Lipoic acid rejuvenates aged intestinal stem cells by preventing age‐associated endosome reduction

The age‐associated decline of adult stem cell function is closely related to the decline in tissue function and age‐related diseases. However, the underlying mechanisms that ultimately lead to the observed functional decline of stem cells still remain largely unexplored. This study investigated Drosophila midguts and found a continuous downregulation of lipoic acid synthase, which encodes the key enzyme for the endogenous synthesis of alpha‐lipoic acid (ALA), upon aging. Importantly, orally administration of ALA significantly reversed the age‐associated hyperproliferation of intestinal stem cells (ISCs) and the observed decline of intestinal function, thus extending the lifespan of Drosophila. This study reports that ALA reverses age‐associated ISC dysfunction by promoting the activation of the endocytosis–autophagy network, which decreases in aged ISCs. Moreover, this study suggests that ALA may be used as a safe and effective anti‐aging compound for the treatment of ISC‐dysfunction‐related diseases and for the promotion of healthy aging in humans.