Azhar S, Cao L, Reaven E
Geriatric Research, Education and Clinical Center, Veterans Affairs, Palo Alto Health Care System, California 94304, USA.
J Clin Invest. 1995 Sep;96(3):1414-24. doi: 10.1172/JCI118177.
The goal of this study was to determine to what extent aging affects the antioxidant defense system of the rat adrenal and to evaluate the impact of any change in this system on the recognized age-related decline 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 glutathione; and tissue antioxidant enzyme (Mn 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 events; 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 antioxidants. Aging, on the other hand, results in oxidative changes in adrenal tissue that are generally linked in time to a reduction in efficiency of the normally protective antioxidant defense system and to the decline in corticosterone production. We speculate that these events are causally related, i.e., that the age-related reduction in oxidative mechanisms in adrenal tissues leads to oxidative damage of membrane or cytosolic factors important to cholesterol transport, and, as a consequence of this damage, cholesterol cannot reach appropriate mitochondrial cholesterol side chain cleavage sites, and corticosterone production fails.
本研究的目的是确定衰老在多大程度上影响大鼠肾上腺的抗氧化防御系统，并评估该系统的任何变化对肾上腺皮质细胞类固醇生成能力公认的与年龄相关的下降的影响。研究在年轻（2 - 5个月）和衰老（12 - 27个月）的Sprague-Dawley大鼠上进行，涉及测量类固醇生成、组织的氧化损伤、非酶抗氧化剂如维生素C、E和谷胱甘肽，以及组织抗氧化酶（锰和铜锌超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶）活性和表达（mRNA、蛋白质质量和定位）的程序。还对维持在维生素E缺乏饮食的大鼠进行了一些测量。数据表明，幼龄动物的肾上腺对氧化事件有特别好的保护作用；即这些肾上腺显示出最少的内源性脂质过氧化和对促氧化剂诱导损伤的最高抵抗水平（在所测量的各种组织中），并显示出极高水平的组织抗氧化剂。另一方面，衰老导致肾上腺组织的氧化变化，这些变化通常在时间上与正常保护性抗氧化防御系统效率的降低以及皮质酮产生的下降相关。我们推测这些事件存在因果关系，即肾上腺组织中与年龄相关的氧化机制减少导致对胆固醇转运重要的膜或胞质因子的氧化损伤，并且由于这种损伤，胆固醇无法到达适当的线粒体胆固醇侧链裂解位点，从而导致皮质酮产生失败。
