Substantial evidence suggests that lifespan is increased if an organism restricts its daily calorie intake, a regimen that some say works by simply making life seem longer. A team of scientists from La Jola’s Salk Institute of Biological Studies has discovered a molecular switch flipped by hunger that could not only make longevity more appetizing, but also identify drug targets for patients with aging-related diseases like type II diabetes or cancer. In the Feb. 17 issue of the journal Nature, researchers reported for the first time that deactivation of a protein called CRTC1 in roundworms increases their lifespan, most likely mediating the effects of calorie restriction. Previously, researchers knew hunger promoted longevity by activating an enzyme called AMPK, which senses that food is scarce and pushes cells into a low energy state. “We knew AMPK was a major energy sensor, but didn’t know what it was talking to,” said Andrew Dillin, Ph.D., one of two senior authors of the study. “Our goal was to understand the genetic circuitry that registered that response.” They identified one protein called CRTC1 that is expressed at the same time and place as AMPK. The team fed worms an inhibitory RNA engineered to deplete CRTC1, and in about 3 weeks they found those worms lived a whopping 40 percent longer, suggesting that AMPK retards aging by antagonizing CRTC1 activity. “What we have identified is a binary switch that turns the aging process on and off,” Dillin said.