Microbial Metabolites and Longevity: from the Gut the Secret of the Eternal Youth?

Although the most intimate desire as human creatures is to live longer, does the quality of life in aging meet our expectations? Are we getting the most out of it or desperately dragging our biological clock forward?

As predicted by the World Health Organization, the proportion of people over 60 years old worldwide is expected to exceed 22% by 2050. Despite the healthcare and lifestyle interventions, aging is still a primary risk factor for several pathologies, such as metabolic and cardiovascular disorders, cancer and/or neurodegenerative diseases. 

Longevity is orchestrated by genetic, epigenetic, and environmental factors such as diet, lifestyle, and ethnicity. Among all, gut microbiota acts as a thread, representing a unique, visceral fingerprint telling a secret story.

How? Through the release of microbial metabolites:

1. SCFA: they directly affect host epigenetic, promoting longevity and healthy aging. As potent inhibitors of histone deacetylases, butyrate and propionate promote epigenetic changes on histones in the colon, liver and white adipose tissue. Consistently, dietary supplementation with SCFAs was able to extend lifespan in C. elegans and Drosophila by inhibiting histone deacetylase (HDAC). 

2. Exopolysaccharides: bacteria-derived polysaccharides. They include lipopolysaccharides, teichoic acids and peptidoglycans, acting as protective shields against toxins in the environment. For example, colanic acid, secreted by Escherichia coli, reported a pro-longevity effect in C. elegans, through regulation of mitochondrial dynamics and preventing from amyloid-β accumulation.

3. Bile Acids: increased total bile acid levels have been observed under methionine restriction, a pro-longevity intervention. High concentrations of taurocholate, a conjugate of cholic acid and taurine, strongly correlate with human longevity. In animal models, supplementation with cholic acid, a primary bile acid, extended lifespan in progeroid mice, while lithocholic acid, a secondary bile acid, prolonged the lifespan of yeast and fruit flies. 

4. Polyamines: spermidine, spermine and putrescine are polycationic molecules, essential to cell growth, proliferation and survival. During aging, polyamine levels decrease (except for Centenarians), with a concomitant reduction in the enzymatic activity of ornithine decarboxylase-1, the rate-limiting enzyme for de novo polyamine synthesis. Probiotic supplementation with Bifidobacterium animalis subsp. lactis LKM512 in combination with arginine, promoted an increase in the colonic putrescine, serum spermidine and spermine levels, protecting aged mice from inflammation and memory impairment. 

Are we ready to grow younger? Possibly yes, working efficiently on our gut microbiome!

Link to the paper: https://lnkd.in/d588ZtJP