Department of Medicine, University of California, San Francisco, United States.
Ageing Res Rev. 2011 Apr;10(2):225-37. doi: 10.1016/j.arr.2010.04.001. Epub 2010 Apr 10.
The target of rapamycin (TOR) signal transduction network monitors intra- and extracellular conditions that favor cell growth. Research during the last decade has revealed a modular structure of the TOR signaling network. Each signaling module senses a particular set of signals from the cellular milieu and exerts regulatory control towards TOR activity. The TOR pathway responds to growth factor signals, nutrient availability, and cellular stresses like hypoxia and energy stress. The signaling modules and their molecular components constituting the TOR network are remarkably conserved in both sequence and function across species. In yeast, roundworms, flies, and mice, the TOR pathway has been shown to regulate lifespan. Correspondingly, genetic, dietary or pharmacological manipulation of individual signaling modules as well as TOR activity itself extends lifespan in these model organisms. We discuss the potential impact of manipulating TOR activity for human health and lifespan.
雷帕霉素靶蛋白(TOR)信号转导网络监测有利于细胞生长的细胞内和细胞外环境。过去十年的研究揭示了 TOR 信号网络的模块化结构。每个信号模块从细胞环境中感知特定的信号集,并对 TOR 活性进行调节控制。TOR 途径对生长因子信号、营养物质可用性以及缺氧和能量应激等细胞应激作出反应。在酵母、线虫、苍蝇和老鼠中,TOR 途径已被证明可以调节寿命。相应地,个体信号模块以及 TOR 活性本身的遗传、饮食或药理学操作在这些模型生物中延长了寿命。我们讨论了操纵 TOR 活性对人类健康和寿命的潜在影响。