hcf-1;sir-2.1

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

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
17.5
Lifespan change (compared to wild type)
15.89%
Phenotype
The hcf-1(pk924);sir-2.1(O/E) worms exhibited a lifespan very similar to, or in some cases shorter than, that of hcf-1(pk924) mutants. However, in none of the hcf-1(pk924);sir-2.1(O/E) isolates generated did we observe a lifespan longer than that of hcf-1(pk924) mutants.
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(OE) has a lifespan of 17.5 days, while single mutant sir-2.1(OE) has a lifespan of 17.6 days, single mutant hcf-1(pk924) has a lifespan of 19.4 days and wild type has a lifespan of 15.1 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
19.1
Lifespan change (compared to wild type)
26.49%
Phenotype
The hcf-1(pk924);sir-2.1(O/E) worms exhibited a lifespan very similar to, or in some cases shorter than, that of hcf-1(pk924) mutants. However, in none of the hcf-1(pk924);sir-2.1(O/E) isolates generated did we observe a lifespan longer than that of hcf-1(pk924) mutants.
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(OE) has a lifespan of 19.1 days, while single mutant sir-2.1(OE) has a lifespan of 17.3 days, single mutant hcf-1(pk924) has a lifespan of 18.9 days and wild type has a lifespan of 15.1 days.
Type of interaction
See methods
Almost additive (positive)
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
16.2
Lifespan change (compared to wild type)
5.19%
Phenotype
The hcf-1(pk924);sir-2.1(O/E) worms exhibited a lifespan very similar to, or in some cases shorter than, that of hcf-1(pk924) mutants. However, in none of the hcf-1(pk924);sir-2.1(O/E) isolates generated did we observe a lifespan longer than that of hcf-1(pk924) mutants.
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(OE) has a lifespan of 16.2 days, while single mutant sir-2.1(OE) has a lifespan of 17.5 days, single mutant hcf-1(pk924) has a lifespan of 18.4 days and wild type has a lifespan of 15.4 days.
Type of interaction
See methods
Antagonistic (positive)
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
17.0
Lifespan change (compared to wild type)
10.39%
Phenotype
The hcf-1(pk924);sir-2.1(O/E) worms exhibited a lifespan very similar to, or in some cases shorter than, that of hcf-1(pk924) mutants. However, in none of the hcf-1(pk924);sir-2.1(O/E) isolates generated did we observe a lifespan longer than that of hcf-1(pk924) mutants.
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(OE) has a lifespan of 17.0 days, while single mutant sir-2.1(OE) has a lifespan of 17.5 days, single mutant hcf-1(pk924) has a lifespan of 18.4 days and wild type has a lifespan of 15.4 days.
Type of interaction
See methods
Antagonistic (positive)
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
17.8
Lifespan change (compared to wild type)
15.58%
Phenotype
The hcf-1(pk924);sir-2.1(O/E) worms exhibited a lifespan very similar to, or in some cases shorter than, that of hcf-1(pk924) mutants. However, in none of the hcf-1(pk924);sir-2.1(O/E) isolates generated did we observe a lifespan longer than that of hcf-1(pk924) mutants.
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(OE) has a lifespan of 17.8 days, while single mutant sir-2.1(OE) has a lifespan of 17.5 days, single mutant hcf-1(pk924) has a lifespan of 18.4 days and wild type has a lifespan of 15.4 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
16.7
Lifespan change (compared to wild type)
10.60%
Phenotype
The hcf-1(pk924);sir-2.1(O/E) worms exhibited a lifespan very similar to, or in some cases shorter than, that of hcf-1(pk924) mutants. However, in none of the hcf-1(pk924);sir-2.1(O/E) isolates generated did we observe a lifespan longer than that of hcf-1(pk924) mutants.
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(OE) has a lifespan of 16.7 days, while single mutant sir-2.1(OE) has a lifespan of 17.3 days, single mutant hcf-1(pk924) has a lifespan of 18.9 days and wild type has a lifespan of 15.1 days.
Type of interaction
See methods
Antagonistic (positive)
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
15.9
Lifespan change (compared to wild type)
5.30%
Phenotype
The hcf-1(pk924);sir-2.1(O/E) worms exhibited a lifespan very similar to, or in some cases shorter than, that of hcf-1(pk924) mutants. However, in none of the hcf-1(pk924);sir-2.1(O/E) isolates generated did we observe a lifespan longer than that of hcf-1(pk924) mutants.
