daf-16;hsf-1

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Genetic mutants with daf-16, hsf-1 alterations

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

Temperature °C
25
Diet
HT115; OP55
Lifespan (days)
8.5
Lifespan change (compared to wild type)
-37.04%
Phenotype
Combination of daf-16(mgDf50) and hsf-1(RNAi) did not lead to a further decrease in life span, suggesting that daf-16 and hsf-1 may function in a common pathway to regulate longevity.
Lifespan comparisons
Double mutant daf-16(mgDf50);hsf-1(RNAi) has a lifespan of 8.5 days, while single mutant hsf-1(RNAi) has a lifespan of 9.6 days, single mutant daf-16(mgDf50) has a lifespan of 8.4 days and wild type has a lifespan of 13.5 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Morley JF, Morimoto RI, 2004, Regulation of longevity in Caenorhabditis elegans by heat shock factor and molecular chaperones. Mol Biol Cell. 15(2):657-64 14668486 Click here to select all mutants from this PubMed ID in the graph
Abstract
The correlation between longevity and stress resistance observed in long-lived mutant animals suggests that the ability to sense and respond to environmental challenges could be important for the regulation of life span. We therefore examined the role of heat shock factor (HSF-1), a master transcriptional regulator of stress-inducible gene expression and protein folding homeostasis, in the regulation of longevity. Down-regulation of hsf-1 by RNA interference suppressed longevity of mutants in an insulin-like signaling (ILS) pathway that functions in the nervous system of Caenorhabditis elegans to influence aging. hsf-1 was also required for temperature-induced dauer larvae formation in an ILS mutant. Using tissue-specific expression of wild-type or dominant negative HSF-1, we demonstrated that HSF-1 acts in multiple tissues to regulate longevity. Down-regulation of individual molecular chaperones, transcriptional targets of HSF-1, also decreased longevity of long-lived mutant but not wild-type animals. However, suppression by individual chaperones was to a lesser extent, suggesting an important role for networks of chaperones. The interaction of ILS with HSF-1 could represent an important molecular strategy to couple the regulation of longevity with an ancient genetic switch that governs the ability of cells to sense and respond to stress.

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

Temperature °C
20
Lifespan (days)
8.0
Lifespan change (compared to wild type)
-56.28%
Phenotype
We did observe that the life span of daf-16(mu86) animals could be further shortened by the loss of other life-span regulatory genes such as hsf-1
Lifespan comparisons
Double mutant daf-16(mu86);hsf-1(RNAi) has a lifespan of 8 days, while single mutant daf-16(mu86) has a lifespan of 10.8 days and wild type has a lifespan of 18.3 days.
Type of interaction
See methods
Partially known monotony. Negative epistasis
Citation
View abstract
Wolff S et al., 2006, SMK-1, an essential regulator of DAF-16-mediated longevity. Cell. 124(5):1039-53 16530049 Click here to select all mutants from this PubMed ID in the graph
Abstract
Insulin/IGF-1 signaling (IIS) regulates aging in worms, flies, and mice through a well-characterized, highly conserved core set of components. IIS also regulates early developmental decisions, the reproductive status of the animal, innate immunity, and stress-resistance functions. In C. elegans, the sole insulin/IGF-1 receptor, DAF-2, negatively regulates the FOXO transcription factor, DAF-16. We report here on a new component of the IIS longevity pathway, SMK-1, which specifically influences DAF-16-dependent regulation of the aging process in C. elegans by regulating the transcriptional specificity of DAF-16 activity. Localization analysis of DAF-16 places SMK-1 downstream of DAF-16's phosphorylation-dependent relocation to the nucleus. Physiological and transcription analyses indicate that smk-1 is required for the innate immune, UV, and oxidative stress but not the thermal stress functions of DAF-16. SMK-1 therefore plays a role in longevity by modulating DAF-16 transcriptional specificity without affecting other processes regulated by IIS.

Search genes: daf-16 hsf-1

Entrez ID
Symbol
GenAge
Wormbase ID

172981
daf-16
View on GenAge (daf-16)
WBGene00000912

Forkhead box protein O;hypothetical protein

Locus: CELE_R13H8.1

Wormbase description: daf-16 encodes the sole C. elegans forkhead box O (FOXO) homologue; DAF-16 functions as a transcription factor that acts in the insulin/IGF-1-mediated signaling (IIS) pathway that regulates dauer formation, longevity, fat metabolism, stress response, and innate immunity; DAF-16 regulates these various processes through isoform-specific expression, isoform-specific regulation by different AKT kinases, and differential regulation of target genes; DAF-16 can interact with the CBP-1 transcription cofactor in vitro, and interacts genetically with other genes in the insulin signaling and with daf-12, which encodes a nuclear hormone receptor; DAF-16 is activated in response to DNA damage during development and co-regulated by EGL-27, alleviates DNA-damage-induced developmental arrest by inducing DAF-16-associated element (DAE)-regulated genes; DAF-16 is broadly expressed but displays isoform-specific tissue enrichment; DAF-16 localizes to both the cytoplasm and the nucleus, with the ratio between the two an important regulator of function.

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 daf-16;hsf-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of daf-16 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Foxo6
Mus musculus	Foxo1
Mus musculus	Foxo4
Mus musculus	Foxo3

Orthologs of hsf-1 in SynergyAge

Show in SynergyAge
Species	Gene