Anti-aging effects of chlorpropamide depend on mitochondrial complex-II and the production of mitochondrial reactive oxygen species.
10.1016/j.apsb.2021.08.007
- Author:
Zhifan MAO
1
;
Wenwen LIU
1
;
Yunyuan HUANG
1
;
Tianyue SUN
1
;
Keting BAO
1
;
Jiali FENG
1
;
Alexey MOSKALEV
2
;
Zelan HU
1
;
Jian LI
1
Author Information
1. 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.
2. Laboratory of Geroprotective and Radioprotective Technologies, Institute of Biology, Komi Science Centre, Ural Branch, Russian Academy of Sciences, Syktyvkar 167982, Russia.
- Publication Type:Journal Article
- Keywords:
ATP sensitive potassium channels;
Anti-aging;
Chlorpropamide;
Mitochondrial complex II;
Mitochondrial reactive oxygen species;
Senescence;
Succinate dehydrogenase;
Sulfonylureas
- From:
Acta Pharmaceutica Sinica B
2022;12(2):665-677
- CountryChina
- Language:English
-
Abstract:
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.
