Lee C M, Lopez M E, Weindruch R, Aiken J M
Department of Animal Health and Biomedical Sciences, University of Wisconsin, Madison 53706, USA.
Free Radic Biol Med. 1998 Nov 15;25(8):964-72. doi: 10.1016/s0891-5849(98)00185-3.
The hypothesis that mitochondrial dysfunction contributes to the senescent loss of skeletal muscle was investigated in quadriceps from 2- to 39-year old rhesus monkeys. Histological approaches, both cross-sectional (a single cross-section of the muscle) and longitudinal (multiple cross-sections of individual fibers spanning a 350-1600 microm region), were used to identify muscle fibers with abnormal mitochondrial electron transport system (ETS) enzyme activities and mitochondrial DNA deletions. Fibers were examined for two ETS activities, succinate dehydrogenase (SDH, ETS complex II) and cytochrome c oxidase (COX, ETS complex IV). The number of individual fibers containing ETS abnormalities (predominately negative for cytochrome c oxidase activity and/or hyperreactive for succinate dehydrogenase) increased with age. Deletions of the mitochondrial genome were observed in 89% of these ETS abnormal fibers. Longitudinal analysis allowed characterization of the ETS abnormal phenotype along their length. A decrease in cross-sectional area in 14% of the ETS abnormal fibers supports the hypothesis that deleted mitochondrial genomes may contribute to age-related fiber atrophy.
在2至39岁恒河猴的股四头肌中，研究了线粒体功能障碍导致骨骼肌衰老性丧失的假说。采用组织学方法，包括横断面（肌肉的单个横截面）和纵断面（跨越350 - 1600微米区域的单个纤维的多个横截面），来识别线粒体电子传递系统（ETS）酶活性异常和线粒体DNA缺失的肌纤维。检测纤维的两种ETS活性，即琥珀酸脱氢酶（SDH，ETS复合体II）和细胞色素c氧化酶（COX，ETS复合体IV）。含有ETS异常（主要是细胞色素c氧化酶活性阴性和/或琥珀酸脱氢酶高反应性）的单个纤维数量随年龄增加。在这些ETS异常纤维中，89%观察到线粒体基因组缺失。纵向分析能够沿其长度对ETS异常表型进行特征描述。14%的ETS异常纤维横截面积减小，支持了缺失的线粒体基因组可能导致与年龄相关的纤维萎缩这一假说。
