daf-16;rsks-1

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Genetic mutants with daf-16, rsks-1 alterations

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

Temperature °C
20
Diet
NGM
Lifespan (days)
16.5
Lifespan change (compared to wild type)
-17.09%
Phenotype
daf-16 RNAi treatment for whole life shortened the lifespan of bothrsks-1(tm1714) and wild type animals.
Lifespan comparisons
Double mutant daf-16(RNAi);rsks-1(tm1714) has a lifespan of 16.5 days, while single mutant daf-16(RNAi) has a lifespan of 14.6 days, single mutant rsks-1(tm1714) has a lifespan of 23.3 days and wild type has a lifespan of 19.9 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Seo K et al., 2013, Heat shock factor 1 mediates the longevity conferred by inhibition of TOR and insulin/IGF-1 signaling pathways in C. elegans. Aging Cell. 12(6):1073-81 23879233 Click here to select all mutants from this PubMed ID in the graph
Abstract
Target of rapamycin (TOR) signaling is an evolutionarily well-conserved pathway that regulates various physiologic processes, including aging and metabolism. One of the key downstream components of TOR signaling is ribosomal protein S6 kinase (S6K) whose inhibition extends the lifespan of yeast, Caenorhabditis elegans, Drosophila, and mice. Here, we demonstrate that the activation of heat shock factor 1 (HSF-1), a crucial longevity transcription factor known to act downstream of the insulin/IGF-1 signaling (IIS) pathway, mediates the prolonged lifespan conferred by mutations in C. elegans S6K (rsks-1). We found that hsf-1 is required for the longevity caused by down-regulation of components in TOR signaling pathways, including TOR and S6K. The induction of a small heat-shock protein hsp-16, a transcriptional target of HSF-1, mediates the long lifespan of rsks-1 mutants. Moreover, we show that synergistic activation of HSF-1 is required for the further enhanced longevity caused by simultaneous down-regulation of TOR and IIS pathways. Our findings suggest that HSF-1 acts as an essential longevity factor that intersects both IIS and TOR signaling pathways.

Temperature °C
20
Diet
NGM
Lifespan (days)
14.7
Lifespan change (compared to wild type)
-27.59%
Phenotype
daf-16 RNAi treatment for whole life shortened the lifespan of bothrsks-1(tm1714) and wild type animals.
Lifespan comparisons
Double mutant daf-16(RNAi);rsks-1(tm1714) has a lifespan of 14.7 days, while single mutant daf-16(RNAi) has a lifespan of 15.5 days, single mutant rsks-1(tm1714) has a lifespan of 22.3 days and wild type has a lifespan of 20.3 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Seo K et al., 2013, Heat shock factor 1 mediates the longevity conferred by inhibition of TOR and insulin/IGF-1 signaling pathways in C. elegans. Aging Cell. 12(6):1073-81 23879233 Click here to select all mutants from this PubMed ID in the graph
Abstract
Target of rapamycin (TOR) signaling is an evolutionarily well-conserved pathway that regulates various physiologic processes, including aging and metabolism. One of the key downstream components of TOR signaling is ribosomal protein S6 kinase (S6K) whose inhibition extends the lifespan of yeast, Caenorhabditis elegans, Drosophila, and mice. Here, we demonstrate that the activation of heat shock factor 1 (HSF-1), a crucial longevity transcription factor known to act downstream of the insulin/IGF-1 signaling (IIS) pathway, mediates the prolonged lifespan conferred by mutations in C. elegans S6K (rsks-1). We found that hsf-1 is required for the longevity caused by down-regulation of components in TOR signaling pathways, including TOR and S6K. The induction of a small heat-shock protein hsp-16, a transcriptional target of HSF-1, mediates the long lifespan of rsks-1 mutants. Moreover, we show that synergistic activation of HSF-1 is required for the further enhanced longevity caused by simultaneous down-regulation of TOR and IIS pathways. Our findings suggest that HSF-1 acts as an essential longevity factor that intersects both IIS and TOR signaling pathways.

