Forever chemicals linked to accelerated aging risk in middle-aged men

Per- and polyfluoroalkyl substances (PFAS) are persistent in the environment. They are found in drinking water, soil, and animal tissues. They can remain in the body long after exposure. This persistence is one reason PFAS have been used for many years as part of commercial products. For example, they are in non-stick cookware and fire-fighting foam. These products are designed to resist heat, grease, stains, and corrosion.

Recent studies indicate that two PFAS chemicals (PFNA and PFOSA) may be associated with increased rates of biological aging among a subset of people. Specifically, this association is found in middle-aged men.

Dr. Xiangwei Li, a professor at Shanghai Jiao Tong University School of Medicine, led a study that focused on blood sample and DNA methylation data collected during the National Health and Nutrition Examination Surveys (1999 and 2000). This study included data from 326 adults aged 50 or older in the U.S.

The researchers found that certain PFAS chemicals can increase the risk of biological aging in middle-aged men. They measured methylation levels in blood cells from study participants to assess how PFAS exposure affects the aging process. Furthermore, by establishing a correlation between exposure levels to PFNA and PFOSA and accelerated biological aging, the researchers provided additional evidence to support the hypothesis. This suggests that specific PFAS chemicals may be contributing to accelerated aging in this population.

Blood samples were taken from all participants, and staff at NHANES determined the levels of 11 PFAS chemicals found in the blood serum. In addition, the researchers used a database of methylation profiles created from blood cell samples taken during the NHANES study. This helped evaluate how PFAS exposure influences biological aging through changes in methylation patterns.

The methylation patterns are used to create “epigenetic clocks,” which enable scientists to estimate the biological age of a person. Moreover, Li and colleagues employed data from twelve epigenetic clocks (including older clocks like Horvath and Hannum and newer clocks that account for health risk and mortality, such as GrimAge and GrimAge2Mort). They used the chronological age of individuals to determine their “age acceleration” based on the estimated age on each clock.

Factors such as race/ethnicity, education, poverty income ratio, body mass index, alcohol consumption, C-reactive protein (a marker for inflammation), and leukocyte composition were taken into account when determining what might have confounded the results. In addition, smoking exposure was calculated using a DNA methylation-based model expressed as pack-years.

While PFNA was present in the blood of 95.4% of participants and PFOSA (the name given to PFOS in NHANES) was found in 95.7% of participants, PFOS and PFOA were present in 100% of participants. This is indicative of the prevalence of these “legacy” PFAS around the time of the study. Conversely, PFHS was detected in 99.7% of participants.

The average concentration of each PFAS varied considerably. PFOS exhibited the greatest geometric mean (28.72 ng/mL), and PFOA (4.08 ng/mL). PFNA yielded an average of 0.55 ng/mL, whereas PFOSA had an average of 0.29 ng/mL. Overall, the research did not find a significant difference between men and women regarding the level of each PFAS. Likewise, there was no significant difference between the 50–64 and 65-plus age groups.

However, the association between each compound and biological markers of aging differed.

After adjusting for covariates, PFNA was significantly associated with accelerated aging in DunedinPoAm (β = 0.04, P = 0.0157). Additionally, it was associated with GrimAgeMort acceleration (β = 2.74, P = 0.0017) and GrimAge2Mort acceleration (β = 2.45, P = 0.0100). PFOSA was positively correlated with LinAge acceleration (β = 4.17, P = 0.0230). The authors identified LinAge as an epigenetic clock that may be associated with lipid metabolism.

Several other PFAS, including PFOS, PFOA, PFHS, and two sulfonamido acetic acids, did not demonstrate a statistically significant relationship with any of the 12 epigenetic clocks measured by the authors. This applied in this study.

The associations between PFNA and HorvathAge, GrimAgeMort, and GrimAge2Mort accelerations were not restricted to people living in midlife. As previously mentioned, the largest signals occurred when data were split by both age and sex.

The largest associations between PFNA and LinAge acceleration (β = 6.24, P = 0.0366) occurred for those aged 50–64. However, for those aged 65 and older, PFNA was also associated with LinAge acceleration (β = 3.69, P = 0.0062), but not to the same degree. Conversely, while PFOSA’s association with LinAge acceleration was present in both sexes, it was stronger in men (β = 3.93, P = 0.0140) than in women.

The strongest evidence that midlife is a particularly vulnerable time for individuals is found in comments regarding the biological impact of PFNA on males compared to females during this period. Ya-Qian Xu is the first author and a researcher from the Shanghai Jiao Tong University School of Medicine.

There is another suggestion from Li regarding the influence of lifestyle factors on the markers of aging associated with contaminants among men. He stated, “We believe that men may be at a higher risk due to the contributions of lifestyle factors such as smoking to the ways in which these chemicals negatively affect their bodies.”

The authors highlight a regulatory gap with respect to PFAS.

There is a growing list of chemicals classified as PFAS. However, only a few older compounds, such as PFOS and PFOA, have been the target of elimination by the Stockholm Convention on Persistent Organic Pollutants. While scientists are only beginning to study the impact of the thousands of newer PFAS subsequent to the original group of PFAS, many of these are still being developed and distributed.

Li commented, “The evidence we provide shows that while the use of some newer alternatives reduces risk relative to the older compounds previously studied (those which were the basis for the Stockholm Convention), they still have a considerable amount of associated business risk and appear to have the potential to negatively affect the environment.”

The authors of this paper believe that it is important for regulators to move beyond a single short list of so-called “legacy” compounds and also consider PFNA and PFOSA. PFNA and PFOSA were initially used in the 1950s and 1960s due to their ability to repel water, oils, and stains, and their resistance to heat and corrosion. In addition, they have been classified as having bioaccumulation and persistence. Furthermore, they are considered to have potential negative effects on health.

There is a growing movement to ban PFAS from specific uses such as clothing and cosmetics in some countries. For example, France has created a ban on the use of PFAS in the above products. Meanwhile, the EU is considering developing new regulations to restrict the use of these products.

There are several limitations to the analysis presented in this study that are worth highlighting.

Although data utilized in this analysis come from a nationally representative subset and contain information on both blood PFAS and DNA methylation, this analysis has real limitations. There are only 326 participants included in this research. This makes it difficult to draw meaningful inferences from the data set, especially after splitting it by sex and age. Participants were restricted to individuals who are aged 50 or more. Thus, any inferences made cannot be extrapolated to younger individuals.

Measurements of PFAS exposure also represent a “snapshot” in time from 1999 to 2000. Therefore, they do not take into account the different types of PFAS that are likely to be present in the marketplace today.

Additionally, as this study is cross-sectional, it is unable to determine whether accelerated biological aging was due to PFNA or PFOSA exposure. In fact, the authors suggest that reverse causation may have occurred. This means biological aging may influence the metabolism or excretion of PFAS.

They also point out that some potential findings of the current study are substantially reduced due to false discovery rate adjustment. Therefore, results from this study should only be considered as hypotheses. They require confirmation using alternative methods.

Research findings are available online in the journal Frontiers in Aging.

The original story "Forever chemicals linked to accelerated aging risk in middle-aged men" is published in The Brighter Side of News.

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