Suppression of brain aging and neurodegenerative disorders by dietary restriction and environmental enrichment: molecular mechanisms

Dietary restriction (reduced calorie intake with nutritional maintenance) c an extend lifespan and may increase the resistance of the nervous system to age-related diseases including neurodegenerative disorders. An environment enriched in intellectual and physical activities can also allay many of th e adverse effects of aging on the brain. The mechanisms underlying the bene ficial effects of dietary restriction and environmental enrichment on the b rain involve stimulation of the expression of neurotrophic factors and 'str ess proteins'. The neurotrophic factors and stress proteins induced by diet ary restriction may protect neurons by suppressing oxyradical production, s tabilizing cellular calcium homeostasis and inhibiting a form of programmed cell death called apoptosis. Interestingly, dietary restriction and enviro nmental enrichment also increase numbers of newly-generated neural cells in the adult brain suggesting that these behavioral modifications can increas e the brain's capacity for plasticity and self-repair. A better understandi ng of the cellular and molecular mechanisms underlying these effects of die t and behavior on the brain is leading to novel therapeutic agents that mim ick their beneficial effects. (C) 2001 Published by Elsevier Science irelan d Ltd.