Temperature °C
22.5
Diet
NGM
Lifespan (days)
14.4
Lifespan change (compared to wild type)
-19.10%
Phenotype
daf-16 RNAi treatment for during adulthood shortened the lifespan of both rsks-1(tm1714) and wild type animals.
Lifespan comparisons
Double mutant daf-16(RNAi);rsks-1(tm1714) has a lifespan of 14.4 days, while single mutant daf-16(RNAi) has a lifespan of 12.5 days, single mutant rsks-1(tm1714) has a lifespan of 21.4 days and wild type has a lifespan of 17.8 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Seo K et al., 2013, Heat shock factor 1 mediates the longevity conferred by inhibition of TOR and insulin/IGF-1 signaling pathways in C. elegans. Aging Cell. 12(6):1073-81 23879233 Click here to select all mutants from this PubMed ID in the graph
Abstract
Target of rapamycin (TOR) signaling is an evolutionarily well-conserved pathway that regulates various physiologic processes, including aging and metabolism. One of the key downstream components of TOR signaling is ribosomal protein S6 kinase (S6K) whose inhibition extends the lifespan of yeast, Caenorhabditis elegans, Drosophila, and mice. Here, we demonstrate that the activation of heat shock factor 1 (HSF-1), a crucial longevity transcription factor known to act downstream of the insulin/IGF-1 signaling (IIS) pathway, mediates the prolonged lifespan conferred by mutations in C. elegans S6K (rsks-1). We found that hsf-1 is required for the longevity caused by down-regulation of components in TOR signaling pathways, including TOR and S6K. The induction of a small heat-shock protein hsp-16, a transcriptional target of HSF-1, mediates the long lifespan of rsks-1 mutants. Moreover, we show that synergistic activation of HSF-1 is required for the further enhanced longevity caused by simultaneous down-regulation of TOR and IIS pathways. Our findings suggest that HSF-1 acts as an essential longevity factor that intersects both IIS and TOR signaling pathways.

Temperature °C
22.5
Diet
NGM
Lifespan (days)
12.1
Lifespan change (compared to wild type)
-25.31%
Phenotype
daf-16 RNAi treatment for during adulthood shortened the lifespan of both rsks-1(tm1714) and wild type animals.
Lifespan comparisons
Double mutant daf-16(RNAi);rsks-1(tm1714) has a lifespan of 12.1 days, while single mutant daf-16(RNAi) has a lifespan of 10.8 days, single mutant rsks-1(tm1714) has a lifespan of 18.5 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
Seo K et al., 2013, Heat shock factor 1 mediates the longevity conferred by inhibition of TOR and insulin/IGF-1 signaling pathways in C. elegans. Aging Cell. 12(6):1073-81 23879233 Click here to select all mutants from this PubMed ID in the graph
Abstract
Target of rapamycin (TOR) signaling is an evolutionarily well-conserved pathway that regulates various physiologic processes, including aging and metabolism. One of the key downstream components of TOR signaling is ribosomal protein S6 kinase (S6K) whose inhibition extends the lifespan of yeast, Caenorhabditis elegans, Drosophila, and mice. Here, we demonstrate that the activation of heat shock factor 1 (HSF-1), a crucial longevity transcription factor known to act downstream of the insulin/IGF-1 signaling (IIS) pathway, mediates the prolonged lifespan conferred by mutations in C. elegans S6K (rsks-1). We found that hsf-1 is required for the longevity caused by down-regulation of components in TOR signaling pathways, including TOR and S6K. The induction of a small heat-shock protein hsp-16, a transcriptional target of HSF-1, mediates the long lifespan of rsks-1 mutants. Moreover, we show that synergistic activation of HSF-1 is required for the further enhanced longevity caused by simultaneous down-regulation of TOR and IIS pathways. Our findings suggest that HSF-1 acts as an essential longevity factor that intersects both IIS and TOR signaling pathways.

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

Temperature °C
20
Lifespan (days)
16.0
Lifespan comparisons
Double mutant daf-16(mu86);rsks-1(RNAi) has a lifespan of 16 days, while single mutant daf-16(mu86) has a lifespan of 13.3 days.
Citation
View abstract
Hansen M et al., 2007, Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans. Aging Cell. 6(1):95-110 17266679 Click here to select all mutants from this PubMed ID in the graph
Abstract
Many conditions that shift cells from states of nutrient utilization and growth to states of cell maintenance extend lifespan. We have carried out a systematic lifespan analysis of conditions that inhibit protein synthesis. We find that reducing the levels of ribosomal proteins, ribosomal-protein S6 kinase or translation-initiation factors increases the lifespan of Caenorhabditis elegans. These perturbations, as well as inhibition of the nutrient sensor target of rapamycin (TOR), which is known to increase lifespan, all increase thermal-stress resistance. Thus inhibiting translation may extend lifespan by shifting cells to physiological states that favor maintenance and repair. Interestingly, different types of translation inhibition lead to one of two mutually exclusive outputs, one that increases lifespan and stress resistance through the transcription factor DAF-16/FOXO, and one that increases lifespan and stress resistance independently of DAF-16. Our findings link TOR, but not sir-2.1, to the longevity response induced by dietary restriction (DR) in C. elegans, and they suggest that neither TOR inhibition nor DR extends lifespan simply by reducing protein synthesis.

