He Long, Cho Sungyun, Blenis John
Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA;
Department of Pharmacology, Weill Cornell Medicine, New York, New York 10021, USA.
Genes Dev. 2025 Jan 7;39(1-2):109-131. doi: 10.1101/gad.352084.124.
The mechanistic target of rapamycin (mTOR) pathway senses and integrates various environmental and intracellular cues to regulate cell growth and proliferation. As a key conductor of the balance between anabolic and catabolic processes, mTOR complex 1 (mTORC1) orchestrates the symphonic regulation of glycolysis, nucleic acid and lipid metabolism, protein translation and degradation, and gene expression. Dysregulation of the mTOR pathway is linked to numerous human diseases, including cancer, neurodegenerative disorders, obesity, diabetes, and aging. This review provides an in-depth understanding of how nutrients and growth signals are coordinated to influence mTOR signaling and the extensive metabolic rewiring under its command. Additionally, we discuss the use of mTORC1 inhibitors in various aging-associated metabolic diseases and the current and future potential for targeting mTOR in clinical settings. By deciphering the complex landscape of mTORC1 signaling, this review aims to inform novel therapeutic strategies and provide a road map for future research endeavors in this dynamic and rapidly evolving field.
雷帕霉素的作用机制靶点（mTOR）通路能够感知并整合各种环境和细胞内信号，以调节细胞生长和增殖。作为合成代谢与分解代谢过程平衡的关键调控者，mTOR复合物1（mTORC1）精心协调糖酵解、核酸与脂质代谢、蛋白质翻译与降解以及基因表达的协同调控。mTOR通路的失调与众多人类疾病相关，包括癌症、神经退行性疾病、肥胖症、糖尿病和衰老。本综述深入探讨了营养物质和生长信号如何协同作用以影响mTOR信号传导以及在其调控下的广泛代谢重编程。此外，我们讨论了mTORC1抑制剂在各种与衰老相关的代谢疾病中的应用，以及在临床环境中靶向mTOR的当前和未来潜力。通过解读mTORC1信号传导的复杂格局，本综述旨在为新的治疗策略提供信息，并为这个动态且快速发展的领域中的未来研究工作提供路线图。
