A new analysis of US health data suggests that certain “forever chemicals” may have a disproportionate effect on aging in men in midlife.
Per- and polyfluoroalkyl substances, commonly known as PFAS or forever chemicals, may be contributing to accelerated biological aging in middle-aged men, according to a new study based on U.S. population data.
The findings add to the growing body of evidence that some widely used synthetic chemicals influence how quickly the body ages at a molecular level.
In a study published in Frontiers in Aging, researchers from Shanghai Jiao Tong University School of Medicine report that high blood levels of two PFAS compounds, perfluorononanoic acid (PFNA) and perfluorooctane sulfonamide (PFOSA), are associated with accelerated biological aging in men aged 50 to 64. The same pattern was not observed in women.
The results raise new questions about the safety of certain PFAS compounds that remain widely used even though some early variants have been phased out globally.
Tracking age beyond birthday
Unlike chronological age, biological aging reflects the functional state of tissues and cells. This can be estimated through the so-called epigenetic clock. The clock analyzes patterns of DNA methylation, a chemical modification that regulates the activity of genes without changing the genetic code itself.
The research team analyzed publicly available data from 326 participants enrolled in the 1999-2000 U.S. National Health and Nutrition Examination Survey.
Blood samples from these individuals had been tested for 11 PFAS compounds. Their DNA methylation profiles were also measured, allowing scientists to estimate their biological age using 12 established epigenetic clock models.
PFAS were detected in the majority of participants. PFNA and PFOSA were detected in approximately 95% of blood samples. Statistical analysis showed that middle-aged men with higher concentrations of these two chemicals showed signs of biological aging earlier than their chronological age would suggest.
Other PFAS compounds, such as PFOS, PFOA, and PFHS, were also commonly detected, but did not show any significant association with epigenetic aging in this dataset.
Why focus on PFAS?
PFAS are a large class of synthetic chemicals developed in the mid-20th century. The carbon and fluorine bond is extremely strong and resistant to heat, water, oil, and chemical degradation.
Its durability makes it attractive for use in nonstick cookware, stain-resistant fabrics, food packaging, firefighting foam, and industrial applications.
However, the same chemical stability means that they persist in the environment and accumulate in organisms. PFAS contamination has been documented in water supplies, soil, and human tissues around the world.
Some compounds are associated with cancer risk, metabolic disorders, immune deficiencies, and reproductive problems.
Several “legacy” PFAS, including PFOS and PFOA, are subject to global elimination under the Stockholm Convention on Persistent Organic Pollutants. However, newer or less regulated compounds continue to enter the market and, in some cases, are used as replacements for restricted chemicals.
The current findings suggest that not all alternative PFASs should be assumed to be safer by default, especially from a biological aging perspective.
Vulnerable period in male aging
One of the most striking aspects of this study is the gender- and age-specific patterns. Associations between PFNA, PFOSA, and accelerated biological aging were only evident in men aged 50–64 years.
Researchers propose that midlife may be a biologically sensitive period. At this stage, cumulative exposure to environmental stressors may interact with age-related physiological changes and amplify molecular damage.
Lifestyle factors can also influence men’s aging trajectories. Epigenetic clocks are influenced by behaviors such as smoking, which remains more common among men in many populations.
The combination of chemical exposure with pre-existing risk factors can further exacerbate the effects seen at the molecular level.
Importantly, overall PFAS concentrations were not significantly different between men and women in this study, suggesting that susceptibility, rather than exposure alone, may explain sex-specific patterns.
Regulatory implications and next steps
The study adds to the pressure on regulators to expand their oversight beyond a small number of traditional PFAS. France recently introduced a ban on the use of PFAS in clothing and cosmetics, while the European Union is considering further restrictions across specific uses.
Scientists warn that PFAS rarely occur in isolation. Real-world exposures involve mixtures of multiple chemicals, raising questions about their cumulative effects on biological aging and long-term health effects.
Future research will aim to determine how PFAS interact with other environmental pollutants and whether epigenetic age changes lead to increased risk of age-related diseases.
For now, the findings add to concerns that persistent industrial chemicals may shape the aging process itself, especially in men undergoing the biological transition of midlife.
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