The effect of age and calorie restriction on HIF-1-responsive genes in aged liver

• DOI: 10.1007/s10522-004-7381-z
• Publication Date: 2005-04-14T19:33:51Z
• Authors: Min Ju Kang; Hyon Jeen Kim; Hyung Keun Kim; Ji Young Lee; Dae Hyun Kim; Kyung Jin Jung; Kyu Won Kim; Hyung Suck Baik; Mie Ae Yoo; Byung Pal Yu; Hae Young Chung
• Keywords: Calorie Restriction; Senescence; Hypoxia; Hypoxia-Inducible Factors

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.