Mesaconic Acid as a Beneficial Metabolite Generated in the Gut Microbiome of Centenarians – Fight Aging!

A good deal of research interest is now focused on the composition of the gut microbiome as either (a) a contributing factor in degenerative aging, due to changes that take place with age or (b) a factor in determining natural variations in human life span. For example, a number of research groups have mapped the composition of gut microbiomes in very long-lived individuals. The study here goes a little beyond a map of species and relative population sizes to identify a metabolite produced by microbes that appears to be protective in older individuals, based on results in mice.

The gut microbiota of centenarians plays a vital role in promoting healthy longevity. We performed a cross-sectional study of 224 people from Jiaoling, China, which is globally recognised for the longevity of its residents. Compared with younger people, centenarians showed significantly increased alpha-diversity//en.wikipedia.org/wiki/Alpha_diversity”>alpha-diversity, enrichment of the beneficial bacteria Lactobacillus, Akkermansia, and Christensenella, and increased redox capacity in the gut microbiota. Serum metabolomics of centenarians showed significant enrichment of antioxidant metabolites, including L-ascorbic acid 2-sulphate and lipoic acid.

Finally, we isolated and screened a strain of Lactobacillus plantarum 124 (LP124) with a good antioxidant effect on the gut microbiota of centenarians. Animal experiments further verified that mesaconic acid from LP124 regulates the gut microbiota, is anti-inflammatory, relieves oxidative stress, maintains the intestinal barrier. LP124 derived from the gut microbiota of centenarians and its metabolite mesaconic acid, have a significant positive effect on health and longevity.

Link: https://doi.org/10.1038/s41522-025-00812-9