The evolution of the antiaging action of dietary restriction: a hypothesis.

Reducing the intake of dietary energy by laboratory rodents to well below that of animals allowed to eat ad libitum slows the rate of aging. This phenomenon, which is robust and reproducible, is known as the antiaging action of dietary restriction (DR). We hypothesize that this DR response arose because of its evolutionary advantage with respect to survival during periods of unpredictable, short-term food shortage. In our evolutionary scenario, food shortage led to an adaptive redirection of resources away from reproduction toward somatic maintenance via an enhanced heat shock protein response in invertebrates. In vertebrates, an additional involvement of the hypothalamic-adenohypophyseal-adrenal glucocorticoid system was necessitated to protect against excessive systemic defense responses. We suggest several general implications of our hypothesis.