What determines how long an animal can live? Some have argued that the life-span of a species is limited by a fixed total metabolic potential that is consumed over a lifetime. This follows from the observation that smaller animals have faster metabolic rates and generally shorter life-spans. Consistent with this idea, rats or mice that have existed on a diet reduced in calories live longer than animals that were allowed to eat as much as they liked. A corollary of this view is that the "clock" that times aging might be cumulative damage that is generated by toxic by-products of metabolism, such as oxygen radicals. Others have suggested that life-span may be genetically determined and that these genetic factors override any simple metabolic readout. This could explain why bats and mice, mammals of roughly the same size, have life-spans that differ by a factor of 5 to 10. This view also suggests that the clock is a genetic program set at a different rate in each species. The cloning and sequencing of the
clk-1 gene of Caenorhabditis elegans reported in this issue, along with recent findings discussed below, suggests how