dpy-5;ife-2;let-363;unc-13

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Genetic mutants with dpy-5, ife-2, let-363, unc-13 alterations

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

Temperature °C
20
Lifespan (days)
21.3
Lifespan change (compared to wild type)
17.03%
Phenotype
Knockdown of ife-2 further extends the lifespan of long-lived TORdeficient mutants
Lifespan comparisons
Quadruple mutant dpy-5(e61);ife-2(RNAi);let-363(h98);unc-13(e450) has a lifespan of 21.3 days, while triple mutant dpy-5(e61);let-363(h98);unc-13(e450) has a lifespan of 18 days and wild type has a lifespan of 18.2 days.
Citation
View abstract
Syntichaki P et al., 2007, eIF4E function in somatic cells modulates ageing in Caenorhabditis elegans. Nature. 445(7130):922-6 17277769 Click here to select all mutants from this PubMed ID in the graph
Abstract
Regulation of protein synthesis is critical for cell growth and maintenance. Ageing in many organisms, including humans, is accompanied by marked alterations in both general and specific protein synthesis. Whether these alterations are simply a corollary of the ageing process or have a causative role in senescent decline remains unclear. An array of protein factors facilitates the tight control of messenger RNA translation initiation. The eukaryotic initiation factor 4E (eIF4E), which binds the 7-monomethyl guanosine cap at the 5' end of all nuclear mRNAs, is a principal regulator of protein synthesis. Here we show that loss of a specific eIF4E isoform (IFE-2) that functions in somatic tissues reduces global protein synthesis, protects from oxidative stress and extends lifespan in Caenorhabditis elegans. Lifespan extension is independent of the forkhead transcription factor DAF-16, which mediates the effects of the insulin-like signalling pathway on ageing. Furthermore, IFE-2 deficiency further extends the lifespan of long-lived age and daf nematode mutants. Similarly, lack of IFE-2 enhances the long-lived phenotype of clk and dietary-restricted eat mutant animals. Knockdown of target of rapamycin (TOR), a phosphatidylinositol kinase-related kinase that controls protein synthesis in response to nutrient cues, further increases the longevity of ife-2 mutants. Thus, signalling via eIF4E in the soma is a newly discovered pathway influencing ageing in C. elegans.

Search genes: dpy-5 ife-2 let-363 unc-13 dpy-5;ife-2;let-363;unc-13

Entrez ID
Symbol
GenAge
Wormbase ID

172197
dpy-5
View on GenAge (dpy-5)
WBGene00001067

Cuticle collagen dpy-5

Locus: CELE_F27C1.8

Wormbase description: dpy-5 encodes a Group I cuticle procollagen; dpy-5 activity is required for wild-type body length, cuticle structure (width of the annuli), postembryonic growth rates, and reproduction; dpy-5 is described as an intermediate collagen gene, as its mRNA, which is present in all larval stages, adults, and dauer larvae, increases in abudance two hours prior to the secretion of each new cuticle; a dpy-5::gfp fusion gene is expressed in hypodermal cells from mid-to-late L1 larval stages to adulthood, with notably variable expression in the V lineage-derived seam cells; dpy-5 mutations suppress mutations in bli-4, which encodes a proprotein convertase that may process DPY-5 for normal cuticle production; in addition, dpy-5 is required for normal expression patterns of the COL-19, DPY-7, and DPY-13 cuticle collagens.

Entrez ID
Symbol
GenAge
Wormbase ID

180393
ife-2
View on GenAge (ife-2)
WBGene00002060

Eukaryotic translation initiation factor 4E-2

Locus: CELE_R04A9.4

Wormbase description: ife-2 encodes a translation initiation factor 4F, cap-binding subunit (eIF-4E); by homology, IFE-2 is predicted to function in cap-dependent mRNA translation initiation; loss of ife-2 activity in adult animals extends lifespan.

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

Entrez ID
Symbol
GenAge
Wormbase ID

172497
unc-13
View on GenAge (unc-13)
WBGene00006752

Phorbol ester/diacylglycerol-binding protein unc-13;hypothetical protein

Locus: CELE_ZK524.2

Wormbase description: unc-13 encodes at least five protein isoforms that regulate neurotransmitter release by altering the conformation of syntaxin; UNC-13 proteins are required for normal pharyngeal pumping and thrashing in liquid, normally short lifespan, normally large brood sizes, and full adult body sizes; UNC-13 proteins have orthologs in vertebrates and Drosophila; UNC-13 proteins are complex, with multiple C2, phorbol ester-binding, and DUF1041 domains; UNC-13 protein form is localized to most or all synapses; many of the unc-13 mutant alleles with viable phenotypes are transcript-specific, while homozygotes with an unc-13 null (deletion) allele die as paralyzed first-stage larvae.

Orthologs of dpy-5;ife-2;let-363;unc-13 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Unc13a;Mtor
Mus musculus	Unc13c;Mtor
Mus musculus	Unc13b;Mtor

Orthologs of dpy-5 in SynergyAge

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Species	Gene

Orthologs of ife-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

Orthologs of unc-13 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Unc13a
Mus musculus	Unc13c
Mus musculus	Unc13b