The Middle-Aged Men Study found that men between the ages of 50 and 65 show signs of accelerated biological aging, which researchers linked to exposure to toxic “forever chemicals.” By analyzing blood samples and epigenetic markers, the study estimated tissue aging and highlighted the potential long-term health risks.
Researchers found the strongest associations between perfluoroalkyl and polyfluoroalkyl substances, known as PFAS, and advanced epigenetic aging in middle-aged men. The findings suggest a sex-specific effect, though scientists caution the results do not prove cause and effect.
Study Finds Strongest Aging Links In Middle-Aged Men
The study examined blood samples for 11 types of PFAS and measured the DNA methylome, an epigenetic marker that regulates gene expression. Researchers used a dozen biological “epigenetic clocks” to estimate aging in blood and other tissues.
“The associations between PFAS exposure and accelerated epigenetic aging were strongest in men aged 50 to 65,” said Xiangwei Li, senior author of the study and a professor of epidemiology at the Shanghai Jiao Tong University School of Medicine.
“In younger men and those over 65, the associations were weaker and generally not statistically significant,” Li said in an email. He added that while some associations appeared in women, they were smaller and less consistent.
PFAS are often called “forever chemicals” because they break down slowly and persist in the environment and the human body. The National Academies of Sciences, Engineering, and Medicine estimates that about 98% of Americans have PFAS in their blood.
Epigenetic aging measures biological age rather than chronological age and can reflect cumulative stress and environmental exposures.
Experts Cite Hormone Disruption As Possible Factor
Independent experts say the findings align with what is known about endocrine-disrupting chemicals.
“The findings indicate a sex-specific effect that can be expected for chemicals that disrupt the endocrine system,” said Jane Muncke, managing director and chief scientific officer at the Food Packaging Forum, who was not involved in the research.
The endocrine system regulates growth, metabolism, mood and reproduction. In men, PFAS accumulation may lower testosterone levels, impair sperm quality and increase risks of testicular and kidney cancers, according to prior research.
Earlier studies suggest women may eliminate certain PFAS more quickly through pregnancy, breastfeeding and menstrual blood loss. Researchers have also found that the difference in PFAS accumulation between men and women narrows after menopause.
Muncke cautioned that the new findings “cannot be interpreted as cause-and-effect but rather are puzzle pieces” that support biological plausibility.
Industry representatives raised concerns about the Middle-Aged Men Study. The American Chemistry Council argued that the exploratory research relied on a small sample of older adults and data collected more than two decades ago.
“This paper does not provide evidence that PFAS exposure causes aging,” said Tom Flanagin, the council’s senior director of communications.
Legacy Chemicals Targeted, Newer Compounds Under Review
PFAS have been used since the 1950s in nonstick, oil- and water-repellent and heat-resistant products. They have been linked to cancer, fertility problems, high cholesterol, hormone disruption, liver damage, obesity and thyroid disease.
Some legacy PFAS — including perfluorooctanesulfonic acid, or PFOS, and perfluorooctanoic acid, or PFOA — are targeted for global elimination under the Stockholm Convention on Persistent Organic Pollutants. The United States has signed but not ratified the treaty.
The Middle-Aged Men Study also identified less-studied compounds, including perfluorononanoic acid and perfluorooctanesulfonamide, as strong predictors of faster epigenetic aging in men ages 50 to 64.
“Our results suggest that some less-studied PFAS may also have biologically meaningful associations,” Li said.
In discussing the Middle-Aged Men Study, Li urged caution, stressing that the findings show associations rather than definitive proof. “It’s important not to panic,” he said. “Reducing exposure where feasible — such as using certified water filters and limiting contact with stain- or grease-resistant materials — may be reasonable steps.”
Researchers and public health experts say broader risk reduction will depend largely on regulatory action and environmental cleanup, as many exposures occur at the community level.
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