Oxidative stress protection and vulnerability in aging: putative nutritional implications for intervention

Research indicates that vulnerability to oxidative stress (OSV) may increas e in aging, suggesting that age-related neurodegenerative diseases such as Alzheimer's disease (AD) or vascular dementia (VAD) may be superimposed upo n a vulnerable neuronal environment. Determinations in cell models have sug gested that the enhanced. OSV may be the result of, (a) increases in membra ne lipids, especially sphingomyelin and the sphingomyelin metabolite, sphin gosine-1-phosphate, (b) decreases in glutathione, and (c) CNS distribution of OS-sensitive neuronal muscarinic receptor subtypes (e.g. M1, M2 and M4). These changes appear to enhance, (a) decrements in cellular calcium buffer ing following KCl-induced depolarization, and (b) cell death under OS condi tions. Among the most effective agents that antagonized cellular OSV were t he combination of polyphenolics found in fruits (e.g. blueberry extract) wi th high antioxidant activity. Subsequent experiments using dietary suppleme ntation with fruit (strawberry) or vegetable (spinach) extracts have shown that such extracts are also effective in forestalling and reversing the del eterious effects of behavioral aging in F344 rats. Thus, it appears that th e beneficial effects of the polyphenolics found in fruits and vegetables in neuronal aging and behavior may be similar to those seen with respect to c arcinogenesis and cardiovascular disease. (C) 2000 Published by Elsevier Sc ience Ireland Ltd.