Dietary citrate supplementation enhances longevity, metabolic health, and memory performance through promoting ketogenesis. Issue 12 (31st October 2021)

• Record Type: Journal Article
• Authors: Fan, Shou‐Zen; Lin, Cheng‐Sheng; Wei, Yu‐Wen; Yeh, Sheng‐Rong; Tsai, Yi‐Hsuan; Lee, Andrew Chengyu; Lin, Wei‐Sheng; Wang, Pei‐Yu
• Is Part Of: Aging cell. Volume 20:Issue 12(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-10-31
• Subjects: dendritic spine -- hippocampus -- insulin -- lifespan; Cells -- Aging -- Periodicals; 571.8783605
• DOI: 10.1111/acel.13510
• Languages: English
• ISSNs: 1474-9718

Abstract

Abstract: 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. Abstract : Dietary citrate supplementation can induce lifespan extension in fruit flies, as well as improve memory performance and metabolic health in mice under high‐calorie diets. Our experiments demonstrate that citrate‐induced benefits require Drosophila citrate transporter Indy and act through downstream AMPK and TOR signaling to enhance ketogenesis. These results are critical in implicating citrate as an anti‐aging intervention.