Temperature °C
20
Lifespan (days)
18.0
Lifespan comparisons
Double mutant daf-16(mu86);rsks-1(RNAi) has a lifespan of 18 days, while single mutant daf-16(mu86) has a lifespan of 15.2 days.
Citation
View abstract
Hansen M et al., 2007, Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans. Aging Cell. 6(1):95-110 17266679 Click here to select all mutants from this PubMed ID in the graph
Abstract
Many conditions that shift cells from states of nutrient utilization and growth to states of cell maintenance extend lifespan. We have carried out a systematic lifespan analysis of conditions that inhibit protein synthesis. We find that reducing the levels of ribosomal proteins, ribosomal-protein S6 kinase or translation-initiation factors increases the lifespan of Caenorhabditis elegans. These perturbations, as well as inhibition of the nutrient sensor target of rapamycin (TOR), which is known to increase lifespan, all increase thermal-stress resistance. Thus inhibiting translation may extend lifespan by shifting cells to physiological states that favor maintenance and repair. Interestingly, different types of translation inhibition lead to one of two mutually exclusive outputs, one that increases lifespan and stress resistance through the transcription factor DAF-16/FOXO, and one that increases lifespan and stress resistance independently of DAF-16. Our findings link TOR, but not sir-2.1, to the longevity response induced by dietary restriction (DR) in C. elegans, and they suggest that neither TOR inhibition nor DR extends lifespan simply by reducing protein synthesis.

Temperature °C
20
Diet
NGM; OP50
Lifespan (days)
13.7
Lifespan comparisons
Double mutant daf-16(mu86);rsks-1(RNAi) has a lifespan of 13.7 days, while single mutant daf-16(mu86) has a lifespan of 12.0 days.
Citation
View abstract
Pan KZ et al., 2007, Inhibition of mRNA translation extends lifespan in Caenorhabditis elegans. Aging Cell. 6(1):111-9 17266680 Click here to select all mutants from this PubMed ID in the graph
Abstract
Protein synthesis is a regulated cellular process that links nutrients in the environment to organismal growth and development. Here we examine the role of genes that regulate mRNA translation in determining growth, reproduction, stress resistance and lifespan. Translational control of protein synthesis by regulators such as the cap-binding complex and S6 kinase play an important role during growth. We observe that inhibition of various genes in the translation initiation complex including ifg-1, the worm homologue of eIF4G, which is a scaffold protein in the cap-binding complex; and rsks-1, the worm homologue of S6 kinase, results in lifespan extension in Caenorhabditis elegans. Inhibition of ifg-1 or rsks-1 also slows development, reduces fecundity and increases resistance to starvation. A reduction in ifg-1 expression in dauers was also observed, suggesting an inhibition of protein translation during the dauer state. Thus, mRNA translation exerts pleiotropic effects on growth, reproduction, stress resistance and lifespan in C. elegans.

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

Temperature °C
22.5
Diet
NGM
Lifespan (days)
13.2
Lifespan change (compared to wild type)
-31.96%
Phenotype
The long lifespan of rsks-1(tm1714) mutants was suppressed by daf-16(mu86) mutation.
Lifespan comparisons
Double mutant daf-16(mu86);rsks-1(tm1714) has a lifespan of 13.2 days, while single mutant daf-16(mu86) has a lifespan of 12.2 days, single mutant rsks-1(tm1714) has a lifespan of 22.4 days and wild type has a lifespan of 19.4 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Seo K et al., 2013, Heat shock factor 1 mediates the longevity conferred by inhibition of TOR and insulin/IGF-1 signaling pathways in C. elegans. Aging Cell. 12(6):1073-81 23879233 Click here to select all mutants from this PubMed ID in the graph
Abstract
Target of rapamycin (TOR) signaling is an evolutionarily well-conserved pathway that regulates various physiologic processes, including aging and metabolism. One of the key downstream components of TOR signaling is ribosomal protein S6 kinase (S6K) whose inhibition extends the lifespan of yeast, Caenorhabditis elegans, Drosophila, and mice. Here, we demonstrate that the activation of heat shock factor 1 (HSF-1), a crucial longevity transcription factor known to act downstream of the insulin/IGF-1 signaling (IIS) pathway, mediates the prolonged lifespan conferred by mutations in C. elegans S6K (rsks-1). We found that hsf-1 is required for the longevity caused by down-regulation of components in TOR signaling pathways, including TOR and S6K. The induction of a small heat-shock protein hsp-16, a transcriptional target of HSF-1, mediates the long lifespan of rsks-1 mutants. Moreover, we show that synergistic activation of HSF-1 is required for the further enhanced longevity caused by simultaneous down-regulation of TOR and IIS pathways. Our findings suggest that HSF-1 acts as an essential longevity factor that intersects both IIS and TOR signaling pathways.

