Dietary citrate supplementation enhances longevity, metabolic health, and memory performance through promoting ketogenesis

Citrate is an essential substrate for energy metabolism that plays critical roles in regulating cell growth and survival. However, the action of citrate in regulating metabolism, cognition, and aging at the organismal level remains poorly understood. Here, we report that dietary supplementation with citrate significantly reduces energy status and extends lifespan in Drosophila melanogaster. Our genetic studies in fruit flies implicate a molecular mechanism associated with AMP-activated protein kinase (AMPK), target of rapamycin (TOR), and ketogenesis. Mice fed a high-fat diet that supplemented with citrate or the ketone body β-hydroxybutyrate (βOHB) also display improved metabolic health and memory. These results suggest that dietary citrate supplementation may prove to be a useful intervention in the future treatment of age-related dysfunction.