daf-2;lin-23

There is no network for this step.

Fullscreen mode

Hide graph

Legend

Genetic mutants with daf-2, lin-23 alterations

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

Temperature °C
20
Lifespan (days)
24.3
Lifespan change (compared to wild type)
17.39%
Phenotype
We found that lin-23(ot1) reduced the lifespan extension of daf-2 mutants and also attenuated the lifespan extension induced by daf-2 RNAi. These data showed that lin-23 is required for the extended lifespan of daf-2 mutants for a function that is independent of its developmental role in cell cycle regulation.
Lifespan comparisons
Double mutant daf-2(RNAi);lin-23(ot1) has a lifespan of 24.3 days, while single mutant daf-2(RNAi) has a lifespan of 39.7 days, single mutant lin-23(ot1) has a lifespan of 19.1 days and wild type has a lifespan of 20.7 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
20
Lifespan (days)
21.8
Lifespan change (compared to wild type)
5.31%
Phenotype
We found that lin-23(ot1) reduced the lifespan extension of daf-2 mutants and also attenuated the lifespan extension induced by daf-2 RNAi. These data showed that lin-23 is required for the extended lifespan of daf-2 mutants for a function that is independent of its developmental role in cell cycle regulation.
Lifespan comparisons
Double mutant daf-2(RNAi);lin-23(ot1) has a lifespan of 21.8 days, while single mutant daf-2(RNAi) has a lifespan of 39.7 days, single mutant lin-23(ot1) has a lifespan of 17.2 days and wild type has a lifespan of 20.7 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
25
Lifespan (days)
16.6
Lifespan change (compared to wild type)
1.84%
Phenotype
We found that lin-23(ot1) reduced the lifespan extension of daf-2 mutants and also attenuated the lifespan extension induced by daf-2 RNAi. These data showed that lin-23 is required for the extended lifespan of daf-2 mutants for a function that is independent of its developmental role in cell cycle regulation.
Lifespan comparisons
Double mutant daf-2(RNAi);lin-23(ot1) has a lifespan of 16.6 days, while single mutant daf-2(RNAi) has a lifespan of 26.5 days, single mutant lin-23(ot1) has a lifespan of 13 days and wild type has a lifespan of 16.3 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
25
Lifespan (days)
13.5
Lifespan change (compared to wild type)
-17.18%
Phenotype
We found that lin-23(ot1) reduced the lifespan extension of daf-2 mutants and also attenuated the lifespan extension induced by daf-2 RNAi. These data showed that lin-23 is required for the extended lifespan of daf-2 mutants for a function that is independent of its developmental role in cell cycle regulation.
Lifespan comparisons
Double mutant daf-2(RNAi);lin-23(ot1) has a lifespan of 13.5 days, while single mutant daf-2(RNAi) has a lifespan of 26.5 days, single mutant lin-23(ot1) has a lifespan of 13.2 days and wild type has a lifespan of 16.3 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
25
Lifespan (days)
17.0
Lifespan change (compared to wild type)
4.94%
Phenotype
We found that lin-23(ot1) reduced the lifespan extension of daf-2 mutants and also attenuated the lifespan extension induced by daf-2 RNAi. These data showed that lin-23 is required for the extended lifespan of daf-2 mutants for a function that is independent of its developmental role in cell cycle regulation.
Lifespan comparisons
Double mutant daf-2(RNAi);lin-23(ot1) has a lifespan of 17 days, while single mutant daf-2(RNAi) has a lifespan of 28.9 days, single mutant lin-23(ot1) has a lifespan of 14.7 days and wild type has a lifespan of 16.2 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
25
Lifespan (days)
14.2
Lifespan change (compared to wild type)
-12.35%
Phenotype
We found that lin-23(ot1) reduced the lifespan extension of daf-2 mutants and also attenuated the lifespan extension induced by daf-2 RNAi. These data showed that lin-23 is required for the extended lifespan of daf-2 mutants for a function that is independent of its developmental role in cell cycle regulation.
Lifespan comparisons
Double mutant daf-2(RNAi);lin-23(ot1) has a lifespan of 14.2 days, while single mutant daf-2(RNAi) has a lifespan of 28.9 days, single mutant lin-23(ot1) has a lifespan of 13.4 days and wild type has a lifespan of 16.2 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

