MITOCHONDRIAL ABNORMALITIES CONCURRENT WITH SARCOPENIA AND OXIDATIVE DAMAGE





E. Bua*, J. Cervera, S.H. McKiernan, J. Wanagat, J.M. Aiken

Department of Animal Health and Biomedical Sciences
University of Wisconsin- Madison,
Madison, WI 53706




The hypothesis that the accumulation of electron transport system abnormalities (ETSabn) is associated with sarcopenia and oxidatively damaged nucleic acids was investigated. Muscle mass and fiber number was measured to determine the extent of sarcopenia in soleus, adductor longus and vastus lateralis muscles of 5-, 18-, and 36-month-old male F344XBNF1 hybrid rats. A significant decrease in soleus and vastus lateralis muscle mass was observed with age. Adductor longus did not show any age-associated decrease in muscle mass. Multiple serial muscle sections were analyzed for the activities of two mitochondrial enzymes, cytochrome c oxidase (COX) and succinate dehydrogenase (SDH). The number of fibers exhibiting a COX negative/SDH hyperreactive phenotype (ragged red fibers) increased with age in both vastus lateralis and soleus muscles. No ragged red fibers were identified in adductor longus muscles at any age. These results suggest that different muscles accumulate different levels of ETS abnormalities during normal aging and that this accumulation correlates with the degree of sarcopenia. When cross-sectional areas of individual fibers were measured along a length of 1000 mm, ragged red fibers decreased in cross-sectional area in the abnormal region while normal fibers did not. The vastus lateralis muscle, which undergoes a greater degree of sarcopenia, exhibited more ETS abnormalities and associated fiber atrophy than the soleus and adductor longus muscles, which are more resistant to sarcopenia, suggesting a direct association between sarcopenia and age-associated ETS abnormalities. Monoclonal anti-8OHG Ab was used as a marker for RNA and DNA oxidative damage. This immunohistochemical study revealed that ~ 89% of oxidatively damaged fibers were ETS abnormal and 73% of these ETS abnormal fibers exhibited the ragged red fiber phenotype, suggesting an association between mitochondrial dysfunction and oxidative damage.




Key words: aging, ragged red fiber, rat, muscle atrophy, oxidative damage







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