Association of age-related mitochondrial abnormalities with skeletal muscle fiber atrophy.
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.
Lee
C M
CM
Department of Animal Health and Biomedical Sciences, University of Wisconsin, Madison 53706, USA.
Lopez
M E
ME
Weindruch
R
R
Aiken
J M
JM
D000375:Aging; D000818:Animals; D004272:DNA, Mitochondrial / Q000032:analysis; D004579:Electron Transport; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D017403:In Situ Hybridization; D008253:Macaca mulatta; D008297:Male; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D018485:Muscle Fibers, Skeletal / Q000648:ultrastructure*; D018482:Muscle, Skeletal / Q000648:ultrastructure*; D009133:Muscular Atrophy / Q000473:pathology*; D013385:Succinate Dehydrogenase / Q000378:metabolism
D004272:DNA, Mitochondrial; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV