Apolipoprotein E and its role in aging and survival
Apolipoprotein E and its role in aging and survival
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DOI：
10.1016/j.exger.2009.11.006
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发表时间：
2010-02-01
影响因子：
3.9
通讯作者：
Rezzani, Rita
中科院分区：
文献类型：
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作者：
Bonomini, Francesca;Filippini, Francesca;Rezzani, Rita
在过去的十年中，生物衰老的研究取得了惊人的进展，越来越多的标记物被用于了解随着年龄变化的生理过程。近年来研究表明，载脂蛋白E（apoE）对长寿有重要影响，但其作用机制尚不完全清楚。ApoE缺陷型（E-0）小鼠已被证明是研究自发性高胆固醇血症和随后的动脉粥样硬化病变发展的非常流行的模型，但关于衰老和衰老变化的数据有限。我们使用这种小鼠模型，以更好地表征apoE参与衰老，并评估其在维持正常器官形态的作用。我们的研究结果表明，E-0小鼠在不同年龄（6，12，20周龄）发展的年龄依赖性的形态学和生化变化，包括纤维化（新形成的胶原蛋白），促炎细胞因子（IL-6和iNOS），脂褐质积累，和抗氧化酶（超氧化物歧化酶和过氧化氢酶）在几个器官（肾脏，肝脏和心脏）的减少。值得注意的是，在不同年龄（6、12、20周龄）的E-0小鼠中观察到的退行性发现在6、12和20周龄的对照小鼠（C57 BL）中未发现。因此，由于这些小鼠表现出通常与年龄相关的酶和结构改变，例如脂褐素增加，促炎细胞因子和抗氧化酶减少，我们可以得出结论，apoE在长寿和年龄相关疾病的研究中是一个有用的参与者，例如炎症状态和动脉粥样硬化，它们是已知的功能下降和早期死亡的危险因素。此外，apoE也可能在其他病理状况中起作用，包括例如癌症、类风湿性关节炎和黄斑变性。(C)2009 Elsevier Inc. All rights reserved.
The study of biological aging has seen spectacular progress in the last decade and markers are increasingly employed for understanding physiological processes that change with age. Recently, it has been demonstrated that apolipoprotein E (apoE) has a major impact on longevity, but its mechanisms are still not fully understood. ApoE-deficient (E-0) mice have proved to be a very popular model for studying spontaneous hypercholesterolemia and the subsequent development of atherosclerotic lesions, but only limited data are available with regard to aging and aging changes. We used this murine model to better characterize the involvement of apoE in aging and to evaluate its role in the maintenance of normal organ morphology. Our results show that E-0 mice at different ages (6, 12, 20 weeks old) developed age-dependent morphological and biochemical alterations, including fibrosis (newly formed collagen), pro-inflammatory cytokine (IL-6 and iNOS), lipofuscin accumulation, and decrease of antioxidant enzymes (superoxide dismutase and catalase) in several organs (kidney, liver and heart). It is significant that the observed degenerative findings in E-0 mice at different ages (6, 12, 20 weeks old) were not identified in control mice (C57BL), at 6, 12 and 20 weeks of age. Consequently, since these mice showed enzymatic and structural alterations, normally linked to the age, such as increase of lipofuscin, pro-inflammatory cytokines and decrease of antioxidant enzymes, we can conclude that apoE is a useful player in studies of longevity and age-related diseases, such as inflammatory status and atherosclerosis that are known risk factors for functional decline and early mortality. Moreover, it is possible that apoE may also play a role in other pathological conditions including, for example, cancer, rheumatoid arthritis and macular degeneration. (C) 2009 Elsevier Inc. All rights reserved.