Nutrient Sensing And Chronological Aging

Based on the hypothesis that oxidative damage is one cause of chronological aging, Fabrizio and Longo carried out a screen for mutants with increased chronological life span by selecting for mutations that confer a survival advantage in the presence of paraquat, a superoxide generating agent (Fabrizio et al., 2001). From this screen two genes were identified that play a central role in regulating chronological aging, SCH9 and CYR1. Sch9 is a nutrient responsive kinase with homology to mammalian Akt proteins, and CYR1 codes for adenylate cyclase, an activator of PKA. Deletion of Sch9 increases yeast chronological life span by up to 300%, while a partial loss of function allele in CYR1, cyr1::mTn, increases life span by approximately 70% (Fabrizio et al., 2001). Both of these genes have also been shown to similarly regulate yeast replicative aging (discussed in Conserved nutrient sensing pathways as a mediator of CR in yeast), and RNAi knock-down of the Sch9 ortholog, Sgk-1, increases life span in worms (Hertweck et al., 2004).

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