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 and 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 phase, has allowed the identification and characterization of long-lived strains with mutations in the G-protein Ras2. This paradigm was also used to identify the in vivo sources and targets of reactive oxygen species and to examine the role of antioxidant enzymes in the longevity of yeast. I will review this model system and discuss the striking phenotypic similarities between long-lived mutants ranging from yeast to mammalian neuronal cells. Taken together, the published studies suggest that survival may be regulated by similar fundamental mechanisms in many eukaryotes and that simple model systems will contribute to our understanding of the aging process in mammals.