Impact of dietary restriction on brain aging and neurodegenerative disorders: Emerging findings from experimental and epidemiological studies

Although dietary restriction (DR) extends life span and reduces levels of cellular oxidative stress in several different organ systems of laboratory rodents and monkeys, its impact on the brain is unknown. As is the case with age-related disorders in other organ systems (e.g., cardiovascular disease, diabetes, and many cancers), neurodegenerative disorders such as Alzheimer disease (AD), Parkinson disease (PD), and stroke involve increased levels of cellular oxidative stress and metabolic compromise. Recent studies of experimental rat and mouse models of AD, PD, and stroke have shown that DR increases resistance of neurons to dysfunction and degeneration. DR can attenuate age-related and disease-specific deficits in cognitive and motor functions in rodents. The available data suggest at least two possible mechanisms whereby DR protects neurons. One involves decreased levels of mitochondrial oxyradical production, and the second involves induction of the expression of 'stress proteins' and neurotrophic factors. The latter mechanism is supported by data showing that the neuroprotective effect of DR can be mimicked by administration of 2-deoxyglucose to animals fed ad libitum. Recent findings in epidemiological studies of human populations suggest that individuals with a low daily calorie intake have reduced risk for AD and PD. Collectively, the available data suggest that DR may prove beneficial in reducing both the incidence and severity of neurodegenerative disorders in humans.