Department of Carcinogenesis and Oncogerontology, N.N.Petrov Research Institute of Oncology, St. Petersburg, Russia.
Cell Cycle. 2011 Dec 15;10(24):4230-6. doi: 10.4161/cc.10.24.18486.
The nutrient-sensing TOR (target of rapamycin) pathway is involved in cellular and organismal aging. Rapamycin, an inhibitor of TOR, extends lifespan in yeast, fruit flies and genetically heterogeneous mice. Here, we demonstrate that lifelong administration of rapamycin extends lifespan in female 129/Sv mice characterized by normal mean lifespan of 2 y. Importantly, rapamycin was administrated intermittently (2 weeks per month) starting from the age of 2 mo. Rapamycin inhibited age-related weight gain, decreased aging rate, increased lifespan (especially in the last survivors) and delayed spontaneous cancer. 22.9% of rapamycin-treated mice survived the age of death of the last mouse in control group. Thus we demonstrated for the first time in normal inbred mice that lifespan can be extended by rapamycin. This opens an avenue to develop optimal doses and schedules of rapamycin as an anti-aging modality.
营养感应 TOR（雷帕霉素靶蛋白）途径与细胞和机体衰老有关。雷帕霉素是 TOR 的抑制剂，它能延长酵母、果蝇和遗传异质性小鼠的寿命。在这里，我们证明了终生给予雷帕霉素可以延长 129/Sv 雌性小鼠的寿命，129/Sv 小鼠的平均寿命正常为 2 年。重要的是，雷帕霉素从 2 个月大开始间歇性给药（每月 2 周）。雷帕霉素抑制了与年龄相关的体重增加，降低了衰老速度，延长了寿命（尤其是在最后存活者中），并延缓了自发性癌症。22.9%的雷帕霉素治疗组的小鼠存活到对照组中最后一只小鼠死亡的年龄。因此，我们首次在正常近交系小鼠中证明，雷帕霉素可以延长寿命。这为开发雷帕霉素作为抗衰老药物的最佳剂量和方案开辟了道路。
