Georgia Health Sciences University, Augusta, GA 30912, USA.
Exp Gerontol. 2013 Feb;48(2):290-7. doi: 10.1016/j.exger.2012.11.004. Epub 2012 Nov 21.
The activin A-myostatin-follistatin system is thought to play an important role in the regulation of muscle and bone mass throughout growth, development, and aging; however, the effects of these ligands on progenitor cell proliferation and differentiation in muscle and bone are not well understood. In addition, age-associated changes in the relative expression of these factors in musculoskeletal tissues have not been described. We therefore examined changes in protein levels of activin A, follistatin, and myostatin (GDF-8) in both muscle and bone with age in C57BL6 mice using ELISA. We then investigated the effects of activin A, myostatin and follistatin on the proliferation and differentiation of primary myoblasts and mouse bone marrow stromal cells (BMSCs) in vitro. Myostatin levels and the myostatin:follistatin ratio increased with age in the primarily slow-twitch mouse soleus muscle, whereas the pattern was reversed with age in the fast-twitch extensor digitorum longus muscle. Myostatin levels and the myostatin:follistatin ratio increased significantly (+75%) in mouse bone marrow with age, as did activin A levels (+17%). Follistatin increased the proliferation of primary myoblasts from both young and aged mice, whereas myostatin increased proliferation of younger myoblasts but decreased proliferation of older myoblasts. Myostatin reduced proliferation of both young and aged BMSCs in a dose-dependent fashion, and activin A increased mineralization in both young and aged BMSCs. Together these data suggest that aging in mice is accompanied by changes in the expression of activin A and myostatin, as well as changes in the response of bone and muscle progenitor cells to these factors. Myostatin appears to play a particularly important role in the impaired proliferative capacity of muscle and bone progenitor cells from aged mice.
激活素 A-肌肉生长抑制素-卵泡抑素系统被认为在生长、发育和衰老过程中对肌肉和骨量的调节起着重要作用；然而，这些配体对肌肉和骨骼祖细胞增殖和分化的影响还不是很清楚。此外，骨骼肌组织中这些因子相对表达的年龄相关性变化尚未被描述。因此，我们使用 ELISA 法检测了 C57BL6 小鼠肌肉和骨骼中激活素 A、卵泡抑素和肌肉生长抑制素（GDF-8）的蛋白水平随年龄的变化。然后，我们研究了激活素 A、肌肉生长抑制素和卵泡抑素对原代肌细胞和小鼠骨髓基质细胞（BMSC）体外增殖和分化的影响。在主要的慢收缩型小鼠比目鱼肌中，肌肉生长抑制素水平和肌肉生长抑制素：卵泡抑素比值随年龄增长而增加，而在快速收缩型伸趾长肌中则相反。随着年龄的增长，小鼠骨髓中的肌肉生长抑制素水平和肌肉生长抑制素：卵泡抑素比值显著增加（增加 75%），激活素 A 水平也增加（增加 17%）。卵泡抑素增加了来自年轻和老年小鼠的原代肌细胞的增殖，而肌肉生长抑制素增加了年轻肌细胞的增殖，但减少了老年肌细胞的增殖。肌肉生长抑制素以剂量依赖的方式减少了年轻和老年 BMSC 的增殖，激活素 A 增加了年轻和老年 BMSC 的矿化。这些数据表明，在小鼠衰老过程中，激活素 A 和肌肉生长抑制素的表达发生了变化，同时骨和肌肉祖细胞对这些因子的反应也发生了变化。肌肉生长抑制素似乎在老年小鼠的肌肉和骨骼祖细胞增殖能力受损中起着特别重要的作用。