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

Temperature °C
20
Lifespan (days)
25.0
Phenotype
We found that lin-23(ot1) reduced the lifespan extension of daf-2 mutants and also attenuated the lifespan extension induced by daf-2 RNAi. These data showed that lin-23 is required for the extended lifespan of daf-2 mutants for a function that is independent of its developmental role in cell cycle regulation.
Lifespan comparisons
Double mutant daf-2(e1368);lin-23(ot1) has a lifespan of 25 days, while single mutant daf-2(e1368) has a lifespan of 33.4 days.
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
20
Lifespan (days)
24.3
Phenotype
We found that lin-23(ot1) reduced the lifespan extension of daf-2 mutants and also attenuated the lifespan extension induced by daf-2 RNAi. These data showed that lin-23 is required for the extended lifespan of daf-2 mutants for a function that is independent of its developmental role in cell cycle regulation.
Lifespan comparisons
Double mutant daf-2(e1368);lin-23(ot1) has a lifespan of 24.3 days, while single mutant daf-2(e1368) has a lifespan of 33.4 days.
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
20
Lifespan (days)
21.6
Phenotype
We found that lin-23(ot1) reduced the lifespan extension of daf-2 mutants and also attenuated the lifespan extension induced by daf-2 RNAi. These data showed that lin-23 is required for the extended lifespan of daf-2 mutants for a function that is independent of its developmental role in cell cycle regulation.
Lifespan comparisons
Double mutant daf-2(e1368);lin-23(ot1) has a lifespan of 21.6 days, while single mutant daf-2(e1368) has a lifespan of 36.3 days.
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
20
Lifespan (days)
23.7
Phenotype
We found that lin-23(ot1) reduced the lifespan extension of daf-2 mutants and also attenuated the lifespan extension induced by daf-2 RNAi. These data showed that lin-23 is required for the extended lifespan of daf-2 mutants for a function that is independent of its developmental role in cell cycle regulation.
Lifespan comparisons
Double mutant daf-2(e1368);lin-23(ot1) has a lifespan of 23.7 days, while single mutant daf-2(e1368) has a lifespan of 36.3 days.
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
25
Lifespan (days)
21.2
Phenotype
We found that lin-23(ot1) reduced the lifespan extension of daf-2 mutants and also attenuated the lifespan extension induced by daf-2 RNAi. These data showed that lin-23 is required for the extended lifespan of daf-2 mutants for a function that is independent of its developmental role in cell cycle regulation.
Lifespan comparisons
Double mutant daf-2(e1368);lin-23(ot1) has a lifespan of 21.2 days, while single mutant daf-2(e1368) has a lifespan of 34.1 days.
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
25
Lifespan (days)
22.9
Phenotype
We found that lin-23(ot1) reduced the lifespan extension of daf-2 mutants and also attenuated the lifespan extension induced by daf-2 RNAi. These data showed that lin-23 is required for the extended lifespan of daf-2 mutants for a function that is independent of its developmental role in cell cycle regulation.
Lifespan comparisons
Double mutant daf-2(e1368);lin-23(ot1) has a lifespan of 22.9 days, while single mutant daf-2(e1368) has a lifespan of 34.1 days.
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

