Thérapie des maladies du muscle strié, Institut de Myologie, Université Pierre et Marie Curie, G.H. Pitié-Salpétrière, 47 bd de l'hôpital, Paris, France.
Mech Ageing Dev. 2011 Apr;132(4):154-62. doi: 10.1016/j.mad.2011.02.007. Epub 2011 Feb 25.
Loss of muscle mass and strength is a major problem during aging and the expression of Mechano Growth Factor (MGF), a member of the IGF-1 (insulin-like Growth Factor 1) super family, has been shown to be both exercise and age dependent. MGF, also called IGF-1Ec, has a unique E domain with a 49bp insert in humans (52bp in rodents; IGF-1Eb), which results in a reading frame shift during the IGF-1 gene splicing to produce a distinct mature isoform. We have studied the effects of the MGF-24aa-E peptide on proliferation and differentiation of primary human muscle cell cultures isolated from healthy subjects of different ages. We found that MGF-E peptide significantly increases the proliferative life span and delays senescence of satellite cells isolated from neonatal and young adult but not from old adult muscle, hypertrophy associated with a significant decrease in the percentage of reserve cells was observed in all cultures. It is concluded that the MGF-24aa-E peptide alone has a marked ability to enhance satellite cell activation, proliferation and fusion for muscle repair and maintenance and could provide a new strategy to combat age related sarcopenia without the oncogenic side effects observed for IGF1.
肌肉质量和力量的丧失是衰老过程中的一个主要问题,机械生长因子(MGF)的表达,IGF-1(胰岛素样生长因子 1)超家族的一个成员,已经被证明既依赖于运动,也依赖于年龄。MGF,也称为 IGF-1Ec,在人类中具有独特的 E 结构域,在人类中插入了 49bp(啮齿动物中为 52bp;IGF-1Eb),这导致在 IGF-1 基因剪接过程中产生一个独特的成熟同工型的阅读框移位。我们研究了 MGF-24aa-E 肽对从不同年龄的健康受试者中分离的原代人肌肉细胞培养物的增殖和分化的影响。我们发现,MGF-E 肽显著增加了从新生儿和年轻成年人但不从老年人肌肉中分离的卫星细胞的增殖寿命,并延迟了衰老,在所有培养物中都观察到与肥大相关的储备细胞百分比显著下降。结论是,MGF-24aa-E 肽单独具有显著增强卫星细胞激活、增殖和融合的能力,可用于修复和维持肌肉,同时提供一种新策略来对抗与年龄相关的肌肉减少症,而不会产生 IGF1 观察到的致癌副作用。