The scientific basis of caloric restriction leading to longer life.

PURPOSE OF THE REVIEW: The present review discusses the current state of knowledge regarding the effects of calorie restriction in modulating metabolism and aging. RECENT FINDINGS: There are currently no interventions or gene manipulations that can prevent, stop or reverse the aging process. However, there are a number of interventions that can slow down aging and prolong maximal lifespan up to 60% in experimental animals. Long-term calorie restriction without malnutrition and reduced function mutations in the insulin/IGF-1 signaling pathway are the most robust interventions known to increase maximal lifespan and healthspan in rodents. Although it is currently not known if long-term calorie restriction with adequate nutrition extends maximal lifespan in humans, we do know that long-term calorie restriction without malnutrition results in some of the same metabolic and hormonal adaptations related to longevity in calorie restriction rodents. Moreover, calorie restriction with adequate nutrition protects against obesity, type 2 diabetes, hypertension and atherosclerosis, which are leading causes of morbidity, disability and mortality. SUMMARY: More studies are needed to elucidate the molecular mechanisms underlying the beneficial effects of calorie restriction in humans and to characterize new markers of aging/longevity that can assist clinicians in predicting mortality and morbidity of the general population.