4.7 Article

MiR-199-3p enhances muscle regeneration and ameliorates aged muscle and muscular dystrophy

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COMMUNICATIONS BIOLOGY
卷 4, 期 1, 页码 -

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NATURE RESEARCH
DOI: 10.1038/s42003-021-01952-2

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  1. Japan Agency for Medical Research and Development (AMED) [17ek0109190h0002, 20ek0109315h0003]
  2. AMED-CREST
  3. Ministry of Health, Labour and Welfare of Japan
  4. Japan Society for the Promotion of Science [16K19003]
  5. Mitsui Sumitomo Insurance Welfare Foundation Research Grant 2017
  6. Grants-in-Aid for Scientific Research [16K19003] Funding Source: KAKEN

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The study reveals that cell-free miR-199-3p in the blood is significantly decreased in aged mice compared to young mice, and supplementing it can enhance muscle regeneration and improve muscle strength. This finding holds potential for hypertrophic effect in aged muscle fibers and as a novel RNA therapeutic for diseases like DMD.
Parabiosis experiments suggest that molecular factors related to rejuvenation and aging circulate in the blood. Here, we show that miR-199-3p, which circulates in the blood as a cell-free miRNA, is significantly decreased in the blood of aged mice compared to young mice; and miR-199-3p has the ability to enhance myogenic differentiation and muscle regeneration. Administration of miR-199 mimics, which supply miR-199-3p, to aged mice resulted in muscle fiber hypertrophy and delayed loss of muscle strength. Systemic administration of miR-199 mimics to mdx mice, a well-known animal model of Duchenne muscular dystrophy (DMD), markedly improved the muscle strength of mice. Taken together, cell-free miR-199-3p in the blood may have an anti-aging effect such as a hypertrophic effect in aged muscle fibers and could have potential as a novel RNA therapeutic for DMD as well as age-related diseases. The findings provide us with new insights into blood-circulating miRNAs as age-related molecules. Fukuoka et al. investigate the possible role of miR-199-3p during aging, which significantly decreases in the blood of aged mice compared to young mice. They also show that miR-199-3p enhance muscle regeneration, and administering miR-199 mimics to mdx mice, a dystrophy animal model, markedly improves muscle strength of the mice, highlighting its therapeutic potential.

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