The clinical antiprotozoal drug nitazoxanide and its metabolite tizoxanide extend Caenorhabditis elegans lifespan and healthspan

The drugs extending healthspan in clinic have always been searched. Nitazoxanide is an FDA-approved clinical antiprotozoal drug. Nitazoxanide is rapidly metabolized to tizoxanide after absorption in vivo . Our previous studies find that nitazoxanide and its metabolite tizoxanide induce mild mitochondrial uncoupling and activate cellular AMPK, oral nitazoxanide protects against experimental hyperlipidemia, hepatic steatosis, and atherosclerosis. Here, we demonstrate that both nitazoxanide and tizoxanide extend the lifespan and healthspan of Caenorhabditis elegans through Akt/AMPK/sir 2.1/daf16 pathway. Additionally, both nitazoxanide and tizoxanide improve high glucose-induced shortening of C. elegans lifespan. Nitazoxanide has been a clinical drug with a good safety profile, we suggest that it is a novel anti-aging drug. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. This is an open access article under the CC BY-NCND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).