The effect of age and calorie restriction on HIF-1-responsive genes in aged liver
The effect of age and calorie restriction on HIF-1-responsive genes in aged liver
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DOI：
10.1007/s10522-004-7381-z
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发表时间：
2005-01-01
期刊：
影响因子：
4.5
通讯作者：
Chung, HY
中科院分区：
文献类型：
--
作者：
Kang, MJ;Kim, HJ;Chung, HY
低氧诱导因子-1(HIF-1)调节多种基因在低氧条件下的反式激活。我们探讨了衰老过程中肝脏HIF-1应答基因的调控以及幼年和老年大鼠肝脏HIF-1相关基因活化的增龄性变化。结果表明，衰老过程诱导了HIF-1α的激活，并伴随着HIF-1 DNA结合的增加。这种结合活性的增加伴随着HIF-1依赖基因的增加，这些基因包括血红素加氧酶-1(HO-1)、血管内皮生长因子(VEGF)、促红细胞生成素(EPO)和诱导型一氧化氮合酶(INOS)，它们在衰老过程中都表现出显著的上调。相反，限制热量摄入可有效抑制老年大鼠肝脏HIF-1相关基因表达的增加。我们认为，与年龄相关的HIF-1结合活性可能很好地受到老年动物增加的促氧化条件的影响，这上调了HIF-1依赖的基因表达。
Hypoxia inducible factor-1 (HIF-1) regulates transactivation of several genes in response to hypoxia condition. We explore hepatic HIF-1 responsive gene regulation during aging and the age-related changes of the HIF-1 related gene activation in young and old rats. Results indicate that the aging process induces the activation of HIF-1 alpha, which is accompanied by increased HIF-1 DNA binding. This increased binding activity is accompanied by the increase of HIF-1-dependent genes, heme oxygenase-1 (HO-1), vascular endothelial growth factor (VEGF), erythropoietin (EPO), and inducible nitric oxide synthase (iNOS), which all showed remarkable up-regulation during aging process. In contrast, the increased HIF-1 related gene expression was effectively blunted by the anti-oxidative action of calorie restriction in aged rat liver. We propose that age-related HIF-1 binding activity may well be influenced by the increased pro-oxidative conditions of aged animals, which up-regulate HIF-1-dependent gene expression.