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

Temperature °C
20
Lifespan (days)
37.4
Phenotype
We found that lin-23(ot1) reduced the lifespan extension of daf-2 mutants and also attenuated the lifespan extension induced by daf-2 RNAi. These data showed that lin-23 is required for the extended lifespan of daf-2 mutants for a function that is independent of its developmental role in cell cycle regulation.
Lifespan comparisons
Double mutant daf-2(e1370);lin-23(ot1) has a lifespan of 37.4 days, while single mutant daf-2(e1370) has a lifespan of 55.2 days.
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
20
Lifespan (days)
38.8
Phenotype
We found that lin-23(ot1) reduced the lifespan extension of daf-2 mutants and also attenuated the lifespan extension induced by daf-2 RNAi. These data showed that lin-23 is required for the extended lifespan of daf-2 mutants for a function that is independent of its developmental role in cell cycle regulation.
Lifespan comparisons
Double mutant daf-2(e1370);lin-23(ot1) has a lifespan of 38.8 days, while single mutant daf-2(e1370) has a lifespan of 55.2 days.
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
20
Lifespan (days)
37.3
Phenotype
We found that lin-23(ot1) reduced the lifespan extension of daf-2 mutants and also attenuated the lifespan extension induced by daf-2 RNAi. These data showed that lin-23 is required for the extended lifespan of daf-2 mutants for a function that is independent of its developmental role in cell cycle regulation.
Lifespan comparisons
Double mutant daf-2(e1370);lin-23(ot1) has a lifespan of 37.3 days, while single mutant daf-2(e1370) has a lifespan of 55.2 days.
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
20
Lifespan (days)
42.2
Phenotype
We found that lin-23(ot1) reduced the lifespan extension of daf-2 mutants and also attenuated the lifespan extension induced by daf-2 RNAi. These data showed that lin-23 is required for the extended lifespan of daf-2 mutants for a function that is independent of its developmental role in cell cycle regulation.
Lifespan comparisons
Double mutant daf-2(e1370);lin-23(ot1) has a lifespan of 42.2 days, while single mutant daf-2(e1370) has a lifespan of 55.2 days.
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
20
Lifespan (days)
36.0
Phenotype
We found that lin-23(ot1) reduced the lifespan extension of daf-2 mutants and also attenuated the lifespan extension induced by daf-2 RNAi. These data showed that lin-23 is required for the extended lifespan of daf-2 mutants for a function that is independent of its developmental role in cell cycle regulation.
Lifespan comparisons
Double mutant daf-2(e1370);lin-23(ot1) has a lifespan of 36 days, while single mutant daf-2(e1370) has a lifespan of 55.2 days.
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
20
Lifespan (days)
39.6
Phenotype
We found that lin-23(ot1) reduced the lifespan extension of daf-2 mutants and also attenuated the lifespan extension induced by daf-2 RNAi. These data showed that lin-23 is required for the extended lifespan of daf-2 mutants for a function that is independent of its developmental role in cell cycle regulation.
Lifespan comparisons
Double mutant daf-2(e1370);lin-23(ot1) has a lifespan of 39.6 days, while single mutant daf-2(e1370) has a lifespan of 51.1 days.
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
20
Lifespan (days)
35.3
Phenotype
We found that lin-23(ot1) reduced the lifespan extension of daf-2 mutants and also attenuated the lifespan extension induced by daf-2 RNAi. These data showed that lin-23 is required for the extended lifespan of daf-2 mutants for a function that is independent of its developmental role in cell cycle regulation.
Lifespan comparisons
Double mutant daf-2(e1370);lin-23(ot1) has a lifespan of 35.3 days, while single mutant daf-2(e1370) has a lifespan of 51.1 days.
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
20
Lifespan (days)
34.6
Phenotype
We found that lin-23(ot1) reduced the lifespan extension of daf-2 mutants and also attenuated the lifespan extension induced by daf-2 RNAi. These data showed that lin-23 is required for the extended lifespan of daf-2 mutants for a function that is independent of its developmental role in cell cycle regulation.
Lifespan comparisons
Double mutant daf-2(e1370);lin-23(ot1) has a lifespan of 34.6 days, while single mutant daf-2(e1370) has a lifespan of 51.1 days.
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
20
Lifespan (days)
32.0
Phenotype
We found that lin-23(ot1) reduced the lifespan extension of daf-2 mutants and also attenuated the lifespan extension induced by daf-2 RNAi. These data showed that lin-23 is required for the extended lifespan of daf-2 mutants for a function that is independent of its developmental role in cell cycle regulation.
Lifespan comparisons
Double mutant daf-2(e1370);lin-23(ot1) has a lifespan of 32 days, while single mutant daf-2(e1370) has a lifespan of 51.1 days.
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
20
Lifespan (days)
38.1
Phenotype
We found that lin-23(ot1) reduced the lifespan extension of daf-2 mutants and also attenuated the lifespan extension induced by daf-2 RNAi. These data showed that lin-23 is required for the extended lifespan of daf-2 mutants for a function that is independent of its developmental role in cell cycle regulation.
Lifespan comparisons
Double mutant daf-2(e1370);lin-23(ot1) has a lifespan of 38.1 days, while single mutant daf-2(e1370) has a lifespan of 51.1 days.
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
20
Lifespan (days)
36.8
Phenotype
We found that lin-23(ot1) reduced the lifespan extension of daf-2 mutants and also attenuated the lifespan extension induced by daf-2 RNAi. These data showed that lin-23 is required for the extended lifespan of daf-2 mutants for a function that is independent of its developmental role in cell cycle regulation.
Lifespan comparisons
Double mutant daf-2(e1370);lin-23(ot1) has a lifespan of 36.8 days, while single mutant daf-2(e1370) has a lifespan of 51.1 days.
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
25
Lifespan (days)
42.7
Phenotype
lin-23(ot1) extended the lifespan of daf-2(e1370) mutants at 25oC. The reason underlying this temperature-dependent lifespan effect is unclear, but the phenomenon is reminiscent of the lifespan extension produced by the daf-2(e1370) mutation in combination with other longevity mutations such as sir-2.1(ok434) (1) and daf-12(m20) (2) . Similar to lin-23, sir-2.1 and daf-12 are longevity-promoting genes in other contexts
Lifespan comparisons
Double mutant daf-2(e1370);lin-23(ot1) has a lifespan of 42.7 days, while single mutant daf-2(e1370) has a lifespan of 40.7 days.
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
25
Lifespan (days)
44.8
Phenotype
lin-23(ot1) extended the lifespan of daf-2(e1370) mutants at 25oC. The reason underlying this temperature-dependent lifespan effect is unclear, but the phenomenon is reminiscent of the lifespan extension produced by the daf-2(e1370) mutation in combination with other longevity mutations such as sir-2.1(ok434) (1) and daf-12(m20) (2) . Similar to lin-23, sir-2.1 and daf-12 are longevity-promoting genes in other contexts
Lifespan comparisons
Double mutant daf-2(e1370);lin-23(ot1) has a lifespan of 44.8 days, while single mutant daf-2(e1370) has a lifespan of 40.7 days.
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
25
Lifespan (days)
46.6
Phenotype
lin-23(ot1) extended the lifespan of daf-2(e1370) mutants at 25oC. The reason underlying this temperature-dependent lifespan effect is unclear, but the phenomenon is reminiscent of the lifespan extension produced by the daf-2(e1370) mutation in combination with other longevity mutations such as sir-2.1(ok434) (1) and daf-12(m20) (2) . Similar to lin-23, sir-2.1 and daf-12 are longevity-promoting genes in other contexts
Lifespan comparisons
Double mutant daf-2(e1370);lin-23(ot1) has a lifespan of 46.6 days, while single mutant daf-2(e1370) has a lifespan of 40.7 days.
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
25
Lifespan (days)
52.1
Phenotype
lin-23(ot1) extended the lifespan of daf-2(e1370) mutants at 25oC. The reason underlying this temperature-dependent lifespan effect is unclear, but the phenomenon is reminiscent of the lifespan extension produced by the daf-2(e1370) mutation in combination with other longevity mutations such as sir-2.1(ok434) (1) and daf-12(m20) (2) . Similar to lin-23, sir-2.1 and daf-12 are longevity-promoting genes in other contexts
Lifespan comparisons
Double mutant daf-2(e1370);lin-23(ot1) has a lifespan of 52.1 days, while single mutant daf-2(e1370) has a lifespan of 40.7 days.
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
25
Lifespan (days)
51.3
Phenotype
lin-23(ot1) extended the lifespan of daf-2(e1370) mutants at 25oC. The reason underlying this temperature-dependent lifespan effect is unclear, but the phenomenon is reminiscent of the lifespan extension produced by the daf-2(e1370) mutation in combination with other longevity mutations such as sir-2.1(ok434) (1) and daf-12(m20) (2) . Similar to lin-23, sir-2.1 and daf-12 are longevity-promoting genes in other contexts
Lifespan comparisons
Double mutant daf-2(e1370);lin-23(ot1) has a lifespan of 51.3 days, while single mutant daf-2(e1370) has a lifespan of 40.7 days.
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
25
Lifespan (days)
55.4
Phenotype
lin-23(ot1) extended the lifespan of daf-2(e1370) mutants at 25oC. The reason underlying this temperature-dependent lifespan effect is unclear, but the phenomenon is reminiscent of the lifespan extension produced by the daf-2(e1370) mutation in combination with other longevity mutations such as sir-2.1(ok434) (1) and daf-12(m20) (2) . Similar to lin-23, sir-2.1 and daf-12 are longevity-promoting genes in other contexts
Lifespan comparisons
Double mutant daf-2(e1370);lin-23(ot1) has a lifespan of 55.4 days, while single mutant daf-2(e1370) has a lifespan of 40.7 days.
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Search genes: daf-2 lin-23

