hsp-16.1;hsp-16.11;hsp-16.2;rsks-1

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Genetic mutants with hsp-16.1, hsp-16.11, hsp-16.2, rsks-1 alterations

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

Temperature °C
22.5
Diet
NGM
Lifespan (days)
21.3
Lifespan change (compared to wild type)
19.66%
Phenotype
hsp-16.1/2/11 RNAi, which targets hsp-16.1, hsp-16.2, and hsp-16.11, suppressed the longevity conferred by rsks-1(tm1714) mutations in three of four trials (two of two trials at 20 °C and one of two trials at 22.5 °C.). We speculate that the inconsistency might originate from the differences in temperatures (20 °C vs. 22.5 °C). In addition, we cannot exclude the possibility that hsp-16.1/2/11 RNAi did not work for one trial that did not display the longevity suppression or the RNAi exhibited variations among trials. Note that hsp-16.1/2/11 RNAi was designed to target hsp-16.1, but because of over 88% sequence identity among hsp-16.1, hsp-16.2, and hsp-16.11 genes, the RNAi clone is expected to target hsp-16.1, hsp-16.2, and hsp-16.11 genes.
Lifespan comparisons
Quadruple mutant hsp-16.1(RNAi);hsp-16.11(RNAi);hsp-16.2(RNAi);rsks-1(tm1714) has a lifespan of 21.3 days, while triple mutant hsp-16.1(RNAi);hsp-16.11(RNAi);hsp-16.2(RNAi) has a lifespan of 16.9 days, single mutant rsks-1(tm1714) has a lifespan of 21.4 days and wild type has a lifespan of 17.8 days.
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)
15.0
Lifespan change (compared to wild type)
-7.41%
Phenotype
hsp-16.1/2/11 RNAi, which targets hsp-16.1, hsp-16.2, and hsp-16.11, suppressed the longevity conferred by rsks-1(tm1714) mutations in three of four trials (two of two trials at 20 °C and one of two trials at 22.5 °C.). We speculate that the inconsistency might originate from the differences in temperatures (20 °C vs. 22.5 °C). In addition, we cannot exclude the possibility that hsp-16.1/2/11 RNAi did not work for one trial that did not display the longevity suppression or the RNAi exhibited variations among trials. Note that hsp-16.1/2/11 RNAi was designed to target hsp-16.1, but because of over 88% sequence identity among hsp-16.1, hsp-16.2, and hsp-16.11 genes, the RNAi clone is expected to target hsp-16.1, hsp-16.2, and hsp-16.11 genes.
Lifespan comparisons
Quadruple mutant hsp-16.1(RNAi);hsp-16.11(RNAi);hsp-16.2(RNAi);rsks-1(tm1714) has a lifespan of 15.0 days, while triple mutant hsp-16.1(RNAi);hsp-16.11(RNAi);hsp-16.2(RNAi) has a lifespan of 14.5 days, single mutant rsks-1(tm1714) has a lifespan of 18.5 days and wild type has a lifespan of 16.2 days.
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: hsp-16.1 hsp-16.11 hsp-16.2 rsks-1 hsp-16.1;hsp-16.11;hsp-16.2;rsks-1

Entrez ID
Symbol
GenAge
Wormbase ID

179286
hsp-16.1
View on GenAge (hsp-16.1)
WBGene00002015

Heat shock protein Hsp-16.1/Hsp-16.11

Locus: CELE_T27E4.8

Wormbase description: hsp-16.1 encodes a 16-kD heat shock protein (HSP) that is a member of the hsp16/hsp20/alphaB-crystallin (HSP16) family of heat shock proteins, and that is identical to the protein encoded by hsp-16.11; an hsp-16.1 reporter fusion, expressed broadly but most strongly in muscle and hypodermis, is induced solely in response to heat shock or other environmental stresses; expression is detectable in somatic tissues in post-gastrulation embryos, all larval stages, and in adults; HSP-16.1 is likely to function as a passive ligand temporarily preventing unfolded proteins from aggregating.

Entrez ID
Symbol
GenAge
Wormbase ID

179289
hsp-16.11
View on GenAge (hsp-16.11)
WBGene00002017

Heat shock protein Hsp-16.1/Hsp-16.11

Locus: CELE_T27E4.2

Wormbase description: hsp-16.11 encodes a 16-kD heat shock protein (HSP) that is a member of the hsp16/hsp20/alphaB-crystallin (HSP16) family of heat shock proteins, and that is identical to the protein encoded by hsp-16.1; hsp-16.11 expression is induced in response to heat shock or other environmental stresses; HSP-16.11 is likely to function as passive ligand temporarily preventing unfolded proteins from aggregating; HSP-16.11 has been shown to interact with intracellular human beta amyloid peptide, a primary component of the extracellular plaques found in Alzheimer's disease.

