Canagliflozin (Cana) is an inhibitor of the sodium glucose transporter 2 (SGLT2), and is thought to act by blocking renal reuptake and intestinal absorption of glucose. Cana is FDA-approved for treatment of diabetes, and affords protection from cardiovascular and kidney diseases. In the context of the mouse Interventions Testing Program, genetically heterogeneous mice were given chow containing 180 ppm Cana at 7 months of age until their death. Cana extended median survival of male mice by 14%, with p < 0.001 by log-rank test. Cana also increased by 9% the age for 90th percentile survival (p < 0.001 by Wang/Allison test), with parallel effects seen at each of three test sites. Cana did not alter the distribution of inferred cause of death, nor of incidental pathology findings at end-of-life necropsies. No benefits were seen in female mice. The lifespan benefit of Cana is likely to reflect blunting of peak glucose levels, because similar longevity effects are seen in mice given acarbose, a diabetes drug that blocks glucose surges through a distinct mechanism, i.e. slowing breakdown of carbohydrate in the intestine. Interventions that control daily peak glucose levels deserve attention as possible preventive medicines to protect from a wide range of late-life neoplastic and degenerative diseases.

中文翻译：

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Canagliflozin延长了遗传异质雄性小鼠的寿命，而不延长雌性小鼠的寿命

Canagliflozin（Cana）是钠葡萄糖转运蛋白2（SGLT2）的抑制剂，被认为通过阻断肾脏的再摄取和肠道对葡萄糖的吸收而起作用。Cana经FDA批准可用于治疗糖尿病，并提供保护免受心血管和肾脏疾病的侵害。在小鼠干预测试计划的背景下，对遗传异质小鼠在7个月大时给予其含有180 ppm Cana的食物，直到它们死亡。Cana将雄性小鼠的中位生存期延长了14％，通过对数秩检验，p <0.001。在第90个百分位的存活率中，Cana的年龄也增加了9％（Wang / Allison测试，p <0.001），在三个测试点的每一个都看到了相似的效果。Cana并未改变推断的死亡原因的分布，也没有改变临终尸检时的偶然病理发现。在雌性小鼠中未见任何益处。Cana的终身益处很可能反映了峰值葡萄糖水平的减弱，因为在给予阿卡波糖的小鼠中观察到了类似的寿命影响，阿卡波糖是一种通过独特的机制阻止葡萄糖激增的糖尿病药物，即减缓肠道中碳水化合物的分解。控制每日葡萄糖峰值水平的干预措施应作为可能的预防药物而引起关注，以预防各种晚期肿瘤和变性疾病。