The Genetics of Hypoxia

Recent work has shown that stabilization of the nematode hypoxia inducible factor protein (HIF-1) extends longevity in Caenorhabditis elegans.  However, stabilization of mammalian HIF-1α has been implicated in tumor growth and cancer development.  For the hypoxic response to benefit mammalian aging, we must determine the components of the response that contribute to longevity and separate them from those that cause harms in mammals.  We have recently published a paper focused on activating the hypoxic response by subjecting adult worms to a low oxygen environment.  We found that growth in hypoxia increases longevity in wild-type worms, but not in animals lacking HIF-1 or FOXO-family transcription factor DAF-16, and shortens lifespan in combination with overexpression of transcription factor SKN-1.  Hypoxia extends lifespan variably in combination with mutations to other longevity factors and in dietary restricted animals.  Collectively, our results show that hypoxia modulates longevity in a complex manner, likely involving components in addition to stimulating HIF-1.

People: Scott Leiser, Marissa Fletcher, Ani Begun