Aging Cell: Dietary supplementation of citrate can promote longevity

Citrate is a key substrate that mediates cell energy metabolism
.

In mitochondria, citrate is produced by the condensation of acetyl CoA and oxaloacetate through the catalyzed condensation of citrate synthase

Existing studies have shown that mutations in genes encoding D.
melanogaster and C.
elegans plasma membrane citrate transporters can lead to an increase in the body's metabolic capacity and an extension of lifespan
.

The null mutation of mammal Indy (mIndy, also called SLC13A5) under high-fat diet also gave mice superior metabolic health, further supporting the importance of citrate in aging-related metabolic regulation

Intracellular citrate can also be used as a sensor to regulate energy production, because it can inhibit or activate several strategic enzymes involved in glycolysis, TCA cycle, glucose production and fatty acid synthesis
.

Due to its inhibitory effect on glycolysis and TCA cycle, high-concentration citrate supplementation has been proposed as an anti-cancer intervention, which causes cell growth to stop through ATP consumption and ultimately leads to cell death

A similar approach to limiting cell energy is achieved through dietary restriction (DR, 20%-40% reduction in food intake), which is a well-documented program that has been determined to be the most effective way to extend the healthy lifespan of multiple species.
Effective intervention measures
.

Studies investigating the underlying mechanism of DR have identified signaling pathways involved in nutrient sensing and metabolism, such as sirtuins (Sir), AMP-activated protein kinase (AMPK), target of rapamycin (TOR), and downstream ketogenic pathways

Citrate-induced lifespan extension is related to AMPK and TOR pathways

Citrate-induced lifespan extension is related to AMPK and TOR pathways Citrate-induced lifespan extension is related to AMPK and TOR pathways

Recently, researchers reported that supplementation of citrate in the diet can significantly reduce energy status and extend the lifespan of Drosophila melanogaster
.

Researchers’ genetic studies in Drosophila suggest a molecular mechanism related to AMP-activated protein kinase (AMPK), rapamycin (TOR) targets, and ketogenesis

Citrate supplementation in the diet can significantly reduce energy status and extend the lifespan of Drosophila melanogaster

Mice fed a high-fat diet also showed improvements in metabolic health and memory after supplementation with citrate or ketone body β-hydroxybutyrate (βOHB)

Metabolic health and memory improvement Metabolic health and memory improvement

Taken together, these results indicate that supplementation of citrate in the diet may prove to be a useful intervention for the treatment of age-related dysfunction in the future

Citrate supplementation in the diet may prove to be a useful intervention for the treatment of age-related dysfunction in the future.

Original source:

Original source:

Shou-Zen Fan et al.

Shou-Zen Fan et al.

 

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