Lithocholic acid significantly extends the lifespan in Drosophila melanogaster by targeting multiple lifespan-extending pathways

Primary bile acids are produced in the liver whereas secondary bile acids such as lithocholic acid (LCA) are generated by gut bacteria from primary bile acids that escape the ileal absorption. Besides their well-known function as detergents in lipid digestion, bile acids are important signaling molecules mediating effects on the hosts metabolism. As energy metabolism is closely linked to aging and longevity we supplemented fruit flies (Drosophila melanogaster) with 50 mol/l LCA either for 30 days or throughout their lifetime. LCA supplementation resulted in a significant induction of the mean (+12 days), median (+10 days) and maximum lifespan (+ 11 days) in comparison to untreated control flies. This lifespan extension was accompanied by an induction of spargel (srl), the fly homolog of mammalian PPARG co-activator 1a(PGC1A. In srl mutant flies, LCA failed to induce longevity emphasizing the essential role of srl in the observed lifespan extension. In addition, the administration of antibiotics to wild type flies abrogated LCA-mediated effects on both lifespan and srl expression, suggesting a substantial contribution of the intestinal microbiota to the LCA-induced longevity.

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Staats S, Rimbach G, Kuenstner A, Graspeuntner S, Rupp J, Busch H, Sina C, Ipharraguerre IR, Wagner AE