New analysis of US health data suggests certain ‘forever chemicals’ may disproportionately affect male ageing during midlife.
Per- and polyfluoroalkyl substances, widely known as PFAS or forever chemicals, may be contributing to faster biological ageing in middle-aged men, according to new research based on US population data.
The findings add to growing 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 higher blood concentrations of two PFAS compounds – perfluorononanoic acid (PFNA) and perfluorooctanesulfonamide (PFOSA) – were associated with accelerated biological ageing in men aged 50 to 64. The same pattern was not observed in women.
The results raise fresh questions about the safety of certain PFAS compounds that remain in widespread use, even as some earlier variants have been phased out globally.
Tracking age beyond birthdays
Unlike chronological age, biological ageing reflects the functional state of tissues and cells. It can be estimated through so-called epigenetic clocks, which analyse patterns of DNA methylation – chemical modifications that regulate gene activity without altering the genetic code itself.
The research team analysed publicly available data from 326 participants enrolled in the 1999–2000 cycle of the US 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 biological age using 12 established epigenetic clock models.
PFAS were detectable in the vast majority of participants. PFNA and PFOSA appeared in roughly 95% of blood samples. Statistical analysis showed that men in midlife with higher levels of these two chemicals showed signs of faster biological ageing than their chronological age would suggest.
Other PFAS compounds, including PFOS, PFOA and PFHS, were also commonly detected but did not show a significant link with epigenetic ageing in this dataset.
Why focus on PFAS?
PFAS are a large class of synthetic chemicals developed in the mid-20th century. Their carbon–fluorine bonds are exceptionally strong, making them resistant to heat, water, oil and chemical degradation.
That durability has made them attractive for use in non-stick cookware, stain-resistant fabrics, food packaging, firefighting foams and industrial applications.
However, the same chemical stability means they persist in the environment and accumulate in living organisms. PFAS contamination has been documented in water supplies, soils and human tissues worldwide.
Some compounds have been associated with cancer risk, metabolic disorders, immune disruption and reproductive problems.
Several ‘legacy’ PFAS, including PFOS and PFOA, were targeted for global elimination under the Stockholm Convention on Persistent Organic Pollutants. Yet newer or less regulated compounds continue to enter the market, sometimes as substitutes for restricted chemicals.
The current findings suggest that not all replacement PFAS should be assumed safer by default, particularly in the context of biological ageing.
A vulnerable window in male ageing
One of the most striking aspects of the study is the sex- and age-specific pattern. The association between PFNA, PFOSA, and accelerated biological ageing was evident only in men aged 50-64 years.
The researchers propose that midlife may represent a biologically sensitive period. During this phase, cumulative exposure to environmental stressors may interact with age-related physiological changes, potentially amplifying molecular damage.
Lifestyle factors could also play a role in male ageing trajectories. Epigenetic clocks are influenced by behaviours such as smoking, which remains more prevalent among men in many populations.
Chemical exposures layered onto existing risk factors may compound the effects seen at the molecular level.
Importantly, overall PFAS concentrations did not differ significantly between men and women in the study, suggesting that susceptibility, rather than exposure alone, may explain the sex-specific pattern.
Regulatory implications and next steps
The study adds to mounting pressure on regulators to broaden scrutiny beyond a handful of legacy PFAS. France recently introduced a ban on PFAS use in clothing and cosmetics, while the European Union is evaluating further restrictions across specific applications.
Scientists caution that PFAS rarely occur in isolation. Real-world exposure involves mixtures of multiple chemicals, raising questions about cumulative effects on biological ageing and long-term health outcomes.
Future research aims to clarify how PFAS interact with other environmental pollutants and whether epigenetic ageing changes translate into higher risks of age-related disease.
For now, the findings reinforce concerns that persistent industrial chemicals may shape the ageing process itself – particularly in men navigating the biological transitions of midlife.