Metabolic Aspects of Aging.

Metabolic interventions involving undernutrition but not malnutrition (e.g., caloric restriction, CR) are effective strategies for improving both health and longevity in species ranging from lower organisms to nonhuman primates. Initial human trials to test the effects of sustained, reduced energy intake have yielded promising health benefits. Through intense research efforts in understanding the molecular mechanisms of CR, three cellular pathways have now been identified although the precise details remain unknown. More recently, circadian regulation has been recognized as a novel mediator for CR effects in mice. Harnessing the molecular insights into CR, novel nutritional interventions and pharmacological application of CR mimetics have been tested showing great promise in simultaneously improving metabolic function and providing overall health benefits. Additional research is needed to identify efficacious therapeutics that can be safely and practically translated to human studies in promoting healthspan.