title: RPN-6 determines C. elegans longevity under proteotoxic stress conditions.
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.
authors.affiliation: Howard Hughes Medical Institute, Glenn Center for Aging Research, Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: David
authors.initials: D
authors.lastname: Vilchez
authors.forename: Ianessa
authors.initials: I
authors.lastname: Morantte
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Peter M
authors.initials: PM
authors.lastname: Douglas
authors.forename: Carsten
authors.initials: C
authors.lastname: Merkwirth
authors.forename: Ana P C
authors.initials: AP
authors.lastname: Rodrigues
authors.forename: Gerard
authors.initials: G
authors.lastname: Manning
authors.forename: Andrew
authors.initials: A
authors.lastname: Dillin
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002469:Cell Separation; D005260:Female; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism; D018869:Heat-Shock Response / Q000235:genetics; D006706:Homeostasis / Q000528:radiation effects; D008136:Longevity / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D009154:Mutation / Q000235:genetics; D018384:Oxidative Stress / Q000502:physiology; D010455:Peptides / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological / Q000502:physiology* / Q000528:radiation effects; D014157:Transcription Factors / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D010455:Peptides; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C097188:polyglutamine; D046988:Proteasome Endopeptidase Complex; C575985:RPN-6.1 protein, C elegans