The association of circulating bioenergetic metabolites with healthy human aging

Aging is an inevitable and gradual decline in several biological functions. Mitochondrial dysfunction is one of the most important hallmarks of aging. In this context, alterations in metabolites associated with mitochondrial dysfunction may serve as a significant biomarker. This study aimed to investigate the existence of a relationship between the key metabolites involved in bioenergetics metabolism and aging. 53 volunteers ranged 20-85 years participated in the study. We tested the association between different tricarboxylic acid (TCA) cycle metabolites, fatty acid metabolism, and amino acid metabolism with age, sex, body composition, and proxy markers of aging such as walking speed, grip strength and chair test. We found that lactic acid negatively correlated with age while several fatty acid metabolites, such as azelaic, sebacic, and linoleic acids, showed positive correlations with age (p < 0.05). Sex-specific trends, such as glycerol, and dodecanoic acid, were also observed for certain metabolites. Furthermore, citric acid levels were found to have a significant association with physical function and body composition measures. Participants with higher citric acid levels displayed improved performance in physical tests and favorable body composition indices. Additionally, fumaric acid and adipic acid showed positive correlations with fat-free body mass, while sebacic acid was negatively associated with measures of fat mass. These findings underscore the importance of understanding the role of circulating bioenergetics metabolites with age, sex variations, and their potential implications in body composition and physical performance.