Scientists reveal the secret of longevity. It's all about one important molecule

The authors published their findings in two articles in Nature (2024).

In parallel, Professor David Sinclair from Harvard Medical School (Harvard Medical School) published a review (News & Views) in the same issue, where he summarised the historical context of such studies and explained the importance of the new work.

It has long been hypothesised that calorie restriction can not only improve health but also prolong life in some organisms, including fruit flies and roundworms. However, it is extremely difficult to test this directly on humans, because we live much longer. Therefore, scientists have turned their attention to intestinal processes and, in particular, to the metabolites that are formed there when the caloric content of the diet is reduced.

In the new study, experts focused on lithocholic acid (LCA). This substance belongs to a group of bile acids produced by bacteria in the gut. Historically, LCA was considered a toxin, but more recent data indicate that in small doses it can have a positive effect on the body. In particular, scientists have found that LCA is linked to increased production of the protein AMPK, which is known to play a key role in regulating energy balance and slowing the process of age-related muscle atrophy.

During the experiments, the research team monitored hundreds of metabolites in the intestines of mice when they were reduced in calories. The cell cultures were then "fed" these substances to find out which metabolite stimulated the right processes. The results showed that LCA is one of the main activators of molecular mechanisms characteristic of a restricted diet. However, the effect on longevity of this acid specifically was not confirmed.

In the second phase of the work, the researchers found that LCA triggers AMPK through the participation of some signalling pathways associated with the sirtuin family of enzymes (sirtuins). The scientists suggest that this process is mediated by the TULP3 protein, with which LCA can interact, but the detailed mechanisms still require further research. The authors intend to continue the experiments to determine exactly how LCA or other metabolites may be beneficial to humans, and whether they are indeed able to slow age-related changes without negative effects.

Research references:

1. Qu et al. Lithocholic acid binds TULP3 to activate sirtuins and AMPK to slow down ageing, Nature (2024). DOI: 10.1038/s41586-024-08348-2
2. Qu et al. Lithocholic acid phenocopies anti-aging effects of calorie restriction, Nature (2024). DOI: 10.1038/s41586-024-08329-5
3. Sinclair D.A. A bile acid could explain how calorie restriction slows ageing, Nature (2024). DOI: 10.1038/d41586-024-04062-1