In animal studies, the key to engaging the sirtuin program appears to be keeping things on the razor’s edge through calorie restriction—just enough food to function in healthy ways and no more. This makes sense. It engages the survival circuit, telling longevity genes to do what they have been doing since primordial times: boost cellular defenses, keep organisms alive during times of adversity, ward off disease and deterioration, minimize epigenetic change, and slow down aging.