age-1;hcf-1

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Genetic mutants with age-1, hcf-1 alterations

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

Temperature °C
25
Diet
NGM; OP51
Lifespan (days)
26.5
Lifespan change (compared to wild type)
82.76%
Phenotype
RNAi knock down of age-1 in the hcf-1(ok559) mutant lived considerably longer than either the hcf-1(ok559) or age-1 RNAi single mutant.
Lifespan comparisons
Double mutant age-1(RNAi);hcf-1(ok559) has a lifespan of 26.5 days, while single mutant age-1(RNAi) has a lifespan of 21.1 days, single mutant hcf-1(ok559) has a lifespan of 16.0 days and wild type has a lifespan of 14.5 days.
Type of interaction
See methods
Synergistic (positive)
Citation
View abstract
Li J et al., 2008, Caenorhabditis elegans HCF-1 functions in longevity maintenance as a DAF-16 regulator. PLoS Biol. 6(9):e233 18828672 Click here to select all mutants from this PubMed ID in the graph
Abstract
The transcription factor DAF-16/forkhead box O (FOXO) is a critical longevity determinant in diverse organisms, however the molecular basis of how its transcriptional activity is regulated remains largely unknown. We report that the Caenorhabditis elegans homolog of host cell factor 1 (HCF-1) represents a new longevity modulator and functions as a negative regulator of DAF-16. In C. elegans, hcf-1 inactivation caused a daf-16-dependent lifespan extension of up to 40% and heightened resistance to specific stress stimuli. HCF-1 showed ubiquitous nuclear localization and physically associated with DAF-16. Furthermore, loss of hcf-1 resulted in elevated DAF-16 recruitment to the promoters of its target genes and altered expression of a subset of DAF-16-regulated genes. We propose that HCF-1 modulates C. elegans longevity and stress response by forming a complex with DAF-16 and limiting a fraction of DAF-16 from accessing its target gene promoters, and thereby regulates DAF-16-mediated transcription of selective target genes. As HCF-1 is highly conserved, our findings have important implications for aging and FOXO regulation in mammals.

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

Temperature °C
25
Diet
NGM; OP51
Lifespan (days)
26.7
Lifespan change (compared to wild type)
99.25%
Phenotype
The age-1(mg44);hcf-1(ok559) double mutant worms lived considerably longer than either the age-1(mg44) or hcf-1(ok559) single mutant.
Lifespan comparisons
Double mutant age-1(mg44);hcf-1(ok559) has a lifespan of 26.7 days, while single mutant hcf-1(ok559) has a lifespan of 15.6 days, single mutant age-1(mg44) has a lifespan of 20.0 days and wild type has a lifespan of 13.4 days.
Type of interaction
See methods
Synergistic (positive)
Citation
View abstract
Li J et al., 2008, Caenorhabditis elegans HCF-1 functions in longevity maintenance as a DAF-16 regulator. PLoS Biol. 6(9):e233 18828672 Click here to select all mutants from this PubMed ID in the graph
Abstract
The transcription factor DAF-16/forkhead box O (FOXO) is a critical longevity determinant in diverse organisms, however the molecular basis of how its transcriptional activity is regulated remains largely unknown. We report that the Caenorhabditis elegans homolog of host cell factor 1 (HCF-1) represents a new longevity modulator and functions as a negative regulator of DAF-16. In C. elegans, hcf-1 inactivation caused a daf-16-dependent lifespan extension of up to 40% and heightened resistance to specific stress stimuli. HCF-1 showed ubiquitous nuclear localization and physically associated with DAF-16. Furthermore, loss of hcf-1 resulted in elevated DAF-16 recruitment to the promoters of its target genes and altered expression of a subset of DAF-16-regulated genes. We propose that HCF-1 modulates C. elegans longevity and stress response by forming a complex with DAF-16 and limiting a fraction of DAF-16 from accessing its target gene promoters, and thereby regulates DAF-16-mediated transcription of selective target genes. As HCF-1 is highly conserved, our findings have important implications for aging and FOXO regulation in mammals.

Search genes: age-1 hcf-1

Entrez ID
Symbol
GenAge
Wormbase ID

174762
age-1
View on GenAge (age-1)
WBGene00000090

Phosphatidylinositol 3-kinase age-1;hypothetical protein

Locus: CELE_B0334.8

Wormbase description: age-1 encodes the C. elegans ortholog of the phosphoinositide 3-kinase (PI3K) p110 catalytic subunit; AGE-1, supplied maternally and embryonically, is a central component of the C. elegans insulin-like signaling pathway, lying downstream of the DAF-2/insulin receptor and upstream of both the PDK-1 and AKT-1/AKT-2 kinases and the DAF-16 forkhead type transcription factor, whose negative regulation is the key output of the insulin signaling pathway; in accordance with its role in insulin signaling, AGE-1 activity is required for regulation of metabolism, life span, dauer formation, stress resistance, salt chemotaxis learning, fertility, and embryonic development; although the age-1 expression pattern has not yet been reported, ectopic expression studies indicate that pan-neuronal age-1 expression is sufficient to rescue life-span defects, while neuronal, intestinal, or muscle expression can partially rescue dauer formation, and neuronal or muscle expression can rescue metabolic defects.

Entrez ID
Symbol
GenAge
Wormbase ID

177560
hcf-1
View on GenAge (hcf-1)
WBGene00001827

human HCF1 related

Locus: CELE_C46A5.9

Wormbase description: hcf-1 encodes the C. elegans ortholog of human host cell factor (HCF-1), a transcriptional regulator that associates with histone modification enzymes and plays a role in cell cycle progression; in C. elegans, hcf-1 plays a role in regulation of cell division and mitotic histone modification; in addition, HCF-1 functions in determination of adult lifespan as a negative regulator of DAF-16, with which it physically interacts; HCF-1 is a ubiquitously expressed protein that localizes to the nucleus.

Orthologs of age-1;hcf-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Hcf;Pi3K92E
Mus musculus	Hcfc1;Pik3cd
Mus musculus	Hcfc1;Pik3ca
Mus musculus	Hcfc1;Pik3cb
Mus musculus	Hcfc1;Pik3cg

Orthologs of age-1 in SynergyAge

Show in SynergyAge
Species	Gene
Drosophila melanogaster	Pi3K92E

Not in SynergyAge
Species	Gene
Mus musculus	Pik3cd
Mus musculus	Pik3ca
Mus musculus	Pik3cb
Mus musculus	Pik3cg

Orthologs of hcf-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Hcf
Mus musculus	Hcfc1