文献类型：期刊文献

英文题名：Anti-aging effects of chlorpropamide depend on mitochondrial complex-II and the production of mitochondrial reactive oxygen species

作者：Mao, Zhifan[1];Liu, Wenwen[1];Huang, Yunyuan[1];Sun, Tianyue[1];Bao, Keting[1];Feng, Jiali[1];Moskalev, Alexey[2];Hu, Zelan[1];Li, Jian[1,3,4]

机构：[1]East China Univ Sci & Technol, Frontiers Sci Ctr Materiobiol & Dynam Chem, State Key Lab Bioreactor Engn, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[2]Russian Acad Sci, Komi Sci Ctr, Inst Biol, Ural Branch,Lab Geroprotect & Radioprotect Techno, Syktyvkar 167982, Russia;[3]Dali Univ, Coll Pharm, Yunnan Key Lab Screening & Res Antipathogen Plant, Dali 671000, Peoples R China;[4]Tongji Univ, Shanghai Peoples Hosp 10, Clin Med Sci & Tech Innovat Ctr, Sch Med, Shanghai 200092, Peoples R China

年份：2022

卷号：12

期号：2

起止页码：665

外文期刊名：ACTA PHARMACEUTICA SINICA B

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000760951600011)】；

基金：Financial support for this research provided by the National Natural Science Foundation of China (22037002 and 81772689) , the Program for Professor of Special Appointment (Eastern Scholar TP2018025, China) at Shanghai Institutions of Higher Learning, the Innovative Research Team of High-level Local Universities in Shanghai, and the Chinese Special Fund for State Key Laboratory of Bioreactor Engineering (2060204, China) . Strains of Caenorhabditis elegans were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440) .

语种：英文

外文关键词：Sulfonylureas; Chlorpropamide; Anti-aging; Mitochondrial complex II; Mitochondrial reactive oxygen species; ATP sensitive potassium channels; Senescence; Succinate dehydrogenase

摘要：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 studied with special emphasis on the interaction of chlorpropamide with mitochondrial ATP-sensitive K+ (mitoK-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 significantly 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 provides mechanistic insight into the anti-aging effects of sulfonylureas in C. elegans. (c) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).