Sulfonylureas are widely used oral anti-diabetic drugs.However,its long-term usage effects on patients'lifespan remain controversial,with no reports of influence on animal longevity.Hence,the anti-aging effects of chlorpropamide along with glimepiride,glibenclamide,and tolbutamide were stud-ied with special emphasis on the interaction of chlorpropamide with mitochondrial ATP-sensitive K+(mi-toK-ATP)channels and mitochondrial complex Ⅱ.Chlorpropamide delayed aging in Caenorhabditis elegans,human lung fibroblast MRC-5 cells and reduced doxorubicin-induced senescence in both MRC-5 cells and mice.In addition,the mitochondrial membrane potential and ATP levels were signif-icantly increased in chlorpropamide-treated worms,which is consistent with the function of its reported targets,mitoK-ATP channels.Increased levels of mitochondrial reactive oxygen species(mtROS)were observed in chlorpropamide-treated worms.Moreover,the lifespan extension by chlorpropamide required complex Ⅱ and increased mtROS levels,indicating that chlorpropamide acts on complex Ⅱ directly or indirectly via mitoK-ATP to increase the production of mtROS as a pro-longevity signal.This study pro-vides mechanistic insight into the anti-aging effects of sulfonylureas in C.elegans.

Zhifan Mao;Wenwen Liu;Yunyuan Huang;Tianyue Sun;Keting Bao;Jiali Feng;Alexey Moskalev;Zelan Hu;Jian Li

State Key Laboratory of Bioreactor Engineering,Frontiers Science Center for Materiobiology and Dynamic Chemistry,Shanghai Key Laboratory of New Drug Design,East China University of Science and Technology,Shanghai 200237,China;Laboratory of Geroprotective and Radioprotective Technologies,Institute of Biology,Komi Science Centre,Ural Branch,Russian Academy of Sciences,Syktyvkar 167982,Russia;Yunnan Key Laboratory of Screening and Research on Anti-pathogenic Plant Resources from West Yunnan,College of Pharmacy,Dali University,Dali 671000,China;Clinical Medicine Scientific and Technical Innovation Center,Shanghai Tenth People's Hospital,Tongji University School of Medicine,Shanghai 200092,China

药学学报（英文版）

[1]Zhifan Mao;Wenwen Liu;Yunyuan Huang;Tianyue Sun;Keting Bao;Jiali Feng;Alexey Moskalev;Zelan Hu;Jian Li-.Anti-aging effects of chlorpropamide depend on mitochondrial complex-Ⅱ and the production of mitochondrial reactive oxygen species)[J].药学学报（英文版）,2022(02):665-677

chlorpropamide,Sulfonylureas,glimepiride,tolbutamide,toK,Chlorpropamide,mitoK

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