Effects of reduced energy intake on the biology of aging: the primate model.

Dietary energy restriction is the only proven method for extending lifespan and slowing aging in mammals, while maintaining health and vitality. Although the first experiments in this area were conducted over 60 y ago in rodents, possible applicability to primates has only been examined in controlled studies since 1987. Our project at the National Institute on Aging began with 3-0 male rhesus and 30 male squirrel monkeys of various ages over their respective life spans. Subsequently, it has been expanded to include female rhesus monkeys, and several other laboratories have initiated related studies. Experimental animals are generally fed 30% less than controls, and diets are supplemented with micronutrients to achieve undernutrition without malnutrition. These calorically restricted (CR) monkeys are lighter, with less fat and lean mass than controls. Bone mass is also slightly reduced, but in approximate proportion to the smaller body size. CR animals mature more slowly and achieve shorter stature than controls as well. Metabolically, CR monkeys have slightly lower body temperature and initial energy expenditure following onset of restriction, and better glucose tolerance and insulin sensitivity. The latter suggest a reduced predisposition towards diabetes as the animals age. Other potential anti-disease effects include biomarkers suggestive of lessened risk of cardiovascular disease and possibly cancer. Candidate biomarkers of aging, including the age-related decrease in plasma dehydroepiandrosterone sulfate (DHEAS), suggest that the CR animals may be aging more slowly than controls in some respects, although sufficient survival data will require more time to accumulate. In summary, nearly all CR effects detected in rodents, which have thus far been examined in primates, exhibit similar phenomenology. Potential applicability of these beneficial effects to humans is discussed.