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To assess which membrane properties are modulated by the action of food restriction, characteristics of liver membrane structures of ad libitum-fed and food restricted Fischer 344 rats were analyzed over a wide age range. The results show that the yields of mitochondrial and microsomal membranes decreased in ad libitum-fed rats, but this age-related loss did not occur in food restricted rats until 30 months. Changes in membrane fatty acid composition which occurred with age were substantially modified by food restriction. Linoleic acid content progressively decreased in the membranes of ad libitum-fed rats with a concomitant increase of docosapentaenoic acid while an opposite pattern of change occurred in food restricted rats. Furthermore, food restriction maintained a low docosahexaenoic acid level in microsomes at all ages studied. While serum tocopherol increased markedly with age, there was little change in membrane tocopherol content in ad libitum-fed rats.

The cytosolic status during aging of several antioxidants and enzymatic activities which protect the cell from oxidative damage was explored in the liver of ad libitum-fed and food restricted rats. Restricting calories effectively prevented the age-related decrease in cellular glutathione that occurs in ad libitum-fed rats. Although glutathione reductase exhibited little change with age in ad libitum-fed rats, dietary restriction resulted in greater activity of this enzyme than that of ad libitum-fed animals. Glutathione S-transferase activity of ad libitum-fed rats decreased significantly with age in ad libitum-fed rats but not in food restricted rats. The glutathione peroxidase activity which increased until 12 months in the ad libitum-fed rats declined by 24 months; there was little change with adult age in this enzymatic activity in food restricted rats. Catalase activity declined steadily from 3-24 months in the ad libitum-fed rats, and food restriction prevented this age-related decline. The significance of antioxidants and the related protective enzymes is discussed relative to membrane alterations and the anti-oxidative action of food restriction in relation to age-related degenerative damages.