A group from Sapporo Medical University and Hokkaido University found that in normal mice, exercise promotes muscle regeneration due to cell senescence of skeletal muscle mesenchymal progenitor cells (FAPs). discovered.On the other hand, in the case of mice with chronic inflammation of skeletal muscle, it was clarified that FAP aging did not occur sufficiently and that exercise rather exacerbated the fibrotic pathology of skeletal muscle.
Exercise has been shown to be an effective treatment for restoring muscle function in chronic inflammatory myopathy, in which muscle function declines due to persistent inflammation and fibrosis.However, it is said that inflammation and fibrosis may worsen in some cases, and the two-sided mystery of why exercise promotes muscle regeneration and sometimes promotes inflammation and fibrosis is known. I didn't.
In this study, we focused on FAP, which is deeply involved in both skeletal muscle regeneration and degeneration, and analyzed it using acute myositis model mice, which are curable inflammation, and chronic myositis model mice.As a result, in mice with acute myitis, FAP shows strong expression of cell senescence factor, while in mice with chronic myitis, expression of cell senescence factor is weak, and FAP shows resistance to cell death, immune avoidance mechanism, etc. It turned out that it would accumulate.
Normally, damaged cells age and increase the recruitment of immune cells by causing a phenomenon called Senescence-Associated Secretory Phenotype (SASP).This is the system required for aging cells to be cleared by immune cells for normal tissue remodeling.However, it has now been found that in chronic myositis, this cellular senescence system does not work properly, thus inhibiting the induction of muscle regeneration, leading to chronic inflammation and fibrosis.
Therefore, in order to induce cell aging of FAP, a combination therapy of drug treatment that activates AMP-activated protein kinase (AMPK) and exercise was performed on chronic myitis model mice, and cell aging of FAP was induced, resulting in muscle. It is said that the reproduction of was promoted.
This result is expected to lead to the development of effective treatments for muscle diseases.
Paper information:[Nature Communications] Exercise enhances skeletal muscle regeneration by promoting senescence infibro-adipogenic progenitors