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

Long term chronic calorie restriction (CR) of adult nonhuman primates signi ficantly reduces morbidity and increases median age of death. The present r eview is focused upon an ongoing study of sustained adult-onset calorie res triction, which has been underway for 15 years. Monkeys, initially calorie restricted at about 10 years of age, are now approximately 25 years old. Th e median life span of these restricted monkeys is increasing, now exceeding that of ad libitum (AL)-fed monkeys. In our laboratory, maximum life span for AL-fed monkeys appears to be about 40 years. Thus, whether CR can also increase maximal life span, as it does in rodents, cannot be determined for at least another 15 years. The earliest detectable positive benefit on mor bidity in these monkeys was previously reported as the prevention of obesit y. Current evidence, as reviewed here, suggests that much obesity-associate d morbidity is also mitigated by sustained calorie restraint in nonhuman pr imates. Furthermore, probably because of the prevention of obesity, diabete s has also been prevented. Recent findings include the identification of ex traordinary changes in the glycogen synthesis pathway, and on the phosphory lation of glycogen synthase in response to insulin. This calorie restrictio n-induced prevention of morbidity does not require excessive leanness, but is clearly present when body fat is within the normal range of 10 to 22%, a nd this is likely to be true in humans as well.