Fukuoka Masashi, Fujita Hiromi, Numao Kosumo, Nakamura Yasuko, Shimizu Hideo, Sekiguchi Masayuki, Hohjoh Hirohiko
Department of Molecular Pharmacology, National Institute of Neuroscience, NCNP, Tokyo, Japan.
Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Tokyo, Japan.
Commun Biol. 2021 Mar 29;4(1):427. doi: 10.1038/s42003-021-01952-2.
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.
联体共生实验表明，与年轻化和衰老相关的分子因子在血液中循环。在此，我们发现，作为游离于细胞外的微小RNA（miRNA）在血液中循环的miR-199-3p，与年轻小鼠相比，在老年小鼠血液中的含量显著降低；并且miR-199-3p具有增强肌源性分化和肌肉再生的能力。向老年小鼠施用可提供miR-199-3p的miR-199模拟物，导致肌纤维肥大，并延缓肌肉力量的丧失。向杜氏肌营养不良症（DMD）的著名动物模型mdx小鼠全身施用miR-199模拟物，显著改善了小鼠的肌肉力量。综上所述，血液中游离的miR-199-3p可能具有抗衰老作用，如对老年肌纤维的肥大作用，并且可能作为治疗DMD以及与年龄相关疾病的新型RNA疗法具有潜力。这些发现为我们将血液循环中的miRNA视为与年龄相关的分子提供了新的见解。
