daf-2;let-60

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Genetic mutants with daf-2, let-60 alterations

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

Temperature °C
22.5
Lifespan (days)
24.5
Lifespan change (compared to wild type)
39.20%
Phenotype
let-60(gf) enhances the daf-2longevity (Age) phenotype, while reduction of Ras signaling partially suppresses it
Lifespan comparisons
Double mutant daf-2(e1369);let-60(n1046) has a lifespan of 24.5 days, while single mutant daf-2(e1369) has a lifespan of 24.6 days and wild type has a lifespan of 17.6 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Nanji M et al., 2005, LET-60 RAS modulates effects of insulin/IGF-1 signaling on development and aging in Caenorhabditis elegans. Aging Cell. 4(5):235-45 16164423 Click here to select all mutants from this PubMed ID in the graph
Abstract
The DAF-2 insulin/insulin-like growth factor 1 (IGF-1) receptor signals via a phosphatidylinositol 3-kinase (PI3K) pathway to control dauer larva formation and adult longevity in Caenorhabditis elegans. Yet epistasis analysis suggests signal bifurcation downstream of DAF-2. We have used epistasis analysis to test whether the Ras pathway (which plays a role in signaling from mammalian insulin receptors) acts downstream of DAF-2. We find that an activated Ras mutation, let-60(n1046gf), weakly suppresses constitutive dauer diapause in daf-2 and age-1 (PI3K) mutants. Moreover, increased Ras pathway signaling partially suppresses the daf-2 mutant feeding defect, while reduced Ras pathway signaling enhances it. By contrast, activated Ras extends the longevity induced by mutation of daf-2, while reduced Ras pathway signaling partially suppresses it. Thus, Ras pathway signaling appears to act with insulin/IGF-1 signaling during larval development, but against it during aging.

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

Temperature °C
22.5
Lifespan (days)
18.0
Lifespan change (compared to wild type)
2.27%
Phenotype
let-60(gf) enhances the daf-2longevity (Age) phenotype, while reduction of Ras signaling partially suppresses it
Lifespan comparisons
Double mutant daf-2(e1370);let-60(n1046) has a lifespan of 18 days, while single mutant daf-2(e1370) has a lifespan of 18.4 days and wild type has a lifespan of 17.6 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Nanji M et al., 2005, LET-60 RAS modulates effects of insulin/IGF-1 signaling on development and aging in Caenorhabditis elegans. Aging Cell. 4(5):235-45 16164423 Click here to select all mutants from this PubMed ID in the graph
Abstract
The DAF-2 insulin/insulin-like growth factor 1 (IGF-1) receptor signals via a phosphatidylinositol 3-kinase (PI3K) pathway to control dauer larva formation and adult longevity in Caenorhabditis elegans. Yet epistasis analysis suggests signal bifurcation downstream of DAF-2. We have used epistasis analysis to test whether the Ras pathway (which plays a role in signaling from mammalian insulin receptors) acts downstream of DAF-2. We find that an activated Ras mutation, let-60(n1046gf), weakly suppresses constitutive dauer diapause in daf-2 and age-1 (PI3K) mutants. Moreover, increased Ras pathway signaling partially suppresses the daf-2 mutant feeding defect, while reduced Ras pathway signaling enhances it. By contrast, activated Ras extends the longevity induced by mutation of daf-2, while reduced Ras pathway signaling partially suppresses it. Thus, Ras pathway signaling appears to act with insulin/IGF-1 signaling during larval development, but against it during aging.

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

Temperature °C
22.5
Lifespan (days)
15.1
Lifespan change (compared to wild type)
-14.20%
Phenotype
let-60(gf) enhances the daf-2longevity (Age) phenotype, while reduction of Ras signaling partially suppresses it
Lifespan comparisons
Double mutant daf-2(e979);let-60(n1046) has a lifespan of 15.1 days, while single mutant daf-2(e979) has a lifespan of 22.8 days and wild type has a lifespan of 17.6 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Nanji M et al., 2005, LET-60 RAS modulates effects of insulin/IGF-1 signaling on development and aging in Caenorhabditis elegans. Aging Cell. 4(5):235-45 16164423 Click here to select all mutants from this PubMed ID in the graph
Abstract
The DAF-2 insulin/insulin-like growth factor 1 (IGF-1) receptor signals via a phosphatidylinositol 3-kinase (PI3K) pathway to control dauer larva formation and adult longevity in Caenorhabditis elegans. Yet epistasis analysis suggests signal bifurcation downstream of DAF-2. We have used epistasis analysis to test whether the Ras pathway (which plays a role in signaling from mammalian insulin receptors) acts downstream of DAF-2. We find that an activated Ras mutation, let-60(n1046gf), weakly suppresses constitutive dauer diapause in daf-2 and age-1 (PI3K) mutants. Moreover, increased Ras pathway signaling partially suppresses the daf-2 mutant feeding defect, while reduced Ras pathway signaling enhances it. By contrast, activated Ras extends the longevity induced by mutation of daf-2, while reduced Ras pathway signaling partially suppresses it. Thus, Ras pathway signaling appears to act with insulin/IGF-1 signaling during larval development, but against it during aging.

