Toescu E C, Myronova N, Verkhratsky A
Department of Physiology, Division Medical Sciences, The University of Birmingham, Edgbaston, UK.
Cell Calcium. 2000 Nov-Dec;28(5-6):329-38. doi: 10.1054/ceca.2000.0167.
Normal ageing is associated with a gradual decline in the capacity of various cell types, including neurones, to respond to metabolic stress and return to the resting state. An important factor in the decrease of this 'homeostatic reserve' is the gradual, age-dependent impairment of mitochondrial function. In this article we review some of the major structural and functional changes in mitochondria associated with ageing. Apart from the increased mutations in mitochondrial DNA and the evidence for increased oxidative stress with ageing, we also discuss, in some detail, the importance of the mitochondrial membrane structure and composition (in particular lipid composition) for mitochondrial function in general and during ageing. Although some of the neurodegenerative diseases are also associated with some degree of mitochondrial dysfunction, it is not yet clear if these changes are due to the underlining process of normal, physiological ageing or due to the specific pathophysiologic agents responsible for the neurodegenerative processes. Furthermore, we are proposing that there are important differences between normal ageing and neurodegeneration.
正常衰老与包括神经元在内的各种细胞类型应对代谢应激并恢复静息状态的能力逐渐下降有关。这种“稳态储备”减少的一个重要因素是线粒体功能随年龄增长而逐渐受损。在本文中，我们综述了与衰老相关的线粒体的一些主要结构和功能变化。除了线粒体DNA突变增加以及衰老过程中氧化应激增加的证据外，我们还详细讨论了线粒体膜结构和组成（特别是脂质组成）对于一般线粒体功能以及衰老过程中线粒体功能的重要性。尽管一些神经退行性疾病也与一定程度的线粒体功能障碍有关，但尚不清楚这些变化是由于正常生理衰老的潜在过程，还是由于导致神经退行性过程的特定病理生理因素。此外，我们提出正常衰老和神经退行性变之间存在重要差异。
