age-1;cup-4

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Genetic mutants with age-1, cup-4 alterations

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

Temperature °C
20
Diet
NGM
Lifespan (days)
18.2
Lifespan change (compared to wild type)
6.43%
Lifespan comparisons
Double mutant age-1(hx546);cup-4(RNAi) has a lifespan of 18.2 days, while single mutant age-1(hx546) has a lifespan of 20.3 days and wild type has a lifespan of 17.1 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Park SK et al., 2010, Life-span extension by dietary restriction is mediated by NLP-7 signaling and coelomocyte endocytosis in C. elegans. FASEB J. 24(2):383-92 19783783 Click here to select all mutants from this PubMed ID in the graph
Abstract
Recent studies have shown that the rate of aging can be modulated by diverse interventions. Dietary restriction is the most widely used intervention to promote longevity; however, the mechanisms underlying the effect of dietary restriction remain elusive. In a previous study, we identified two novel genes, nlp-7 and cup-4, required for normal longevity in Caenorhabditis elegans. nlp-7 is one of a set of neuropeptide-like protein genes; cup-4 encodes an ion-channel involved in endocytosis by coelomocytes. Here, we assess whether nlp-7 and cup-4 mediate longevity increases by dietary restriction. RNAi of nlp-7 or cup-4 significantly reduces the life span of the eat-2 mutant, a genetic model of dietary restriction, but has no effect on the life span of long-lived mutants resulting from reduced insulin/IGF-1 signaling or dysfunction of the mitochondrial electron transport chain. The life-span extension observed in wild-type N2 worms by dietary restriction using bacterial dilution is prevented significantly in nlp-7 and cup-4 mutants. RNAi knockdown of genes encoding candidate receptors of NLP-7 and genes involved in endocytosis by coelomocytes also specifically shorten the life span of the eat-2 mutant. We conclude that two novel pathways, NLP-7 signaling and endocytosis by coelomocytes, are required for life extension under dietary restriction in C. elegans.

Temperature °C
20
Diet
NGM
Lifespan (days)
20.9
Lifespan change (compared to wild type)
20.81%
Lifespan comparisons
Double mutant age-1(hx546);cup-4(RNAi) has a lifespan of 20.9 days, while single mutant age-1(hx546) has a lifespan of 20.4 days and wild type has a lifespan of 17.3 days.
Type of interaction
See methods
Partially known monotony. Positive epistasis
Citation
View abstract
Park SK et al., 2010, Life-span extension by dietary restriction is mediated by NLP-7 signaling and coelomocyte endocytosis in C. elegans. FASEB J. 24(2):383-92 19783783 Click here to select all mutants from this PubMed ID in the graph
Abstract
Recent studies have shown that the rate of aging can be modulated by diverse interventions. Dietary restriction is the most widely used intervention to promote longevity; however, the mechanisms underlying the effect of dietary restriction remain elusive. In a previous study, we identified two novel genes, nlp-7 and cup-4, required for normal longevity in Caenorhabditis elegans. nlp-7 is one of a set of neuropeptide-like protein genes; cup-4 encodes an ion-channel involved in endocytosis by coelomocytes. Here, we assess whether nlp-7 and cup-4 mediate longevity increases by dietary restriction. RNAi of nlp-7 or cup-4 significantly reduces the life span of the eat-2 mutant, a genetic model of dietary restriction, but has no effect on the life span of long-lived mutants resulting from reduced insulin/IGF-1 signaling or dysfunction of the mitochondrial electron transport chain. The life-span extension observed in wild-type N2 worms by dietary restriction using bacterial dilution is prevented significantly in nlp-7 and cup-4 mutants. RNAi knockdown of genes encoding candidate receptors of NLP-7 and genes involved in endocytosis by coelomocytes also specifically shorten the life span of the eat-2 mutant. We conclude that two novel pathways, NLP-7 signaling and endocytosis by coelomocytes, are required for life extension under dietary restriction in C. elegans.

Search genes: age-1 cup-4

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

176104
cup-4
View on GenAge (cup-4)
WBGene00000845

Acetylcholine receptor-like protein cup-4

Locus: CELE_C02C2.3

Wormbase description: cup-4 encodes a non-alpha ligand-gated ion channel with similarity to the nicotinic acetylcholine receptors; cup-4 is required cell autonomously for efficient fluid endocytosis in coelomocytes; cup-4 mutant animals display reduced levels of plasma membrane phosphatidylinositol 4,5-bisphosphate, suggesting that CUP-4 may regulate endocytosis via regulation of phospholipase C activity; in addition, cup-4 mutants display disorganized clathrin and RME-1 at the coelomocyte plasma membrane; CUP-4::GFP is expressed in coelomocytes where it localizes to the cytoplasm, primarily to cytoplasmic vesicles.

Orthologs of age-1;cup-4 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene

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 cup-4 in SynergyAge

Show in SynergyAge
Species	Gene