Ingram Thomas, Chakrabarti Lisa
SVMS, Faculty of Medicine, University of Nottingham, Sutton Bonington, LE12 5RD, UK.
Aging (Albany NY). 2016 Dec 13;8(12):3161-3179. doi: 10.18632/aging.101131.
Mitochondrial dysfunction is evident in numerous neurodegenerative and age-related disorders. It has also been linked to cellular ageing, however our current understanding of the mitochondrial changes that occur are unclear. Functional studies have made some progress reporting reduced respiration, dynamic structural modifications and loss of membrane potential, though there are conflicts within these findings. Proteomic analyses, together with functional studies, are required in order to profile the mitochondrial changes that occur with age and can contribute to unravelling the complexity of the ageing phenotype. The emergence of improved protein separation techniques, combined with mass spectrometry analyses has allowed the identification of age and cell-type specific mitochondrial changes in energy metabolism, antioxidants, fusion and fission machinery, chaperones, membrane proteins and biosynthesis pathways. Here, we identify and review recent data from the analyses of mitochondria from rodent brains. It is expected that knowledge gained from understanding age-related mitochondrial changes of the brain should lead to improved biomarkers of normal ageing and also age-related disease progression.
线粒体功能障碍在众多神经退行性疾病和与年龄相关的疾病中很明显。它也与细胞衰老有关，然而我们目前对所发生的线粒体变化的理解尚不清楚。功能研究已取得一些进展，报告了呼吸作用降低、动态结构改变和膜电位丧失，尽管这些发现存在矛盾之处。为了描绘随着年龄增长而发生的线粒体变化，并有助于揭示衰老表型的复杂性，需要进行蛋白质组学分析以及功能研究。改进的蛋白质分离技术的出现，结合质谱分析，使得在能量代谢、抗氧化剂、融合与裂变机制、伴侣蛋白、膜蛋白和生物合成途径中能够识别出与年龄和细胞类型相关的线粒体变化。在此，我们识别并综述了来自啮齿动物大脑线粒体分析的最新数据。预计从了解与年龄相关的大脑线粒体变化中获得的知识将有助于改进正常衰老以及与年龄相关疾病进展的生物标志物。
