Forever chemicals have been detected in many sources of groundwater nationwide. (zimmytws/Shutterstock)
In A Nutshell
- A new study found that a PFAS compound called PFNA was linked to accelerated biological aging in adults over 50, with the strongest associations seen in men aged 50 to 64.
- Researchers used epigenetic clocks, tools that estimate biological age from DNA patterns in blood, to measure how PFAS exposure corresponded with faster aging at the molecular level.
- A second compound, PFSA, was associated with a different aging marker tied to fat metabolism, particularly in adults 65 and older.
- The study cannot prove PFAS cause faster aging, but the findings add to growing concern about lesser-known forever chemicals that have so far received less regulatory attention than PFOA and PFOS.
Middle-aged men may face a hidden biological risk after decades of exposure to so-called “forever chemicals.” A study found that certain PFAS compounds detected in human blood were tied to accelerated aging at the DNA level, with men between 50 and 64 showing the most pronounced associations.
PFAS, short for per- and polyfluoroalkyl substances, are a family of man-made chemicals used in nonstick cookware, food packaging, waterproof clothing, and firefighting foam. They earned the nickname “forever chemicals” because they don’t break down in the environment or the human body. According to the Environmental Working Group, more than 200 million Americans may have been exposed through contaminated drinking water alone. Some PFAS compounds take up to 8.5 years just to reduce by half in the bloodstream, meaning they accumulate quietly, long before any health effects become visible.
Researchers have long connected PFAS to elevated cholesterol, liver damage, reduced vaccine response, and increased cancer risk. This study took a different approach, asking whether these chemicals are also associated with faster biological aging at the molecular level. For middle-aged men, the data suggest a meaningful association.
How Scientists Measure Aging From a Blood Sample
Most people think of age as a number. Scientists increasingly think of it as two numbers: the one on your birth certificate and the one written in your DNA. Biological age, measured through a process called DNA methylation, reflects how worn out the body actually is at the cellular level. Chemical markers attach to DNA over time and shift in predictable patterns, and researchers have developed tools called epigenetic clocks that can read those patterns from a blood sample and estimate how fast someone is aging on the inside. When biological age outpaces chronological age, that gap is called age acceleration, and it has been linked to higher mortality risk and worse long-term health outcomes.
Researchers analyzed blood data from 326 adults aged 50 and older drawn from the National Health and Nutrition Examination Survey, a federally run program that tracks the health of U.S. civilians. All participants had both PFAS measurements and DNA methylation data available, a rare combination that made this kind of analysis possible. The team calculated 12 different epigenetic aging scores for each person and tested whether PFAS levels were associated with faster biological aging, controlling for smoking history, body weight, income, race, and markers of inflammation.
The Chemicals Showing the Strongest Associations in Men
Two PFAS compounds stood out from the rest. Perfluorononanoic acid, or PFNA, showed the strongest and most consistent links to accelerated biological aging. It was significantly associated with two epigenetic clocks called GrimAge and GrimAge2, which are specifically designed to estimate mortality risk based on DNA patterns. In plain terms, men with higher PFNA in their blood showed markers of biological aging linked to higher risk of disease and earlier death.
When researchers split the data by sex and age, the picture sharpened. Men showed far stronger associations than women, and among men aged 50 to 64 specifically, the association was even more pronounced than in those 65 and older. PFNA was also linked to age acceleration on the Horvath clock in men, one of the original and most respected epigenetic aging measures. No significant associations were observed in women.
A second compound, known in the NHANES dataset as PFSA, referring to perfluorooctane sulfonamide, was linked to a different aging marker tied to lipid metabolism and lifespan prediction. That association was stronger in adults 65 and older, suggesting this compound may be associated with biological aging through different pathways and at different life stages.
More familiar PFAS compounds like PFOA and PFOS, which have faced the most regulatory pressure over the years, did not show significant links to epigenetic aging here. The authors suggest the finding may relate to how the GrimAge clock captures inflammation- and metabolism-related DNA patterns, which may be more sensitive to the kinds of inflammation and metabolic changes that PFNA has been linked to in other research.
Why Midlife May Be the Most Vulnerable Window
The fact that men in their early 50s and early 60s showed the strongest associations is not entirely surprising. Midlife is already a period when cardiovascular disease, metabolic disorders, and early tissue breakdown tend to surface. The body’s repair systems are beginning to slow, which may make it more susceptible to the effects of chemical exposure.
PFNA, in particular, has been shown in other research to be associated with disruptions in fat transport, cellular signaling, and oxidative stress pathways, which overlap with the biological processes the GrimAge clock is designed to detect. The authors also note, drawing on broader scientific literature rather than anything directly tested in this dataset, that PFAS may interfere with cellular systems involved in growth and aging at the molecular level, which could help explain why certain epigenetic aging markers appear sensitive to PFNA exposure.
Why men appear more vulnerable than women remains an open question. Differences in hormones, body composition, and immune function all affect how the body handles environmental chemicals, and any of these could help explain the gap. The researchers flagged this as a question that future studies need to address directly.
Men over 50 are already at elevated risk for the conditions GrimAge is built to flag. Whether PFNA and PFSA are contributing to that risk at the biological level, or simply tracking alongside other factors associated with aging, is something only longer-term studies can sort out. What this research does make clear is that these lesser-known compounds may deserve closer regulatory scrutiny than they have received so far.
This study, published in Frontiers in Aging, does not prove that PFAS cause faster aging, but it adds to growing evidence that these chemicals may affect the body in ways scientists are only beginning to understand.
Disclaimer: This article is based on a single observational study and does not establish that PFAS exposure causes accelerated aging. Findings are associations, not proof of direct harm. Consult a healthcare provider with questions about environmental chemical exposure and personal health risk.
Paper Notes
Limitations
The study’s sample of 326 adults is relatively small, limiting its ability to detect subtler effects within specific subgroups. All participants were 50 or older, so the findings cannot be extended to younger adults. Because PFAS measurements were taken between 1999 and 2000, they may not reflect current exposure patterns given that some legacy compounds have since been phased out. Most critically, the cross-sectional design, where data is captured at a single point in time, means the study cannot establish causation. It is possible that other factors linked to both PFAS exposure and biological aging are driving the observed associations. Some results also weakened after statistical correction for false discovery rate, and the authors caution that certain findings should be treated as preliminary until confirmed in larger, more diverse studies. Proposed mechanisms such as effects on cellular signaling pathways were not directly tested within this dataset.
Funding and Disclosures
This work was supported by Shanghai Jiao Tong University’s “New Young Teachers Launch Plan,” a startup fund for Principal Investigators from the School of Medicine at Shanghai Jiao Tong University, and the Strategic Priority Research Program of the Chinese Academy of Sciences. The authors declared no commercial or financial conflicts of interest and stated that no generative AI was used in creating the manuscript.
Publication Details
Authored by Ya-Qian Xu, Chongyu Ding, Hui Zhang, Yulu Gong, Darong Hao, Xuetong Zhao, Kai Li, and Xiangwei Li, all affiliated with Shanghai Jiao Tong University School of Medicine, with Kai Li also affiliated with the Yangtze Delta Region Institute of Tsinghua University. Published February 26, 2026, in Frontiers in Aging, Volume 6. Title: “Emerging PFAS contaminants PFNA and PFSA amplify epigenetic aging: sex- and age-stratified risks in an aging population.” DOI: 10.3389/fragi.2025.1722675.
