Department of Biochemistry, Institute of Postgraduate Medical Education and Research, Kolkata, India.
Aging Dis. 2011 Jun;2(3):242-56. Epub 2011 Mar 23.
Mitochondrial dysfunction and oxidative stress are two interdependent and reinforcing damage mechanisms that play a central role in brain aging. Oxidative stress initiated and propagated by active oxyradicals and various other free radicals in the presence of catalytic metal ions not only can damage the phospholipid, protein and DNA molecules within the cell but can also modulate cell signalling pathways and gene expression pattern and all these processes may be of critical importance in the aging of brain. The present article describes the mechanism of formation of reactive oxyradicals within mitochondria and then explains how these can initiate mitochondrial biogenesis program and activate various transcriptional factors in the cytosol to boost up the antioxidative capacity of the mitochondria and the cell. However, a high level of oxidative stress finally inflicts critical damage to the oxidative phosphorylation machinery and mitochondrial DNA (mtDNA). The latter part of the article is a catalogue showing the accumulating evidence in favour of oxidative inactivation of mitochondrial functions in aged brain and the detailed reports of various studies with antioxidant supplementation claiming variable success in preventing the age-related brain mitochondrial decay and cognitive decline. The antioxidant supplementation approach may be of potential help in the management of neurodegenerative diseases like Alzheimer's disease. The newly developed mitochondria-targeted antioxidants have brought a new direction to experimental studies related to oxidative damage and they may provide potential drugs in near future for a variety of diseases or degenerative conditions including brain aging and neurodegenerative disorders.
线粒体功能障碍和氧化应激是两种相互依赖和增强的损伤机制，它们在大脑衰老中起着核心作用。在催化金属离子存在下，由活性氧自由基和其他各种自由基引发和传播的氧化应激不仅可以破坏细胞内的磷脂、蛋白质和 DNA 分子，还可以调节细胞信号通路和基因表达模式，所有这些过程在大脑衰老中可能都具有至关重要的意义。本文描述了活性氧自由基在线粒体中的形成机制，然后解释了它们如何启动线粒体生物发生程序，并激活细胞质中的各种转录因子，以提高线粒体和细胞的抗氧化能力。然而，高水平的氧化应激最终会对氧化磷酸化机制和线粒体 DNA（mtDNA）造成严重损伤。文章的后半部分是一个目录，展示了越来越多的证据支持氧化应激导致衰老大脑中线粒体功能失活，以及各种抗氧化剂补充研究的详细报告，这些研究声称在预防与年龄相关的大脑线粒体衰退和认知能力下降方面取得了不同程度的成功。抗氧化剂补充方法可能有助于管理阿尔茨海默病等神经退行性疾病。新开发的线粒体靶向抗氧化剂为与氧化损伤相关的实验研究带来了新的方向，它们可能在不久的将来为包括大脑衰老和神经退行性疾病在内的各种疾病或退行性疾病提供潜在的药物。
