ddl-1;hsb-1

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Genetic mutants with ddl-1, hsb-1 alterations

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

Temperature °C
20
Lifespan (days)
28.1
Lifespan change (compared to wild type)
47.89%
Phenotype
Inhibition of ddl-1 does not further increase the lifespan of hsb-1(cg116) mutants, while it typically increases N2 lifespan by up to 33%.
Lifespan comparisons
Double mutant ddl-1(ok2916);hsb-1(cg116) has a lifespan of 28.1 days, while single mutant ddl-1(ok2916) has a lifespan of 23.4 days, single mutant hsb-1(cg116) has a lifespan of 29.1 days and wild type has a lifespan of 19.0 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Chiang WC et al., 2012, HSF-1 regulators DDL-1/2 link insulin-like signaling to heat-shock responses and modulation of longevity. Cell. 148(1-2):322-34 22265419 Click here to select all mutants from this PubMed ID in the graph
Abstract
Extended longevity is often correlated with increased resistance against various stressors. Insulin/IGF-1-like signaling (IIS) is known to have a conserved role in aging and cellular mechanisms against stress. In C. elegans, genetic studies suggest that heat-shock transcription factor HSF-1 is required for IIS to modulate longevity. Here, we report that the activity of HSF-1 is regulated by IIS. This regulation occurs at an early step of HSF-1 activation via two HSF-1 regulators, DDL-1 and DDL-2. Inhibition of DDL-1/2 increases longevity and thermotolerance in an hsf-1-dependent manner. Furthermore, biochemical analyses suggest that DDL-1/2 negatively regulate HSF-1 activity by forming a protein complex with HSF-1. The formation of this complex (DHIC) is affected by the phosphorylation status of DDL-1. Both the formation of DHIC and the phosphorylation of DDL-1 are controlled by IIS. Our findings point to DDL-1/2 as a link between IIS and the HSF-1 pathway.

Temperature °C
20
Lifespan (days)
29.2
Lifespan change (compared to wild type)
60.44%
Phenotype
Inhibition of ddl-1 does not further increase the lifespan of hsb-1(cg116) mutants, while it typically increases N2 lifespan by up to 33%.
Lifespan comparisons
Double mutant ddl-1(ok2916);hsb-1(cg116) has a lifespan of 29.2 days, while single mutant ddl-1(ok2916) has a lifespan of 24.1 days, single mutant hsb-1(cg116) has a lifespan of 30.8 days and wild type has a lifespan of 18.2 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Chiang WC et al., 2012, HSF-1 regulators DDL-1/2 link insulin-like signaling to heat-shock responses and modulation of longevity. Cell. 148(1-2):322-34 22265419 Click here to select all mutants from this PubMed ID in the graph
Abstract
Extended longevity is often correlated with increased resistance against various stressors. Insulin/IGF-1-like signaling (IIS) is known to have a conserved role in aging and cellular mechanisms against stress. In C. elegans, genetic studies suggest that heat-shock transcription factor HSF-1 is required for IIS to modulate longevity. Here, we report that the activity of HSF-1 is regulated by IIS. This regulation occurs at an early step of HSF-1 activation via two HSF-1 regulators, DDL-1 and DDL-2. Inhibition of DDL-1/2 increases longevity and thermotolerance in an hsf-1-dependent manner. Furthermore, biochemical analyses suggest that DDL-1/2 negatively regulate HSF-1 activity by forming a protein complex with HSF-1. The formation of this complex (DHIC) is affected by the phosphorylation status of DDL-1. Both the formation of DHIC and the phosphorylation of DDL-1 are controlled by IIS. Our findings point to DDL-1/2 as a link between IIS and the HSF-1 pathway.

Search genes: ddl-1 hsb-1

Entrez ID
Symbol
GenAge
Wormbase ID

173954
ddl-1
View on GenAge (ddl-1)
WBGene00019125

WASH complex subunit homolog 3

Locus: CELE_F59E12.10

Wormbase description: ddl-1 encodes a coiled-coil protein orthologous to vertebrate CCD53; loss of ddl-1 activity via RNAi results in a daf-16-dependent increase in lifespan.

Entrez ID
Symbol
GenAge
Wormbase ID

178208
hsb-1
View on GenAge (hsb-1)
WBGene00002002

Heat Shock factor Binding protein

Locus: CELE_K08E7.2

Wormbase description: none available

Orthologs of ddl-1;hsb-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	CCDC53;CG5446
Mus musculus	Hsbp1;Washc3
Mus musculus	CG5446;CCDC53

Orthologs of ddl-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	CCDC53
Mus musculus	Washc3

Orthologs of hsb-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	CG5446
Mus musculus	Hsbp1