daf-16;ifg-1

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Genetic mutants with daf-16, 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)
15.8
Lifespan change (compared to wild type)
-22.17%
Lifespan comparisons
Double mutant daf-16(RNAi);ifg-1(cxTi9279) has a lifespan of 15.8 days, while single mutant daf-16(RNAi) has a lifespan of 12.8 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
Opposite lifespan effects of single mutants
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
Lifespan (days)
23.61
Lifespan change (compared to wild type)
0.25%
Lifespan comparisons
Double mutant daf-16(mgDf47);ifg-1(RNAi) has a lifespan of 23.61 days, while single mutant daf-16(mgDf47) has a lifespan of 21.07 days and wild type has a lifespan of 23.55 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Wang J et al., 2010, RNAi screening implicates a SKN-1-dependent transcriptional response in stress resistance and longevity deriving from translation inhibition. PLoS Genet. 6(8). pii: e1001048 20700440 Click here to select all mutants from this PubMed ID in the graph
Abstract
Caenorhabditis elegans SKN-1 (ortholog of mammalian Nrf1/2/3) is critical for oxidative stress resistance and promotes longevity under reduced insulin/IGF-1-like signaling (IIS), dietary restriction (DR), and normal conditions. SKN-1 inducibly activates genes involved in detoxification, protein homeostasis, and other functions in response to stress. Here we used genome-scale RNA interference (RNAi) screening to identify mechanisms that prevent inappropriate SKN-1 target gene expression under non-stressed conditions. We identified 41 genes for which knockdown leads to activation of a SKN-1 target gene (gcs-1) through skn-1-dependent or other mechanisms. These genes correspond to multiple cellular processes, including mRNA translation. Inhibition of translation is known to increase longevity and stress resistance and may be important for DR-induced lifespan extension. One model postulates that these effects derive from reduced energy needs, but various observations suggest that specific longevity pathways are involved. Here we show that translation initiation factor RNAi robustly induces SKN-1 target gene transcription and confers skn-1-dependent oxidative stress resistance. The accompanying increases in longevity are mediated largely through the activities of SKN-1 and the transcription factor DAF-16 (FOXO), which is required for longevity that derives from reduced IIS. Our results indicate that the SKN-1 detoxification gene network monitors various metabolic and regulatory processes. Interference with one of these processes, translation initiation, leads to a transcriptional response whereby SKN-1 promotes stress resistance and functions together with DAF-16 to extend lifespan. This stress response may be beneficial for coping with situations that are associated with reduced protein synthesis.

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

Temperature °C
20
Lifespan (days)
13.6
Lifespan comparisons
Double mutant daf-16(mu86);ifg-1(RNAi) has a lifespan of 13.6 days, while single mutant daf-16(mu86) has a lifespan of 12.9 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
20
Lifespan (days)
15.6
Lifespan comparisons
Double mutant daf-16(mu86);ifg-1(RNAi) has a lifespan of 15.6 days, while single mutant daf-16(mu86) has a lifespan of 15.2 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
20
Lifespan (days)
12.8
Lifespan comparisons
Double mutant daf-16(mu86);ifg-1(RNAi) has a lifespan of 12.8 days, while single mutant daf-16(mu86) has a lifespan of 13.3 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
20
Lifespan (days)
13.2
Lifespan comparisons
Double mutant daf-16(mu86);ifg-1(RNAi) has a lifespan of 13.2 days, while single mutant daf-16(mu86) has a lifespan of 14.3 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
Diet
NGM
Lifespan (days)
16.9
Lifespan change (compared to wild type)
-33.46%
Lifespan comparisons
Double mutant daf-16(mu86);ifg-1(RNAi) has a lifespan of 16.9 days, while single mutant ifg-1(RNAi) has a lifespan of 28.7 days, single mutant daf-16(mu86) has a lifespan of 15.6 days and wild type has a lifespan of 25.4 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
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.

Temperature °C
25
Diet
NGM
Lifespan (days)
14.2
Lifespan change (compared to wild type)
-30.05%
Lifespan comparisons
Double mutant daf-16(mu86);ifg-1(RNAi) has a lifespan of 14.2 days, while single mutant ifg-1(RNAi) has a lifespan of 26.7 days, single mutant daf-16(mu86) has a lifespan of 13.1 days and wild type has a lifespan of 20.3 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
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.

Temperature °C
20
Diet
NGM; OP50
Lifespan (days)
15.2
Lifespan comparisons
Double mutant daf-16(mu86);ifg-1(RNAi) has a lifespan of 15.2 days, while single mutant daf-16(mu86) has a lifespan of 12.0 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.

Search genes: daf-16 ifg-1

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

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-16;ifg-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Eif4g1;Foxo6
Mus musculus	Eif4g3;Foxo6
Mus musculus	Eif4g1;Foxo1
Mus musculus	Eif4g3;Foxo1
Mus musculus	Eif4g1;Foxo4
Mus musculus	Eif4g3;Foxo4
Mus musculus	Eif4g1;Foxo3
Mus musculus	Eif4g3;Foxo3

Orthologs of daf-16 in SynergyAge

Show in SynergyAge
Species	Gene

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

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