Lees Simon J, Rathbone Christopher R, Booth Frank W
Dept. of Biomedical Sciences, Univ. of Missouri-Columbia, Veterinary Medicine Bldg., 1600 East Rollins, Rm. E102, Columbia, MO 65211, USA.
Am J Physiol Cell Physiol. 2006 Feb;290(2):C609-15. doi: 10.1152/ajpcell.00408.2005. Epub 2005 Sep 28.
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 approximately 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.
肌肉前体细胞（MPCs）是骨骼肌再生、修复和/或肥大所必需的，而这些过程在肌肉减少症中是不足的。在本研究中，我们探讨了MPC分化过程中与年龄相关的变化问题。从年轻和老年大鼠的骨骼肌中分离出包括卫星细胞在内的MPCs，其具有高度的成肌纯度（>90%的MyoD和结蛋白呈阳性）。与从3月龄大鼠骨骼肌中分离的MPCs相比，从32月龄大鼠骨骼肌中分离的MPCs向肌管的分化能力下降，肌球蛋白重链（MHC）和肌肉肌酸激酶（CK-M）的表达也降低。p27（Kip1）是一种细胞周期蛋白依赖性激酶抑制剂，已被证明可增强培养中的肌肉分化。在此我们描述了我们的发现，即从32月龄大鼠骨骼肌中分离的正在分化的MPCs中的p27（Kip1）蛋白低于3月龄大鼠骨骼肌中的p27（Kip1）蛋白。虽然从32月龄大鼠中分离的正在分化的MPCs中MHC和CK-M的表达大约低50%，但MyoD蛋白含量没有差异，而生肌调节因子蛋白浓度则高出两倍。这些数据表明，从肌肉减少症肌肉中分离的MPCs从细胞周期停滞过渡到形成肌管的过程中，细胞信号传导存在内在差异。此外，尽管MyoD正常且生肌调节因子水平升高，但正在分化的MPCs中肌肉特异性蛋白表达仍存在与年龄相关的下降。
