Inhibition of the Mechanistic Target of Rapamycin (mTOR)-Rapamycin and Beyond.
Inhibition of the Mechanistic Target of Rapamycin (mTOR)-Rapamycin and Beyond.
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DOI：
10.1101/cshperspect.a025924
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发表时间：
2016-05-02
影响因子：
5.4
通讯作者：
Lamming DW
中科院分区：
文献类型：
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作者：
Lamming DW
雷帕霉素是一种经fda批准的免疫抑制剂和抗癌剂，于20世纪70年代初在复活节岛的土壤中发现。雷帕霉素是一种有效的选择性雷帕霉素靶蛋白激酶（mTOR）抑制剂，作为营养信号通路的中心整合器。在过去的十年中，已经发现mTOR通路信号的遗传和药物抑制可以促进酵母、蠕虫、苍蝇和小鼠的寿命。在本章中，我们将讨论雷帕霉素作用的分子生物学基础及其生理效应；雷帕霉素作为抗衰老化合物的证据；雷帕霉素延长寿命的机制；以及雷帕霉素作为抗衰老分子的潜在局限性。最后，我们将讨论可能的策略，使我们能够安全地抑制mTOR信号，同时最大限度地减少副作用，并从减缓衰老过程中获得健康、社会和经济效益。
Rapamycin is an FDA-approved immunosuppressant and anti-cancer agent discovered in the soil of Easter Island in the early 1970s. Rapamycin is a potent and selective inhibitor of the mTOR (mechanistic Target Of Rapamycin) protein kinase, which acts as a central integrator of nutrient signaling pathways. During the last decade, genetic and pharmaceutical inhibition of mTOR pathway signaling has been found to promote longevity in yeast, worms, flies and mice. In this chapter, we will discuss the molecular biology underlying the effects of rapamycin and its physiological effects; evidence for rapamycin as an anti-aging compound; mechanisms by which rapamycin may extend lifespan; and the potential limitations of rapamycin as an anti-aging molecule. Finally, we will discuss possible strategies that may allow us to inhibit mTOR signaling safely while minimizing side effects, and reap the health, social and economic benefits from slowing the aging process.