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PMID:22922647

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Citation

Vilchez, D, Morantte, I, Liu, Z, Douglas, PM, Merkwirth, C, Rodrigues, AP, Manning, G and Dillin, A (2012) RPN-6 determines C. elegans longevity under proteotoxic stress conditions. Nature 489:263-8

Abstract

Organisms that protect their germ-cell lineages from damage often do so at considerable cost: limited metabolic resources become partitioned away from maintenance of the soma, leaving the ageing somatic tissues to navigate survival amid an environment containing damaged and poorly functioning proteins. Historically, experimental paradigms that limit reproductive investment result in lifespan extension. We proposed that germline-deficient animals might exhibit heightened protection from proteotoxic stressors in somatic tissues. We find that the forced re-investment of resources from the germ line to the soma in Caenorhabditis elegans results in elevated somatic proteasome activity, clearance of damaged proteins and increased longevity. This activity is associated with increased expression of rpn-6, a subunit of the 19S proteasome, by the FOXO transcription factor DAF-16. Ectopic expression of rpn-6 is sufficient to confer proteotoxic stress resistance and extend lifespan, indicating that rpn-6 is a candidate to correct deficiencies in age-related protein homeostasis disorders.

Links

PubMed Online version:10.1038/nature11315

Keywords

Animals; Animals, Genetically Modified; Caenorhabditis elegans/cytology; Caenorhabditis elegans/genetics; Caenorhabditis elegans/metabolism; Caenorhabditis elegans/physiology; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism; Cell Separation; Female; Gene Expression Regulation; Germ Cells/cytology; Germ Cells/metabolism; Heat-Shock Response/genetics; Homeostasis/radiation effects; Longevity/genetics; Longevity/physiology; Longevity/radiation effects; Male; Mutation/genetics; Oxidative Stress/physiology; Peptides/metabolism; Proteasome Endopeptidase Complex/chemistry; Proteasome Endopeptidase Complex/genetics; Proteasome Endopeptidase Complex/metabolism; Stress, Physiological/physiology; Stress, Physiological/radiation effects; Transcription Factors/metabolism; Ultraviolet Rays

Significance

Annotations

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

CAEEL:FOXO

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:FOXO

located_in

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:PS11A

involved_in

GO:0008340: determination of adult lifespan

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:PS11A

involved_in

GO:0006511: ubiquitin-dependent protein catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:PS11A

part_of

GO:0022624: proteasome accessory complex

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

CAEEL:PS11A

involved_in

GO:0043248: proteasome assembly

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:FOXO

involved_in

GO:0008340: determination of adult lifespan

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:FOXO

involved_in

GO:0006974: cellular response to DNA damage stimulus

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:FOXO

part_of

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:FOXO

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:FOXO

enables

GO:0003700: DNA-binding transcription factor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

See also

References

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