skn-1;vang-1

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Genetic mutants with skn-1, vang-1 alterations

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

Temperature °C
25
Diet
OP50
Lifespan (days)
13.0
Lifespan change (compared to wild type)
27.45%
Phenotype
RNAi against skn-1 did reduce tm1422 life span significantly about 17%. Inhibition of insulin/IGF-1-like signaling in tm1422 may explain this result. Like DAF-16, SKN-1 is also repressed by DAF-2 downstream kinases, AKT-1/2 and SGK-1 and possibly acts as a key player in a positive feedback loop to extend life span.
Lifespan comparisons
Double mutant skn-1(RNAi);vang-1(tm1422) has a lifespan of 13.0 days, while single mutant skn-1(RNAi) has a lifespan of 13.0 days, single mutant vang-1(tm1422) has a lifespan of 14.3 days and wild type has a lifespan of 10.2 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Honnen SJ et al., 2012;7(2):e32183., C. elegans VANG-1 modulates life span via insulin/IGF-1-like signaling. PLoS One. 7(2):e32183 22359667 Click here to select all mutants from this PubMed ID in the graph
Abstract
The planar cell polarity (PCP) pathway is highly conserved from Drosophila to humans and a PCP-like pathway has recently been described in the nematode Caenorhabditis elegans. The developmental function of this pathway is to coordinate the orientation of cells or structures within the plane of an epithelium or to organize cell-cell intercalation required for correct morphogenesis. Here, we describe a novel role of VANG-1, the only C. elegans ortholog of the conserved PCP component Strabismus/Van Gogh. We show that two alleles of vang-1 and depletion of the protein by RNAi cause an increase of mean life span up to 40%. Consistent with the longevity phenotype vang-1 animals also show enhanced resistance to thermal- and oxidative stress and decreased lipofuscin accumulation. In addition, vang-1 mutants show defects like reduced brood size, decreased ovulation rate and prolonged reproductive span, which are also related to gerontogenes. The germline, but not the intestine or neurons, seems to be the primary site of vang-1 function. Life span extension in vang-1 mutants depends on the insulin/IGF-1-like receptor DAF-2 and DAF-16/FoxO transcription factor. RNAi against the phase II detoxification transcription factor SKN-1/Nrf2 also reduced vang-1 life span that might be explained by gradual inhibition of insulin/IGF-1-like signaling in vang-1. This is the first time that a key player of the PCP pathway is shown to be involved in the insulin/IGF-1-like signaling dependent modulation of life span in C. elegans.

Search genes: skn-1 vang-1

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.

Entrez ID
Symbol
GenAge
Wormbase ID

180579
vang-1
View on GenAge (vang-1)
WBGene00015171

Vang-like protein

Locus: CELE_B0410.2

Wormbase description: vang-1 encodes an ortholog of Drosophila STRABISMUS/VAN GOGH; vang-1 enables Wnt-directed planar cell polarity; VANG-1 is required for the fully asymmetrical division of B.a versus B.p cells, though this requirement is quantitatively weak; vang-1 also negatively regulates adult lifespan via the DAF-2/IGFR insulin signaling pathway, and also plays a role in thermal tolerance and response to oxidative stress.

Orthologs of skn-1;vang-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Nfe2;Vangl1
Mus musculus	Nfe2;Vangl2
Mus musculus	Nfe2l2;Vangl1
Mus musculus	Nfe2l2;Vangl2
Mus musculus	Nfe2l1;Vangl1
Mus musculus	Nfe2l1;Vangl2

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

Orthologs of vang-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Vang
Mus musculus	Vangl1
Mus musculus	Vangl2