Chondrogianni Niki, Gonos Efstathios S
National Hellenic Research Foundation, Institute of Biological Research and Biotechnology, Athens 11635, Greece.
IUBMB Life. 2008 Oct;60(10):651-5. doi: 10.1002/iub.99.
Homeostasis is a key feature of cellular lifespan. Maintenance of cellular homeostasis influences the rate of aging and is determined by several factors, including efficient proteolysis of damaged proteins. Protein degradation is predominantly catalyzed by the proteasome. Specifically, the proteasome is responsible for cell clearance of abnormal, denatured or in general damaged proteins as well as for the regulated degradation of short-lived proteins. As proteasome has an impaired function during aging, emphasis has been given recently in identifying ways of its activation. A number of studies have shown that the proteasome can be activated by genetic manipulations as well as by factors that affect its conformation and stability. Importantly the developed proteasome activated cell lines exhibit an extended lifespan. This review article discusses in details the various factors that are involved in proteasome biosynthesis and assembly and how they contribute to its activation. Finally as few natural compounds have been identified having proteasome activation properties, we discuss the advantages of this novel antiaging strategy.
细胞内稳态是细胞寿命的一个关键特征。维持细胞内稳态会影响衰老速度，且由多种因素决定，包括对受损蛋白质的高效蛋白水解作用。蛋白质降解主要由蛋白酶体催化。具体而言，蛋白酶体负责清除细胞内异常、变性或一般受损的蛋白质，以及对短命蛋白质进行有调控的降解。由于蛋白酶体在衰老过程中功能受损，最近人们重点关注如何激活它。多项研究表明，蛋白酶体可以通过基因操作以及影响其构象和稳定性的因素来激活。重要的是，已建立的蛋白酶体激活细胞系显示出延长的寿命。这篇综述文章详细讨论了参与蛋白酶体生物合成和组装的各种因素，以及它们如何促进蛋白酶体的激活。最后，由于已鉴定出少数具有蛋白酶体激活特性的天然化合物，我们讨论了这种新型抗衰老策略的优势。
