Kadenbach B, Münscher C, Frank V, Müller-Höcker J, Napiwotzki J
Fachbereich Chemie der Philipps-Universität, Marburg, Germany.
Mutat Res. 1995 Oct;338(1-6):161-72. doi: 10.1016/0921-8734(95)00021-w.
Deletions and point mutations of mitochondrial DNA (mtDNA), which are characteristic of various human mitochondrial diseases, have been identified mainly in postmitotic tissues like brain, heart and skeletal muscle of healthy humans of advanced age but not in young people. An exponential increase with age was described for deletions of mtDNA. This paper reviews the molecular basis and experimental results on mutations of mtDNA in patients with mitochondrial diseases and in aged individuals. In addition new data on the exponential increase of point mutations of mtDNA, characteristic for MERRF and MELAS disease, in extraocular muscle from elderly humans are shown. Finally the 'mitochondrial hypothesis on aging' based on stochastic somatic mutations of mtDNA is presented.
线粒体DNA(mtDNA)的缺失和点突变是各种人类线粒体疾病的特征,主要在老年健康人的有丝分裂后组织如脑、心脏和骨骼肌中被发现,而在年轻人中未被发现。mtDNA缺失随年龄呈指数增加。本文综述了线粒体疾病患者和老年人中mtDNA突变的分子基础和实验结果。此外,还展示了老年人类眼外肌中mtDNA点突变呈指数增加的新数据,这是肌阵挛性癫痫伴破碎红纤维病(MERRF)和线粒体脑肌病伴乳酸血症和卒中样发作(MELAS)疾病的特征。最后提出了基于mtDNA随机体细胞突变的“衰老线粒体假说”。