Reduced insulin/insulin-like growth factor-1 signaling and dietary restriction inhibit translation but preserve muscle mass in Caenorhabditis elegans

Mol Cell Proteomics. 2013 Dec;12(12):3624-39. doi: 10.1074/mcp.M113.027383. Epub 2013 Sep 3.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Caloric Restriction
  • Chromatography, Liquid
  • Energy Metabolism / genetics
  • Forkhead Transcription Factors
  • Gene Expression Regulation
  • Insulin / genetics
  • Insulin / metabolism*
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Longevity / genetics
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Muscles / metabolism*
  • Mutation
  • Protein Biosynthesis
  • Proteomics / methods
  • Receptor, Insulin / genetics
  • Receptor, Insulin / metabolism
  • Ribosomes / genetics
  • Ribosomes / metabolism
  • Signal Transduction*
  • Tandem Mass Spectrometry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Forkhead Transcription Factors
  • Insulin
  • Muscle Proteins
  • Transcription Factors
  • daf-16 protein, C elegans
  • Insulin-Like Growth Factor I
  • DAF-2 protein, C elegans
  • Receptor, Insulin