Mitochondrial oxidative stress in aging and healthspan.
Mitochondrial oxidative stress in aging and healthspan.
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DOI：
10.1186/2046-2395-3-6
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Rabinovitch PS
中科院分区：
文献类型：
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作者：
Dai DF;Chiao YA;Marcinek DJ;Szeto HH;Rabinovitch PS
衰老的自由基理论认为，活性氧(ROS)诱导的细胞大分子损伤的积累是衰老的主要驱动力和寿命的主要决定因素。尽管这一理论是对衰老原因最流行的解释之一，但抗氧化剂操作的几个实验啮齿动物模型都未能影响寿命。此外，抗氧化剂补充剂的临床试验在很大程度上令人失望。线粒体衰老学说更明确地指出，线粒体既是ROS的主要来源，也是ROS损伤的主要靶点。除了对寿命和衰老的影响外，线粒体ROS已被证明在许多重要器官系统的健康寿命中发挥核心作用。本文综述了支持线粒体氧化应激、线粒体损伤和功能障碍在衰老和健康寿命中的作用的证据，包括心脏老化、年龄依赖性心血管疾病、骨骼肌衰老、神经退行性疾病、胰岛素抵抗和糖尿病以及与年龄相关的癌症。简要介绍了线粒体ROS、氧化还原和其他细胞信号的串扰。综述了在衰老和健康过程中改善线粒体功能的潜在治疗策略，重点介绍了线粒体保护性药物，如线粒体抗氧化剂MitoQ、SkQ1和线粒体保护肽SS-31。
The free radical theory of aging proposes that reactive oxygen species (ROS)-induced accumulation of damage to cellular macromolecules is a primary driving force of aging and a major determinant of lifespan. Although this theory is one of the most popular explanations for the cause of aging, several experimental rodent models of antioxidant manipulation have failed to affect lifespan. Moreover, antioxidant supplementation clinical trials have been largely disappointing. The mitochondrial theory of aging specifies more particularly that mitochondria are both the primary sources of ROS and the primary targets of ROS damage. In addition to effects on lifespan and aging, mitochondrial ROS have been shown to play a central role in healthspan of many vital organ systems. In this article we review the evidence supporting the role of mitochondrial oxidative stress, mitochondrial damage and dysfunction in aging and healthspan, including cardiac aging, age-dependent cardiovascular diseases, skeletal muscle aging, neurodegenerative diseases, insulin resistance and diabetes as well as age-related cancers. The crosstalk of mitochondrial ROS, redox, and other cellular signaling is briefly presented. Potential therapeutic strategies to improve mitochondrial function in aging and healthspan are reviewed, with a focus on mitochondrial protective drugs, such as the mitochondrial antioxidants MitoQ, SkQ1, and the mitochondrial protective peptide SS-31.