Ras: the other pro-aging pathway.

Studies in worms, flies, and mice point to the insulin/insulin-like growth factor-1 (IGF-1)/phosphatidylinositol 3-kinase/Akt-like pathway as a central regulator of longevity. A similar pathway, which includes Sch9, a functional mammalian Akt/protein kinase B homolog, regulates longevity in yeast. Chronological aging in yeast is also regulated by a second pathway that includes Ras, adenylate cyclase, protein kinase A, the transcription factors Msn2 and Msn4, and Sod2. Although Ras proteins have not been implicated in longevity regulation in worms or flies, the major role of Ras in mammalian IGF-1 signaling raises the possibility that homologs of yeast Ras2 might accelerate aging in mammals. Here I review the data from experiments at both the organismal and cellular levels that support a role for Ras in the regulation of stress resistance and life span in eukaryotes.