daf-9;eat-2;let-363

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Genetic mutants with daf-9, eat-2, let-363 alterations

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

Temperature °C
20
Diet
NGM
Lifespan (days)
18.29
Lifespan comparisons
Triple mutant daf-9(rh50);eat-2(ad1116);let-363(RNAi) has a lifespan of 18.29 days, while double mutant eat-2(ad1116);let-363(RNAi) has a lifespan of 21.27 days.
Citation
View abstract
Thondamal M et al., 2014, Steroid hormone signalling links reproduction to lifespan in dietary-restricted Caenorhabditis elegans. Nat Commun. 5:4879 25209682 Click here to select all mutants from this PubMed ID in the graph
Abstract
Dietary restriction (DR) increases healthspan and longevity in many species, including primates, but it is often accompanied by impaired reproductive function. Whether signals associated with the reproductive system contribute to or are required for DR effects on lifespan has not been established. Here we show that expression of the cytochrome P450 DAF-9/CYP450 and production of the steroid hormone Δ(7)-dafachronic acid (DA) are increased in C. elegans subjected to DR. DA signalling through the non-canonical nuclear hormone receptor NHR-8/NHR and the nutrient-responsive kinase let-363/mTOR is essential for DR-mediated longevity. Steroid signalling also affects germline plasticity in response to nutrient deprivation and this is required to achieve lifespan extension. These data demonstrate that steroid signalling links germline physiology to lifespan when nutrients are limited, and establish a central role for let-363/mTOR in integrating signals derived from nutrients and steroid hormones.

Search genes: daf-9 eat-2 let-363 daf-9;eat-2;let-363

Entrez ID
Symbol
GenAge
Wormbase ID

180889
daf-9
View on GenAge (daf-9)
WBGene00000905

Cytochrome P450 daf-9

Locus: CELE_T13C5.1

Wormbase description: daf-9 encodes a cytochrome P450 of the CYP2 subfamily that by homology is predicted to function as a steroidogenic or fatty acid hydroxylase; DAF-9 likely functions cell nonautonomously in hypodermal and neuronal cells to produce, for the DAF-12 nuclear receptor, a lipophilic hormone whose presence is necessary for bypassing entry into the alternative L3/dauer larval stage and promoting reproductive development; in regulating dauer formation, daf-9 acts downstream of the DAF-2/insulin/IGF receptor and the DAF-7/TGFbeta ligand, suggesting that at least two of the signaling pathways that control dauer formation converge, in part, upon daf-9; in addition, daf-9 activity is required for gonadal cell migration; a DAF-9::GFP fusion is expressed in the XXXL/R head cells at all developmental stages, in hypodermal cells from the L2 to L4 larval stages, and in the spermatheca of adult hermaphrodites.

Entrez ID
Symbol
GenAge
Wormbase ID

175072
eat-2
View on GenAge (eat-2)
WBGene00001133

Neuronal acetylcholine receptor subunit eat-2

Locus: CELE_Y48B6A.4

Wormbase description: eat-2 encodes a ligand-gated ion channel subunit most closely related to the non-alpha-subunits of nicotinic acetylcholine receptors (nAChR); EAT-2 functions postsynaptically in pharyngeal muscle to regulate the rate of pharyngeal pumping; eat-2 is also required for normal life span and defecation; a functional EAT-2::GFP fusion protein localizes to two small dots near the junction of pharyngeal muscles pm4 and pm5, which is the site of the posterior-most MC motor neuron processes and the MC synapse; eat-2 genetically interacts with eat-18, which encodes a predicted novel transmembrane protein expressed in pharyngeal muscle and required for proper function of pharyngeal nicotonic receptors.

Entrez ID
Symbol
GenAge
Wormbase ID

172167
let-363
View on GenAge (let-363)
WBGene00002583

Target of rapamycin homolog

Locus: CELE_B0261.2

Wormbase description: none available

Orthologs of daf-9;eat-2;let-363 in SynergyAge

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Species	Gene

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Species	Gene

Orthologs of daf-9 in SynergyAge

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Species	Gene

Orthologs of eat-2 in SynergyAge

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Species	Gene

Orthologs of let-363 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Tor
Mus musculus	Mtor

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.