eat-2;pha-4

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Genetic mutants with eat-2, pha-4 alterations

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

Temperature °C
15
Lifespan (days)
13.7
Lifespan change (compared to wild type)
-24.31%
Phenotype
RNA interference (RNAi) of pha-4 completely suppressed the long lifespan of eat-2(ad1116) mutant animals
Lifespan comparisons
Double mutant eat-2(ad1116);pha-4(RNAi) has a lifespan of 13.7 days, while single mutant eat-2(ad1116) has a lifespan of 23.8 days and wild type has a lifespan of 18.1 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Panowski SH et al., 2007, PHA-4/Foxa mediates diet-restriction-induced longevity of C. elegans. Nature. 447(7144):550-5 17476212 Click here to select all mutants from this PubMed ID in the graph
Abstract
Reduced food intake as a result of dietary restriction increases the lifespan of a wide variety of metazoans and delays the onset of multiple age-related pathologies. Dietary restriction elicits a genetically programmed response to nutrient availability that cannot be explained by a simple reduction in metabolism or slower growth of the organism. In the nematode worm Caenorhabditis elegans, the transcription factor PHA-4 has an essential role in the embryonic development of the foregut and is orthologous to genes encoding the mammalian family of Foxa transcription factors, Foxa1, Foxa2 and Foxa3. Foxa family members have important roles during development, but also act later in life to regulate glucagon production and glucose homeostasis, particularly in response to fasting. Here we describe a newly discovered, adult-specific function for PHA-4 in the regulation of diet-restriction-mediated longevity in C. elegans. The role of PHA-4 in lifespan determination is specific for dietary restriction, because it is not required for the increased longevity caused by other genetic pathways that regulate ageing.

Search genes: eat-2 pha-4

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

180357
pha-4
View on GenAge (pha-4)
WBGene00004013

Defective pharyngeal development protein 4

Locus: CELE_F38A6.1

Wormbase description: pha-4 encodes a FoxA transcription factor; during embryonic development, PHA-4 functions as an organ identity gene whose activity is necessary and sufficient for development of the pharynx/foregut; in addition, PHA-4 plays a key role in regulation of diet-restriction-induced longevity in adult animals; PHA-4 expression begins early in embryogenesis and is seen in pharyngeal and intestinal cells (foregut and midgut); PHA-4 is also expressed later in the developing somatic gonad.

Orthologs of eat-2;pha-4 in SynergyAge

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Species	Gene

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Species	Gene

Orthologs of eat-2 in SynergyAge

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Species	Gene

Orthologs of pha-4 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	FoxK

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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.