Nutrition and physiological function: Edited by Wim H.M. Saris, Steven B. Heymsfield and William J. EvansCaloric restriction and brain functionGillette-Guyonnet, Sophiea,b; Vellas, Brunoa,b Author Information aGérontopôle Toulouse, France bInserm, U558, Toulouse, France Correspondence to Sophie Gillette-Guyonnet, PhD, Service de Médecine Interne et de Gérontologie Clinique, CHU Purpan-Casselardit, 170 chemin de Casselardit, 31300 Toulouse, France Tel: +33 5 61 77 76 49; fax: +33 5 61 77 25 93; e-mail: [email protected] Current Opinion in Clinical Nutrition and Metabolic Care 11(6):p 686-692, November 2008. | DOI: 10.1097/MCO.0b013e328313968f Buy Metrics Abstract Purpose of review In addition to extending lifespan, animal research shows that specific diets benefit brain functioning. Indeed, it has been proven that caloric restriction prevents age-related neuronal damage. What are those mechanisms involved in the effects of caloric restriction on brain functioning? Could caloric restriction be proposed in the future to prevent or treat neurodegenerative disorders such as Alzheimer's disease? Is there a future for caloric restriction interventions in adults? Recent findings Hypotheses linking caloric restriction to cognitive capability include anti-inflammatory mechanisms, reduction of neural oxidative stress, promotion of synaptic plasticity, induction of various stress and neurotrophic/neuroprotective factors. Caloric restriction may also prevent β-amyloid neuropathology in Alzheimer transgenic models. Finally, both exercise and caloric restriction enhance neurogenesis via different mechanisms suggesting that their combination may decrease the risk of neurodegenerative disease. Summary It is now well established that caloric restriction could be used to promote successful brain aging. Data from randomized controlled trials in humans are limited. No positive effect on cognitive impairment was found probably due to methodological limitations. The long-term effects of caloric restriction in adults must be clarified before engaging in such preventive strategy. Additional animal studies must be conducted in the future to test the effects of ‘multidomain’ interventions (caloric restriction plus regular exercise) on age-related cognitive decline. © 2008 Lippincott Williams & Wilkins, Inc.