The function of hypoxia-inducible factor 1 (HIF-1) is impaired in senescent mice.
Senescent organisms respond poorly to hypoxic stress. The transcription factor hypoxia-inducible factor 1 (HIF-1) plays a critical role in the coordinated genetic program that is induced in all tissues to adapt to hypoxic stress by binding to a specific DNA hypoxia-responsive recognition element (HRE). This study was designed to address whether aging is associated with an alteration in HIF-1 production and function. Young and old mice were exposed to hypoxia for various lengths of time. We found a severe impairment in the capacity of the old animals to form a HIF-1-HRE complex. This attenuation in the capacity to form HIF-1-HRE complexes in senescent tissues may explain the decreased ability of such tissues to respond to hypoxic stress.
Frenkel-Denkberg
G
G
Department of Biology, Technion-Israel Institute of Technology, Haifa, Israel.
Gershon
D
D
Levy
A P
AP
D000375:Aging / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D000860:Hypoxia / Q000378:metabolism; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007668:Kidney / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; C497443:Hif1a protein, mouse; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors