Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Premature senescence in vitro has been attributed to oxidative stress leading to a DNA damage response. In the absence of oxidative damage that occurs at atmospheric oxygen levels, proliferation of untransformed cells continues for extended periods of time. We have investigated the role of the hypoxia-inducible factor 1alpha (HIF1alpha) transcription factor in preventing senescence in aerobic and hypoxic conditions. Using embryonic fibroblasts from a conditional HIF1alpha knockout mouse, we found that loss of HIF1alpha under aerobic conditions significantly accelerated the onset of cellular senescence, and decreased proliferation under hypoxia. Furthermore, we identify the macrophage migration inhibitory factor (MIF) as a crucial effector of HIF1alpha that delays senescence. Inhibition of MIF phenocopies loss of HIF1alpha. Our findings highlight a novel role for HIF1alpha under aerobic conditions, and identify MIF as a target responsible for this function.

Original publication

DOI

10.1101/gad.1471106

Type

Journal article

Journal

Genes Dev

Publication Date

15/12/2006

Volume

20

Pages

3366 - 3371

Keywords

Aerobiosis, Animals, Cell Hypoxia, Cellular Senescence, Fibroblasts, Gamma Rays, Gene Expression Regulation, Hypoxia-Inducible Factor 1, alpha Subunit, Intramolecular Oxidoreductases, Macrophage Migration-Inhibitory Factors, Mice, Mice, Knockout, Transcription, Genetic