The function of hypoxia-inducible factor 1 (HIF-1) is impaired in senescent mice

Senescent organisms respond poorly to hypoxic stress. The transcription fac tor hypoxia-inducible factor 1 (HIF-1) plays a critical role in the coordin ated genetic program that is induced in all tissues to adapt to hypoxic str ess by binding to a specific DNA hypoxia-responsive recognition element (HR E). This study was designed to address whether aging is associated with an alteration in HIF-1 production and function. Young and old mice were expose d to hypoxia for various lengths of time. We found a severe impairment in t he capacity of the old animals to form a HIF-1-HRE complex. This attenuatio n in the capacity to form HIF-1-HRE complexes in senescent tissues may expl ain the decreased ability of such tissues to respond to hypoxic stress, (C) 1999 Federation of European Biochemical Societies.