Mutations in signal transduction proteins increase stress resistance and longevity in yeast, nematodes, fruit flies, and mammalian neuronal cells

Mutations in Ras and other signal transduction proteins increase survival a nd resistance to oxidative stress and starvation in stationary phase yeast, nematodes, fruit flies, and in neuronal PC12 cells. The chronological life span of yeast, based on the survival of nondividing cells in stationary ph ase, has allowed the identification and characterization of long-lived stra ins with mutations in the G-protein Ras2. This paradigm was also used to id entify the in vivo sources and targets of reactive oxygen species and to ex amine the role of antioxidant enzymes in the longevity of yeast. I will rev iew this model system and discuss the striking phenotypic similarities betw een long-lived mutants ranging from yeast to mammalian neuronal cells. Take n together, the published studies suggest that survival may be regulated by similar fundamental mechanisms in many eukaryotes and that simple model sy stems will contribute to our understanding of the aging process in mammals. (C) 1999 Elsevier Science Inc. All rights reserved.