A) A model for the conserved nutrient signaling pathways that regulate longevity in various organisms and mammals (see text). The role of the TOR-S6K pathway in promoting aging appears to be conserved from yeast to mammals. By contrast, both the AC-PKA pathways and the and TOR-S6K pathway promote aging in yeast and mammals, whereas an insulin/IGF-I-like receptor accelerates aging in worm, flies, and possibly mice. Similar transcription factors (GIS1, MSN2/4, DAF-16, FOXO) affect either stress resistance or aging in all the major model organisms. Notably, in the multicellular worms, flies and mice, it is the function of these genes and pathways in particular cell types that affect aging and stress resistance, as depicted for mammals in panel B (see text). B) Deficiency in GH/IGF-I signaling leads to life span extension and increased stress resistance in various mouse cell types (see text).