kri-1;raga-1

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Genetic mutants with kri-1, raga-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)
31.21
Lifespan change (compared to wild type)
30.26%
Phenotype
Knockdown of raga-1 extended the lifespan of kri-1 mutants, in which the GSC pathway is blocked.
Lifespan comparisons
Double mutant kri-1(ok1251);raga-1(RNAi) has a lifespan of 31.21 days, while single mutant raga-1(RNAi) has a lifespan of 30.48 days, single mutant kri-1(ok1251) has a lifespan of 23.13 days and wild type has a lifespan of 23.96 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)
31.64
Lifespan change (compared to wild type)
32.11%
Phenotype
Knockdown of raga-1 extended the lifespan of kri-1 mutants, in which the GSC pathway is blocked.
Lifespan comparisons
Double mutant kri-1(ok1251);raga-1(RNAi) has a lifespan of 31.64 days, while single mutant raga-1(RNAi) has a lifespan of 30.13 days, single mutant kri-1(ok1251) has a lifespan of 22.43 days and wild type has a lifespan of 23.95 days.
Type of interaction
See methods
Enhancer, opposite lifespan effects
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)
30.83
Lifespan change (compared to wild type)
28.67%
Phenotype
Knockdown of raga-1 extended the lifespan of kri-1 mutants, in which the GSC pathway is blocked.
Lifespan comparisons
Double mutant kri-1(ok1251);raga-1(RNAi) has a lifespan of 30.83 days, while single mutant raga-1(RNAi) has a lifespan of 30.65 days, single mutant kri-1(ok1251) has a lifespan of 23.74 days and wild type has a lifespan of 23.96 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: kri-1 raga-1

Entrez ID
Symbol
GenAge
Wormbase ID

191275
kri-1
View on GenAge (kri-1)
WBGene00013955

human KRIT 1 (Krev interaction trapped/cerebral cavernous malformation 1) homolog

Locus: CELE_ZK265.1

Wormbase description: kri-1 encodes an ankyrin repeat and FERM domain-containing protein orthologous to human KRIT1 (Krev interaction trapped/cerebral cavernous malformation 1, OMIM:604214); kri-1 was identified in RNAi screens for genes required for DAF-16-dependent lifespan extension in germline-depleted animals; subsequent analysis of kri-1 mutations suggests that KRI-1 is required for proper localization of DAF-16 in the intestine in response to germline loss; a rescuing KRI-1::GFP construct is expressed in larval and adult stages in pharyngeal and intestinal cells; the KRI-1::GFP is generally diffuse, but also localizes to apical and apicolateral cell surfaces as well as to intestinal nuclei in some animals.

Entrez ID
Symbol
GenAge
Wormbase ID

174726
raga-1
View on GenAge (raga-1)
WBGene00006414

RAs-related GTP-binding protein A

Locus: CELE_T24F1.1

Wormbase description: raga-1 encodes the C. elegans ortholog of the ras-related GTPase RagA; in C. elegans RAGA-1 functions as a modifier of behavioral aging and adult lifespan (particularly under high food concentration); raga-1 mutations also affect body size and reproduction; genetic analyses suggest that raga-1 functions in the let-363/Tor pathway to regulate behavioral aging and lifespan and also interacts with the daf-2/daf-16 insulin signaling pathway and skn-1; raga-1 reporter fusions are widely expressed in larvae, with more restricted expression (gut, head and tail neurons, somatic gonad, hypodermis) seen in adults.

Orthologs of kri-1;raga-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Krit1;Rragb
Mus musculus	Krit1;Rraga
Mus musculus	Rragb;Krit1
Mus musculus	Rraga;Krit1

Orthologs of kri-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Krit1

Orthologs of raga-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	RagA-B
Mus musculus	Rragb
Mus musculus	Rraga