Age-related deficits in skeletal muscle recovery following disuse are associated with neuromuscular junction instability and ER stress, not impaired protein synthesis.
Age-related deficits in skeletal muscle recovery following disuse are associated with neuromuscular junction instability and ER stress, not impaired protein synthesis.
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DOI：
10.18632/aging.100879
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发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Bodine SC
中科院分区：
文献类型：
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作者：
Baehr LM;West DW;Marcotte G;Marshall AG;De Sousa LG;Baar K;Bodine SC
短暂萎缩刺激后肌肉质量的恢复受损，可加速肌肉质量和力量的萎缩相关损失。本研究的目的是确定机制的衰减恢复肌肉质量和力量在老年大鼠废用性萎缩。成年（9个月）和老年（29个月）雄性F344BN大鼠进行后肢卸载（HU），然后重新加载。HU在成年大鼠（17 - 38%）和老年大鼠（8 - 29%）中均诱导后肢肌肉显著萎缩，但只有成年大鼠在重新加载后表现出肌肉质量和力量的完全恢复。重新加载后，总RNA和蛋白质合成增加到成人和老年肌肉相似的程度。然而，在基线和重新加载后，蛋白酶体介导的降解被抑制，导致泛素标记的蛋白质和p62的积累。此外，ER应激，如通过CHOP表达所测量的，在老年大鼠中在基线和再负荷时升高。mRNA表达分析显示，HDAC4，Runx1，肌生成素，Gadd45a和AChRs在老年大鼠中增加，表明神经肌肉接头不稳定/去神经支配。总的来说，我们的数据表明，随着年龄的增长，受损的神经肌肉传递和蛋白质稳态网络的缺陷有助于肌纤维重塑和肌肉质量和力量的功能恢复的缺陷。
Age-related loss of muscle mass and strength can be accelerated by impaired recovery of muscle mass following a transient atrophic stimulus. The aim of this study was to identify the mechanisms underlying the attenuated recovery of muscle mass and strength in old rats following disuse-induced atrophy. Adult (9 month) and old (29 month) male F344BN rats underwent hindlimb unloading (HU) followed by reloading. HU induced significant atrophy of the hindlimb muscles in both adult (17-38%) and old (8-29%) rats, but only the adult rats exhibited full recovery of muscle mass and strength upon reloading. Upon reloading, total RNA and protein synthesis increased to a similar extent in adult and old muscles. At baseline and upon reloading, however, proteasome-mediated degradation was suppressed leading to an accumulation of ubiquitin-tagged proteins and p62. Further, ER stress, as measured by CHOP expression, was elevated at baseline and upon reloading in old rats. Analysis of mRNA expression revealed increases in HDAC4, Runx1, myogenin, Gadd45a, and the AChRs in old rats, suggesting neuromuscular junction instability/denervation. Collectively, our data suggests that with aging, impaired neuromuscular transmission and deficits in the proteostasis network contribute to defects in muscle fiber remodeling and functional recovery of muscle mass and strength.