Abstract
The ultimate goal of Alzheimer's disease (AD) research is to prevent the onset of the neurodegenerative process and thereby allow successful aging without cognitive decline. Herein I argue that a simple and effective preventative approach for AD may be in hand. AD is a disorder associated with the aging process and is, accordingly, characterized by cellular and molecular changes that occur in age-related diseases in other organ systems. Such changes include increased levels of oxidative stress, perturbed energy metabolism, and accumulation of insoluble (oxidatively modified) proteins (prominent among which are amyloid beta-peptide and tau). The risk of several other prominent age-related disorders, including cardiovascular disease, cancer, and diabetes, is known to be influenced by the level of food intake--high food intake increases risk, and low food intake reduces risk. An overwhelming body of data from studies of rodents and monkeys has documented the profound beneficial effects of dietary restriction (DR) in extending life span and reducing the incidence of age-related diseases. Reduced levels of cellular oxidative stress and enhancement of energy homeostasis contribute to the beneficial effects of DR. Recent findings suggest that DR may enhance resistance of neurons in the brain to metabolic, excitotoxic, and oxidative insults relevant to the pathogenesis of AD and other neurodegenerative disorders. While further studies will be required to establish the extent to which DR will reduce the incidence of AD, it would seem prudent (based on existing data) to recommend DR as widely applicable preventative approach for age-related disorders including neurodegenerative disorders.
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