Reduced eIF2alpha phosphorylation and increased proapoptotic proteins in aging

Biochem Biophys Res Commun. 2007 Apr 6;355(2):365-70. doi: 10.1016/j.bbrc.2007.01.156. Epub 2007 Feb 6.


A decline in relative levels and phosphorylation of many of the eukaryotic initiation factors (eIFs) including S6, the 40S ribosomal subunit protein in many of the rat tissues during chronological aging is accompanied by elevated levels of eIF2alpha kinases, such as PKR and PERK, but not their activity. Concomitant with increased eIF2alpha phosphorylation, young tissues displayed a higher level of eIF2B to tolerate the toxic effect of eIF2alpha phosphorylation on translation, ATF4, a b-zip transcriptional factor that is produced as part of the gene expression programme in response to eIF2alpha phosphorylation, and BiP, an endoplasmic reticulum (ER) molecular chaperone and regulator of ER stress sensors. Decline in eIF2alpha phosphorylation in aged tissues is associated with a higher level of GADD34, a subunit of eIF2alpha phosphatase, and proapoptotic proteins like CHOP/GADD153 and phospho JNK, suggesting that young tissues possess an efficient ER stress adaptive mechanism that declines with aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 4 / metabolism
  • Aging / metabolism*
  • Animals
  • Apoptosis*
  • Eukaryotic Initiation Factor-2 / metabolism*
  • Heat-Shock Proteins / metabolism
  • Molecular Chaperones / metabolism
  • Phosphorylation
  • Rats
  • Signal Transduction


  • Atf4 protein, rat
  • Eukaryotic Initiation Factor-2
  • GRP78 protein, rat
  • Heat-Shock Proteins
  • Molecular Chaperones
  • Activating Transcription Factor 4