Both caloric and chemosensory mechanisms influence lifespan, but the relative importance of each of these mechanisms in mediating effects of dietary restriction on lifespan has been unclear. Here we demonstrate that chemosensory mechanisms consistently influence initial mortality rate, whereas caloric mechanisms consistently influence age-dependent acceleration of mortality rate. Based on this analysis, life-extending effects of dietary restriction are mediated primarily by caloric mechanisms in rats and nematodes and by both mechanisms in mice and flies.