Inhibition of elongin C promotes longevity and protein homeostasis via HIF-1 in C. elegans.

The transcription factor hypoxia-inducible factor 1 (HIF-1) is crucial for responses to low oxygen and promotes longevity in Caenorhabditis elegans. We previously performed a genomewide RNA interference screen and identified many genes that act as potential negative regulators of HIF-1. Here, we functionally characterized these genes and found several novel genes that affected lifespan. The worm ortholog of elongin C, elc-1, encodes a subunit of E3 ligase and transcription elongation factor. We found that knockdown of elc-1 prolonged lifespan and delayed paralysis caused by impaired protein homeostasis. We further showed that elc-1 RNA interference increased lifespan and protein homeostasis by upregulating HIF-1. The roles of elongin C and HIF-1 are well conserved in eukaryotes. Thus, our study may provide insights into the aging regulatory pathway consisting of elongin C and HIF-1 in complex metazoans. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Citation

Wooseon Hwang, Murat Artan, Mihwa Seo, Dongyeop Lee, Hong Gil Nam, Seung-Jae V Lee. Inhibition of elongin C promotes longevity and protein homeostasis via HIF-1 in C. elegans. Aging cell. 2015 Dec;14(6):995-1002

PMID: 26361075

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