People who live to age 100 and beyond often owe their exceptional longevity to a mix of protective genes and healthy habits. Researchers estimate that genetics account for as much as 50% of the ability to reach extreme old age, while lifestyle factors such as eating a plant forward diet, staying physically active through regular natural movement, and maintaining strong social relationships also play an important role. Although scientists have identified unique immune system traits in many centenarians, the metabolic changes associated with healthy aging have remained less clear.
A new study from the Boston University Chobanian & Avedisian School of Medicine has now identified a distinct pattern of blood metabolites in centenarians that appears to represent more than simply growing older. The researchers found that people who reached 100 years of age had unusually high levels of certain primary and secondary bile acids along with preserved levels of several steroids. These metabolic patterns differed from those seen during typical aging and were associated with a lower risk of death.
"Our study points to measurable chemical fingerprints in the blood that are associated with living a very long and healthy life. If we can understand those fingerprints, we may identify biological pathways that could contribute to protecting people from age-related decline," explains corresponding author Stefano Monti, PhD, professor of medicine at the school.
The research team analyzed blood samples from 213 participants in the New England Centenarian Study, one of the largest investigations of exceptionally long lived people in North America. Led by Thomas Perls, MD, professor of medicine at the school, the study included 70 centenarians, their children (offspring), and age matched control participants.
Using an untargeted metabolomics assay, the scientists measured approximately 1,495 small molecules in blood serum. They compared metabolite levels among centenarians, offspring, and controls, while also identifying molecules that changed with chronological age. To strengthen their findings, they compared the results with four additional metabolomics studies (some that included long-lived people and some that did not) to determine which metabolic signals appeared consistently.
The researchers also examined which metabolites or groups of metabolites were linked to how long participants lived after their blood samples were collected (survival analysis). In addition, they developed a machine-learning model "metabolomic clock") that estimated biological age from metabolite levels and evaluated whether being biologically younger or older than a person's chronological age was associated with survival.
According to the researchers, the metabolites and metabolic patterns identified in the study could eventually serve as biomarkers for estimating biological age, identifying people at higher or lower risk of age related decline, and tracking how individuals respond to lifestyle changes or medications designed to improve health as they age.
They also believe several biological pathways deserve additional study as possible targets for future therapies or dietary approaches. These include pathways involving bile acids, NAD-related pathways, gut bacterial metabolites, oxidative stress markers and certain steroids.
"We hope this study helps point to measurable metabolic signs of healthy aging that can be tracked and targeted. However, the study's cross-sectional design means we cannot yet determine cause and effect, and these findings need validation in larger, diverse populations. Ultimately, our goal is to translate these insights into tests and safe interventions that help people stay healthier and more active for longer," adds Monti.
The findings were published online in the journal GeroScience.
Materials provided by Boston University School of Medicine. Note: Content may be edited for style and length.
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