RAGGED-RED FIBERS IN NORMAL AGING AND INFLAMMATORY MYOPATHY

Ragged Fed fibers are an important marker for mitochondrial disease. T o evaluate the hypothesis that mitochondrial dysfunction may play a co le in the pathogenesis of aging and inclusion body myositis, we studie d the frequency of ragged red fibers in muscle biopsy specimens from 1 5 young and 13 old normal adults, and from 27 patients with inclusion body myositis, polymyositis, or dermatomyositis. Serial transverse cry ostat sections were stained with modified Gomori trichrome, modified s uccinic dehydrogenase, and cytochrome c oxidase. The frequency of ragg ed red fibers, determined by measuring the percent number of succinic dehydrogenase-positive ragged red fiber equivalents, was significantly higher in old compared to young normal subjects (0.33 vs. 0.02%, p < 0.0001). With the exception of a single polymyositis biopsy specimen s howing a large number of ragged red fibers, the frequency of ragged re d fibers in patients with polymyositis or dermatomyositis was similar to that of age-matched normal control subjects. The frequency of ragge d red fibers was more than 1% in 7 of 8 patients with inclusion body m yositis (maximum, 15%). The modified succinic dehydrogenase stain was more sensitive than the modified Gomori trichrome in detecting accumul ation of mitochondria in muscle fibers. Cytochrome c oxidase activity was deficient in most ragged red fibers. We conclude that the number o f ragged red fibers increases with normal aging and may reflect an age -related decline in muscle mitochondrial oxidative metabolism The freq uent occurrence of ragged red fibers in inclusion body myositis sugges ts that mitochondrial function may be impaired in this disease.