Rapamycin increases lifespan and inhibits spontaneous tumorigenesis in inbred female mice
Rapamycin increases lifespan and inhibits spontaneous tumorigenesis in inbred female mice
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DOI：
10.4161/cc.10.24.18486
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发表时间：
2011-12-15
期刊：
影响因子：
4.3
通讯作者：
Blagosklonny, Mikhail V.
中科院分区：
文献类型：
--
作者：
Anisimov, Vladimir N.;Zabezhinski, Mark A.;Blagosklonny, Mikhail V.
营养感应TOR（雷帕霉素的目标）途径参与细胞和有机体衰老。雷帕霉素是TOR的抑制剂，可以延长酵母、果蝇和遗传异质性小鼠的寿命。在这里，我们证明了雷帕霉素的终身给药延长了雌性129/Sv小鼠的寿命，其特征是正常的平均寿命为2年。重要的是，雷帕霉素从2月龄开始间歇给药（每月2周）。雷帕霉素抑制与年龄相关的体重增加，降低衰老率，延长寿命（特别是在最后的幸存者中）和延迟自发性癌症。22.9%的雷帕霉素治疗组小鼠存活至对照组最后一只小鼠的死亡年龄。因此，我们首次在正常近交系小鼠中证明了雷帕霉素可以延长寿命。这为开发雷帕霉素作为抗衰老方式的最佳剂量和时间表开辟了一条途径。
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.