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(OE) has a lifespan of 15.9 days, while single mutant sir-2.1(OE) has a lifespan of 17.6 days, single mutant hcf-1(pk924) has a lifespan of 19.4 days and wild type has a lifespan of 15.1 days.
Type of interaction
See methods
Antagonistic (positive)
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
16.5
Lifespan change (compared to wild type)
9.27%
Phenotype
The hcf-1(pk924);sir-2.1(O/E) worms exhibited a lifespan very similar to, or in some cases shorter than, that of hcf-1(pk924) mutants. However, in none of the hcf-1(pk924);sir-2.1(O/E) isolates generated did we observe a lifespan longer than that of hcf-1(pk924) mutants.
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(OE) has a lifespan of 16.5 days, while single mutant sir-2.1(OE) has a lifespan of 17.6 days, single mutant hcf-1(pk924) has a lifespan of 19.4 days and wild type has a lifespan of 15.1 days.
Type of interaction
See methods
Antagonistic (positive)
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
17.3
Lifespan change (compared to wild type)
14.57%
Phenotype
The hcf-1(pk924);sir-2.1(O/E) worms exhibited a lifespan very similar to, or in some cases shorter than, that of hcf-1(pk924) mutants. However, in none of the hcf-1(pk924);sir-2.1(O/E) isolates generated did we observe a lifespan longer than that of hcf-1(pk924) mutants.
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(OE) has a lifespan of 17.3 days, while single mutant sir-2.1(OE) has a lifespan of 17.3 days, single mutant hcf-1(pk924) has a lifespan of 18.9 days and wild type has a lifespan of 15.1 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
17.1
Lifespan change (compared to wild type)
13.25%
Phenotype
The hcf-1(pk924);sir-2.1(O/E) worms exhibited a lifespan very similar to, or in some cases shorter than, that of hcf-1(pk924) mutants. However, in none of the hcf-1(pk924);sir-2.1(O/E) isolates generated did we observe a lifespan longer than that of hcf-1(pk924) mutants.
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(OE) has a lifespan of 17.1 days, while single mutant sir-2.1(OE) has a lifespan of 17.6 days, single mutant hcf-1(pk924) has a lifespan of 19.4 days and wild type has a lifespan of 15.1 days.
Type of interaction
See methods
Antagonistic (positive)
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
18.4
Lifespan change (compared to wild type)
22.67%
Phenotype
The hcf-1(pk924);sir-2.1(O/E) worms exhibited a lifespan very similar to, or in some cases shorter than, that of hcf-1(pk924) mutants. However, in none of the hcf-1(pk924);sir-2.1(O/E) isolates generated did we observe a lifespan longer than that of hcf-1(pk924) mutants.
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(OE) has a lifespan of 18.4 days, while single mutant sir-2.1(OE) has a lifespan of 18.1 days, single mutant hcf-1(pk924) has a lifespan of 18.9 days and wild type has a lifespan of 15.0 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
15.5
Lifespan change (compared to wild type)
3.33%
Phenotype
The hcf-1(pk924);sir-2.1(O/E) worms exhibited a lifespan very similar to, or in some cases shorter than, that of hcf-1(pk924) mutants. However, in none of the hcf-1(pk924);sir-2.1(O/E) isolates generated did we observe a lifespan longer than that of hcf-1(pk924) mutants.
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(OE) has a lifespan of 15.5 days, while single mutant sir-2.1(OE) has a lifespan of 18.1 days, single mutant hcf-1(pk924) has a lifespan of 18.9 days and wild type has a lifespan of 15.0 days.
Type of interaction
See methods
Antagonistic (positive)
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
18.9
Lifespan change (compared to wild type)
25.17%
Phenotype
The hcf-1(pk924);sir-2.1(O/E) worms exhibited a lifespan very similar to, or in some cases shorter than, that of hcf-1(pk924) mutants. However, in none of the hcf-1(pk924);sir-2.1(O/E) isolates generated did we observe a lifespan longer than that of hcf-1(pk924) mutants.
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(OE) has a lifespan of 18.9 days, while single mutant sir-2.1(OE) has a lifespan of 17.6 days, single mutant hcf-1(pk924) has a lifespan of 19.4 days and wild type has a lifespan of 15.1 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

