What biological systems trigger the beneficial effects of calorie restriction? The response to limited calorie intake is an evolutionary adaptation to periods of famine that extends longevity in most species tested so far. The mechanisms that determine whether or not to trigger this response are still under investigation, but some intriguing results are surfacing. Last year, scientists demonstrated that sense of smell is important for calorie restriction in flies:

A team of scientists [found] that the average life span of fruit flies on restricted diets decreased when they were exposed to food odors. The findings [suggest] that the flies are "actually perceiving the environment," thinking they are in a nutrient-rich place and then their bodies are "adaptively responding to it."

A recent experiment demonstrates the opposite effect in nematode worms, another favored experimental animal:

Many animals live longer when raised on low calorie diets. But now [researchers] have shown that they can extend the life spans of roundworms even when the worms are well fed - it just takes a chemical that blocks their sense of smell.

...

it's possible that sensory perception cues have important metabolic consequences independent of what we actually eat. "Emerging evidence suggests that core metabolic pathways that modulate lifespan in worms also modulate lifespan in vertebrates such as mice and perhaps humans. Sensory pathways might also be fairly universal. In an ancient common ancestor, these pathways might have caused metabolic adjustments that affect lifespan. That could be reflected in our own biology."

It wouldn't be surprising to uncover some influence on the metabolic changes of calorie restriction from sensory systems in more complex animals like us - but whether or not it exists and is significant is pure speculation at this stage. It does present another possible place to start looking for ways to trick the body into enacting these changes independently of diet, however.