A regulatory growth factor pathway has been implicated in determination of longevity in a variety of species. Altered signaling in this pathway confers not only extended life spans but also increased resistance to oxidative stress. A new report using mice engineered to express fewer receptors for insulin-like growth factor (IGF-I), therefore reducing the signaling through this pathway, provides strong supporting evidence that IGF-I signaling does play a significant role in longevity. The IGF-I receptor knockdown mice were fertile, slightly smaller and resisted oxidative stressors more effectively when compared with normal littermate mice. This, along with other recent evidence, could provide clues towards potential therapeutic intervention to extend life span in humans.