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Study team uses metabolomics to study longevity

Apr. 30, 2015, 8:45 AM

The oldest living person in the United States will turn 116 this month.

“It’s coming from above,” said Jeralean Talley of Detroit when pressed by her local media for the key to her longevity. “That’s the best advice I can give you. It’s not in my hands or your hands.”

She may be partially correct. The keys to longevity have been a source of curiosity and the basis of many research studies for years, yet the mechanisms underlying a person’s ability to live a long life are still not fully understood.

In a study published in Nature Communications this month, researchers found that alterations in metabolism may influence life span in humans. Previous studies indicated this to be the case in experimental models.

“Obviously, if you have signature diseases like cardiovascular disease and cancer, we understand why those individuals have shorter life spans. As it turns out, after taking those co-morbidities and others into account, there is a large amount of variability in how long people live that is difficult to explain,” said Thomas Wang, M.D., the study’s senior author, and director of the Division of Cardiovascular Medicine and physician-in-chief of the Vanderbilt Heart and Vascular Institute (VHVI).

Thomas Wang, M.D.

“Presumably, some of this variability is driven by biological factors that we haven’t discovered yet. That was the rationale for the study: to use a biochemical profiling tool known as metabolomics to see if we could find any clues to suggest why some individuals live longer than others.”

Metabolomics provide a snapshot of circulating metabolites in the bloodstream. Metabolites are molecules that are typically smaller than proteins that are the product of multiple biologic processes. The researchers studied a panel of 217 metabolites in plasma samples taken from 2,327 participants in the Framingham Offspring Study.

“We have the ability to look forward in time because these blood samples were collected several decades ago. We could see if any of the patterns from the baseline blood samples were associated with a tendency to live longer.

“For the purpose of this study we defined longevity as getting to age 80, although that is admittedly an arbitrary definition,” Wang said.

Of the source study sample, 647 individuals reached age 80.

The researchers found a number of circulating metabolites that were associated with living longer. Specifically, higher levels of isocitrate, which is related to energy usage in the body, and taurocholate, a bile acid with ties to fat metabolism, were associated with lower odds of longevity.

“Why these metabolites are associated with longevity is not exactly clear. They certainly provide some interesting clues, particularly the findings related to energy metabolism, because there is a fair amount of experimental data linking the citric acid pathway with lifespan in animal models,” Wang said.

The researchers extended these analyses beyond Framingham to a Swedish cohort and were able to replicate both of these findings.

“Isocitrate and taurocholate made it through a comprehensive set of statistical analyses. In our study these two metabolites had the strongest association with longevity,” Wang said.

Given that this was the first study to report these findings, a next logical step would be to replicate this association in different populations, he added.

“It focuses further attention on the broad hypothesis that pathways involved in energy metabolism may have some fundamentally important effect on the lifespan. This may be partially mediated by cardiovascular risk, but it doesn’t appear as if it is entirely explained by increased cardiovascular risk.

“Although you can see some of these associations in experimental models, it is intriguing to see this evidence in humans.”

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