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Two distinct aspects of skeletal muscle aging: primary sarcopenia and aged muscle regeneration

Madoka Uezumi, Ph.D.

Researcher (Gerontology of motor system)

Currently, the gap between average life expectancy and healthy life expectancy in Japan is approximately 10 years. Improving healthy life expectancy is important for achieving healthy aging. Skeletal muscles play a major role in physical activity or exercise and therefore, are indispensable for healthy life. Furthermore, recent studies have reported that people who maintain their muscle mass have a lower risk of diseases and a longer life. Therefore, maintaining skeletal muscles will result in good health and longevity. However, muscle mass and function progressively decline with age, resulting in sarcopenia. There are two distinct aspects of skeletal muscle aging. The first aspect is the onset of sarcopenia that solely depends on aging and is known as primary sarcopenia. Sarcopenia increases the frequency of falls and fractures, which can trigger muscle injuries. The second aspect is the process of recovery after muscle injuries. The first aspect may be attributed to age-related changes in the mechanisms of muscle maintenance in a steady state. In contrast, the second aspect is attributed to age-related changes that occur in stem cells and during muscle regeneration. We previously reported that a decrease in the number of muscle stem cells (satellite cells) and deterioration of the muscle environment contribute to age-related decline in the muscle regenerative capacity. Further, we found a decrease in pro-insulin-like growth factor-II (pro-IGF-II) levels as an environmental factor, and pro-IGF-II supplementation improved the declined muscle regenerative capacity of aged mice. Unlike the injured state, muscle regeneration and stem cells are not involved in muscle maintenance in the steady state, and factors other than muscle fiber (e.g., innervation and extracellular matrix) are more important for muscle maintenance. Therefore, these two aspects should be carefully distinguished for studying skeletal muscle aging, and we are currently investigating factors that are critical for each of these aspects of muscle aging.