The hypoxia-inducible factor HIF-1 functions as both a positive and negative modulator of aging.

In the past year and a half, five studies have independently established a direct connection between the hypoxic response transcription factor, HIF-1, and aging in Caenorhabditis elegans. These studies demonstrated that HIF-1 can both promote and limit longevity via pathways that are mechanistically distinct. Here, we review the current state of knowledge regarding modulation of aging by HIF-1 and speculate on potential aspects of HIF-1 function that could be relevant for mammalian longevity and healthspan.