Age-associated decrease in muscle precursor cell differentiation
Age-associated decrease in muscle precursor cell differentiation
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DOI：
10.1152/ajpcell.00408.2005
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发表时间：
2006-02-01
影响因子：
5.5
通讯作者：
Booth, FW
中科院分区：
文献类型：
--
作者：
Lees, SJ;Rathbone, CR;Booth, FW
肌肉前体细胞（MPC）是骨骼肌再生、再生和/或肥大所必需的，而骨骼肌在肌肉减少症中缺乏。在本研究中，我们已经解决了MPC分化的年龄相关变化的问题。MPC，包括卫星细胞，从年轻和老年大鼠骨骼肌中分离，具有高度的肌原性纯度（> 90% MyoD和结蛋白阳性）。从32月龄大鼠骨骼肌分离的MPC表现出减少分化成肌管，并表现出减少肌球蛋白重链（MHC）和肌肉肌酸激酶（CK-M）的表达相比，从3月龄大鼠分离的MPC。p27（Kip 1）是一种细胞周期蛋白依赖性激酶抑制剂，已被证明可以增强培养中的肌肉分化。在这里，我们描述了我们的发现，p27（Kip 1）蛋白是较低的分化MPC从骨骼肌的32个月大的大鼠比在3个月大的大鼠骨骼肌。虽然MHC和CK-M的表达类似于50%的低分化的MPC分离自32个月大的大鼠，MyoD蛋白含量是没有什么不同和myogenin蛋白浓度高出一倍。这些数据表明，在从肌肉减少肌分离的MPC中，从细胞周期停滞到肌管形成的过渡期间，细胞信号传导存在固有差异。此外，尽管MyoD正常和肌细胞生成素水平升高，但分化中的MPC中肌肉特异性蛋白表达存在年龄相关性降低。
Muscle precursor cells (MPCs) are required for the regrowth, regeneration, and/or hypertrophy of skeletal muscle, which are deficient in sarcopenia. In the present investigation, we have addressed the issue of age-associated changes in MPC differentiation. MPCs, including satellite cells, were isolated from both young and old rat skeletal muscle with a high degree of myogenic purity ( > 90% MyoD and desmin positive). MPCs isolated from skeletal muscle of 32-mo-old rats exhibited decreased differentiation into myotubes and demonstrated decreased myosin heavy chain (MHC) and muscle creatine kinase (CK-M) expression compared with MPCs isolated from 3-mo-old rats. p27(Kip1) is a cyclin-dependent kinase inhibitor that has been shown to enhance muscle differentiation in culture. Herein we describe our finding that p27(Kip1) protein was lower in differentiating MPCs from skeletal muscle of 32-mo-old rats than in 3-mo-old rat skeletal muscle. Although MHC and CK-M expression were similar to 50% lower in differentiating MPCs isolated from 32-mo-old rats, MyoD protein content was not different and myogenin protein concentration was twofold higher. These data suggest that there are inherent differences in cell signaling during the transition from cell cycle arrest to the formation of myotubes in MPCs isolated from sarcopenic muscle. Furthermore, there is an age-associated decrease in muscle-specific protein expression in differentiating MPCs despite normal MyoD and elevated myogenin levels.