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. RESTRICTING the food intake by laboratory mice andrats by 20 to 60 % below that eaten by ad libitum-fed animals increases the mean and maximum life span of these rodent populations (Weindruch and Walford, 1988). This dietary manipulation also slows the postmaturational rate of increase in age-specific mortality resulting in a marked increase in the mortality rate doubling time of the population (Masoro, 1995). In addition to its effects on mortality, restricting food intake also maintains the physiological proc-esses in a youthful state (Yu, 1995) and retards many (most) age-associated disease processes in a variety of mouse and rat strains (Masoro, 1993). Notably, these phenomena, which are often referred to by gerontologists as the antiaging action of dietary restriction (DR), are primarily due to a reduction in the intake of energy (calories) rather than of a specific nutrient or adventitious contaminant (Masoro, 1988) and occur without a reduction in mass-specific metabolic rate or level of physical activity (McCarter and Palmer