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.

磺脲类药物是广泛使用的口服抗糖尿病药物。然而，其长期使用对患者寿命的影响仍然存在争议，没有关于对动物寿命影响的报道。因此，研究了氯磺丙脲与格列美脲、格列本脲和甲苯磺丁脲的抗衰老作用，特别强调了氯磺丙脲与线粒体 ATP 敏感 K ⁺ (mitoK-ATP) 通道和线粒体复合物 II 的相互作用。氯丙酰胺延缓秀丽隐杆线虫的衰老，人肺成纤维细胞 MRC-5 细胞和减少多柔比星诱导的 MRC-5 细胞和小鼠的衰老。此外，氯磺丙脲处理线虫的线粒体膜电位和 ATP 水平显着增加，这与其报道的靶点 mitoK-ATP 通道的功能一致。在氯磺丙胺处理的蠕虫中观察到线粒体活性氧 (mtROS) 水平升高。此外，氯磺丙脲延长寿命需要复合物 II 和增加的 mtROS 水平，这表明氯磺丙胺通过mitoK-ATP 直接或间接作用于复合物 II，以增加 mtROS 的产生作为延长寿命的信号。这项研究提供了关于磺脲类药物在秀丽隐杆线虫中的抗衰老作用的机理性见解。