Calorie restriction attenuates age-related alterations in the plasma membrane antioxidant system in rat liver
Calorie restriction attenuates age-related alterations in the plasma membrane antioxidant system in rat liver
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DOI：
10.1016/j.exger.2003.12.003
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发表时间：
2004-03-01
影响因子：
3.9
通讯作者：
Navas, P
中科院分区：
文献类型：
--
作者：
De Cabo, R;Cabello, R;Navas, P
衰老与活性氧的产生增加和氧化诱导的细胞内结构和膜损伤有关。热量限制（CR）是唯一被证明可以延长哺乳动物寿命的非遗传方法。尽管CR的机制仍有待明确阐明，但在几个模型系统中，氧化应激的减少已显示出延长寿命。CR可减轻氧化应激。线粒体和质膜（PM）是自由基的正常来源。PM具有跨膜氧化还原系统，其提供电子以再循环亲脂性抗氧化剂，例如α-生育酚和辅酶Q（CoQ）。在这项研究中发展的想法是，PM密切参与细胞生理学控制细胞与其环境的关系。PM是在老化过程中保护细胞完整性的关键。具体来说，我们已经调查了年龄相关的变化和CR的影响，在反式PM氧化还原（抗氧化剂）系统在大鼠肝脏。我们发现，与自由采食（AL）的大鼠相比，CR可减弱肝脏PM中辅酶Q（10）/辅酶Q（9）和α-生育酚比值的年龄相关性下降。辅酶Q依赖性NAD（P）H酶在CR老年大鼠肝PM中增加。因此，CR老年大鼠的肝脏PM比AL大鼠更能抵抗氧化应激引起的脂质过氧化反应。因此，我们的研究结果表明，CR诱导老年大鼠肝脏PM中NAD（P）H氧化能力更高，因此，对氧化应激诱导的损伤具有更高的抵抗力。(C)2004年爱思唯尔公司All rights reserved.
Aging is associated with increased production of reactive oxygen species and oxidation-induced damage to intracellular structures and membranes. Caloric restriction (CR) is the only non-genetic method proven to extend lifespan in mammals. Although the mechanisms of CR remain to be clearly elucidated, reductions in oxidative stress have been shown to increase lifespan in several model systems. Oxidative stress can be attenuated by CR. Mitochondria and plasma membrane (PM) are normal sources of free radicals. The PM has a trans-membrane redox system that provides electrons to recycle lipophilic antioxidants, such as alpha-tocopherol and coenzyme Q (CoQ). The idea developed in this study is that the PM is intimately involved in cellular physiology controlling the relationship of the cell to its environment. PM is the key for protecting cellular integrity during aging. Specifically, we have investigated age-related alterations and the effects of CR in the trans-PM redox (antioxidant) system in rat liver. We found that age-related declines in the ratio of CoQ(10)/CoQ(9) and alpha-tocopherol in liver PM were attenuated by CR compared to those fed ad libitum (AL). CoQ-dependent NAD(P)H dehydrogenases were increased in CR old rat liver PMs. As a consequence, the liver PM of CR old rats was more resistant to oxidative stress-induced lipid peroxidation than AL rats. Thus, our results suggest that CR induces a higher capacity to oxidize NAD(P)H in the PM of old rat livers and as a result, a higher resistance to oxidative stress-induced damage. (C) 2004 Elsevier Inc. All rights reserved.