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

174058
lin-23
View on GenAge (lin-23)
WBGene00003009

F-box/WD repeat-containing protein lin-23;hypothetical protein

Locus: CELE_K10B2.1

Wormbase description: lin-23 encodes an F-box- and WD-repeat-containing protein homologous to Saccharomyces cerevisiae MET30 and human beta-TRCP (OMIM:603482), components of SCF (Skp1, Cullin, F-box) ubiquitin-ligase complexes that function in ubiquitin-mediated protein degradation; LIN-23 negatively regulates postembryonic cell divsions in all tissue types, and specifically, has been shown to function cell autonomously in the vulva to negatively regulate cell cycle progression and allow for cell cycle exit; LIN-23 also functions cell autonomously in some neurons to regulate neurite outgrowth and functions to regulate postsynaptic abundance of the GLR-1 glutamate receptor via a Wnt signaling pathway and LIN-23-mediated degradation of BAR-1/beta-catenin; LIN-23 expression is first detected broadly during gastrulation, with expression continuing postembryonically in body wall and enteric muscle, hypodermal cells, and many but not all neurons; LIN-23 localizes to the cytoplasm.

Orthologs of daf-2;lin-23 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	InR;slmb
Mus musculus	Btrc;Insr
Mus musculus	Fbxw11;Insr
Mus musculus	Btrc;Igf1r
Mus musculus	Fbxw11;Igf1r
Mus musculus	Btrc;Insrr
Mus musculus	Fbxw11;Insrr
Mus musculus	Insr;Btrc
Mus musculus	Insr;Fbxw11
Mus musculus	Igf1r;Btrc
Mus musculus	Igf1r;Fbxw11
Mus musculus	Insrr;Btrc
Mus musculus	Insrr;Fbxw11

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 lin-23 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	slmb
Mus musculus	Btrc
Mus musculus	Fbxw11