Muscle fiber type specific alterations of mitochondrial respiratory function and morphology in aged female mice.

Mitochondrial dysfunction is considered to be a major cause of sarcopenia, defined as age-related muscle fiber atrophy and muscle weakness, as reduced mitochondrial respiration and morphological changes such as ragged red fibers (RRFs) are observed in aging muscles. However, the role of mitochondrial dysfunction in sarcopenia is not fully elucidated. Although previous studies have suggested that aging has a fiber type-specific effect on mitochondrial function, little is known about mitochondrial changes in individual fiber types. Here, we used C57BL/6NCr female mice to identify fiber type-specific pathological changes, examine the significance of pathological changes in sarcopenia, and identify possible mechanisms behind mitochondrial changes in slow-twitch soleus muscle (SOL) and fast-twitch extensor digitorum longus muscle (EDL). We observed reduced type I fiber-specific mitochondrial respiratory enzyme activity, impaired respiration, and subsarcolemmal mitochondrial accumulation in aged SOL, which was different from RRFs. These pathological alterations were not directly associated with fiber atrophy. Additionally, we found increased oxidative stress markers in aged SOL, suggesting that oxidative stress is involved in the pathological and functional changes in mitochondria. Meanwhile, obvious mitochondrial changes were not seen in aged EDL. Thus, age-related mitochondrial dysfunction is specific to the fiber type and may correlate with the muscle quality rather than the muscle mass. • Age-related mitochondrial dysfunction, including reduced type I fiber-specific mitochondrial respiratory enzyme activities, OXPHOS impairment, and subsarcolemmal mitochondrial accumulation, was predominantly observed in slow-twitch SOL but not in fast-twitch EDL. • The characteristics of subsarcolemmal mitochondrial accumulation are quite different from those of ragged red fibers. • Age-related mitochondrial dysfunction has fiber-type specificity that may correlate with muscle weakness due to the decline of oxidative metabolism rather than fiber atrophy. • Hypoxia-mediated oxidative stress may be involved in the pathological and functional changes of mitochondria in aged SOL. [ABSTRACT FROM AUTHOR]