Maintenance of Skeletal Muscles and Stem Cells – Programmed Research
|Research Subject||A01-3 Understanding the Molecular Foundations of Load Dependency in the Development, Maintenance, and Atrophy of Skeletal Muscles|
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There are two known types of muscle atrophy: reversible and irreversible. The former is caused by a decreased mechanical load, while the latter is due to aging or disease. The irreversibility of the latter cannot be accounted for by the ubiquitin-proteasome pathway for degradation of muscle proteins, which is common in muscle atrophy. Recent studies have shown that the decrease in the number of muscle stem cells and the degradation of their function cause irreversible muscle atrophy. Muscle stem cells of aged mice cannot maintain the resting phase (G0 phase), undergo further excessive differentiation, and experience a decline in their regenerative capacity, which lead to muscular atrophy. In contrast, juvenile mice have an active agent in the blood serum that prevents such deterioration or failure.
This study will address the question of reversibility and irreversibility of muscle atrophy by elucidating the mechanism of muscle atrophy due to various factors – primarily atrophy attributed to a prolonged stay in Space. Our approach involves the following three steps. (1) Analyze global gene expression (profiling) using next-generation genome sequencing of zebrafish raised in a microgravity environment of the Space Station. (2) Compare the results with the change in the gene expression of skeletal muscles associated with reduced exercise and aging. (3) Identify the changes of gene expression common to these two or unique to either, while noting the relationship with the mechanism of skeletal muscle development to elucidate a new mechanism of muscle maintenance and atrophy.