Age-related differences in signal transduction during recovery in atrophied plantaris muscle induced by immobilization

最近有报道认为Akt/mTor/p70；S6K&gt；/S6和钙调神经磷酸酶(Calcineurin，CaN)在骨骼肌细胞内信号整合中发挥重要作用，以应对停用和增加肌肉负荷。这些实验研究了在制动诱导的肌肉萎缩后的恢复期，Akt/mTor/p70^&lt；S6K&gt；/S6和CaN下游信号转导通路的年龄相关差异。分别于青年(10周)、成年(1岁)、老年(2岁)一侧小腿后肢，采用石膏石膏固定足底屈位，固定10d。石膏摘除后第0、7和15天，萎缩的足底肌肉和对侧足底肌肉均被摘除，所有实验动物均出现明显的肌肉萎缩。经过10天的恢复期，幼年动物的肌肉质量恢复到-90%，而成年和老年动物则没有恢复。幼年大鼠萎缩肌肉中磷酸化Akt、磷酸化mTOR和磷酸化p70、S6K、GT的表达在各个恢复期均显著高于对照组，以恢复期第15天的变化最大，而成年和老年动物的变化不明显。在恢复7天和15天后，幼鼠肌肉中磷酸化的56的水平更高。在成年大鼠中也观察到了类似的趋势，但在老年大鼠中则没有。在恢复期和实验组萎缩的肌肉中，磷酸化eIF4E和钙调神经磷酸酶的表达均无变化。恢复7天和15天后，年轻大鼠肌肉中磷酸化eIF4G的水平较高，但成年和老年大鼠则没有。这些结果表明，在萎缩的足底肌肉中，参与蛋白质合成的Akt/mTOR信号通路的激活程度随年龄的不同而不同。

It has been recently reported that Akt/mTOR/p70^<S6K>/S6 and calcineurin (CaN) are both postulated to play important roles in integrating intracellular signaling in skeletal muscle in response to both disuse and increased muscle loading. These experiments investigated the age-related differences in signal transduction of the downstream pathways of both Akt/mTOR/p70^<S6K>/S6 and CaN during a period of recovery following immobilization-induced muscle atrophy. The hindlimb muscles of one leg in young (10 weeks), adult (1 year) and old (2 years) were immobilized in plantar flexion position using a plaster cast for 10 days. At 0,7 and-15 days after the removal of plaster cast, both the atrophic and the contralateral plantaris muscles were removed.Immobilization resulted in significant muscle atrophy in all experimntal animals. Muscle mass in young animal recovered up to -90% following 10-days of recovery period, but not in adult and old animals. The expressions of phospho-Akt, phospho-mTOR and phospho- p70^<S6K> in atrophied muscles from young rats were significantly higher in all of recovery period compared with control muscles, with the greatest changes seen in recovery day 15, but not in adult and old animals. Muscle levels of phosphorylated 56 in young rats were higher following 7-and 15 days of recovery. A similar tendency was observed in adult rats, but not in old rats. The expressions of phospho-eIF4E and calcineurin in atrophied muscles were unchanged in all of recovery period and experimental groups. Muscle levels of phosphorylated eIF4G in young rats were higher following 7-and 15 days of recovery, but not in adult and old rats. These results show that the activation of Akt/mTOR signaling pathways involved in the protein synthesis during recovery in atrophied plantaris muscle differ with age.