Lopez M E, Van Zeeland N L, Dahl D B, Weindruch R, Aiken J M
Department of Animal Health and Biomedical Sciences, VA GRECC and Wisconsin Regional Primate Research Center, University of Wisconsin, Madison 53706, USA.
Mutat Res. 2000 Jul 20;452(1):123-38. doi: 10.1016/s0027-5107(00)00059-2.
Rhesus monkey vastus lateralis muscle was examined histologically for age-associated electron transport system (ETS) abnormalities: fibers lacking cytochrome c oxidase activity (COX(-)) and/or exhibiting succinate dehydrogenase hyperreactivity (SDH(++)). Two hundred serial cross-sections (spanning 1600 microm) were obtained and analyzed for ETS abnormalities at regular intervals. The abundance and length of ETS abnormal regions increased with age. Extrapolating the data to the entire length of the fiber, up to 60% of the fibers were estimated to display ETS abnormalities in the oldest animal studied (34 years) compared to 4% in a young adult animal (11 years). ETS abnormal phenotypes varied with age and fiber type. Middle-aged animals primarily exhibited the COX(-) phenotype, while COX(-)/SDH(++) abnormalities were more common in old animals. Transition region phenotype was affected by fiber type with type 2 fibers first displaying COX(-) and then COX(-)/SDH(++) while type 1 fibers progressed from normal to SDH(++) and then to COX(-)/SDH(++). In situ hybridizations studies revealed an association of ETS abnormalities with deletions of the mitochondrial genome. By measuring cross-sectional area along the length of ETS abnormal fibers, we demonstrated that some of these fibers exhibit atrophy. Our data suggest mitochondrial (mtDNA) deletions and associated ETS abnormalities are contributors to age-associated fiber atrophy.
对恒河猴的股外侧肌进行组织学检查，以观察与年龄相关的电子传递系统（ETS）异常情况：缺乏细胞色素c氧化酶活性（COX(-)）和/或表现出琥珀酸脱氢酶高反应性（SDH(++)）的纤维。获取了200个连续的横截面（跨越1600微米），并定期分析ETS异常情况。ETS异常区域的丰度和长度随年龄增加。将数据外推至纤维的全长，估计在研究的最老动物（34岁）中，高达60%的纤维显示出ETS异常，而在年轻成年动物（11岁）中这一比例为4%。ETS异常表型随年龄和纤维类型而变化。中年动物主要表现为COX(-)表型，而COX(-)/SDH(++)异常在老年动物中更为常见。过渡区域表型受纤维类型影响，2型纤维先表现为COX(-)，然后是COX(-)/SDH(++)，而1型纤维从正常发展为SDH(++)，然后是COX(-)/SDH(++)。原位杂交研究揭示了ETS异常与线粒体基因组缺失之间的关联。通过测量ETS异常纤维全长的横截面积，我们证明其中一些纤维表现出萎缩。我们的数据表明，线粒体（mtDNA）缺失及相关的ETS异常是与年龄相关的纤维萎缩的原因。