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

Temperature °C
22.5
Lifespan (days)
13.8
Lifespan change (compared to wild type)
-21.59%
Phenotype
let-60(gf) enhances the daf-2longevity (Age) phenotype, while reduction of Ras signaling partially suppresses it
Lifespan comparisons
Double mutant daf-2(m577);let-60(n1046) has a lifespan of 13.8 days, while single mutant daf-2(m577) has a lifespan of 23.3 days and wild type has a lifespan of 17.6 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Nanji M et al., 2005, LET-60 RAS modulates effects of insulin/IGF-1 signaling on development and aging in Caenorhabditis elegans. Aging Cell. 4(5):235-45 16164423 Click here to select all mutants from this PubMed ID in the graph
Abstract
The DAF-2 insulin/insulin-like growth factor 1 (IGF-1) receptor signals via a phosphatidylinositol 3-kinase (PI3K) pathway to control dauer larva formation and adult longevity in Caenorhabditis elegans. Yet epistasis analysis suggests signal bifurcation downstream of DAF-2. We have used epistasis analysis to test whether the Ras pathway (which plays a role in signaling from mammalian insulin receptors) acts downstream of DAF-2. We find that an activated Ras mutation, let-60(n1046gf), weakly suppresses constitutive dauer diapause in daf-2 and age-1 (PI3K) mutants. Moreover, increased Ras pathway signaling partially suppresses the daf-2 mutant feeding defect, while reduced Ras pathway signaling enhances it. By contrast, activated Ras extends the longevity induced by mutation of daf-2, while reduced Ras pathway signaling partially suppresses it. Thus, Ras pathway signaling appears to act with insulin/IGF-1 signaling during larval development, but against it during aging.

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

Temperature °C
22.5
Lifespan (days)
23.8
Lifespan change (compared to wild type)
35.23%
Phenotype
All three Ras pathway mutations partially suppressed the daf-2 Age phenotype
Lifespan comparisons
Double mutant daf-2(m577);let-60(n2021) has a lifespan of 23.8 days, while single mutant daf-2(m577) has a lifespan of 33.8 days and wild type has a lifespan of 17.6 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Nanji M et al., 2005, LET-60 RAS modulates effects of insulin/IGF-1 signaling on development and aging in Caenorhabditis elegans. Aging Cell. 4(5):235-45 16164423 Click here to select all mutants from this PubMed ID in the graph
Abstract
The DAF-2 insulin/insulin-like growth factor 1 (IGF-1) receptor signals via a phosphatidylinositol 3-kinase (PI3K) pathway to control dauer larva formation and adult longevity in Caenorhabditis elegans. Yet epistasis analysis suggests signal bifurcation downstream of DAF-2. We have used epistasis analysis to test whether the Ras pathway (which plays a role in signaling from mammalian insulin receptors) acts downstream of DAF-2. We find that an activated Ras mutation, let-60(n1046gf), weakly suppresses constitutive dauer diapause in daf-2 and age-1 (PI3K) mutants. Moreover, increased Ras pathway signaling partially suppresses the daf-2 mutant feeding defect, while reduced Ras pathway signaling enhances it. By contrast, activated Ras extends the longevity induced by mutation of daf-2, while reduced Ras pathway signaling partially suppresses it. Thus, Ras pathway signaling appears to act with insulin/IGF-1 signaling during larval development, but against it during aging.

