New Molecule Identified in Diet-Restricted Animals May Slow

[patricjfrenn]

A research collaboration between institutions in China and the U.S. has discovered a molecule that could play a role in slowing the aging process in some animals on a restricted diet. The team has published two papers on their findings in Nature, providing new insights into health promotion linked to calorie-restricted diets.

David Sinclair from Harvard Medical School also contributed a News & Views article in the same journal issue, offering a brief history of the search for factors associated with health benefits from restricted diets, as well as commentary on the team's new research.

Previous studies have shown that low-calorie diets can improve health and even extend the lifespan of certain animals, such as fruit flies and nematodes. However, testing this effect in humans is challenging due to the long human lifespan, which has led researchers to explore other avenues for evidence.

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One promising area of research has been the study of molecules in the gut, particularly lithocholic acid (LCA), a bile acid produced by gut bacteria. While earlier studies suggested that LCA was a toxin, recent research has revealed that in small doses, it may provide health benefits. For example, mice given low doses of LCA were found to produce more of a protein called AMPK, which is linked to slowing muscle atrophy.

The team conducted experiments to track changes in metabolites in the mouse gut when placed on a restricted diet, uncovering hundreds of different metabolites. Upon feeding these metabolites to mouse cells, they discovered that LCA was a key driver of activation. This finding suggests that LCA may contribute to some of the health benefits observed in diet-restricted mice, though it was not found to affect their lifespan.

In a second study, the researchers investigated how LCA activates AMPK and found that its activation depends on signaling from sirtuins, a family of enzymes. While they made significant progress, the researchers plan to continue their studies to determine whether LCA could offer health benefits for humans, or to identify other metabolites that might be involved in the process.