Conley Kevin E, Marcinek David J, Villarin Jason
Department of Radiology, University of Washington Medical Center, Seattle, Washington, USA.
Curr Opin Clin Nutr Metab Care. 2007 Nov;10(6):688-92. doi: 10.1097/MCO.0b013e3282f0dbfb.
Mitochondrial dysfunction is commonly thought to result from oxidative damage that leads to defects in the electron transport chain (ETC). In this review, we highlight new research indicating that there are early changes in mitochondrial function that precede ETC defects and are reversible thereby providing the possibility of slowing the tempo of mitochondrial aging and cell death.
Increased mitochondrial uncoupling - reduced adenosine triphosphate (ATP) produced per O2 uptake - and cell ATP depletion are evident in human muscle nearly a decade before accumulation of irreversible DNA damage that causes ETC defects. New evidence points to reduction in activators of biogenesis (e.g. PGC-1alpha) and to degradation of mitochondria allowing accumulation of molecular and membrane damage in aged mitochondria. The early dysfunction appears to be reversible based on improved mitochondrial function in vivo and elevated gene expression levels after exercise training.
New molecular and in vivo findings regarding the onset and reversibility of mitochondrial dysfunction with age indicate the potential: 1) for diagnostic tools to identify patients at risk for severe irreversible defects later in life; and 2) of an intervention to delay the tempo of aging and improve the quality of life of the elderly.
线粒体功能障碍通常被认为是由氧化损伤导致电子传递链（ETC）缺陷引起的。在本综述中，我们重点介绍了新的研究，这些研究表明线粒体功能在ETC缺陷之前就有早期变化，并且是可逆的，从而为减缓线粒体衰老和细胞死亡的速度提供了可能性。
在导致ETC缺陷的不可逆DNA损伤积累近十年前，人体肌肉中就明显出现线粒体解偶联增加（每摄取一分子氧气产生的三磷酸腺苷（ATP）减少）和细胞ATP耗竭。新证据表明生物发生激活剂（如PGC-1α）减少，线粒体降解，导致衰老线粒体中分子和膜损伤积累。基于体内线粒体功能改善和运动训练后基因表达水平升高，早期功能障碍似乎是可逆的。
关于线粒体功能障碍随年龄增长的发生和可逆性的新分子和体内研究结果表明：1）有潜力开发诊断工具，以识别晚年有严重不可逆缺陷风险的患者；2）有可能进行干预，以延缓衰老速度，提高老年人的生活质量。
