daf-16;rheb-1

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Genetic mutants with daf-16, rheb-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)
21.01
Lifespan change (compared to wild type)
-11.24%
Phenotype
RNAi against rheb-1 gene did not increase lifespan in daf-16 mutants, in contrast to the daf-16 independent longevity associated with TOR kinase inhibition.
Lifespan comparisons
Double mutant daf-16(mgDf47);rheb-1(RNAi) has a lifespan of 21.01 days, while single mutant rheb-1(RNAi) has a lifespan of 28.51 days, single mutant daf-16(mgDf47) has a lifespan of 20.61 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)
20.14
Lifespan change (compared to wild type)
-12.74%
Phenotype
RNAi against rheb-1 gene did not increase lifespan in daf-16 mutants, in contrast to the daf-16 independent longevity associated with TOR kinase inhibition.
Lifespan comparisons
Double mutant daf-16(mgDf47);rheb-1(RNAi) has a lifespan of 20.14 days, while single mutant rheb-1(RNAi) has a lifespan of 27.22 days, single mutant daf-16(mgDf47) has a lifespan of 19.15 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)
20.09
Lifespan change (compared to wild type)
-12.16%
Phenotype
RNAi against rheb-1 gene did not increase lifespan in daf-16 mutants, in contrast to the daf-16 independent longevity associated with TOR kinase inhibition.
Lifespan comparisons
Double mutant daf-16(mgDf47);rheb-1(RNAi) has a lifespan of 20.09 days, while single mutant rheb-1(RNAi) has a lifespan of 28.62 days, single mutant daf-16(mgDf47) has a lifespan of 19.7 days and wild type has a lifespan of 22.87 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)
21.69
Lifespan change (compared to wild type)
-12.43%
Phenotype
RNAi against rheb-1 gene did not increase lifespan in daf-16 mutants, in contrast to the daf-16 independent longevity associated with TOR kinase inhibition.
Lifespan comparisons
Double mutant daf-16(mgDf47);rheb-1(RNAi) has a lifespan of 21.69 days, while single mutant rheb-1(RNAi) has a lifespan of 29.6 days, single mutant daf-16(mgDf47) has a lifespan of 22.09 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: daf-16 rheb-1

Entrez ID
Symbol
GenAge
Wormbase ID

172981
daf-16
View on GenAge (daf-16)
WBGene00000912

Forkhead box protein O;hypothetical protein

Locus: CELE_R13H8.1

Wormbase description: daf-16 encodes the sole C. elegans forkhead box O (FOXO) homologue; DAF-16 functions as a transcription factor that acts in the insulin/IGF-1-mediated signaling (IIS) pathway that regulates dauer formation, longevity, fat metabolism, stress response, and innate immunity; DAF-16 regulates these various processes through isoform-specific expression, isoform-specific regulation by different AKT kinases, and differential regulation of target genes; DAF-16 can interact with the CBP-1 transcription cofactor in vitro, and interacts genetically with other genes in the insulin signaling and with daf-12, which encodes a nuclear hormone receptor; DAF-16 is activated in response to DNA damage during development and co-regulated by EGL-27, alleviates DNA-damage-induced developmental arrest by inducing DAF-16-associated element (DAE)-regulated genes; DAF-16 is broadly expressed but displays isoform-specific tissue enrichment; DAF-16 localizes to both the cytoplasm and the nucleus, with the ratio between the two an important regulator of function.

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.

Orthologs of daf-16;rheb-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Foxo6;Rheb
Mus musculus	Foxo6;Rhebl1
Mus musculus	Foxo1;Rheb
Mus musculus	Foxo1;Rhebl1
Mus musculus	Foxo4;Rheb
Mus musculus	Foxo4;Rhebl1
Mus musculus	Foxo3;Rheb
Mus musculus	Foxo3;Rhebl1

Orthologs of daf-16 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Foxo6
Mus musculus	Foxo1
Mus musculus	Foxo4
Mus musculus	Foxo3

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