daf-16;daf-18

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Genetic mutants with daf-16, daf-18 alterations

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

Temperature °C
25
Diet
NGM
Lifespan (days)
9.8
Lifespan change (compared to wild type)
-19.67%
Phenotype
daf-16 RNAi inhibits lifespan extension of daf-18 (mg198).
Lifespan comparisons
Double mutant daf-16(RNAi);daf-18(mg198) has a lifespan of 9.8 days, while single mutant daf-16(RNAi) has a lifespan of 9.7 days, single mutant daf-18(mg198) has a lifespan of 10.0 days and wild type has a lifespan of 12.2 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Masse I et al., 2005, Lifespan and dauer regulation by tissue-specific activities of Caenorhabditis elegans DAF-18. Dev Biol. 286(1):91-101 16153634 Click here to select all mutants from this PubMed ID in the graph
Abstract
In Caenorhabditis elegans, the insulin/IGF-1 DAF-2 receptor controls entry into dauer and longevity. DAF-2 signaling cascade includes the PI3 kinase homolog AGE-1 and the FOXO transcription factor DAF-16. The DAF-2 pathway is downregulated by DAF-18 which is encoded by the ortholog of the human tumor suppressor gene PTEN. We have previously shown that, like PTEN, DAF-18 antagonizes the activity of PI3 kinase/AGE-1. To further explore the role of DAF-18 in the regulation of the insulin pathway, we investigated which tissue(s) DAF-18 functions in to regulate dauer formation and lifespan. Our data show that complete dauer formation requires daf-18 expression in several tissues and that the remodeling of dauer tissues depends on both cell autonomous and cell nonautonomous daf-18 function(s). Conversely, daf-18 expression increases adult lifespan in all individual tissues tested. Furthermore, we show that the role of DAF-18 in dauer and lifespan control depends on DAF-16 activation, which is regulated by both cell autonomous and cell nonautonomous DAF-18 function(s) and in a tissue-specific manner. Overall, our data strongly suggest that several tissues act as signaling centers to mediate DAF-18 function and that DAF-18 could act outside the canonical DAF-2/DAF-16 pathway to regulate dauer and lifespan.

Search genes: daf-16 daf-18

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

176869
daf-18
View on GenAge (daf-18)
WBGene00000913

Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase daf-18

Locus: CELE_T07A9.6

Wormbase description: daf-18 encodes a lipid phosphatase homologous to the human PTEN tumor suppresor (OMIM:601728, mutated in Cowden disease and several cancers); DAF-18 negatively regulates insulin-like signaling mediated by DAF-2/IR and AGE-1/PI3K and thus plays a role in metabolism, development, and longevity; based on sequence and genetic analysis, DAF-18 is predicted to dephosphorylate AGE-1-generated PIP3 in order to limit activation of the downstream AKT-1 and AKT-2 kinases that negatively regulate DAF-16.

Orthologs of daf-16;daf-18 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of daf-16 in SynergyAge

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Species	Gene

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

Orthologs of daf-18 in SynergyAge

Show in SynergyAge
Species	Gene

About

SynergyAge database hosts high-quality, manually curated information about the synergistic and antagonistic lifespan effects of genetic interventions in model organisms, also allowing users to explore the longevity relationships between genes in a visual way.