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

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
17.0
Lifespan change (compared to wild type)
18.88%
Phenotype
sir-2.1(ok434) mutants exhibited lifespan similar to that of wild-type worms and always substantially shorter than that of hcf-1(pk924).
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(ok434) has a lifespan of 17.0 days, while single mutant sir-2.1(ok434) has a lifespan of 13.3 days, single mutant hcf-1(pk924) has a lifespan of 17.8 days and wild type has a lifespan of 14.3 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
18.0
Lifespan change (compared to wild type)
29.50%
Phenotype
sir-2.1(ok434) mutants exhibited lifespan similar to that of wild-type worms and always substantially shorter than that of hcf-1(pk924).
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(ok434) has a lifespan of 18.0 days, while single mutant sir-2.1(ok434) has a lifespan of 12.8 days, single mutant hcf-1(pk924) has a lifespan of 17.5 days and wild type has a lifespan of 13.9 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
20.6
Lifespan change (compared to wild type)
43.06%
Phenotype
sir-2.1(ok434) mutants exhibited lifespan similar to that of wild-type worms and always substantially shorter than that of hcf-1(pk924).
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(ok434) has a lifespan of 20.6 days, while single mutant sir-2.1(ok434) has a lifespan of 15.6 days, single mutant hcf-1(pk924) has a lifespan of 19.7 days and wild type has a lifespan of 14.4 days.
Type of interaction
See methods
Almost additive (positive)
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
18.3
Lifespan change (compared to wild type)
27.08%
Phenotype
sir-2.1(ok434) mutants exhibited lifespan similar to that of wild-type worms and always substantially shorter than that of hcf-1(pk924).
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(ok434) has a lifespan of 18.3 days, while single mutant sir-2.1(ok434) has a lifespan of 15.6 days, single mutant hcf-1(pk924) has a lifespan of 19.7 days and wild type has a lifespan of 14.4 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
21.2
Lifespan change (compared to wild type)
47.22%
Phenotype
sir-2.1(ok434) mutants exhibited lifespan similar to that of wild-type worms and always substantially shorter than that of hcf-1(pk924).
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(ok434) has a lifespan of 21.2 days, while single mutant sir-2.1(ok434) has a lifespan of 15.6 days, single mutant hcf-1(pk924) has a lifespan of 19.7 days and wild type has a lifespan of 14.4 days.
Type of interaction
See methods
Synergistic (positive)
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
20.4
Lifespan change (compared to wild type)
41.67%
Phenotype
sir-2.1(ok434) mutants exhibited lifespan similar to that of wild-type worms and always substantially shorter than that of hcf-1(pk924).
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(ok434) has a lifespan of 20.4 days, while single mutant sir-2.1(ok434) has a lifespan of 15.6 days, single mutant hcf-1(pk924) has a lifespan of 19.7 days and wild type has a lifespan of 14.4 days.
Type of interaction
See methods
Almost additive (positive)
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
17.4
Lifespan change (compared to wild type)
20.00%
Phenotype
sir-2.1(ok434) mutants exhibited lifespan similar to that of wild-type worms and always substantially shorter than that of hcf-1(pk924).
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(ok434) has a lifespan of 17.4 days, while single mutant sir-2.1(ok434) has a lifespan of 15.3 days, single mutant hcf-1(pk924) has a lifespan of 18.0 days and wild type has a lifespan of 14.5 days.
Type of interaction
See methods
Synergistic (positive)
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
18.8
Lifespan change (compared to wild type)
29.66%
Phenotype
