ddl-1;ddl-2

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Genetic mutants with ddl-1, ddl-2 alterations

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

Temperature °C
20
Lifespan (days)
24.0
Lifespan change (compared to wild type)
42.86%
Phenotype
Inhibition of both ddl-1 and ddl-2 by RNAi does not lead to a larger lifespan extension compared to animals treated with ddl-1 or ddl-2 RNAi alone, suggesting that ddl-1 and ddl-2may have common effectors and act in the same genetic pathway.
Lifespan comparisons
Double mutant ddl-1(RNAi);ddl-2(RNAi) has a lifespan of 24.0 days, while single mutant ddl-2(RNAi) has a lifespan of 23.5 days, single mutant ddl-1(RNAi) has a lifespan of 22.3 days and wild type has a lifespan of 16.8 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-1 ddl-2

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

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.

Orthologs of ddl-1;ddl-2 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	CCDC53;wash
Mus musculus	Washc1;Washc3
Mus musculus	wash;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 ddl-2 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	wash
Mus musculus	Washc1

About

SynergyAge database hosts high-quality, manually curated information about the synergistic and antagonistic lifespan effects of genetic interventions in model organisms, also allowing users to explore the longevity relationships between genes in a visual way.