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• W1531012008 abstract "During normal development or during disease, animal cells experience hypoxic (low oxygen) conditions, and the hypoxia-inducible factor (HIF) transcription factors implement most of the critical changes in gene expression that enable animals to adapt to this stress. Here, we examine the roles of HIF-1 in post-mitotic aging. We examined the effects of hif-1 loss-of-function mutations and of HIF-1 over-expression on longevity in C. elegans, a powerful genetic system in which adult somatic cells are post-mitotic. We constructed transgenic lines that expressed varying levels of HIF-1 protein and discovered a positive correlation between HIF-1 expression levels and longevity. The data further showed that HIF-1 acted in parallel to the SKN-1/ NRF and DAF-16/ FOXO transcription factors to promote longevity. HIF-1 over-expression also conferred increased resistance to heat and oxidative stress. We isolated and characterized additional hif-1 mutations, and we found that each of 3 loss-of-function mutations conferred increased longevity in normal lab culture conditions, but, unlike HIF-1 over-expression, a hif-1 deletion mutation did not extend the lifespan of daf-16 or skn-1 mutants. We conclude that HIF-1 over-expression and hif-1 loss-of-function mutations promote longevity by different pathways. These data establish HIF-1 as one of the key stress-responsive transcription factors that modulate longevity in C." @default.
• W1531012008 created "2016-06-24" @default.
• W1531012008 creator A5044544424 @default.
• W1531012008 date "2018-08-10" @default.
• W1531012008 modified "2023-09-27" @default.
• W1531012008 title "Hypoxia-inducible regulatory networks and their roles in aging in C. elegans" @default.
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