daf-2;ifg-1

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Genetic mutants with daf-2, ifg-1 alterations

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

Temperature °C
25
Diet
NGM
Lifespan (days)
44.8
Lifespan change (compared to wild type)
120.69%
Lifespan comparisons
Double mutant daf-2(RNAi);ifg-1(cxTi9279) has a lifespan of 44.8 days, while single mutant daf-2(RNAi) has a lifespan of 30.6 days, single mutant ifg-1(cxTi9279) has a lifespan of 27.8 days and wild type has a lifespan of 20.3 days.
Type of interaction
See methods
Synergistic (positive)
Citation
View abstract
Rogers AN et al., 2011, Life span extension via eIF4G inhibition is mediated by posttranscriptional remodeling of stress response gene expression in C. elegans. Cell Metab. 14(1):55-66 21723504 Click here to select all mutants from this PubMed ID in the graph
Abstract
Reducing protein synthesis slows growth and development but can increase adult life span. We demonstrate that knockdown of eukaryotic translation initiation factor 4G (eIF4G), which is downregulated during starvation and dauer state, results in differential translation of genes important for growth and longevity in C. elegans. Genome-wide mRNA translation state analysis showed that inhibition of IFG-1, the C. elegans ortholog of eIF4G, results in a relative increase in ribosomal loading and translation of stress response genes. Some of these genes are required for life span extension when IFG-1 is inhibited. Furthermore, enhanced ribosomal loading of certain mRNAs upon IFG-1 inhibition was correlated with increased mRNA length. This association was supported by changes in the proteome assayed via quantitative mass spectrometry. Our results suggest that IFG-1 mediates the antagonistic effects on growth and somatic maintenance by regulating mRNA translation of particular mRNAs based, in part, on transcript length.

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

Temperature °C
20
Diet
NGM; OP50
Lifespan (days)
52.3
Lifespan comparisons
Double mutant daf-2(e1370);ifg-1(RNAi) has a lifespan of 52.3 days, while single mutant daf-2(e1370) has a lifespan of 30.8 days.
Citation
View abstract
Pan KZ et al., 2007, Inhibition of mRNA translation extends lifespan in Caenorhabditis elegans. Aging Cell. 6(1):111-9 17266680 Click here to select all mutants from this PubMed ID in the graph
Abstract
Protein synthesis is a regulated cellular process that links nutrients in the environment to organismal growth and development. Here we examine the role of genes that regulate mRNA translation in determining growth, reproduction, stress resistance and lifespan. Translational control of protein synthesis by regulators such as the cap-binding complex and S6 kinase play an important role during growth. We observe that inhibition of various genes in the translation initiation complex including ifg-1, the worm homologue of eIF4G, which is a scaffold protein in the cap-binding complex; and rsks-1, the worm homologue of S6 kinase, results in lifespan extension in Caenorhabditis elegans. Inhibition of ifg-1 or rsks-1 also slows development, reduces fecundity and increases resistance to starvation. A reduction in ifg-1 expression in dauers was also observed, suggesting an inhibition of protein translation during the dauer state. Thus, mRNA translation exerts pleiotropic effects on growth, reproduction, stress resistance and lifespan in C. elegans.

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

Temperature °C
25
Lifespan (days)
26.9
Lifespan comparisons
Double mutant daf-2(mu150);ifg-1(RNAi) has a lifespan of 26.9 days, while single mutant daf-2(mu150) has a lifespan of 31.8 days.
Citation
View abstract
Hansen M et al., 2007, Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans. Aging Cell. 6(1):95-110 17266679 Click here to select all mutants from this PubMed ID in the graph
Abstract
Many conditions that shift cells from states of nutrient utilization and growth to states of cell maintenance extend lifespan. We have carried out a systematic lifespan analysis of conditions that inhibit protein synthesis. We find that reducing the levels of ribosomal proteins, ribosomal-protein S6 kinase or translation-initiation factors increases the lifespan of Caenorhabditis elegans. These perturbations, as well as inhibition of the nutrient sensor target of rapamycin (TOR), which is known to increase lifespan, all increase thermal-stress resistance. Thus inhibiting translation may extend lifespan by shifting cells to physiological states that favor maintenance and repair. Interestingly, different types of translation inhibition lead to one of two mutually exclusive outputs, one that increases lifespan and stress resistance through the transcription factor DAF-16/FOXO, and one that increases lifespan and stress resistance independently of DAF-16. Our findings link TOR, but not sir-2.1, to the longevity response induced by dietary restriction (DR) in C. elegans, and they suggest that neither TOR inhibition nor DR extends lifespan simply by reducing protein synthesis.

Temperature °C
25
Lifespan (days)
26.3
Lifespan comparisons
Double mutant daf-2(mu150);ifg-1(RNAi) has a lifespan of 26.3 days, while single mutant daf-2(mu150) has a lifespan of 31.1 days.
Citation
View abstract
Hansen M et al., 2007, Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans. Aging Cell. 6(1):95-110 17266679 Click here to select all mutants from this PubMed ID in the graph
Abstract
Many conditions that shift cells from states of nutrient utilization and growth to states of cell maintenance extend lifespan. We have carried out a systematic lifespan analysis of conditions that inhibit protein synthesis. We find that reducing the levels of ribosomal proteins, ribosomal-protein S6 kinase or translation-initiation factors increases the lifespan of Caenorhabditis elegans. These perturbations, as well as inhibition of the nutrient sensor target of rapamycin (TOR), which is known to increase lifespan, all increase thermal-stress resistance. Thus inhibiting translation may extend lifespan by shifting cells to physiological states that favor maintenance and repair. Interestingly, different types of translation inhibition lead to one of two mutually exclusive outputs, one that increases lifespan and stress resistance through the transcription factor DAF-16/FOXO, and one that increases lifespan and stress resistance independently of DAF-16. Our findings link TOR, but not sir-2.1, to the longevity response induced by dietary restriction (DR) in C. elegans, and they suggest that neither TOR inhibition nor DR extends lifespan simply by reducing protein synthesis.

Search genes: daf-2 ifg-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

174322
ifg-1
View on GenAge (ifg-1)
WBGene00002066

Initiation Factor 4G (eIF4G) family

Locus: CELE_M110.4

Wormbase description: ifg-1 encodes, by alternative splicing, two orthologs of the translation initiation factor 4F, ribosome/mRNA-bridging subunit (eIF-4G); by homology, IFG-1 is predicted to function in poly(A) tail-dependent translation initiation; loss of ifg-1 activity in adult animals extends lifespan.

Orthologs of daf-2;ifg-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	eIF4G2;InR
Mus musculus	Eif4g1;Insr
Mus musculus	Eif4g3;Insr
Mus musculus	Eif4g1;Igf1r
Mus musculus	Eif4g3;Igf1r
Mus musculus	Eif4g1;Insrr
Mus musculus	Eif4g3;Insrr

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 ifg-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	eIF4G2
Mus musculus	Eif4g1
Mus musculus	Eif4g3