Pan Haihui, Finkel Toren
From the Center for Molecular Medicine, NHLBI, National Institutes of Health, Bethesda, Maryland 20892.
From the Center for Molecular Medicine, NHLBI, National Institutes of Health, Bethesda, Maryland 20892
J Biol Chem. 2017 Apr 21;292(16):6452-6460. doi: 10.1074/jbc.R116.771915. Epub 2017 Mar 6.
Here, we review three sets of key proteins and their corresponding downstream pathways that have been linked to extending lifespan and promoting health span in a wide range of organisms. In particular, we review the biology of the sirtuin family of proteins, the insulin/insulin-like growth factor (IGF) signaling (IIS) pathway, and the mechanistic target of rapamycin (mTOR). Using insights derived from simple model organisms, mice, and humans we discuss how these proteins and pathways may potentially alter the rate of aging. We further describe how knowledge of these pathways may lead to the rational design of small molecules that modulate aging and hence alter the propensity for a host of age-related diseases.
在此,我们回顾了三组关键蛋白质及其相应的下游信号通路,这些蛋白质和信号通路在广泛的生物体中与延长寿命和促进健康寿命有关。特别是,我们回顾了sirtuin蛋白家族、胰岛素/胰岛素样生长因子(IGF)信号传导(IIS)通路以及雷帕霉素作用靶点(mTOR)的生物学特性。利用从简单模式生物、小鼠和人类中获得的见解,我们讨论了这些蛋白质和信号通路如何可能改变衰老速度。我们进一步描述了对这些信号通路的了解如何可能导致合理设计调节衰老的小分子,从而改变患一系列与年龄相关疾病的倾向。