Temperature °C
22.5
Lifespan (days)
27.4
Lifespan change (compared to wild type)
55.68%
Phenotype
All three Ras pathway mutations partially suppressed the daf-2 Age phenotype
Lifespan comparisons
Double mutant daf-2(m577);let-60(n2021) has a lifespan of 27.4 days, while single mutant daf-2(m577) has a lifespan of 32.2 days and wild type has a lifespan of 17.6 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Nanji M et al., 2005, LET-60 RAS modulates effects of insulin/IGF-1 signaling on development and aging in Caenorhabditis elegans. Aging Cell. 4(5):235-45 16164423 Click here to select all mutants from this PubMed ID in the graph
Abstract
The DAF-2 insulin/insulin-like growth factor 1 (IGF-1) receptor signals via a phosphatidylinositol 3-kinase (PI3K) pathway to control dauer larva formation and adult longevity in Caenorhabditis elegans. Yet epistasis analysis suggests signal bifurcation downstream of DAF-2. We have used epistasis analysis to test whether the Ras pathway (which plays a role in signaling from mammalian insulin receptors) acts downstream of DAF-2. We find that an activated Ras mutation, let-60(n1046gf), weakly suppresses constitutive dauer diapause in daf-2 and age-1 (PI3K) mutants. Moreover, increased Ras pathway signaling partially suppresses the daf-2 mutant feeding defect, while reduced Ras pathway signaling enhances it. By contrast, activated Ras extends the longevity induced by mutation of daf-2, while reduced Ras pathway signaling partially suppresses it. Thus, Ras pathway signaling appears to act with insulin/IGF-1 signaling during larval development, but against it during aging.

Search genes: daf-2 let-60

Entrez ID
Symbol
GenAge
Wormbase ID

175410
daf-2
View on GenAge (daf-2)
WBGene00000898

Insulin-like receptor subunit beta;Receptor protein-tyrosine kinase;hypothetical protein

Locus: CELE_Y55D5A.5

Wormbase description: daf-2 encodes a receptor tyrosine kinase that is the C. elegans insulin/IGF receptor ortholog; DAF-2 activity is required for a number of processes in C. elegans, including embryonic and larval development, formation of the developmentally arrested dauer larval stage (diapause), larval developmental timing, adult longevity, reproduction, fat storage, salt chemotaxis learning, and stress resistance, including response to high temperature, oxidative stress, and bacterial infection; DAF-2 signals through a conserved PI 3-kinase pathway to negatively regulate the activity of DAF-16, a Forkhead-related transcription factor, by inducing its phosphorylation and nuclear exclusion; in addition, DAF-2 negatively regulates the nuclear localization, and hence transcriptional activity, of SKN-1 in intestinal nuclei; amongst the 38 predicted insulin-like molecules in C. elegans, genetic and microarray analyses suggest that at least DAF-28, INS-1, and INS-7 are likely DAF-2 ligands; genetic mosaic and tissue-specific promoter studies indicate that daf-2 can function cell nonautonomously and within multiple cell types to influence dauer formation and adult lifespan, likely by regulating the production of secondary endocrine signals that coordinate growth and longevity throughout the animal; temporal analysis of daf-2 function indicates that daf-2 regulates lifespan, reproduction, and diapause independently, at distinct times during the animal's life cycle.

Entrez ID
Symbol
GenAge
Wormbase ID

178104
let-60
View on GenAge (let-60)
WBGene00002335

Ras protein let-60

Locus: CELE_ZK792.6

Wormbase description: let-60 encodes a member of the GTP-binding RAS protooncogene family; let-60 activity is required for viability, vulval development, spicule development, germ line meiotic progression, posterior development of the hypodermis, chemotaxis, sex myoblast migration, and muscle membrane extension; let-60 acts genetically downstream of let-23 with respect to vulval development and upstream of the MAPK pathway with respect to chemotaxis; let-60 is expressed in neural, muscle, and hypodermal lineages.

Orthologs of daf-2;let-60 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	InR;Ras85D
Mus musculus	Insr;Kras
Mus musculus	Hras;Insr
Mus musculus	Igf1r;Kras
Mus musculus	Hras;Igf1r
Mus musculus	Insrr;Kras
Mus musculus	Hras;Insrr

Orthologs of daf-2 in SynergyAge

Show in SynergyAge
Species	Gene
Drosophila melanogaster	InR

Not in SynergyAge
Species	Gene
Mus musculus	Insr
Mus musculus	Igf1r
Mus musculus	Insrr

Orthologs of let-60 in SynergyAge

Show in SynergyAge
Species	Gene