Restriction of caloric intake increases longevity, slows the rate of functional decline, and reduces incidence of age-related disease in a variety of species. Most laboratory rodent studies have initiated restriction before puberty, whereas ongoing studies in nonhuman primates utilize restriction in adulthood. The mechanism of action of caloric restriction remains unknown; however, data suggest that cellular functions are altered in such a way that destructive by-products of metabolism are reduced, and defense or repair systems are enhanced by this nutritional manipulation.