钠-葡萄糖协同转运蛋白抑制剂 (SLGTi) 最初被批准作为 2 型糖尿病的降糖疗法，可降低许多最常见的衰老疾病的风险，包括心力衰竭、慢性肾病、全因住院、心房颤动纤维颤动、癌症、痛风、肺气肿、神经退行性疾病/痴呆、肺气肿、非酒精性脂肪肝、动脉粥样硬化性疾病和感染。研究还表明 SLGTi 可以提高整体预期寿命并降低心血管疾病死亡和癌症死亡的风险。这些广泛的健康益处在很大程度上无法用 SLGTi 引起的标准风险因素的适度改善来解释。 SLGTi 上调营养剥夺信号，同时触发下调营养过剩信号。这反过来又促进自噬-细胞内务管理，使衰老和受损的细胞器被分解和回收，这有助于维持细胞完整性并防止细胞凋亡。 SLGTi 减少氧化应激和内质网应激，恢复线粒体健康，刺激线粒体生物发生，并减少促炎和促纤维化途径。这些作用有助于使衰老的细胞、组织和器官恢复活力。它们在预防过早疾病和死亡方面的累积效应表明，SLGTi 可能会延缓衰老并提高预期寿命，其作用机制为这一假设提供了很强的生物学合理性。有必要进行进一步的随机试验来测试 SLGTi（一种安全且耐受性良好的每日一次药丸）是否可以改善寿命和健康状况。版权所有 © 2023。由 Elsevier Inc. 出版。

Sodium-glucose cotransporter inhibitor (SLGTi), initially approved as a glucose-lowering therapy for type 2 diabetes is associated with decreased risks for many of the most common conditions of aging, including heart failure, chronic kidney disease, all-cause hospitalization, atrial fibrillation, cancer, gout, emphysema, neurodegenerative disease/dementia, emphysema, non-alcoholic fatty liver disease, atherosclerotic disease, and infections. Studies also suggest SLGTi improves overall life expectancy and reduces risks of cardiovascular disease death and cancer death. These wide-ranging health benefits are largely unexplained by the modest SLGTi -induced improvements in standard risk factors. SLGTi produces upregulation of nutrient deprivation signaling, while simultaneously triggering downregulation of nutrient surplus signaling. This in turn promotes autophagy-cellular housekeeping whereby senescent and damaged organelles are broken down and recycled, which helps to maintain cellular integrity and prevent apoptotic cell death. SLGTi decreases oxidative stress and endoplasmic reticulum stress, restores of mitochondrial health, stimulates mitochondrial biogenesis, and diminishes proinflammatory and profibrotic pathways. These actions help to revitalize senescent cells, tissues, and organs. Their cumulative effects in preventing premature disease and death suggest that SLGTi may slow aging and improve life expectancy, and its mechanisms of action lend strong biological plausibility to this hypothesis. Further randomized trials are warranted to test whether SLGTi -a safe and well-tolerated, once-daily pill, might improve lifespan and healthspan.Copyright © 2023. Published by Elsevier Inc.