Impairment of IGF-I expression and anabolic signaling following ischemia/reperfusion in skeletal muscle of old mice.

Impairment of IGF-I expression and anabolic signaling following ischemia/reperfusion in skeletal muscle of old mice.
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DOI:
10.1016/j.exger.2010.11.002
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发表时间:
2011-04
影响因子:
3.9
通讯作者:
Farrar, Roger P.
Farrar, Roger P.
中科院分区:
医学2区
文献类型:
--
作者:
Hammers, David W.;Matheny, Ronald W., Jr.;Sell, Christian;Adamo, Martin L.;Walters, Thomas J.;Estep, J. Scot;Farrar, Roger P.

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随着年龄的增长,骨骼肌的质量、功能和再生能力逐渐下降。以前,我们的实验室已经报道了止血带(TK)诱导的骨骼肌缺血/再灌注(I/R)后IGF-I基因的恢复和局部诱导表达随年龄的降低。在这项研究中,年轻(6个月)和老年(24-28个月)小鼠接受TK诱导的后肢缺血2小时,然后再灌注1、3、5或7天。实时荧光定量聚合酶链式反应分析显示,IGF-I和单个IGF-I EA和EB剪接变异体的表达随着年龄的增加而明显减少和时间上的变化。酶联免疫吸附试验证实,在TK恢复后7天,IGF-I肽随年龄的增加而降低。Western blotting显示,在老年小鼠的肌肉中,Akt、mTOR和FOX03的磷酸化程度都降低了,这三个指标都是合成代谢活性的指标。这些数据表明,损伤后确实存在与年龄相关的IGF-I表达和细胞内信号转导受损,并可能在骨骼肌随年龄增长而受损的恢复中发挥作用。
With the advancement of age, skeletal muscle undergoes a progressive decline in mass, function, and regenerative capacity. Previously, our laboratory has reported an age-reduction in recovery and local induction of IGF-I gene expression with age following tourniquet (TK)-induced skeletal muscle ischemia/reperfusion (I/R). In this study, young (6 mo) and old (24–28 mo) mice were subjected to 2 hours of TK-induced ischemia of the hindlimb followed by 1, 3, 5, or 7 days of reperfusion. Real time-PCR analysis revealed clear age-related reductions and temporal alterations in the expression of IGF-I and individual IGF-I Ea and Eb splice variants. ELISA verified a reduction of IGF-I peptide with age following 7 days recovery from TK. Western blotting showed that the phosphorylation of Akt, mTOR, and FoxO3, all indicators of anabolic activity, were reduced in the muscles of old mice. These data indicate an age-related impairment of IGF-I expression and intracellular signaling does exist following injury, and potentially has a role in the impaired recovery of skeletal muscle with age.
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