【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,
【机 构】
：
State Key Laboratory of Bioreactor Engineering,Frontiers Science Center for Materiobiology and Dynam
论文部分内容阅读
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.
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