Cadena Sandoval Marti, Heberle Alexander Martin, Rehbein Ulrike, Barile Cecilia, Ramos Pittol José Miguel, Thedieck Kathrin
Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria.
Laboratory of Pediatrics, Section Systems Medicine of Metabolism and Signaling, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Front Aging. 2021 Oct 13;2:761333. doi: 10.3389/fragi.2021.761333. eCollection 2021.
The mechanistic target of rapamycin complex 1 (mTORC1) kinase is a master regulator of metabolism and aging. A complex signaling network converges on mTORC1 and integrates growth factor, nutrient and stress signals. Aging is a dynamic process characterized by declining cellular survival, renewal, and fertility. Stressors elicited by aging hallmarks such as mitochondrial malfunction, loss of proteostasis, genomic instability and telomere shortening impinge on mTORC1 thereby contributing to age-related processes. Stress granules (SGs) constitute a cytoplasmic non-membranous compartment formed by RNA-protein aggregates, which control RNA metabolism, signaling, and survival under stress. Increasing evidence reveals complex crosstalk between the mTORC1 network and SGs. In this review, we cover stressors elicited by aging hallmarks that impinge on mTORC1 and SGs. We discuss their interplay, and we highlight possible links in the context of aging and age-related diseases.
雷帕霉素复合物1（mTORC1）激酶的作用机制靶点是代谢和衰老的主要调节因子。一个复杂的信号网络汇聚于mTORC1，并整合生长因子、营养和应激信号。衰老是一个动态过程，其特征是细胞存活率、更新能力和生育能力下降。由衰老标志引发的应激源，如线粒体功能障碍、蛋白质稳态丧失、基因组不稳定和端粒缩短，会影响mTORC1，从而导致与年龄相关的过程。应激颗粒（SGs）是由RNA-蛋白质聚集体形成的细胞质非膜性区室，在应激条件下控制RNA代谢、信号传导和细胞存活。越来越多的证据揭示了mTORC1网络与应激颗粒之间复杂的相互作用。在这篇综述中，我们涵盖了由衰老标志引发的、影响mTORC1和应激颗粒的应激源。我们讨论了它们之间的相互作用，并强调了在衰老和与年龄相关疾病背景下可能存在的联系。