Entrez ID
Symbol
GenAge
Wormbase ID

178659
hsp-16.2
View on GenAge (hsp-16.2)
WBGene00002016

Heat Shock Protein;Heat shock protein Hsp-16.2

Locus: CELE_Y46H3A.3

Wormbase description: hsp-16.2 encodes a 16-kD heat shock protein (HSP) that is a member of the hsp16/hsp20/alphaB-crystallin (HSP16) family of heat shock proteins; hsp-16.2 expression, strongest in intestine and pharynx, is induced in response to heat shock or other environmental stresses; HSP-16.2 has been shown to interact with intracellular human beta amyloid peptide, a primary component of the extracellular plaques found in Alzheimer's disease; HSP-16.2 is likely to function as a passive ligand temporarily preventing unfolded proteins from aggregating.

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 hsp-16.1;hsp-16.11;hsp-16.2;rsks-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Hsp22;Hsp22;Hsp22;S6k
Drosophila melanogaster	Hsp22;Hsp22;Hsp23;S6k
Drosophila melanogaster	Hsp22;Hsp22;Hsp26;S6k
Drosophila melanogaster	Hsp22;Hsp22;Hsp27;S6k
Drosophila melanogaster	Hsp22;Hsp22;Hsp67Bc;S6k
Drosophila melanogaster	Hsp22;Hsp23;Hsp23;S6k
Drosophila melanogaster	Hsp22;Hsp23;Hsp26;S6k
Drosophila melanogaster	Hsp22;Hsp23;Hsp27;S6k
Drosophila melanogaster	Hsp22;Hsp23;Hsp67Bc;S6k
Drosophila melanogaster	Hsp22;Hsp26;Hsp26;S6k
Drosophila melanogaster	Hsp22;Hsp26;Hsp27;S6k
Drosophila melanogaster	Hsp22;Hsp26;Hsp67Bc;S6k
Drosophila melanogaster	Hsp22;Hsp27;Hsp27;S6k
Drosophila melanogaster	Hsp22;Hsp27;Hsp67Bc;S6k
Drosophila melanogaster	Hsp22;Hsp67Bc;Hsp67Bc;S6k
Drosophila melanogaster	Hsp23;Hsp23;Hsp23;S6k
Drosophila melanogaster	Hsp23;Hsp23;Hsp26;S6k
Drosophila melanogaster	Hsp23;Hsp23;Hsp27;S6k
Drosophila melanogaster	Hsp23;Hsp23;Hsp67Bc;S6k
Drosophila melanogaster	Hsp23;Hsp26;Hsp26;S6k
Drosophila melanogaster	Hsp23;Hsp26;Hsp27;S6k
Drosophila melanogaster	Hsp23;Hsp26;Hsp67Bc;S6k
Drosophila melanogaster	Hsp23;Hsp27;Hsp27;S6k
Drosophila melanogaster	Hsp23;Hsp27;Hsp67Bc;S6k
Drosophila melanogaster	Hsp23;Hsp67Bc;Hsp67Bc;S6k
Drosophila melanogaster	Hsp26;Hsp26;Hsp26;S6k
Drosophila melanogaster	Hsp26;Hsp26;Hsp27;S6k
Drosophila melanogaster	Hsp26;Hsp26;Hsp67Bc;S6k
Drosophila melanogaster	Hsp26;Hsp27;Hsp27;S6k
Drosophila melanogaster	Hsp26;Hsp27;Hsp67Bc;S6k
Drosophila melanogaster	Hsp26;Hsp67Bc;Hsp67Bc;S6k
Drosophila melanogaster	Hsp27;Hsp27;Hsp27;S6k
Drosophila melanogaster	Hsp27;Hsp27;Hsp67Bc;S6k
Drosophila melanogaster	Hsp27;Hsp67Bc;Hsp67Bc;S6k
Drosophila melanogaster	Hsp67Bc;Hsp67Bc;Hsp67Bc;S6k

Orthologs of hsp-16.1 in SynergyAge

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Species	Gene

Orthologs of hsp-16.11 in SynergyAge

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Species	Gene

Orthologs of hsp-16.2 in SynergyAge

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Species	Gene

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