title: Reduced insulin/insulin-like growth factor-1 signaling and dietary restriction inhibit translation but preserve muscle mass in Caenorhabditis elegans.
abstract: Reduced signaling through the C. elegans insulin/insulin-like growth factor-1-like tyrosine kinase receptor daf-2 and dietary restriction via bacterial dilution are two well-characterized lifespan-extending interventions that operate in parallel or through (partially) independent mechanisms. Using accurate mass and time tag LC-MS/MS quantitative proteomics, we detected that the abundance of a large number of ribosomal subunits is decreased in response to dietary restriction, as well as in the daf-2(e1370) insulin/insulin-like growth factor-1-receptor mutant. In addition, general protein synthesis levels in these long-lived worms are repressed. Surprisingly, ribosomal transcript levels were not correlated to actual protein abundance, suggesting that post-transcriptional regulation determines ribosome content. Proteomics also revealed the increased presence of many structural muscle cell components in long-lived worms, which appeared to result from the prioritized preservation of muscle cell volume in nutrient-poor conditions or low insulin-like signaling. Activation of DAF-16, but not diet restriction, stimulates mRNA expression of muscle-related genes to prevent muscle atrophy. Important daf-2-specific proteome changes include overexpression of aerobic metabolism enzymes and general activation of stress-responsive and immune defense systems, whereas the increased abundance of many protein subunits of the proteasome core complex is a dietary-restriction-specific characteristic.
authors.affiliation: Biology Department, Ghent University, Proeftuinstraat 86 N1, B-9000 Ghent, Belgium;
authors.forename: Geert
authors.initials: G
authors.lastname: Depuydt
authors.forename: Fang
authors.initials: F
authors.lastname: Xie
authors.forename: Vladislav A
authors.initials: VA
authors.lastname: Petyuk
authors.forename: Nilesh
authors.initials: N
authors.lastname: Shanmugam
authors.forename: Arne
authors.initials: A
authors.lastname: Smolders
authors.forename: Ineke
authors.initials: I
authors.lastname: Dhondt
authors.forename: Heather M
authors.initials: HM
authors.lastname: Brewer
authors.forename: David G
authors.initials: DG
authors.lastname: Camp
authors.forename: Richard D
authors.initials: RD
authors.lastname: Smith
authors.forename: Bart P
authors.initials: BP
authors.lastname: Braeckman
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D031204:Caloric Restriction; D002853:Chromatography, Liquid; D004734:Energy Metabolism / Q000235:genetics; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008136:Longevity / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism*; D009154:Mutation; D014176:Protein Biosynthesis; D040901:Proteomics / Q000379:methods; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D053719:Tandem Mass Spectrometry; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D007328:Insulin; D009124:Muscle Proteins; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D007334:Insulin-Like Growth Factor I; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin