Possible mechanisms underlying the antiaging actions of caloric restriction.

Restricting the food intake of mice and rats to well below that of ad libitum-fed animals markedly slows the aging processes. This action is reflected in an increase in longevity, a decrease in the age-associated increase in age-specific mortality rate, the maintenance of the physiological processes in a youthful state even at advanced ages, and the delaying of the onset or slowing of the progression or both of most age-associated diseases. The dietary factor responsible is the reduction in energy (caloric) intake. Many hypotheses have been proposed regarding mechanisms underlying this antiaging action. Hypotheses relating the antiaging action to the retardation of growth and development, the reduction of adipose mass, and the reduction of metabolic rate have been found to be wanting. Two of the proposed hypotheses have some evidence in their support. One involves the altered metabolic characteristics of glucose fuel use and of oxidative metabolism. The other relates to the enhanced ability of the rodents restricted in food intake to cope with challenges, which in turn has been linked to the glucocorticoid system and to the heat-shock protein system.