daf-2;kri-1

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Genetic mutants with daf-2, kri-1 alterations

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

Temperature °C
20
Lifespan (days)
30.3
Lifespan comparisons
Double mutant daf-2(e1368);kri-1(RNAi) has a lifespan of 30.3 days, while single mutant daf-2(e1368) has a lifespan of 30.2 days.
Citation
View abstract
Berman JR, Kenyon C, 2006, Germ-cell loss extends C. elegans life span through regulation of DAF-16 by kri-1 and lipophilic-hormone signaling. Cell. 124(5):1055-68 16530050 Click here to select all mutants from this PubMed ID in the graph
Abstract
In C. elegans, removing the germ cells extends life span by triggering the nuclear localization and activation of the DAF-16/FOXO transcription factor in the intestine. In this study, we identify and analyze genes required for germline removal to extend life span. We find that the reproductive system communicates with the intestine through lipophilic-hormone signaling and that a gene called kri-1 is likely to act in the intestine to promote DAF-16 nuclear localization in response to this signal. This lipophilic-signaling pathway and kri-1 are not required for DAF-16's nuclear localization and life-span extension in animals with decreased insulin/IGF-1 signaling. Thus, this pathway specifically enables the integration of cues from the reproductive system with central DAF-16-activation pathways to influence the aging of the animal.

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

Temperature °C
20
Lifespan (days)
54.4
Phenotype
kri-1 RNAi did not shorten the life span of daf-2(e1370) mutants; instead, surprisingly, it increased lifespan by up to 23%.
Lifespan comparisons
Double mutant daf-2(e1370);kri-1(RNAi) has a lifespan of 54.4 days, while single mutant kri-1(RNAi) has a lifespan of 19.8 days and single mutant daf-2(e1370) has a lifespan of 45.4 days.
Citation
View abstract
Berman JR, Kenyon C, 2006, Germ-cell loss extends C. elegans life span through regulation of DAF-16 by kri-1 and lipophilic-hormone signaling. Cell. 124(5):1055-68 16530050 Click here to select all mutants from this PubMed ID in the graph
Abstract
In C. elegans, removing the germ cells extends life span by triggering the nuclear localization and activation of the DAF-16/FOXO transcription factor in the intestine. In this study, we identify and analyze genes required for germline removal to extend life span. We find that the reproductive system communicates with the intestine through lipophilic-hormone signaling and that a gene called kri-1 is likely to act in the intestine to promote DAF-16 nuclear localization in response to this signal. This lipophilic-signaling pathway and kri-1 are not required for DAF-16's nuclear localization and life-span extension in animals with decreased insulin/IGF-1 signaling. Thus, this pathway specifically enables the integration of cues from the reproductive system with central DAF-16-activation pathways to influence the aging of the animal.

Temperature °C
20
Lifespan (days)
48.0
Phenotype
kri-1 RNAi did not shorten the life span of daf-2(e1370) mutants; instead, surprisingly, it increased lifespan by up to 23%.
Lifespan comparisons
Double mutant daf-2(e1370);kri-1(RNAi) has a lifespan of 48.0 days, while single mutant kri-1(RNAi) has a lifespan of 18.6 days and single mutant daf-2(e1370) has a lifespan of 43.9 days.
Citation
View abstract
Berman JR, Kenyon C, 2006, Germ-cell loss extends C. elegans life span through regulation of DAF-16 by kri-1 and lipophilic-hormone signaling. Cell. 124(5):1055-68 16530050 Click here to select all mutants from this PubMed ID in the graph
Abstract
In C. elegans, removing the germ cells extends life span by triggering the nuclear localization and activation of the DAF-16/FOXO transcription factor in the intestine. In this study, we identify and analyze genes required for germline removal to extend life span. We find that the reproductive system communicates with the intestine through lipophilic-hormone signaling and that a gene called kri-1 is likely to act in the intestine to promote DAF-16 nuclear localization in response to this signal. This lipophilic-signaling pathway and kri-1 are not required for DAF-16's nuclear localization and life-span extension in animals with decreased insulin/IGF-1 signaling. Thus, this pathway specifically enables the integration of cues from the reproductive system with central DAF-16-activation pathways to influence the aging of the animal.

Search genes: daf-2 kri-1

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

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.

Orthologs of daf-2;kri-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Insr;Krit1
Mus musculus	Igf1r;Krit1
Mus musculus	Insrr;Krit1

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 kri-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Krit1