Muscles can be built without breaking them, defying the common sense of strength training

Although building of muscle was thought to require muscles to be broken through strength training, it was found that muscles can be built without breaking muscle fibers. In joint research with Akiyoshi Uezumi of Tokyo Metropolitan Institute of Gerontology, the research group of Graduate Student Akihiro Kaneshige (doctoral course), Associate Professor So-ichiro Fukada, and colleagues of the Graduate School of Pharmaceutical Sciences at Osaka University showed for the first time in the world that mesenchymal progenitor cells respond to stimulation of strength training and that transmission of this stimulation from stem cells to satellite cells in skeletal muscle leads to an increase in the number of muscle cell nuclei, which is important for increasing muscle mass. Their findings were published in Cell Stem Cell.

The muscle is the largest organ that occupies 30%-40% of the body and comprises multinucleated cells called muscle fibers. Muscles atrophy if they continue to be unused when bedridden or during cast immobilization. In addition, muscle mass decreases with aging, which can be a cause of fractures because of falls and decreased activity. Thus, methods for prevention and treatment of muscle atrophy are being vigorously studied and developed worldwide.

In contrast, muscles grow through training, such as strength training. Increased protein synthesis of muscle fibers and increased number of nuclei in muscle fibers are important for muscle growth. In addition, the proliferation of muscle-specific stem cells, called satellite cells, is needed to increase the number of nuclei in muscle fibers.

However, how satellite cells proliferate is not known. Previously, it was believed that satellite cells proliferate owing to muscle breakdown, but this was not supported by sufficient scientific evidence. Conversely, the research group of Associate Professor Fukada and colleagues previously observed that satellite cells were able to proliferate without breaking muscles.

In this study, the research group discovered that induction of the strength training model in mice results in little satellite cell proliferation in the absence of muscle-resident mesenchymal progenitor cells. Furthermore, they found that Yap/Taz, which translocate to the nucleus when physical force is applied to the cells, are highly important for mesenchymal progenitor cells during strength training. This suggests that mesenchymal progenitor cells sense the physical forces generated by strength training.

They also found that the translocation of Yap/Taz to the nucleus triggers mesenchymal progenitor cells to secrete thrombospondin 1 and stimulates CD47 expression by satellite cells, which induces satellite cell proliferation. They also showed that proliferation of satellite cells through CD47 stimulation requires reduced expression of calcitonin receptors expressed by satellite cells.

Thus, mesenchymal progenitor cells secrete the substance necessary for the proliferation of satellite cells, eventually resulting in an increase in the number of nuclei in muscle fibers and muscle hypertrophy. This allows satellite cells to proliferate and increases the number of nuclei in muscle fibers through the action of mesenchymal progenitor cells in a mechanical load-dependent manner, even if the muscles are not broken.

Currently, research is underway to regenerate broken muscles by transplanting satellite cells for muscular dystrophy and other diseases. In addition, the possibility of a new treatment method of increasing the original systemic satellite cells with drugs has been demonstrated.

Associate Professor Fukada commented, "The proliferation of satellite cells during strength training is said to be because of muscle breakdown. In this study, we first examined this premise and provided evidence that satellite cells proliferate even without muscle breakdown. In the field of skeletal muscle, the fatigue theory of lactic acid accumulation is also said to be wrong. There are many pieces of information that lack sufficient scientific evidence, even if they are pervasive among the general public; these can serve as research topics that defy the common sense in the world."