Liver regeneration and aging: a current perspective.
Liver regeneration and aging: a current perspective.
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DOI：
10.1155/2011/526379
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发表时间：
2011
影响因子：
--
通讯作者：
Sanchez H
中科院分区：
文献类型：
--
作者：
Schmucker DL;Sanchez H
许多器官系统都表现出明显的与年龄相关的缺陷，但是，根据对老年啮齿动物和老年人的研究，肝脏似乎相对来说没有受到这种变化的影响。肝脏的一个显著特征是其在部分肝切除术后再生肿块的能力。报告显示，衰老损害了肝脏的再生能力，无论是在速度上还是在器官原始体积恢复的程度上。关于调节肝脏再生的细胞和分子机制受衰老影响，目前还没有明确的信息。肝脏对生长因子（例如表皮生长因子（EGF））敏感性的变化似乎会影响老年动物的再生。研究表明：(a) EGF与肝细胞膜的结合减少60%，(b)肝脏高亲和力EGF受体的表达减少，(c) EGF刺激后老龄大鼠细胞周期的G1期和s期之间出现阻滞。最近的研究表明，EGF受体磷酸化和二聚化的减少，细胞外信号调节激酶途径激活和随后的细胞增殖的关键步骤是负责的。其他研究表明，衰老会影响叉头盒转录因子FoxM1B的上调，FoxM1B对于生长激素刺激的肝切除小鼠的肝脏再生至关重要。衰老似乎通过影响几种途径来损害肝脏再生，其结果是再生速度降低，但器官恢复到原来体积的能力却没有下降。
Many organ systems exhibit significant age-related deficits, but, based on studies in old rodents and elderly humans, the liver appears to be relatively protected from such changes. A remarkable feature of the liver is its capacity to regenerate its mass following partial hepatectomy. Reports suggests that aging compromises the liver's regenerative capacity, both in the rate and to the extent the organ's original volume is restored. There has been modest definitive information as to which cellular and molecular mechanisms regulating hepatic regeneration are affected by aging. Changes in hepatic sensitivity to growth factors, for example, epidermal growth factor (EGF), appear to influence regeneration in old animals. Studies have demonstrated (a) a 60% decline in EGF binding to hepatocyte plasma membranes, (b) reduced expression of the hepatic high affinity EGF receptor and (c) a block between G1 and S-phases of the cell cycle in old rats following EGF stimulation. Recent studies suggest that reduced phosphorylation and dimerization of the EGF receptor, critical steps in the activation of the extracellular signal-regulated kinase pathway and subsequent cell proliferation are responsible. Other studies have demonstrated that aging affects the upregulation of a Forkhead Box transcription factor, FoxM1B, which is essential for growth hormone-stimulated liver regeneration in hepatectomized mice. Aging appears to compromise liver regeneration by influencing several pathways, the result of which is a reduction in the rate of regeneration, but not in the capacity to restore the organ to its original volume.