Proteasome activation as a novel antiaging strategy

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 predominately 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. (C) 2008 IUBMB.