Yen T C, Pang C Y, Hsieh R H, Su C H, King K L, Wei Y H
Department of Biochemistry and General Surgery, National Yang-Ming Medical College, Taipei, Taiwan, Republic of China.
Biochem Int. 1992 Mar;26(3):457-68.
Using PCR technique, restriction mapping and DNA sequencing, we analyzed liver mitochondrial DNA (mtDNA) of 2 stillborn babies and 62 Chinese subjects with non-liver disease from 27 to 86 years old. The results showed an age-dependent 6,063 bp deletion in the liver mtDNA of older subjects. We found a TAACAGAC sequence flanking the 5'-end breakpoint at 7,842 nucleotide position and an imperfect repeat sequence CAACATAC flanking the 3'-end breakpoint at 13,905 nucleotide position. The incidence of the deleted mtDNA was found to increase with age. The deleted mtDNA was not detected in the liver of the stillbirth or blood cells of all the subjects. This is the first account that an age-related 6,063 bp deletion occurs in the liver mtDNA of old humans. The occurrence of this and previously reported 4,977 bp deletions is consistent with our recent finding that liver mitochondrial respiratory functions decline with age and support the hypothesis that continuous accumulation of mtDNA mutations is an important contributor to ageing process in the human.
利用聚合酶链反应（PCR）技术、限制性酶切图谱分析和DNA测序，我们分析了2例死产儿以及62名年龄在27至86岁之间、患有非肝脏疾病的中国受试者的肝脏线粒体DNA（mtDNA）。结果显示，老年受试者肝脏mtDNA中存在一种与年龄相关的6063 bp缺失。我们在核苷酸位置7842处5'端断点侧翼发现了TAACAGAC序列，在核苷酸位置13905处3'端断点侧翼发现了不完全重复序列CAACATAC。发现缺失的mtDNA发生率随年龄增长而增加。在所有受试者的死产儿肝脏或血细胞中均未检测到缺失的mtDNA。这是首次报道在老年人类肝脏mtDNA中出现与年龄相关的6063 bp缺失。此次发现以及先前报道的4977 bp缺失与我们最近的研究结果一致，即肝脏线粒体呼吸功能随年龄下降，并支持了线粒体DNA突变的持续积累是人类衰老过程重要因素的假说。
