Müller-Höcker J
Institute of Pathology, University of Munich, Federal Republic of Germany.
Brain Pathol. 1992 Apr;2(2):149-58. doi: 10.1111/j.1750-3639.1992.tb00683.x.
This work reviews the role of mitochondria in the ageing process and summarizes pathomorphological biochemical and molecular genetic data. The pathophysiological mechanisms underlying the phenomenon of ageing are only partly understood. There is, however, increasing evidence that mitochondria are essentially involved. In various tissues of various species a decline in the respiratory chain capacity is seen with ageing. Enzyme histochemistry of cytochrome c oxidase (complex IV of the respiratory chain) has revealed an age-related increase of randomly distributed defective fibres/cells in the skeletal and heart muscle the random pattern probably indicating cellular heterogeneity of the ageing process. Observed deletions of mitochondrial DNA during ageing may represent one causative factor. Similar to primary mitochondrial myopathies point mutations and depletion of the mtDNA are probably also involved. There is some evidence that damage of the mitochondrial genome and of other mitochondrial structures might be due to increased oxygen radical production during ageing. The role of nuclear influences on the degeneration of mitochondrial function remains, however, also to be determined. Nevertheless, the decline of respiratory chain function with ageing represents an important factor for the decline of functional organ reserve capacity in senescence.
这项工作回顾了线粒体在衰老过程中的作用,并总结了病理形态学、生化和分子遗传学数据。衰老现象背后的病理生理机制仅得到部分理解。然而,越来越多的证据表明线粒体在其中起着重要作用。在不同物种的各种组织中,随着衰老可见呼吸链能力下降。细胞色素c氧化酶(呼吸链复合体IV)的酶组织化学显示,骨骼肌和心肌中随机分布的缺陷纤维/细胞随年龄增长而增加,这种随机模式可能表明衰老过程中细胞的异质性。衰老过程中观察到的线粒体DNA缺失可能是一个致病因素。与原发性线粒体肌病类似,点突变和线粒体DNA耗竭可能也与之有关。有证据表明,衰老过程中线粒体基因组和其他线粒体结构的损伤可能是由于氧自由基产生增加所致。然而,核因素对线粒体功能退化的作用仍有待确定。尽管如此,随着衰老呼吸链功能的下降是衰老过程中功能性器官储备能力下降的一个重要因素。