Temperature °C
22.5
Diet
NGM
Lifespan (days)
14.2
Lifespan change (compared to wild type)
-29.70%
Phenotype
The long lifespan of rsks-1(tm1714) mutants was suppressed by daf-16(mu86) mutation.
Lifespan comparisons
Double mutant daf-16(mu86);rsks-1(tm1714) has a lifespan of 14.2 days, while single mutant daf-16(mu86) has a lifespan of 13.3 days, single mutant rsks-1(tm1714) has a lifespan of 25.2 days and wild type has a lifespan of 20.2 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Seo K et al., 2013, Heat shock factor 1 mediates the longevity conferred by inhibition of TOR and insulin/IGF-1 signaling pathways in C. elegans. Aging Cell. 12(6):1073-81 23879233 Click here to select all mutants from this PubMed ID in the graph
Abstract
Target of rapamycin (TOR) signaling is an evolutionarily well-conserved pathway that regulates various physiologic processes, including aging and metabolism. One of the key downstream components of TOR signaling is ribosomal protein S6 kinase (S6K) whose inhibition extends the lifespan of yeast, Caenorhabditis elegans, Drosophila, and mice. Here, we demonstrate that the activation of heat shock factor 1 (HSF-1), a crucial longevity transcription factor known to act downstream of the insulin/IGF-1 signaling (IIS) pathway, mediates the prolonged lifespan conferred by mutations in C. elegans S6K (rsks-1). We found that hsf-1 is required for the longevity caused by down-regulation of components in TOR signaling pathways, including TOR and S6K. The induction of a small heat-shock protein hsp-16, a transcriptional target of HSF-1, mediates the long lifespan of rsks-1 mutants. Moreover, we show that synergistic activation of HSF-1 is required for the further enhanced longevity caused by simultaneous down-regulation of TOR and IIS pathways. Our findings suggest that HSF-1 acts as an essential longevity factor that intersects both IIS and TOR signaling pathways.

Search genes: daf-16 rsks-1

Entrez ID
Symbol
GenAge
Wormbase ID

172981
daf-16
View on GenAge (daf-16)
WBGene00000912

Forkhead box protein O;hypothetical protein

Locus: CELE_R13H8.1

Wormbase description: daf-16 encodes the sole C. elegans forkhead box O (FOXO) homologue; DAF-16 functions as a transcription factor that acts in the insulin/IGF-1-mediated signaling (IIS) pathway that regulates dauer formation, longevity, fat metabolism, stress response, and innate immunity; DAF-16 regulates these various processes through isoform-specific expression, isoform-specific regulation by different AKT kinases, and differential regulation of target genes; DAF-16 can interact with the CBP-1 transcription cofactor in vitro, and interacts genetically with other genes in the insulin signaling and with daf-12, which encodes a nuclear hormone receptor; DAF-16 is activated in response to DNA damage during development and co-regulated by EGL-27, alleviates DNA-damage-induced developmental arrest by inducing DAF-16-associated element (DAE)-regulated genes; DAF-16 is broadly expressed but displays isoform-specific tissue enrichment; DAF-16 localizes to both the cytoplasm and the nucleus, with the ratio between the two an important regulator of function.

Entrez ID
Symbol
GenAge
Wormbase ID

176554
rsks-1
View on GenAge (rsks-1)
WBGene00012929

Ribosomal protein S6 kinase beta

Locus: CELE_Y47D3A.16

Wormbase description: rsks-1 encodes a putative ribosomal protein S6 kinase (S6K) required additively with IFG-1 for normally high levels of protein synthesis, and for normally short lifespan; RSKS-1's effect on lifespan is independent of DAF-16, ISP-1, and SIR-2.1, and does not correlate with juglone resistance, but does correlate with abnormally high resistance to starvation and (perhaps) thermotolerance; RSKS-1 is required for normal juglone resistance, as well as normally rapid growth and normal brood sizes; RSKS-1 is expressed in E-lineage embryonic cells, and in pharyngeal and hypodermal cells of larvae and adults; RSKS-1 is orthologous to human RPS6KB1 (OMIM:608938) and RPS6KB2 (OMIM:608939).

Orthologs of daf-16;rsks-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Foxo6;Rps6kb1
Mus musculus	Foxo6;Rps6kb2
Mus musculus	Foxo1;Rps6kb1
Mus musculus	Foxo1;Rps6kb2
Mus musculus	Foxo4;Rps6kb1
Mus musculus	Foxo4;Rps6kb2
Mus musculus	Foxo3;Rps6kb1
Mus musculus	Foxo3;Rps6kb2
Mus musculus	Rps6kb1;Foxo6
Mus musculus	Rps6kb1;Foxo1
Mus musculus	Rps6kb1;Foxo4
Mus musculus	Rps6kb1;Foxo3
Mus musculus	Rps6kb2;Foxo6
Mus musculus	Rps6kb2;Foxo1
Mus musculus	Rps6kb2;Foxo4
Mus musculus	Rps6kb2;Foxo3

Orthologs of daf-16 in SynergyAge

Show in SynergyAge
Species	Gene

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

Orthologs of rsks-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	S6k
Mus musculus	Rps6kb1
Mus musculus	Rps6kb2