Metabolite Signatures of Chronological Age, Aging, Survival and Longevity

Metabolism plays a crucial role in both aging and aging-related diseases processes and there is substantial interest in the identification and characterization of the metabolites that serve as pivotal biomarkers of aging. We will describe an analysis of 408 plasma metabolites in Long Life Family Study participants that we published recently. In this analysis, we identified 308 metabolites associated with chronological age, 258 metabolites that changed over time, 230 metabolites associated with extreme longevity, and 152 metabolites associated with mortality risk. We replicated many of the found associations in independent studies, including the New England Centenarian Study and the Baltimore Longitudinal Study of Aging. The intersection of the results from the various analyses suggests that there is not a single metabolomic signature of chronological age, of extreme longevity, or of mortality but rather a variety of signatures with different clinical and biological interpretations, and translational potential. Specifically, we summarized the results into 19 signatures that highlight important differences between metabolites that may mark aging-associated compensatory mechanisms from metabolites that mark cumulative damage of aging and from metabolites that characterize extreme longevity. To further summarize the data, we generated and validated a metabolomic clock that predicts biological age. We also conducted a network analysis of the age-associated metabolites that highlighted a critical role of essential fatty acids to connect lipids with other metabolic processes. These results characterize many metabolites involved in aging and point to nutrients as targets for powerful healthy-aging interventions but also point to the need for carefully designed intervention studies that assess dosage and possible interactions of multiple nutrients on healthy aging and longevity.