS, were not associated with significant shifts in the main models.
“We suspect that men may be at higher risk because the aging markers we analyzed are heavily influenced by lifestyle factors such as smoking, which can compound the damaging effects of these pollutants,” said corresponding author Xiangwei Li in a press release.
The researchers suggest the results support looking beyond legacy PFAS when assessing age-related effects, particularly since PFNA and PFSA showed associations that were not seen for several more familiar compounds.
“Looking ahead, we are actively modeling how PFAS interacts with other common pollutants, as we need to understand the cumulative health risks of these chemical mixtures,” Li said.
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