daf-2;xbp-1

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Genetic mutants with daf-2, xbp-1 alterations

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

Lifespan (days)
24.2
Lifespan change (compared to wild type)
30.11%
Lifespan comparisons
Double mutant daf-2(e1368);xbp-1(RNAi) has a lifespan of 24.2 days, while single mutant daf-2(e1368) has a lifespan of 33.7 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Lifespan (days)
29.0
Lifespan comparisons
Double mutant daf-2(e1368);xbp-1(RNAi) has a lifespan of 29.0 days, while single mutant daf-2(e1368) has a lifespan of 31.5 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Lifespan (days)
18.6
Lifespan change (compared to wild type)
-7.92%
Lifespan comparisons
Double mutant daf-2(e1368);xbp-1(RNAi) has a lifespan of 18.6 days, while single mutant xbp-1(RNAi) has a lifespan of 18.2 days, single mutant daf-2(e1368) has a lifespan of 27.5 days and wild type has a lifespan of 20.2 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

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

Lifespan (days)
23.6
Lifespan change (compared to wild type)
34.86%
Phenotype
A putative xbp-1–null mutation, which causes truncation of the XBP-1 protein before its DNA binding domain, shortened the lifespan of daf-2 mutants more than it shortened the lifespan of wild type without affecting the apparent health of the animals.
Lifespan comparisons
Double mutant daf-2(e1368);xbp-1(zc12) has a lifespan of 23.6 days, while single mutant xbp-1(zc12) has a lifespan of 16.7 days, single mutant daf-2(e1368) has a lifespan of 32.8 days and wild type has a lifespan of 17.5 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Lifespan (days)
22.9
Lifespan change (compared to wild type)
7.01%
Phenotype
A putative xbp-1–null mutation, which causes truncation of the XBP-1 protein before its DNA binding domain, shortened the lifespan of daf-2 mutants more than it shortened the lifespan of wild type without affecting the apparent health of the animals.
Lifespan comparisons
Double mutant daf-2(e1368);xbp-1(zc12) has a lifespan of 22.9 days, while single mutant xbp-1(zc12) has a lifespan of 17.9 days, single mutant daf-2(e1368) has a lifespan of 27.7 days and wild type has a lifespan of 21.4 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Lifespan (days)
22.3
Lifespan change (compared to wild type)
49.66%
Phenotype
A putative xbp-1–null mutation, which causes truncation of the XBP-1 protein before its DNA binding domain, shortened the lifespan of daf-2 mutants more than it shortened the lifespan of wild type without affecting the apparent health of the animals.
Lifespan comparisons
Double mutant daf-2(e1368);xbp-1(zc12) has a lifespan of 22.3 days, while single mutant xbp-1(zc12) has a lifespan of 15.8 days, single mutant daf-2(e1368) has a lifespan of 29.7 days and wild type has a lifespan of 14.9 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

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

Lifespan (days)
36.2
Lifespan change (compared to wild type)
94.62%
Lifespan comparisons
Double mutant daf-2(e1370);xbp-1(RNAi) has a lifespan of 36.2 days, while single mutant xbp-1(RNAi) has a lifespan of 15.6 days, single mutant daf-2(e1370) has a lifespan of 44.6 days and wild type has a lifespan of 18.6 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Lifespan (days)
47.8
Lifespan change (compared to wild type)
156.99%
Lifespan comparisons
Double mutant daf-2(e1370);xbp-1(RNAi) has a lifespan of 47.8 days, while single mutant daf-2(e1370) has a lifespan of 46.9 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Lifespan (days)
36.1
Lifespan change (compared to wild type)
79.60%
Lifespan comparisons
Double mutant daf-2(e1370);xbp-1(RNAi) has a lifespan of 36.1 days, while single mutant xbp-1(RNAi) has a lifespan of 15.4 days, single mutant daf-2(e1370) has a lifespan of 38.9 days and wild type has a lifespan of 20.1 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Lifespan (days)
38.0
Lifespan change (compared to wild type)
88.12%
Lifespan comparisons
Double mutant daf-2(e1370);xbp-1(RNAi) has a lifespan of 38.0 days, while single mutant xbp-1(RNAi) has a lifespan of 18.2 days, single mutant daf-2(e1370) has a lifespan of 42.5 days and wild type has a lifespan of 20.2 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Lifespan (days)
46.5
Lifespan change (compared to wild type)
130.20%
Lifespan comparisons
Double mutant daf-2(e1370);xbp-1(RNAi) has a lifespan of 46.5 days, while single mutant daf-2(e1370) has a lifespan of 52.2 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Lifespan (days)
46.6
Lifespan change (compared to wild type)
130.69%
Lifespan comparisons
Double mutant daf-2(e1370);xbp-1(RNAi) has a lifespan of 46.6 days, while single mutant daf-2(e1370) has a lifespan of 53.1 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

