ddl-2;hsb-1

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Genetic mutants with ddl-2, hsb-1 alterations

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

Temperature °C
20
Lifespan (days)
29.2
Lifespan change (compared to wild type)
49.74%
Phenotype
The lifespan of hsb-1(cg116); ddl-2(ok3235) double mutants is not statistically different from hsb-1(cg116) single mutants.
Lifespan comparisons
Double mutant ddl-2(ok3235);hsb-1(cg116) has a lifespan of 29.2 days, while single mutant ddl-2(ok3235) has a lifespan of 24.0 days, single mutant hsb-1(cg116) has a lifespan of 27.8 days and wild type has a lifespan of 19.5 days.
Type of interaction
See methods
Almost additive (positive)
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)
27.9
Lifespan change (compared to wild type)
63.16%
Phenotype
The lifespan of hsb-1(cg116); ddl-2(ok3235) double mutants is not statistically different from hsb-1(cg116) single mutants.
Lifespan comparisons
Double mutant ddl-2(ok3235);hsb-1(cg116) has a lifespan of 27.9 days, while single mutant ddl-2(ok3235) has a lifespan of 21.8 days, single mutant hsb-1(cg116) has a lifespan of 26.6 days and wild type has a lifespan of 17.1 days.
Type of interaction
See methods
Almost additive (positive)
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-2 hsb-1

Entrez ID
Symbol
GenAge
Wormbase ID

190025
ddl-2
View on GenAge (ddl-2)
WBGene00013000

Daf-16-Dependent Longevity (WT but not daf-16 lifespan increased)

Locus: CELE_Y48E1B.1

Wormbase description: ddl-2 encodes a novel, proline-rich protein; loss of ddl-2 activity via RNAi results in a daf-16-dependent increase in lifespan and enhanced dauer formation, but not extended lifespan, of daf-2(e1370) mutant animals.

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-2;hsb-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	CG5446;wash
Mus musculus	Hsbp1;Washc1
Mus musculus	Washc1;Hsbp1

Orthologs of ddl-2 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	wash
Mus musculus	Washc1

Orthologs of hsb-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	CG5446
Mus musculus	Hsbp1