ddl-2;hsf-1

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Genetic mutants with ddl-2, hsf-1 alterations

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

Temperature °C
20
Lifespan (days)
15.4
Lifespan change (compared to wild type)
-14.44%
Phenotype
RNAi treatment of ddl-2 failed to produce any significant lifespan extension on hsf-1(sy441) mutants, while reducing expression of ddl-2 by RNAi extends lifespan in wild type. This finding suggests that hsf-1 is required for the extended lifespan observed in ddl-2 RNAi treated animals.
Lifespan comparisons
Double mutant ddl-2(RNAi);hsf-1(sy441) has a lifespan of 15.4 days, while single mutant ddl-2(RNAi) has a lifespan of 20.2 days, single mutant hsf-1(sy441) has a lifespan of 14.9 days and wild type has a lifespan of 18.0 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
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)
13.1
Lifespan change (compared to wild type)
-23.84%
Phenotype
RNAi treatment of ddl-2 failed to produce any significant lifespan extension on hsf-1(sy441) mutants, while reducing expression of ddl-2 by RNAi extends lifespan in wild type. This finding suggests that hsf-1 is required for the extended lifespan observed in ddl-2 RNAi treated animals.
Lifespan comparisons
Double mutant ddl-2(RNAi);hsf-1(sy441) has a lifespan of 13.1 days, while single mutant ddl-2(RNAi) has a lifespan of 19.9 days, single mutant hsf-1(sy441) has a lifespan of 13.1 days and wild type has a lifespan of 17.2 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
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 hsf-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

173078
hsf-1
View on GenAge (hsf-1)
WBGene00002004

Heat Shock Factor

Locus: CELE_Y53C10A.12

Wormbase description: hsf-1 encodes the C. elegans heat-shock transcription factor ortholog; HSF-1 functions as a transcriptional regulator of stress-induced gene expression whose activity is required for heat-shock and proteotoxicity response, larval development, innate immunity, and regulation of adult lifespan; HSF-1 binds bovine calmodulin in vitro in a calcium-dependent manner.

Orthologs of ddl-2;hsf-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of ddl-2 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	wash
Mus musculus	Washc1

Orthologs of hsf-1 in SynergyAge

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Species	Gene