A new study, led by Paola Sebastiani, PhD, Director of the Center for Quantitative Methods and Data Science at Tufts Medical Center, has identified more than 300 unique metabolic markers associated with aging, extreme longevity, and mortality. The study, "Metabolite Signatures of Chronological Age, Aging, Survival and Longevity," was published in Cell Reports today.
"Metabolism plays a critical role in both the aging process and aging-related diseases, but the specific metabolites and lipids that serve as pivotal biomarkers of these processes are not well-understood," said Dr. Sebastiani, the study's First Author. "Aging is such a complex phenomenon. Identifying these biomarkers could offer new insights into how we age, improve early prediction of age-related diseases, and suggest interventions for promoting healthy longevity."
The researchers analyzed the plasma of participants in the Long Life Family Study--2,764 people, ages mid-20s to 110 years, from 540 families in the U.S. and Denmark with family traits of extreme longevity. The subjects included a large number of centenarians, who provided blood samples and whose metabolites were repeatedly measured and assessed over several years to identify metabolic markers associated with age, extreme longevity, and mortality. Physical function, cognitive function, and cardiac and pulmonary function were all closely tracked over time. The researchers measured a total of 408 metabolites and discovered 308 metabolites associated with the aging process, 258 metabolites that changed over time, 230 metabolites connected to extreme longevity and 152 metabolites linked with varying mortality risk.
To better understand the roles of these metabolites in age, longevity and mortality, the researchers organized their findings into 19 distinct groups, called "signatures". These signatures included metabolites that change with age, those associated with higher mortality risk, and those that were elevated in centenarians. The signatures helped the researchers differentiate between metabolites that may mark aging-associated compensatory mechanisms, those that characterize extreme longevity and metabolites that mark the cumulative damage of aging.
"It's important to note that clearly not everything that changes with age is bad and should be reversed. Some of these changes may be protective and contribute to healthy aging and longevity. It is useful to be able to distinguish which markers are really important to target."
Paola Sebastiani, PhD
One of the study's most important findings was identifying a possible association between nutrition and many of the metabolites connected with healthy longevity. Eating a plant-based diet rich in ergothioneine (abundant in mushrooms and asparagus) and flavones (high levels in celery and parsley) was found to be a marker for longevity. Consuming dark chocolate and other foods associated with salsolinol appeared to yield similar health and longevity benefits. Both flavones and salsolinol were found to be at surprisingly youthful levels in centenarians, suggesting that eating certain foods and following specific dietary patterns may contribute to a long, healthy life.
Additionally, the researchers aggregated the effects of 137 age-associated metabolites to develop a novel "metabolomic clock" to predict biological age based on metabolomic markers. While the clock is still preliminary, and is not yet ready for clinical application, it is designed to estimate whether a person's metabolic age is older or younger than their chronological age; those with an older metabolic age than chronological age were at a higher risk of mortality, while those with a younger metabolic age than chronological age were more likely to live longer, healthier lives.
"This study emphasizes the complexity of aging as a multifaceted process involving many biological pathways," said Dr. Sebastiani. "While genetics is likely a major cause for human longevity, more research is needed on metabolites' roles in these processes to confirm our findings, discover aging biomarkers and ultimately develop therapeutic interventions to keep people living longer, healthier lives."
Study collaborators included Senior Author Gary Patti, PhD, Director of the Center for Mass Spectrometry and Metabolic Tracing and Director of the Clinical Research Core in Medicine, at Washington University in St Louis; Co-Author Michael Lustgarten, PhD, Scientist II at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University; and Co-Author Anastasia Leshchyk, a PhD student in Bioinformatics at Boston University. The research was supported by the National Institute on Aging, National Institute for Health. Data from the study are available through the ELITE portal.