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

Lifespan (days)
36.6
Lifespan change (compared to wild type)
121.82%
Phenotype
A putative xbp-1–null mutation, which causes truncation of the XBP-1 protein before its DNA binding domain, shortened the lifespan of daf-2 mutants more than it shortened the lifespan of wild type without affecting the apparent health of the animals.
Lifespan comparisons
Double mutant daf-2(e1370);xbp-1(zc12) has a lifespan of 36.6 days, while single mutant xbp-1(zc12) has a lifespan of 16.2 days, single mutant daf-2(e1370) has a lifespan of 42.0 days and wild type has a lifespan of 16.5 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Lifespan (days)
24.4
Lifespan change (compared to wild type)
14.02%
Phenotype
A putative xbp-1–null mutation, which causes truncation of the XBP-1 protein before its DNA binding domain, shortened the lifespan of daf-2 mutants more than it shortened the lifespan of wild type without affecting the apparent health of the animals.
Lifespan comparisons
Double mutant daf-2(e1370);xbp-1(zc12) has a lifespan of 24.4 days, while single mutant xbp-1(zc12) has a lifespan of 17.9 days, single mutant daf-2(e1370) has a lifespan of 36.3 days and wild type has a lifespan of 21.4 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Lifespan (days)
28.5
Lifespan change (compared to wild type)
33.18%
Phenotype
A putative xbp-1–null mutation, which causes truncation of the XBP-1 protein before its DNA binding domain, shortened the lifespan of daf-2 mutants more than it shortened the lifespan of wild type without affecting the apparent health of the animals.
Lifespan comparisons
Double mutant daf-2(e1370);xbp-1(zc12) has a lifespan of 28.5 days, while single mutant xbp-1(zc12) has a lifespan of 17.9 days, single mutant daf-2(e1370) has a lifespan of 36.3 days and wild type has a lifespan of 21.4 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Lifespan (days)
30.1
Lifespan change (compared to wild type)
72.00%
Phenotype
A putative xbp-1–null mutation, which causes truncation of the XBP-1 protein before its DNA binding domain, shortened the lifespan of daf-2 mutants more than it shortened the lifespan of wild type without affecting the apparent health of the animals.
Lifespan comparisons
Double mutant daf-2(e1370);xbp-1(zc12) has a lifespan of 30.1 days, while single mutant xbp-1(zc12) has a lifespan of 16.7 days, single mutant daf-2(e1370) has a lifespan of 45.2 days and wild type has a lifespan of 17.5 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Lifespan (days)
32.2
Lifespan change (compared to wild type)
116.11%
Lifespan comparisons
Double mutant daf-2(e1370);xbp-1(zc12) has a lifespan of 32.2 days, while single mutant daf-2(e1370) has a lifespan of 44.7 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

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

Lifespan (days)
17.3
Lifespan change (compared to wild type)
7.45%
Lifespan comparisons
Double mutant daf-2(mu150);xbp-1(RNAi) has a lifespan of 17.3 days, while single mutant xbp-1(RNAi) has a lifespan of 10.9 days, single mutant daf-2(mu150) has a lifespan of 36.0 days and wild type has a lifespan of 16.1 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Lifespan (days)
14.6
Lifespan change (compared to wild type)
-0.68%
Lifespan comparisons
Double mutant daf-2(mu150);xbp-1(RNAi) has a lifespan of 14.6 days, while single mutant xbp-1(RNAi) has a lifespan of 10.1 days, single mutant daf-2(mu150) has a lifespan of 28.1 days and wild type has a lifespan of 14.7 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Search genes: daf-2 xbp-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

175541
xbp-1
View on GenAge (xbp-1)
WBGene00006959

X-box Binding Protein homolog

Locus: CELE_R74.3

Wormbase description: xbp-1 encodes a bZIP transcription factor orthologous to yeast Hac1 and mammalian X box-binding protein 1 (XBP-1, OMIM:194355); XBP-1 is required for the unfolded protein response (UPR) that counteracts cellular stress induced by accumulation of unfolded proteins in the endoplasmic reticulum (ER); xbp-1 mRNA is spliced by the IRE-1 endoribonuclease to promote translation of transcriptionally active XBP-1 that positively regulates UPR gene expression to maintain ER homeostasis and promote normal development; loss of xbp-1 activity also results in near-complete loss of myo-2 pharnygeal myosin expression, although pharyngeal muscle is still present.

Orthologs of daf-2;xbp-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene

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 xbp-1 in SynergyAge

Show in SynergyAge
Species	Gene