Dill R P, Chadan S G, Li C, Parkhouse W S
School of Kinesiology, Metabolic Biochemistry Laboratory, Simon Fraser University, Burnaby, V5A 1S6, British Columbia, Canada.
Mech Ageing Dev. 2001 May 15;122(6):533-45. doi: 10.1016/s0047-6374(01)00216-0.
In order to gain a better understanding of tissue plasticity with aging, we investigated the adaptive responses of young and adult animals to both 7 and 28 days of hypobaric hypoxia. Senescence is associated with a decreased tolerance to hypoxia that may be related to an age-associated decline in glucose transporter system plasticity. In addition, elucidation of the factors contributing to the decreased hypoxia tolerance with aging may provide insights into ischemia for older individuals. Following 7 days of hypobaric hypoxia, soleus and plantaris muscle Glut-4 contents were increased 23-45% with a greater increase in the soleus muscle for both ages. A parallel decline in insulin receptor content was observed in both the young (soleus 56%; plantaris 74%) and adult (soleus 26%; plantaris 37%) animals over 7 days. Similar responses were observed in cardiac muscle over 7 days, with increases in content for both Glut-4 (young 25%; adult 23%) and Glut-1 (young 33%; adult 44%) and a decline in insulin receptor (young 27%; adult 15%). Following 28 days of hypobaric hypoxia, adult soleus, and both age groups plantaris muscle Glut-4 and insulin receptor contents were similar to control. However, the young soleus muscle Glut-4 and insulin receptor contents were still significantly different from control but only altered about half as much as following 7 days of exposure to hypobaric hypoxia. In contrast to what was observed for skeletal muscle, cardiac Glut-4 content was further elevated in both young (33%) and adult (44%) animals with longer exposure to hypobaric hypoxia. The young animals also showed a further decrease in heart insulin receptor content, while the adult did not. Interestingly, cardiac Glut-1 levels returned to normal values for both young and adult animals with prolonged exposure. An adaptive coregulation of Glut-4 and insulin receptor content appears to optimize the use of glucose during chronic hypobaric hypoxia within these tissues. Differences are apparent in the magnitude and time course of the response between young and adult animals.
为了更好地理解衰老过程中的组织可塑性，我们研究了幼年和成年动物对7天和28天低压缺氧的适应性反应。衰老与对缺氧的耐受性降低有关，这可能与年龄相关的葡萄糖转运体系统可塑性下降有关。此外，阐明导致衰老时缺氧耐受性降低的因素可能为老年个体的缺血问题提供见解。低压缺氧7天后，比目鱼肌和跖肌的Glut-4含量增加了23%-45%，两个年龄段的比目鱼肌增加幅度更大。在7天内，幼年（比目鱼肌56%；跖肌74%）和成年（比目鱼肌26%；跖肌37%）动物的胰岛素受体含量均出现平行下降。在7天内，心肌也观察到类似反应，Glut-4（幼年25%；成年23%）和Glut-1（幼年33%；成年44%）含量增加，胰岛素受体下降（幼年27%；成年15%）。低压缺氧28天后，成年比目鱼肌以及两个年龄组的跖肌Glut-4和胰岛素受体含量与对照组相似。然而，幼年比目鱼肌的Glut-4和胰岛素受体含量仍与对照组有显著差异，但仅比暴露于低压缺氧7天后的变化幅度小约一半。与骨骼肌不同，长期暴露于低压缺氧后，幼年（33%）和成年（44%）动物的心脏Glut-4含量进一步升高。幼年动物的心脏胰岛素受体含量也进一步下降，而成年动物则没有。有趣的是，随着暴露时间延长，幼年和成年动物的心脏Glut-1水平均恢复到正常水平。在这些组织的慢性低压缺氧过程中，Glut-4和胰岛素受体含量的适应性共同调节似乎优化了葡萄糖的利用。幼年和成年动物在反应的幅度和时间进程上存在明显差异。
