Insulin-like signaling determines survival during stress via posttranscriptional mechanisms in C. elegans

Cell Metab. 2010 Sep 8;12(3):260-72. doi: 10.1016/j.cmet.2010.08.004.

Abstract

The insulin-like signaling (ILS) pathway regulates metabolism and is known to modulate adult life span in C. elegans. Altered stress responses and resistance to a wide range of stressors are also associated with changes in ILS and contribute to enhanced longevity. The transcription factors DAF-16 and HSF-1 are key effectors of the longevity phenotype. We demonstrate that increased intrinsic thermotolerance, due to lower ILS, is not dependent on stress-induced transcriptional responses but instead requires active protein translation. Translation profiling experiments reveal genes that are posttranscriptionally regulated in response to altered ILS during heat shock in a DAF-16-dependent manner. Furthermore, several novel proteins are specifically required for ILS effects on thermotolerance. We propose that lowered ILS results in metabolic and physiological changes. These DAF-16-induced changes precondition a translational response under acute stress to modulate survival.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Forkhead Transcription Factors
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism
  • Hot Temperature
  • Insulin / metabolism*
  • Microarray Analysis
  • Promoter Regions, Genetic
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, Insulin / genetics
  • Receptor, Insulin / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Ribosomes / metabolism
  • Signal Transduction / physiology*
  • Stress, Physiological / physiology*
  • Survival Rate*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic*

Substances

  • Caenorhabditis elegans Proteins
  • Forkhead Transcription Factors
  • Heat-Shock Proteins
  • Insulin
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Transcription Factors
  • daf-16 protein, C elegans
  • DAF-2 protein, C elegans
  • Receptor, Insulin