Sarcopenia is an age-associated decline of skeletal muscle mass and function and is known to lead to frailty, cachexia, osteoporosis, metabolic syndromes, and death. Notwithstanding the increasing incidence of sarcopenia, the molecular and cellular mechanisms driving age-related sarcopenia are not completely understood. This article reviews current definitions of sarcopenia, its potential mechanisms, and effects of exercise on sarcopenia. The pathogenesis of age-related sarcopenia is multifactorial and includes myostatin, inflammatory cytokines, and mitochondria-derived problems. Especially, age-induced mitochondrial dysfunction triggers the production of reactive oxygen species (ROS) by mitochondria, impedes mitochondrial dynamics, interrupts mitophagy, and leads to mitochondria-mediated apoptosis. Aerobic exercise provides at least a partial solution to sarcopenia as it ameliorates mitochondria-derived problems, and resistance exercise strengthens muscle mass and function. Furthermore, combinations of these exercise types provide the benefits of both. Collectively, this review summarizes potential mechanisms of age-related sarcopenia and emphasizes the use of exercise as a therapeutic strategy, suggesting that combined exercise provides the most beneficial means of combating age-related sarcopenia.

This study aimed to investigate the effects of single-bout exercise on mitochondrial function, dynamics (fusion, fission), and mitophagy in cardiac and skeletal muscles. Methods: Fischer 344 rats (4 months old) were randomly divided into the control (CON) or acute exercise (EX) group (n = 10 each). The rats performed a single bout of treadmill exercise for 60 minutes. Mitochondrial function (e.g., O2 respiration, H2O2 emission, Ca 2+ retention capacity), mitochondrial fusion (e.g., Mfn1, Mfn2, Opa1), mitochondrial fission (e.g., Drp1, Fis1), and mitophagy (e.g., Parkin, Pink1, LC3II, Bnip3) were measured in permeabilized cardiac (e.g., left ventricle) and skeletal (e.g., soleus, white gastrocnemius) muscles. Results: Mitochondrial O2 respiration and Ca 2+ retention capacity were significantly increased in all tissues of the EX group compared with the CON group. Mitochondrial H2O2 emissions showed tissue-specific results; the emissions showed no significant differences in the left ventricle or soleus (type I fibers) but was significantly increased in the white gastrocnemius (type II fibers) after acute exercise. Mitochondrial fusion and fission were not altered in any tissues of the EX group. Mitophagy showed tissue-specific differences: It was not changed in the left ventricle or white gastrocnemius, whereas Parkin and LC3II were significantly elevated in the soleus muscle. Conclusions: A single bout of aerobic exercise may improve mitochondrial function (e.g., O2 respiration and Ca 2+ retention capacity) in the heart and skeletal muscles without changes in mitochondrial dynamics or mitophagy.

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Obesity is characterized by the induction of skeletal muscle remodeling and mitochondria-mediated apoptosis. Exercise has been reported as a positive regulator of skeletal muscle remodeling and apoptosis. However, the effects of exercise on skeletal muscle remodeling and mitochondria-mediated apoptosis in obese skeletal muscles have not been clearly elucidated. Four-week-old C57BL/6 mice were randomly assigned into four groups: control (CON), control plus exercise (CON + EX), high-fat diet (HFD), and HFD plus exercise groups (HFD + EX). After obesity was induced by 20 weeks of 60% HFD feeding, treadmill exercise was performed for 12 weeks. Exercise ameliorated the obesity-induced increase in extramyocyte space and a decrease in the cross-sectional area of the skeletal muscle. In addition, it protected against increases in mitochondria-mediated apoptosis in obese skeletal muscles. These results suggest that exercise as a protective intervention plays an important role in regulating skeletal muscle structure and apoptosis in obese skeletal muscles.

PurposeChemotherapy is associated with the side effects including damage to the mitochondrial DNA. Doxorubicin (DOX) serves as a chemotherapeutic agent for the patients with breast cancer or prostate cancer. DOX causes muscle weakness and fatigue. We investigated the effects of treadmill exercise on DOX-induced apoptosis and mitochondrial dysfunction in relation to central fatigue. For this study, we used the rat model of DOX-induced muscle damage.MethodsDOX (2 mg/kg) was intraperitoneally injected 1 time per week for 4 weeks. Treadmill running continued 5 days per week for 4 weeks. Muscle strength and fatigue index in the gastrocnemius were measured. Immunohistochemistry for the expressions of tryptophan hydroxylase (TPH) and 5-hydroxytryptamine (5-HT) in the dorsal raphe was conducted. We used western blot analysis for the expressions of Bax, Bcl-2, and caspases-3 in the gastrocnemius. Mitochondrial function in the gastrocnemius was also evaluated.ResultsDOX treatment decreased muscle strength with increase of fatigue index in the gastrocnemius. Mitochondria function was deteriorated and apoptosis in the gastrocnemius was enhanced by DOX treatment. Expressions of TPH and 5-HT in the dorsal raphe were increased by DOX treatment. Treadmill exercise attenuated DOX-induced muscle fatigue and impairment of mitochondria function. Apoptosis in the gastrocnemius was inhibited and over-expression of TPH and 5-HT was suppressed by treadmill exercise.ConclusionsApoptosis was enhanced and mitochondria function was deteriorated by DOX treatment, resulting in muscle weakness and central fatigue. Treadmill exercise suppressed apoptosis and prevented deterioration of mitochondria function in muscle, resulting in alleviation of muscle weakness and central fatigue during DOX therapy.