All of this leads us back to the spectacular benefits of semi-starvation on the health and longevity of laboratory animals. If we take a young rat and restrict its eating to less than two-thirds the calories of its preferred diet, and if we keep this up for its entire life, our rat will likely live 30 to 50 percent longer than had we let it eat to satiation, and any age-related diseases—cancer in particular—will be delayed in their onset and slowed in their progression. This has been shown to hold true for mice and other rodents, and for yeast, protozoans, fruit flies, and worms (and maybe even monkeys).

Two possibilities for how these diets work are that the animals live longer because they are less encumbered by body fat, or because they’re leaner all around and so weigh less. Neither of these can explain the evidence, however. Consider a strain of mice known as ob/ob mice. These have a mutation in a single gene that results in such extreme obesity that a mouse ends up looking like a loaf of bread with fur, eyes, whiskers, and a mouth. Nonetheless, these mice can be kept at a normal weight by restricting their food consumption to half of what they would naturally prefer to eat. They are normally short-lived, which supports the idea that the greater the body fat the shorter the lifespan, but on a lifelong very low-calorie diet they will live as long as or longer than lean mice of a similar genetic inheritance but without the mutation that causes obesity. They will do this even though they still have more than twice the body fat of the lean mice. Indeed, when these experiments were done in the early 1980s by David Harrison of the Jackson Laboratory in Bar Harbor, Maine, these calorically restricted ob/ob mice lived just as long as calorically restricted lean mice, even though the former were nearly four times as fat as the latter. “Longevities,” Harrison concluded, “were related to food consumption rather than to the degree of adiposity.” This has inevitably been the case, whenever these experiments are done. The calorie-restricted animals live longer because of some metabolic or hormonal consequence of semi-starvation, not because they are necessarily leaner or lighter.

So what does eating less do physiologically that leanness does not? With each new study, researchers have honed their hypothesis of why semi-starvation leads to these anti-aging and disease-delaying processes, and what this says about human aging and disease. This has led to some remarkable revelations about insulin and insulin-like growth factor, and what is likely to happen when these two hormone/growth factors are perturbed by modern diets.