Researchers found that α-lipoic acid (ALA) levels drop significantly in the small intestines of older humans and mice due to reduced expression of the biosynthetic enzyme LIAS. Supplementing ALA in human intestinal organoids and old mice restored intestinal stem cell (ISC) proliferation, differentiation, and mitochondrial health. Critically, ALA's anti-aging effects required intact Paneth cells — the specialized niche cells adjacent to ISCs. ALA inhibited mTOR signaling in Paneth cells, boosting secretion of the pro-ISC molecule cyclic ADP ribose (cADPR) and reducing the Wnt inhibitor Notum. These findings identify ALA as a promising therapeutic candidate for age-related intestinal diseases in humans.
