People who live to be over 100 years old often owe their extraordinary longevity to a combination of protective genes and healthy habits. Researchers estimate that up to 50% of a person’s ability to reach extreme old age is due to genetics, but lifestyle factors such as eating a plant-forward diet, staying physically active through regular natural exercise, and maintaining strong social relationships also play an important role. Although scientists have identified immune system characteristics unique to many centenarians, the metabolic changes that accompany healthy aging are still unclear.
A new study from Boston University’s Chobanian and Avedisyan School of Medicine has identified distinct patterns of blood metabolites in centenarians that may represent more than just aging. Researchers found that people who reached the age of 100 had abnormally high levels of certain primary and secondary bile acids, along with preserved levels of some steroids. These metabolic patterns were different from those seen during typical aging and were associated with lower mortality risk.
“Our study shows measurable chemical fingerprints in the blood that are associated with living a very long and healthy life. Understanding those fingerprints may allow us to identify biological pathways that may contribute to protecting people from age-related decline,” explains corresponding author Dr. Stefano Monti, professor of medicine at the school.
Analysis of blood metabolites in centenarians
The researchers analyzed blood samples from 213 participants in the New England Centenarian Study, one of the largest studies of exceptionally long-lived people in North America. The study, led by Thomas Perls, MD, professor of medicine at the school, included 70 centenarians and their children (offspring), as well as age-matched control participants.
The scientists measured approximately 1,495 small molecules in serum using an untargeted metabolomics assay. They compared metabolite levels among centenarians, offspring, and controls, while also identifying molecules that change with chronological age. To strengthen their findings, the researchers compared their results to four additional metabolomics studies (one that included long-lived people and one that did not) to determine which metabolic signals consistently emerged.
The researchers also looked at which metabolites, or groups of metabolites, were associated with how long the participants lived after the blood samples were taken (survival analysis). Furthermore, we developed a machine learning model called the “metabolomic clock” that estimates biological age from metabolite levels and assesses whether being biologically younger or older than chronological age is associated with survival.
Blood biomarkers for healthy aging
The researchers say the metabolites and metabolic patterns identified in this study could ultimately serve as biomarkers to estimate biological age, identify people at high or low risk of age-related decline, and track how individuals respond to lifestyle changes and health-promoting medications as they age.
They also believe that several biological pathways merit additional study as potential targets for future treatments and dietary therapies. These include pathways involving bile acids, NAD-related pathways, gut bacterial metabolites, oxidative stress markers, and certain steroids.
“We hope this study will help show measurable metabolic signs of healthy aging that can be tracked and targeted. However, the study’s cross-sectional design means we have not yet been able to determine cause and effect, and these findings will need to be validated in larger and more 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.”
The findings were published in an online journal Gero science.
