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  • Title: The effect of age and calorie restriction on HIF-1-responsive genes in aged liver.
    Author: Kang MJ, Kim HJ, Kim HK, Lee JY, Kim DH, Jung KJ, Kim KW, Baik HS, Yoo MA, Yu BP, Chung HY.
    Journal: Biogerontology; 2005; 6(1):27-37. PubMed ID: 15834661.
    Abstract:
    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-1alpha, 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.
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