Miyajima Chiharu, Nagasaka Mai, Aoki Hiromasa, Toriuchi Kohki, Yamanaka Shogo, Hashiguchi Sakura, Morishita Daisuke, Aoyama Mineyoshi, Hayashi Hidetoshi, Inoue Yasumichi
Department of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan.
Department of Experimental Chemotherapy, Cancer Chemotherapy Center of JFCR, Tokyo 135-8550, Japan.
Cells. 2024 Dec 26;14(1):13. doi: 10.3390/cells14010013.
The Hippo pathway, a kinase cascade, coordinates with many intracellular signals and mediates the regulation of the activities of various downstream transcription factors and their coactivators to maintain homeostasis. Therefore, the aberrant activation of the Hippo pathway and its associated molecules imposes significant stress on tissues and cells, leading to cancer, immune disorders, and a number of diseases. Cellular senescence, the mechanism by which cells counteract stress, prevents cells from unnecessary damage and leads to sustained cell cycle arrest. It acts as a powerful defense mechanism against normal organ development and aging-related diseases. On the other hand, the accumulation of senescent cells without their proper removal contributes to the development or worsening of cancer and age-related diseases. A correlation was recently reported between the Hippo pathway and cellular senescence, which preserves tissue homeostasis. This review is the first to describe the close relationship between aging and the Hippo pathway, and provides insights into the mechanisms of aging and the development of age-related diseases. In addition, it describes advanced findings that may lead to the development of tissue regeneration therapies and drugs targeting rejuvenation.
Hippo信号通路作为一种激酶级联反应，与许多细胞内信号相互协调，介导对各种下游转录因子及其共激活因子活性的调控，以维持体内平衡。因此，Hippo信号通路及其相关分子的异常激活会给组织和细胞带来巨大压力，从而导致癌症、免疫紊乱以及多种疾病。细胞衰老作为细胞对抗压力的机制，可防止细胞受到不必要的损伤，并导致细胞周期持续停滞。它是抵御正常器官发育和与衰老相关疾病的强大防御机制。另一方面，衰老细胞若不能被及时清除而不断积累，则会促使癌症和与年龄相关疾病的发生或恶化。最近有报道称Hippo信号通路与细胞衰老之间存在关联，而细胞衰老有助于维持组织内稳态。本综述首次阐述了衰老与Hippo信号通路之间的紧密关系，并深入探讨了衰老机制以及与年龄相关疾病的发病过程。此外，还介绍了一些可能推动组织再生疗法及抗衰药物研发的前沿研究成果。
