Rapamycin decelerates cellular senescence
Rapamycin decelerates cellular senescence
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DOI：
10.4161/cc.8.12.8606
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发表时间：
2009-06-15
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：
Demidenko, Zoya N.;Zubova, Svetlana G.;Blagosklonny, Mikhail V.
当细胞周期停止而细胞生长却没有停止时，细胞就会衰老，永久失去增殖能力。在这里，我们证明了细胞周期停滞的持续时间决定了增殖能力的逐渐丧失。在人和啮齿动物细胞系中，雷帕霉素（一种mTOR抑制剂）显著减缓了异位p21、p16和丁酸钠诱导的p21引起的增殖潜能丧失。因此，当细胞周期在雷帕霉素存在的情况下被这些因子阻止时，一旦p21、p16或丁酸钠被去除，细胞就保留了恢复增殖的能力。虽然雷帕霉素阻止了被阻滞细胞增殖潜能的永久丧失，但它并不能迫使被阻滞细胞增殖。在细胞周期阻滞过程中，雷帕霉素将不可逆阻滞转化为可逆条件。我们的数据表明衰老可以被药理学抑制。
When the cell cycle is arrested but cellular growth is not, then cells senesce, permanently losing proliferative potential. Here we demonstrated that the duration of cell cycle arrest determines a progressive loss of proliferative capacity. In human and rodent cell lines, rapamycin (an inhibitor of mTOR) dramatically decelerated loss of proliferative potential caused by ectopic p21, p16 and sodium butyrate-induced p21. Thus, when the cell cycle was arrested by these factors in the presence of rapamycin, cells retained the capacity to resume proliferation, once p21, p16 or sodium butyrate were removed. While rapamycin prevented the permanent loss of proliferative potential in arrested cells, it did not force the arrested cells into proliferation. During cell cycle arrest, rapamycin transformed the irreversible arrest into a reversible condition. Our data demonstrate that senescence can be pharmacologically suppressed.