ALTERATION OF THE ADRENAL ANTIOXIDANT DEFENSE SYSTEM DURING AGING IN RATS

The goal of this study was to determine to what extent aging affects t he antioxidant defense system of the rat adrenal and to evaluate the i mpact of any change in this system on the recognized age-related decli ne in steroidogenic capacity of adrenocortical cells. The studies were conducted on young (2-5 mo) and aging (12-27 mo) Sprague-Dawley rats and involved procedures measuring steroidogenesis; oxidative damage to tissue; non enzymatic antioxidants such as vitamin C, E, and glutathi one; and tissue antioxidant enzyme (Nln and CuZn superoxide dismutases , catalase, and glutathione peroxidase) activity and expression (mRNA, protein mass, and location). Some measurements were made also on rats maintained on vitamin E-deficient diets. The data show that adrenals from young animals are especially well protected against oxidative eve nts; i.e., these adrenals show the least endogenous lipid peroxidation and the highest level of resistance to prooxidant-induced damage (of various tissues measured) and show exceedingly high levels of tissue a ntioxidants. Aging, on the other hand, results in oxidative changes in adrenal tissue that are generally linked in time to a reduction in ef ficiency of the normally protective antioxidant defense system and to the decline in corticosterone production. We speculate that these even ts are causally related, i.e., that the age-related reduction in oxida tive mechanisms in adrenal tissues leads to oxidative damage of membra ne or cytosolic factors important to cholesterol transport, and, as a consequence of this damage, cholesterol cannot reach appropriate mitoc hondrial cholesterol side chain cleavage sites, and corticosterone pro duction fails.