A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span

Dev Cell. 2005 Nov;9(5):605-15. doi: 10.1016/j.devcel.2005.09.017.

Abstract

C. elegans SIR-2.1, a member of the Sir-2 family of NAD(+)-dependent protein deacetylases, has been shown to regulate nematode aging via the insulin/IGF pathway transcription factor daf-16. Treatment of C. elegans with the small molecule resveratrol, however, extends life span in a manner fully dependent upon sir-2.1, but independent of daf-16. Microarray analysis of worms treated with resveratrol demonstrates the transcriptional induction of a family of genes encoding prion-like glutamine/asparagine-rich proteins involved in endoplasmic reticulum (ER) stress response to unfolded proteins. RNA interference of abu-11, a member of this ER stress gene family, abolishes resveratrol-mediated life span extension, and overexpression of abu-11 extends the life span of transgenic animals. Furthermore, SIR-2.1 normally represses transcription of abu-11 and other ER stress gene family members, indicating that resveratrol extends life span by inhibiting sir-2.1-mediated repression of ER stress genes. Our findings demonstrate that abu-11 and other members of its ER stress gene family are positive determinants of C. elegans life span.

Publication types

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

MeSH terms

  • Animals
  • Asparagine / chemistry
  • Caenorhabditis elegans / drug effects
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / genetics*
  • Endoplasmic Reticulum / metabolism*
  • Fungal Proteins / metabolism*
  • Gene Expression Profiling
  • Glutamine / chemistry
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism*
  • Longevity / drug effects
  • Longevity / genetics
  • RNA Interference / drug effects
  • RNA Interference / physiology
  • Resveratrol
  • Sirtuins / metabolism*
  • Stilbenes / pharmacology
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / genetics

Substances

  • Abu-11 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Fungal Proteins
  • Heat-Shock Proteins
  • Stilbenes
  • Glutamine
  • Asparagine
  • SIR-2.1 protein, C elegans
  • Sirtuins
  • Resveratrol