Vicencio José Miguel, Galluzzi Lorenzo, Tajeddine Nicolas, Ortiz Carla, Criollo Alfredo, Tasdemir Ezgi, Morselli Eugenia, Ben Younes Amena, Maiuri Maria Chiara, Lavandero Sergio, Kroemer Guido
INSERM, U848, Paris, France.
Gerontology. 2008;54(2):92-9. doi: 10.1159/000129697. Epub 2008 May 2.
Many features of aging result from the incapacity of cells to adapt to stress conditions. When damage accumulates irreversibly, mitotic cells from renewable tissues rely on either of two mechanisms to avoid replication. They can permanently arrest the cell cycle (cellular senescence) or trigger cell death programs. Apoptosis (self-killing) is the best-described form of programmed cell death, but autophagy (self-eating), which is a lysosomal degradation pathway essential for homeostasis, reportedly contributes to cell death as well. Unlike mitotic cells, postmitotic cells like neurons or cardiomyocytes cannot become senescent since they are already terminally differentiated. The fate of these cells entirely depends on their ability to cope with stress. Autophagy then operates as a major homeostatic mechanism to eliminate damaged organelles, long-lived or aberrant proteins and superfluous portions of the cytoplasm. In this mini-review, we briefly summarize the molecular networks that allow damaged cells either to adapt to stress or to engage in programmed-cell-death pathways.
衰老的许多特征源于细胞无法适应应激条件。当损伤不可逆地积累时，可再生组织中的有丝分裂细胞依靠两种机制之一来避免复制。它们可以永久阻断细胞周期（细胞衰老）或触发细胞死亡程序。凋亡（自我杀伤）是程序性细胞死亡最广为人知的形式，但自噬（自我吞噬）作为维持体内平衡必不可少的溶酶体降解途径，据报道也会导致细胞死亡。与有丝分裂细胞不同，像神经元或心肌细胞这样的终末分化细胞不能衰老，因为它们已经处于终末分化状态。这些细胞的命运完全取决于它们应对应激的能力。自噬于是作为一种主要的稳态机制发挥作用，以清除受损细胞器、长寿命或异常蛋白质以及细胞质的多余部分。在这篇小型综述中，我们简要总结了使受损细胞能够适应应激或进入程序性细胞死亡途径的分子网络。
