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PMID:19783783

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Citation

Park, SK, Link, CD and Johnson, TE (2010) Life-span extension by dietary restriction is mediated by NLP-7 signaling and coelomocyte endocytosis in C. elegans. FASEB J. 24:383-92

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.

Links

PubMed PMC2812037 Online version:10.1096/fj.09-142984

Keywords

Aging/drug effects; Aging/physiology; Animals; Caenorhabditis elegans/cytology; Caenorhabditis elegans Proteins/physiology; Caloric Restriction; Endocytosis/physiology; Longevity/genetics; Neuropeptides/physiology; Oxidative Stress; RNA Interference; Signal Transduction/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CAEEL:G4SNP8

involved_in

GO:0008340: determination of adult lifespan

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q9U298

P

Seeded From UniProt

complete

CAEEL:NEC2

involved_in

GO:0008340: determination of adult lifespan

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q9U298

P

Seeded From UniProt

complete

CAEEL:I7FXD3

involved_in

GO:0008340: determination of adult lifespan

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q9U298

P

Seeded From UniProt

complete

CAEEL:CLH

involved_in

GO:0008340: determination of adult lifespan

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q9U298

P

Seeded From UniProt

complete

CAEEL:COQ7

involved_in

GO:0008340: determination of adult lifespan

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:COQ7

involved_in

GO:0008340: determination of adult lifespan

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P34271
UniProtKB:P34707
UniProtKB:Q19569

P

Seeded From UniProt

complete

CAEEL:P91487

involved_in

GO:0008340: determination of adult lifespan

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q9U298

P

Seeded From UniProt

complete

CAEEL:PHA4

involved_in

GO:0061771: response to caloric restriction

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:NLP7

involved_in

GO:0008340: determination of adult lifespan

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:NLP7

involved_in

GO:0008340: determination of adult lifespan

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q94125

P

Seeded From UniProt

complete

CAEEL:NLP7

involved_in

GO:0008340: determination of adult lifespan

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P48376

P

Seeded From UniProt

complete

CAEEL:NLP7

involved_in

GO:0061771: response to caloric restriction

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:NLP7

involved_in

GO:0061771: response to caloric restriction

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:NLP7

involved_in

GO:1901562: response to paraquat

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:NLP7

involved_in

GO:1901562: response to paraquat

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P34271

P

Seeded From UniProt

complete

CAEEL:NLP7

involved_in

GO:1901046: positive regulation of oviposition

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:Q8T666

involved_in

GO:0008340: determination of adult lifespan

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q9U298

P

Seeded From UniProt

complete

CAEEL:AGE1

involved_in

GO:0008340: determination of adult lifespan

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:AGE1

involved_in

GO:0008340: determination of adult lifespan

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P34271
UniProtKB:P34707
UniProtKB:Q19569

P

Seeded From UniProt

complete

CAEEL:Q9N4R6

involved_in

GO:0008340: determination of adult lifespan

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q9U298

P

Seeded From UniProt

complete

CAEEL:ACH8

involved_in

GO:0008340: determination of adult lifespan

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:CUP4

GO:0005216 : ion channel activity

ECO:0000269:

F

Figure 3D suggests resistance to oxidative resistance at the membrane level. Also, the author states "These findings indicate that NLP-7 and CUP-4 function in the same pathway under DR. Other SKN-1-dependent pathways might be activated by dietary restriction (DR)" .

complete
CACAO 4465

CAEEL:CUP4

involved_in

GO:0061771: response to caloric restriction

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:CUP4

involved_in

GO:1901562: response to paraquat

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:CUP4

involved_in

GO:1901562: response to paraquat

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P34707
UniProtKB:Q19569

P

Seeded From UniProt

complete

CAEEL:CUP4

involved_in

GO:0061771: response to caloric restriction

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:CUP4

involved_in

GO:0008340: determination of adult lifespan

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P34707
UniProtKB:Q19569

P

Seeded From UniProt

complete

CAEEL:CUP4

involved_in

GO:0008340: determination of adult lifespan

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:CUP4

involved_in

GO:1901046: positive regulation of oviposition

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:CUP4

involved_in

GO:0008340: determination of adult lifespan

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P48376

P

Seeded From UniProt

complete

CAEEL:CUP4

involved_in

GO:0008340: determination of adult lifespan

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q94125

P

Seeded From UniProt

complete

CAEEL:SKN1

involved_in

GO:1901562: response to paraquat

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P34271

P

Seeded From UniProt

complete

CAEEL:SKN1

involved_in

GO:0008340: determination of adult lifespan

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P34271

P

Seeded From UniProt

complete

CAEEL:SKN1

involved_in

GO:0008340: determination of adult lifespan

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q19569

P

Seeded From UniProt

complete

CAEEL:SKN1

involved_in

GO:0008340: determination of adult lifespan

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P48376

P

Seeded From UniProt

complete

CAEEL:SKN1

involved_in

GO:0008340: determination of adult lifespan

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q9U298

P

Seeded From UniProt

complete

CAEEL:SKN1

involved_in

GO:0008340: determination of adult lifespan

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q94125

P

Seeded From UniProt

complete


See also

References

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