Molecular basis of the myogenic profile of aged human skeletal muscle satellite cells during differentiation
Molecular basis of the myogenic profile of aged human skeletal muscle satellite cells during differentiation
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DOI：
10.1016/j.exger.2009.05.002
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发表时间：
2009-08-01
影响因子：
3.9
通讯作者：
Fulle, Stefania
中科院分区：
文献类型：
--
作者：
Pietrangelo, Tiziana;Puglielli, Cristina;Fulle, Stefania
肌肉减少症是与年龄相关的肌肉质量、力量和功能的丧失。老年人的人体肌肉蛋白质合成速度比年轻人慢，导致肌肉萎缩和肌肉质量损失，功能能力下降。此外，由于干预卫星细胞的损伤，衰老还伴随着肌肉组织在受伤或过度使用后再生能力的下降，我们之前报道过氧化损伤的证据。本研究的目的是确定衰老对从人类骨骼肌获得的成肌细胞和肌管的影响，并将转录谱表征为与其再生能力的年龄依赖性修饰相关的分子表达模式。我们的数据表明，分化失败并不取决于生肌细胞数量减少，而是取决于分化程序难以完成。这里报道的数据表明了以下发现：（i）分子底物中氧化损伤的积累，可能是由于抗氧化活性受损和修复能力不足，（ii）老年成肌细胞执行完整分化程序的能力有限；融合受限，可能是由于细胞骨架周转改变和细胞外基质降解所致；(iii) 通过激活特定的 FOXO 依赖性程序来激活萎缩机制。 (C) 2009 Elsevier Inc. 保留所有权利。
Sarcopenia is the age-related loss of muscle mass, strength and function. Human muscle proteins are synthesized at a slower rate in the elderly than in young adults, leading to atrophy and muscle mass loss with a decline in the functional capability. Additionally, aging is accompanied by a decrease in the ability of muscle tissue to regenerate following injury or overuse due to the impairment of intervening satellite cells, in which we previously reported oxidative damage evidences. The aim of the present study was to determine the effects of aging on myoblasts and myotubes obtained from human skeletal muscle, and characterize the transcriptional profile as molecular expression patterns in relation to age-dependent modifications in their regenerative capacity. Our data show that the failure to differentiate does not depend on reduced myogenic cell number, but difficulty to complete the differentiation program. Data reported here suggested the following findings: (i) oxidative damage accumulation in molecular substrates, probably due to impaired antioxidant activity and insufficient repair capability, (ii) limited capability of elderly myoblasts to execute a complete differentiation program; restricted fusion, possibly due to altered cytoskeleton turnover and extracellular matrix degradation and (iii) activation of atrophy mechanism by activation of a specific FOXO-dependent program. (C) 2009 Elsevier Inc. All rights reserved.