sir-2.1(ok434) mutants exhibited lifespan similar to that of wild-type worms and always substantially shorter than that of hcf-1(pk924).
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(ok434) has a lifespan of 18.8 days, while single mutant sir-2.1(ok434) has a lifespan of 15.3 days, single mutant hcf-1(pk924) has a lifespan of 18.0 days and wild type has a lifespan of 14.5 days.
Type of interaction
See methods
Synergistic (positive)
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
19.3
Lifespan change (compared to wild type)
33.10%
Phenotype
sir-2.1(ok434) mutants exhibited lifespan similar to that of wild-type worms and always substantially shorter than that of hcf-1(pk924).
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(ok434) has a lifespan of 19.3 days, while single mutant sir-2.1(ok434) has a lifespan of 15.3 days, single mutant hcf-1(pk924) has a lifespan of 18.0 days and wild type has a lifespan of 14.5 days.
Type of interaction
See methods
Synergistic (positive)
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
18.2
Lifespan change (compared to wild type)
25.52%
Phenotype
sir-2.1(ok434) mutants exhibited lifespan similar to that of wild-type worms and always substantially shorter than that of hcf-1(pk924).
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(ok434) has a lifespan of 18.2 days, while single mutant sir-2.1(ok434) has a lifespan of 15.3 days, single mutant hcf-1(pk924) has a lifespan of 18.0 days and wild type has a lifespan of 14.5 days.
Type of interaction
See methods
Synergistic (positive)
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
18.4
Lifespan change (compared to wild type)
28.67%
Phenotype
sir-2.1(ok434) mutants exhibited lifespan similar to that of wild-type worms and always substantially shorter than that of hcf-1(pk924).
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(ok434) has a lifespan of 18.4 days, while single mutant sir-2.1(ok434) has a lifespan of 14.2 days, single mutant hcf-1(pk924) has a lifespan of 18.2 days and wild type has a lifespan of 14.3 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
17.9
Lifespan change (compared to wild type)
25.17%
Phenotype
sir-2.1(ok434) mutants exhibited lifespan similar to that of wild-type worms and always substantially shorter than that of hcf-1(pk924).
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(ok434) has a lifespan of 17.9 days, while single mutant sir-2.1(ok434) has a lifespan of 14.2 days, single mutant hcf-1(pk924) has a lifespan of 18.2 days and wild type has a lifespan of 14.3 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
20.2
Lifespan change (compared to wild type)
41.26%
Phenotype
sir-2.1(ok434) mutants exhibited lifespan similar to that of wild-type worms and always substantially shorter than that of hcf-1(pk924).
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(ok434) has a lifespan of 20.2 days, while single mutant sir-2.1(ok434) has a lifespan of 14.2 days, single mutant hcf-1(pk924) has a lifespan of 18.2 days and wild type has a lifespan of 14.3 days.
Type of interaction
See methods
Enhancer, opposite lifespan effects
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
19.9
Lifespan change (compared to wild type)
39.16%
Phenotype
sir-2.1(ok434) mutants exhibited lifespan similar to that of wild-type worms and always substantially shorter than that of hcf-1(pk924).
Lifespan comparisons
Double mutant hcf-1(pk924);sir-2.1(ok434) has a lifespan of 19.9 days, while single mutant sir-2.1(ok434) has a lifespan of 14.2 days, single mutant hcf-1(pk924) has a lifespan of 18.2 days and wild type has a lifespan of 14.3 days.
Type of interaction
See methods
Enhancer, opposite lifespan effects
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Not in SynergyAge
Species	Gene
Mus musculus	Hcfc1;Sirt1

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Hcf
Mus musculus	Hcfc1

Not in SynergyAge
Species	Gene
Mus musculus	Sirt1

hcf-1;sir-2.1

Genetic mutants with hcf-1, sir-2.1 alterations