Department of Experimental Medicine, University of Lleida, Lleida Biomedical Research Institute (UdL-IRBLleida), E-25198 Lleida, Spain.
Int J Mol Sci. 2022 Aug 6;23(15):8747. doi: 10.3390/ijms23158747.
Decreased content and activity of the mechanistic target of rapamycin (mTOR) signalling pathway, as well as the mTOR complex 1 (mTORC1) itself, are key traits for animal species and human longevity. Since mTORC1 acts as a master regulator of intracellular metabolism, it is responsible, at least in part, for the longevous phenotype. Conversely, increased content and activity of mTOR signalling and mTORC1 are hallmarks of ageing. Additionally, constitutive and aberrant activity of mTORC1 is also found in age-related diseases such as Alzheimer's disease (AD) and cancer. The downstream processes regulated through this network are diverse, and depend upon nutrient availability. Hence, multiple nutritional strategies capable of regulating mTORC1 activity and, consequently, delaying the ageing process and the development of age-related diseases, are under continuous study. Among these, the restriction of calories is still the most studied and robust intervention capable of downregulating mTOR signalling and feasible for application in the human population.
雷帕霉素靶蛋白（mTOR）信号通路的含量和活性降低，以及 mTOR 复合物 1（mTORC1）本身，是动物物种和人类长寿的关键特征。由于 mTORC1 作为细胞内代谢的主调控因子，它至少部分负责长寿表型。相反，mTOR 信号和 mTORC1 的含量和活性增加是衰老的标志。此外，mTORC1 的组成性和异常活性也存在于与年龄相关的疾病中，如阿尔茨海默病（AD）和癌症。通过该网络调节的下游过程多种多样，并且取决于营养物质的可用性。因此，正在不断研究多种能够调节 mTORC1 活性、从而延缓衰老过程和与年龄相关疾病发展的营养策略。在这些策略中，热量限制仍然是研究最多、最有效的干预措施，能够下调 mTOR 信号，并适用于人类。
