Department of Kinesiology, The University of Texas, 1 University Station D3700, Austin, TX 78712, USA.
Exp Gerontol. 2011 Apr;46(4):265-72. doi: 10.1016/j.exger.2010.11.002. Epub 2010 Nov 18.
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 2h 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 day 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 that 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.
随着年龄的增长，骨骼肌的质量、功能和再生能力逐渐下降。此前，我们实验室曾报道过，在止血带（TK）诱导的骨骼肌缺血/再灌注（I/R）后，IGF-I 基因的表达会随着年龄的增长而减少，恢复和局部诱导也会减少。在这项研究中，年轻（6 个月）和年老（24-28 个月）的小鼠接受了 2 小时的 TK 诱导的后肢缺血，然后再进行 1、3、5 或 7 天的再灌注。实时 PCR 分析显示，IGF-I 及其个体 IGF-I Ea 和 Eb 剪接变体的表达存在明显的年龄相关减少和时间改变。ELISA 验证了从 TK 恢复 7 天后，IGF-I 肽的减少与年龄有关。Western blot 显示，衰老小鼠肌肉中的 Akt、mTOR 和 FoxO3 的磷酸化，所有这些都是合成代谢活性的指标，都减少了。这些数据表明，损伤后确实存在 IGF-I 表达和细胞内信号的年龄相关性损伤，并且可能在骨骼肌随年龄恢复受损中起作用。
