Calorie restriction in nonhuman primates: mechanisms of reduced morbidity and mortality

Long term chronic calorie restriction (CR) of adult nonhuman primatessignificantly reduces morbidity and increases median age of death. Thepresent review is focused upon an ongoing study of sustained adult- onsetcalorie restriction, which has been underway for 15 years. Monkeys,initially calorie restricted at about 10 years of age, are nowapproximately 25 years old. The median life span of these restrictedmonkeys is increasing, now exceeding that of ad libitum (AL)-fed monkeys.In our laboratory, maximum life span for AL-fed monkeys appears to be about40 years. Thus, whether CR can also increase maximal life span, as it doesin rodents, cannot be determined for at least another 15 years. Theearliest detectable positive benefit on morbidity in these monkeys waspreviously reported as the prevention of obesity. Current evidence, asreviewed here, suggests that much obesity- associated morbidity is alsomitigated by sustained calorie restraint in nonhuman primates. Furthermore,probably because of the prevention of obesity, diabetes has also beenprevented. Recent findings include the identification of extraordinarychanges in the glycogen synthesis pathway, and on the phosphorylation ofglycogen synthase in response to insulin. This calorie restriction-inducedprevention of morbidity does not require excessive leanness, but is clearlypresent when body fat is within the normal range of 10 to 22%, and this islikely to be true in humans as well.