hif-1;skn-1

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Genetic mutants with hif-1, skn-1 alterations

Names of genes are ordered alphabetically. For the order of interventions, please see the specific paper.

Temperature °C
20
Lifespan (days)
14.8
Lifespan change (compared to wild type)
-26.00%
Phenotype
The hif-1 (ia04) deletion mutation did not extend the lifespan of skn-1(zu67) animals. These data suggest that hif-1 loss-of-function mutations extend life span via a mechanism that requires daf-16 and skn-1 function.
Lifespan comparisons
Double mutant hif-1(ia04);skn-1(zu67) has a lifespan of 14.8 days, while single mutant skn-1(zu67) has a lifespan of 15.4 days, single mutant hif-1(ia04) has a lifespan of 24.1 days and wild type has a lifespan of 20.0 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Zhang Y et al., 2009, The HIF-1 hypoxia-inducible factor modulates lifespan in C. elegans. PLoS One. 4(7):e6348 19633713 Click here to select all mutants from this PubMed ID in the graph
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 over-expression and of hif-1 loss-of-function mutations 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 lifespan. 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. elegans and advance our understanding of the regulatory networks that link oxygen homeostasis and aging.

Search genes: hif-1 skn-1

Entrez ID
Symbol
GenAge
Wormbase ID

180359
hif-1
View on GenAge (hif-1)
WBGene00001851

HIF (Hypoxia Inducible Factor) homologa;Hypoxia-inducible factor 1

Locus: CELE_F38A6.3

Wormbase description: hif-1 encodes an ortholog of the mammalian hypoxia-induced factor HIF-1, and is required for survival in hypoxic environments (1% oxygen) that have no effect on wild-type C. elegans.

Entrez ID
Symbol
GenAge
Wormbase ID

177343
skn-1
View on GenAge (skn-1)
WBGene00004804

Protein skinhead-1;SKiNhead

Locus: CELE_T19E7.2

Wormbase description: skn-1 encodes a bZip transcription factor orthologous to the mammalian Nrf (Nuclear factor-erythroid-related factor) transcription factors; during early embryogenesis, maternally provided SKN-1 is required for specification of the EMS blastomere, a mesendodermal precursor that gives rise to pharyngeal, muscle, and intestinal cells; later, during postembryonic development, SKN-1 functions in the p38 MAPK pathway to regulate the oxidative stress response and in parallel to DAF-16/FOXO in the DAF-2-mediated insulin/IGF-1-like signaling pathway to regulate adult lifespan; in vitro assays indicate that SKN-1 can be directly phosphorylated by the AKT-1, AKT-2, and SGK-1 kinases that lie downstream of DAF-2 in the insulin signaling pathway and in vivo experiments suggest that this phosphorylation is essential for regulation of SKN-1 nuclear accumulation and hence, transcriptional regulator activity; in the early embryo, SKN-1 is detected at highest levels in nuclei of the P1 blastomere and its descendants through the 8-cell stage of embryogenesis; later in embryogenesis, SKN-1 is observed in all hypodermal and intestinal nuclei, with reporter constructs indicating that intestinal expression begins as early as the 50-100-cell stage; in larvae and young adults, SKN-1::GFP reporters are expressed in the intestine and ASI neurons, with expression in intestinal nuclei enhanced under conditions of stress or reduced DAF-2 signaling.

Orthologs of hif-1;skn-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Epas1;Nfe2
Mus musculus	Epas1;Nfe2l2
Mus musculus	Epas1;Nfe2l1
Mus musculus	Hif3a;Nfe2
Mus musculus	Hif3a;Nfe2l2
Mus musculus	Hif3a;Nfe2l1
Mus musculus	Hif1a;Nfe2
Mus musculus	Hif1a;Nfe2l2
Mus musculus	Hif1a;Nfe2l1
Mus musculus	Nfe2;Epas1
Mus musculus	Nfe2;Hif3a
Mus musculus	Nfe2;Hif1a
Mus musculus	Nfe2l2;Epas1
Mus musculus	Nfe2l2;Hif3a
Mus musculus	Nfe2l2;Hif1a
Mus musculus	Nfe2l1;Epas1
Mus musculus	Nfe2l1;Hif3a
Mus musculus	Nfe2l1;Hif1a

Orthologs of hif-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Clk
Mus musculus	Epas1
Mus musculus	Hif3a
Mus musculus	Hif1a

Orthologs of skn-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Nfe2
Mus musculus	Nfe2l2
Mus musculus	Nfe2l1