rheb-1;skn-1

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Genetic mutants with rheb-1, skn-1 alterations

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

Temperature °C
20
Diet
NGM
Lifespan (days)
19.45
Lifespan change (compared to wild type)
-17.83%
Phenotype
Knockdown of TORC1 pathway gene (rheb-1) failed to increase lifespan in a skn-1 mutant.
Lifespan comparisons
Double mutant rheb-1(RNAi);skn-1(zu67) has a lifespan of 19.45 days, while single mutant rheb-1(RNAi) has a lifespan of 28.51 days, single mutant skn-1(zu67) has a lifespan of 18.96 days and wild type has a lifespan of 23.67 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Robida-Stubbs S et al., 2012, TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO. Cell Metab. 15(5):713-24 22560223 Click here to select all mutants from this PubMed ID in the graph
Abstract
The TOR kinase, which is present in the functionally distinct complexes TORC1 and TORC2, is essential for growth but associated with disease and aging. Elucidation of how TOR influences life span will identify mechanisms of fundamental importance in aging and TOR functions. Here we show that when TORC1 is inhibited genetically in C. elegans, SKN-1/Nrf, and DAF-16/FoxO activate protective genes, and increase stress resistance and longevity. SKN-1 also upregulates TORC1 pathway gene expression in a feedback loop. Rapamycin triggers a similar protective response in C. elegans and mice, but increases worm life span dependent upon SKN-1 and not DAF-16, apparently by interfering with TORC2 along with TORC1. TORC1, TORC2, and insulin/IGF-1-like signaling regulate SKN-1 activity through different mechanisms. We conclude that modulation of SKN-1/Nrf and DAF-16/FoxO may be generally important in the effects of TOR signaling in vivo and that these transcription factors mediate an opposing relationship between growth signals and longevity.

Temperature °C
20
Diet
NGM
Lifespan (days)
20.21
Lifespan change (compared to wild type)
-12.44%
Phenotype
Knockdown of TORC1 pathway gene (rheb-1) failed to increase lifespan in a skn-1 mutant.
Lifespan comparisons
Double mutant rheb-1(RNAi);skn-1(zu67) has a lifespan of 20.21 days, while single mutant rheb-1(RNAi) has a lifespan of 27.22 days, single mutant skn-1(zu67) has a lifespan of 17.71 days and wild type has a lifespan of 23.08 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Robida-Stubbs S et al., 2012, TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO. Cell Metab. 15(5):713-24 22560223 Click here to select all mutants from this PubMed ID in the graph
Abstract
The TOR kinase, which is present in the functionally distinct complexes TORC1 and TORC2, is essential for growth but associated with disease and aging. Elucidation of how TOR influences life span will identify mechanisms of fundamental importance in aging and TOR functions. Here we show that when TORC1 is inhibited genetically in C. elegans, SKN-1/Nrf, and DAF-16/FoxO activate protective genes, and increase stress resistance and longevity. SKN-1 also upregulates TORC1 pathway gene expression in a feedback loop. Rapamycin triggers a similar protective response in C. elegans and mice, but increases worm life span dependent upon SKN-1 and not DAF-16, apparently by interfering with TORC2 along with TORC1. TORC1, TORC2, and insulin/IGF-1-like signaling regulate SKN-1 activity through different mechanisms. We conclude that modulation of SKN-1/Nrf and DAF-16/FoxO may be generally important in the effects of TOR signaling in vivo and that these transcription factors mediate an opposing relationship between growth signals and longevity.

Temperature °C
20
Diet
NGM
Lifespan (days)
19.56
Lifespan change (compared to wild type)
-21.03%
Phenotype
Knockdown of TORC1 pathway gene (rheb-1) failed to increase lifespan in a skn-1 mutant.
Lifespan comparisons
Double mutant rheb-1(RNAi);skn-1(zu67) has a lifespan of 19.56 days, while single mutant rheb-1(RNAi) has a lifespan of 29.6 days, single mutant skn-1(zu67) has a lifespan of 20.11 days and wild type has a lifespan of 24.77 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Robida-Stubbs S et al., 2012, TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO. Cell Metab. 15(5):713-24 22560223 Click here to select all mutants from this PubMed ID in the graph
Abstract
The TOR kinase, which is present in the functionally distinct complexes TORC1 and TORC2, is essential for growth but associated with disease and aging. Elucidation of how TOR influences life span will identify mechanisms of fundamental importance in aging and TOR functions. Here we show that when TORC1 is inhibited genetically in C. elegans, SKN-1/Nrf, and DAF-16/FoxO activate protective genes, and increase stress resistance and longevity. SKN-1 also upregulates TORC1 pathway gene expression in a feedback loop. Rapamycin triggers a similar protective response in C. elegans and mice, but increases worm life span dependent upon SKN-1 and not DAF-16, apparently by interfering with TORC2 along with TORC1. TORC1, TORC2, and insulin/IGF-1-like signaling regulate SKN-1 activity through different mechanisms. We conclude that modulation of SKN-1/Nrf and DAF-16/FoxO may be generally important in the effects of TOR signaling in vivo and that these transcription factors mediate an opposing relationship between growth signals and longevity.

Search genes: rheb-1 skn-1

Entrez ID
Symbol
GenAge
Wormbase ID

176327
rheb-1
View on GenAge (rheb-1)
WBGene00010038

GTP-binding protein Rheb homolog 1

Locus: CELE_F54C8.5

Wormbase description: rheb-1 encodes a GTPase orthologous to the mammalian Rheb and Rheb1 GTPases; by homology, RHEB-1 is predicted to function as a regulator of LET_363/TOR function; in C. elegans, rheb-1 plays an essential role in mediating intermittent fasting (IF)-induced longevity; further, loss of rheb-1 activity via RNAi indicates that rheb-1 is involved in the mitochondrial unfolded protein response and that its function is required for normal growth rates, body size, osmoregulation, reproduction, and locomotion.

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 rheb-1;skn-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Nfe2;Rheb
Mus musculus	Nfe2l2;Rheb
Mus musculus	Nfe2l1;Rheb
Mus musculus	Nfe2;Rhebl1
Mus musculus	Nfe2l2;Rhebl1
Mus musculus	Nfe2l1;Rhebl1

Orthologs of rheb-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Rheb
Mus musculus	Rheb
Mus musculus	Rhebl1

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