cbp-1;daf-16

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Genetic mutants with cbp-1, daf-16 alterations

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

Temperature °C
20
Lifespan (days)
12.2
Lifespan change (compared to wild type)
-41.46%
Phenotype
Cbp-1 RNAi blocks life extension by DR produced by three protocols.
Lifespan comparisons
Double mutant cbp-1(RNAi);daf-16(m26) has a lifespan of 12.2 days, while single mutant cbp-1(RNAi) has a lifespan of 14.16 days, single mutant daf-16(m26) has a lifespan of 12.84 days and wild type has a lifespan of 20.84 days.
Type of interaction
See methods
Almost additive (negative)
Citation
View abstract
Zhang M et al., 2009, Role of CBP and SATB-1 in aging, dietary restriction, and insulin-like signaling. PLoS Biol. 7(11):e1000245 19924292 Click here to select all mutants from this PubMed ID in the graph
Abstract
How dietary restriction (DR) increases lifespan and decreases disease burden are questions of major interest in biomedical research. Here we report that hypothalamic expression of CREB-binding protein (CBP) and CBP-binding partner Special AT-rich sequence binding protein 1 (SATB-1) is highly correlated with lifespan across five strains of mice, and expression of these genes decreases with age and diabetes in mice. Furthermore, in Caenorhabditis elegans, cbp-1 is induced by bacterial dilution DR (bDR) and the daf-2 mutation, and cbp-1 RNAi specifically in adults completely blocks lifespan extension by three distinct protocols of DR, partially blocks lifespan extension by the daf-2 mutation but not of cold, and blocks delay of other age-related pathologies by bDR. Inhibiting the C. elegans ortholog of SATB-1 and CBP-binding partners daf-16 and hsf-1 also attenuates lifespan extension by bDR, but not other protocols of DR. In a transgenic Abeta42 model of Alzheimer's disease, cbp-1 RNAi prevents protective effects of bDR and accelerates Abeta42-related pathology. Furthermore, consistent with the function of CBP as a histone acetyltransferase, drugs that enhance histone acetylation increase lifespan and reduce Abeta42-related pathology, protective effects completely blocked by cbp-1 RNAi. Other factors implicated in lifespan extension are also CBP-binding partners, suggesting that CBP constitutes a common factor in the modulation of lifespan and disease burden by DR and the insulin/IGF1 signaling pathway.

Search genes: cbp-1 daf-16

Entrez ID
Symbol
GenAge
Wormbase ID

176380
cbp-1
View on GenAge (cbp-1)
WBGene00000366

Protein cbp-1

Locus: CELE_R10E11.1

Wormbase description: cbp-1 encodes a homolog of the mammalian transcriptional cofactors CBP (OMIM:600140) and p300 (E1A-BINDING PROTEIN, 300-KD; OMIM:602700) that have been shown to possess histone acetyltransferase activity, and which, when mutated, lead to Rubinstein-Taybi syndrome (OMIM:180849) and colorectal cancer (OMIM:114500); at least one splicing form of CBP-1 exhibits histone acetyltransferase (HAT) activity in vitro and has a glutamine/asparagine-rich domain; CBP-1 is required during embryogenesis for differentiation of all non-neuronal somatic cell types; CBP-1 is expressed very early in embryogenesis, suggesting that it may interact with maternally provided transcription factors, such as SKN-1, to specific developmental fates.

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.

Orthologs of cbp-1;daf-16 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Ep300;Foxo6
Mus musculus	Ep300;Foxo1
Mus musculus	Ep300;Foxo4
Mus musculus	Ep300;Foxo3

Orthologs of cbp-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	nej
Mus musculus	Ep300

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