Chronic resistance training activates autophagy and reduces apoptosis of muscle cells by modulating IGF-1 and its receptors, Akt/mTOR and Akt/FOXO3a signaling in aged rats
Chronic resistance training activates autophagy and reduces apoptosis of muscle cells by modulating IGF-1 and its receptors, Akt/mTOR and Akt/FOXO3a signaling in aged rats
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慢性阻力训练通过调节老年大鼠的 IGF-1 及其受体、Akt/mTOR 和 Akt/FOXO3a 信号传导激活自噬并减少肌肉细胞凋亡
DOI：
10.1016/j.exger.2013.02.009
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发表时间：
2013-04-01
影响因子：
3.9
通讯作者：
Qin, Zheng-Hong
中科院分区：
文献类型：
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作者：
Luo, Li;Lu, A-Ming;Qin, Zheng-Hong
阻力运动训练（RET）仍然是老年人肌肉质量和力量损失的最有效治疗方法。然而，潜在的细胞和分子机制还没有很好地理解。最近的证据表明，自噬信号在老年骨骼肌中改变。本研究旨在研究RET是否影响IGF-1及其受体、Akt/mTOR和Akt/FOXO 3a信号通路，并调节18-20月龄大鼠腓肠肌中的自噬和凋亡。结果显示，9周的RET防止了肌肉质量的损失并改善了肌肉力量，同时降低了LC 3-II/LC 3-I比值，降低了p62蛋白水平，并增加了自噬调节蛋白的水平，包括Beclin 1，Atg 5/12，Atg 7和溶酶体酶组织蛋白酶L。RET还降低细胞质中的细胞色素c水平，但增加其在线粒体组分中的水平，并抑制切割的半胱天冬酶3的产生和凋亡。RET可上调IGF-1及其受体的表达，下调Akt和mTOR的磷酸化水平。此外，RET上调总AMPK、磷酸化AMPK和FOXO 3a的表达。综上所述，这些结果表明，RET的益处与通过调节IGF-1及其受体、老年骨骼肌中的Akt/mTOR和Akt/FOXO 3a信号通路来增加自噬活性和减少肌细胞凋亡有关。(C)2013 Elsevier Inc. All rights reserved.
Resistance exercise training (RET) remains the most effective treatment for the loss of muscle mass and strength in elderly people. However, the underlying cellular and molecular mechanisms are not well understood. Recent evidence suggests that autophagic signaling is altered in aged skeletal muscles. This study aimed to investigate if RET affects IGF-1 and its receptors, the Akt/mTOR, and Akt/FOXO3a signaling pathways and regulates autophagy and apoptosis in the gastrocnemius muscles of 18-20 month old rats. The results showed that 9 weeks of RET prevented the loss of muscle mass and improved muscle strength, accompanied by reduced LC3-II/LC3-I ratio, reduced p62 protein levels, and increased levels of autophagy regulatory proteins, including Beclin 1, Atg5/12, Atg7, and the lysosomal enzyme cathepsin L. RET also reduced cytochrome c level in the cytosol but increased its level in mitochondrial fraction, and inhibited cleaved caspase 3 production and apoptosis. Furthermore, RET upregulated the expression of IGF-1 and its receptors but downregulated the phosphorylation of Akt and mTOR. In addition, RET upregulated the expression of total AMPK, phosphorylated AMPK, and FOXO3a. Taken together, these results suggest that the benefits of RET are associated with increased autophagy activity and reduced apoptosis of muscle cells by modulating IGF-1 and its receptors, the Akt/mTOR and Akt/FOXO3a signaling pathways in aged skeletal muscles. (C) 2013 Elsevier Inc. All rights reserved.