daf-16;unc-13

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Genetic mutants with daf-16, unc-13 alterations

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

Temperature °C
20
Diet
NGM
Lifespan (days)
23.9
Lifespan change (compared to wild type)
35.80%
Lifespan comparisons
Double mutant daf-16(mu86);unc-13(e450) has a lifespan of 23.9 days, while single mutant unc-13(e450) has a lifespan of 38.9 days and wild type has a lifespan of 17.6 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Wang Y, Tissenbaum HA, 2006, Overlapping and distinct functions for a Caenorhabditis elegans SIR2 and DAF-16/FOXO. Mech Ageing Dev. 127(1):48-56 16280150 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved SIR2 protein regulates life span in both yeast and worms: in both organisms overexpression of SIR2 can extend life span and in Caenorhabditis elegans this life span extension is dependent on the forkhead transcription factor, DAF-16. Here, we have done extensive genetic analysis with sir-2.1(ok434), a null mutant of C. elegans sir-2.1, the closest homolog to yeast Sir2p and human SIRT1 to further elucidate its function in life span regulation. sir-2.1(ok434) mutants show a slight decrease in life span as well as sensitivity to various stresses. Our genetic analysis suggests that sir-2.1 is required for life span extension by caloric restriction, independent of the insulin/IGF-1 signaling pathway. Importantly, analysis with unc-13 mutants indicates that sir-2.1 and daf-16 have overlapping and distinct roles in life span regulation. Our expression analysis shows that sir-2.1 has overlapping and distinct expression pattern compared with daf-16, consistent with the results from our genetic data. Our data defines a central role for C. elegans SIR2 in regulation of life span by caloric restriction and demonstrates that sir-2.1 and daf-16 have both overlapping and distinct functions in regulation of C. elegans life span.

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

Temperature °C
20
Diet
NGM
Lifespan (days)
21.6
Lifespan change (compared to wild type)
22.73%
Lifespan comparisons
Double mutant daf-16(mu86);unc-13(s69) has a lifespan of 21.6 days, while single mutant unc-13(s69) has a lifespan of 35.7 days and wild type has a lifespan of 17.6 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Wang Y, Tissenbaum HA, 2006, Overlapping and distinct functions for a Caenorhabditis elegans SIR2 and DAF-16/FOXO. Mech Ageing Dev. 127(1):48-56 16280150 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved SIR2 protein regulates life span in both yeast and worms: in both organisms overexpression of SIR2 can extend life span and in Caenorhabditis elegans this life span extension is dependent on the forkhead transcription factor, DAF-16. Here, we have done extensive genetic analysis with sir-2.1(ok434), a null mutant of C. elegans sir-2.1, the closest homolog to yeast Sir2p and human SIRT1 to further elucidate its function in life span regulation. sir-2.1(ok434) mutants show a slight decrease in life span as well as sensitivity to various stresses. Our genetic analysis suggests that sir-2.1 is required for life span extension by caloric restriction, independent of the insulin/IGF-1 signaling pathway. Importantly, analysis with unc-13 mutants indicates that sir-2.1 and daf-16 have overlapping and distinct roles in life span regulation. Our expression analysis shows that sir-2.1 has overlapping and distinct expression pattern compared with daf-16, consistent with the results from our genetic data. Our data defines a central role for C. elegans SIR2 in regulation of life span by caloric restriction and demonstrates that sir-2.1 and daf-16 have both overlapping and distinct functions in regulation of C. elegans life span.

Search genes: daf-16 unc-13

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

172497
unc-13
View on GenAge (unc-13)
WBGene00006752

Phorbol ester/diacylglycerol-binding protein unc-13;hypothetical protein

Locus: CELE_ZK524.2

Wormbase description: unc-13 encodes at least five protein isoforms that regulate neurotransmitter release by altering the conformation of syntaxin; UNC-13 proteins are required for normal pharyngeal pumping and thrashing in liquid, normally short lifespan, normally large brood sizes, and full adult body sizes; UNC-13 proteins have orthologs in vertebrates and Drosophila; UNC-13 proteins are complex, with multiple C2, phorbol ester-binding, and DUF1041 domains; UNC-13 protein form is localized to most or all synapses; many of the unc-13 mutant alleles with viable phenotypes are transcript-specific, while homozygotes with an unc-13 null (deletion) allele die as paralyzed first-stage larvae.

Orthologs of daf-16;unc-13 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Foxo6;Unc13a
Mus musculus	Foxo6;Unc13c
Mus musculus	Foxo6;Unc13b
Mus musculus	Foxo1;Unc13a
Mus musculus	Foxo1;Unc13c
Mus musculus	Foxo1;Unc13b
Mus musculus	Foxo4;Unc13a
Mus musculus	Foxo4;Unc13c
Mus musculus	Foxo4;Unc13b
Mus musculus	Foxo3;Unc13a
Mus musculus	Foxo3;Unc13c
Mus musculus	Foxo3;Unc13b
Mus musculus	Unc13a;Foxo6
Mus musculus	Unc13a;Foxo1
Mus musculus	Unc13a;Foxo4
Mus musculus	Unc13a;Foxo3
Mus musculus	Unc13c;Foxo6
Mus musculus	Unc13c;Foxo1
Mus musculus	Unc13c;Foxo4
Mus musculus	Unc13c;Foxo3
Mus musculus	Unc13b;Foxo6
Mus musculus	Unc13b;Foxo1
Mus musculus	Unc13b;Foxo4
Mus musculus	Unc13b;Foxo3

Orthologs of daf-16 in SynergyAge

Show in SynergyAge
Species	Gene

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

Orthologs of unc-13 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Unc13a
Mus musculus	Unc13c
Mus musculus	Unc13b