Caloric restriction and aging in primates: Relevance to humans and possible CR mimetics.

For nearly 70 years it has been recognized that reduction in caloric intake by 30-40% from ad libitum levels leads to a significant extension of mean and maximal lifespan in a variety of short-lived species. This effect of caloric restriction (CR) on lifespan has been reported in nearly all species tested and has been reproduced hundreds of times under a variety of different laboratory conditions. In addition to prolonging lifespan, CR also prevents or delays the onset of age-related disease and maintains many physiological functions at more youthful levels. Studies in longer-lived species, specifically rhesus and squirrel monkeys, have been underway since the late 1980s. The studies in nonhuman primates are beginning to yield valuable information suggesting that the effect of CR on aging is universal across species and that this nutritional paradigm will have similar effects in humans. Even if CR can be shown to impact upon human aging, it is unlikely that most people will be able to maintain the strict dietary control required for this regimen. Thus, elucidation of the biological mechanisms of CR and development of alternative strategies to yield similar benefits is of primary importance. CR mimetics, or interventions that "mimic" certain protective effects of CR, may represent one such alternative strategy.