I've dabbled with caloric restriction before for brief periods of time. I found that my body adjusted pretty quickly to it in a metabolic sense and the only real issue (and the reason I dabbled but never became a real adherent) was appetite, which I suspect will eventually be solvable via pharmacological means.

Intermittent caloric restriction is also showing promise. You don't have to starve yourself daily -- just a couple of times a week -- to show some of the same benefits. Perhaps not to the same degree, but far more comfortably.