Cutting calories does more than just shrink your waist size–it also increases the lifespan of organisms ranging from yeast to flies to mice. Earlier studies in the roundworm Caenorhabditis elegans pointed to a mysterious interplay between longevity and two regulatory genes called DAF-16 and SMK-1 . In these roundworms, which had abnormally reduced insulin signaling, SMK-1 and DAF-16 together lengthen lifespan when nutrients are scarce. But in subsequent experiments on worms with normal insulin signaling, molecular biologist Andrew Dillin at the Salk Institute for Biological Sciences in San Diego, California, showed that one member of the pair–DAF-16–wasn’t necessary for longer life. So he and his colleagues predicted that SMK-1 might regulate another gene to help lean worms live long.
The team screened the complete C. elegans genome and found 15 genes closely related to DAF-16. Working with a technique called RNA interference, they inactivated each of the genes in turn. This revealed that a gene called PHA-4 , which regulates gut development in the roundworm embryo, is essential to diet-induced longevity. Without this gene, diet-restricted worms lived no longer than control worms maintained on a normal diet, while diet-restricted worms with the intact gene lived about 62% longer than controls.