Ageing is associated with diminished muscle re-growth and myogenic precursor cell expansion early after immobility-induced atrophy in human skeletal muscle
Ageing is associated with diminished muscle re-growth and myogenic precursor cell expansion early after immobility-induced atrophy in human skeletal muscle
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DOI：
10.1113/jphysiol.2013.257121
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发表时间：
2013-08-01
影响因子：
5.5
通讯作者：
Kjaer, M.
中科院分区：
文献类型：
--
作者：
Suetta, C.;Frandsen, U.;Kjaer, M.
年轻人的骨骼肌质量从固定引起的萎缩中恢复得比老年人更快，但细胞机制仍不清楚。我们研究了年轻和老年受试者在两周不动引起的肌肉萎缩后肌肉恢复的细胞和分子调节。再训练包括 9 名老年男性（OM：平均年龄）67.3 岁，范围 61-74 岁）和 11 名年轻男性（YM：平均年龄 24.4，范围 21-30 岁）进行 4 周的监督阻力运动。在 2 周不动 (Imm) 以及 3 天 (+3d) 和 4 周 (+4wks) 的再训练后，进行肌纤维面积 (MFA)、与 I 型和 II 型肌纤维相关的 Pax7 阳性卫星细胞 (SC) 测量，以及与局部骨骼肌环境相关的关键生长和转录因子的基因表达分析。 OM 在 4 周再训练后未发现 MFA（股外侧肌）增加，Pax7 阳性 SC 数量也没有增加，而 YM 在 +3 天和 +4 周时增加了 MFA (P < 0.05)、Pax7 阳性细胞数量，并且每条 II 型纤维的 Pax7 阳性细胞数量比 OM 多 (P < 0.05)。再训练后，IGF-1Ea、MGF、MyoD1 和 HGF 的 mRNA 表达没有观察到与年龄相关的差异，而在 +3d 时，与 OM 相比，YM 中的肌生长抑制素表达水平下调更多（P < 0.05）。总之，老年人固定后肌肉再生减少与卫星细胞增殖反应减弱以及肌肉生长抑制素的年龄特异性调节有关。相反，局部生长因子的表达似乎无法解释肌肉质量恢复中与年龄相关的差异。
Recovery of skeletal muscle mass from immobilisation-induced atrophy is faster in young than older individuals, yet the cellular mechanisms remain unknown. We examined the cellular and molecular regulation of muscle recovery in young and older human subjects subsequent to 2 weeks of immobility-induced muscle atrophy. Retraining consisted of 4 weeks of supervised resistive exercise in 9 older (OM: mean age) 67.3, range 61-74 yrs) and 11 young (YM: mean age 24.4, range 21-30 yrs) males. Measures of myofibre area (MFA), Pax7-positive satellite cells (SCs) associated with type I and type II muscle fibres, as well as gene expression analysis of key growth and transcription factors associated with local skeletal muscle milieu, were performed after 2 weeks immobility (Imm) and following 3 days (+3d) and 4 weeks (+4wks) of retraining. OM demonstrated no detectable gains in MFA (vastus lateralis muscle) and no increases in number of Pax7-positive SCs following 4wks retraining, whereas YM increased their MFA (P < 0.05), number of Pax7-positive cells, and had more Pax7-positive cells per type II fibre than OM at +3d and +4wks (P < 0.05). No age-related differences were observed in mRNA expression of IGF-1Ea, MGF, MyoD1 and HGF with retraining, whereas myostatin expression levels were more down-regulated in YM compared to OM at +3d (P < 0.05). In conclusion, the diminished muscle re-growth after immobilisation in elderly humans was associated with a lesser response in satellite cell proliferation in combination with an age-specific regulation of myostatin. In contrast, expression of local growth factors did not seem to explain the age-related difference in muscle mass recovery.