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

最近有报道称，Akt/mTOR/p70^<S6K>/S6和钙调神经磷酸酶（CaN）都被认为在骨骼肌细胞内信号整合中发挥重要作用，以应对不使用和增加的肌肉负荷。这些实验研究了Akt/mTOR/p70^<S6K>/S6和CaN下游通路在固定运动诱导的肌肉萎缩后恢复期间信号转导的年龄相关差异。将幼龄（10周）、成年（1岁）和老年（2岁）的单腿后肢肌肉用石膏固定于足底屈曲位10天。取石膏模后0、7、15天，同时取萎缩跖肌和对侧跖肌。所有实验动物均出现明显的肌肉萎缩。在10天的恢复期后，幼龄动物的肌肉质量恢复了-90%，而成年和老年动物则没有。幼龄大鼠萎缩肌肉中磷酸化akt、磷酸化mtor和磷酸化p70^<S6K>的表达在各恢复期均显著高于对照组，且在恢复期第15天变化最大，而在成年和老年大鼠中则无明显变化。在恢复7天和15天后，年轻大鼠的肌肉磷酸化56水平更高。在成年大鼠中观察到类似的趋势，但在老年大鼠中没有。各恢复期及实验组萎缩肌肉中磷酸化- eif4e和钙调磷酸酶的表达均无变化。在恢复7天和15天后，年轻大鼠肌肉中磷酸化的eIF4G水平较高，但在成年和老年大鼠中则没有。这些结果表明，在萎缩的植物肌肉恢复过程中，参与蛋白质合成的Akt/mTOR信号通路的激活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.