title: Reducing translation through eIF4G/IFG-1 improves survival under ER stress that depends on heat shock factor HSF-1 in Caenorhabditis elegans.
abstract: Although certain methods of lowering and/or altering mRNA translation are associated with increased lifespan, the mechanisms underlying this effect remain largely unknown. We previously showed that the increased lifespan conferred by reducing expression of eukaryotic translation initiation factor 4G (eIF4G/IFG-1) enhances survival under starvation conditions while shifting protein expression toward factors involved with maintaining ER-dependent protein and lipid balance. In this study, we investigated changes in ER homeostasis and found that lower eIF4G/IFG-1 increased survival under conditions of ER stress. Enhanced survival required the ER stress sensor gene ire-1 and the ER calcium ATPase gene sca-1 and corresponded with increased translation of chaperones that mediate the ER unfolded protein response (UPRER). Surprisingly, the heat-shock transcription factor gene hsf-1 was also required for enhanced survival, despite having little or no influence on the ability of wild-type animals to survive ER stress. The requirement for hsf-1 led us to re-evaluate the role of eIF4G/IFG-1 on thermotolerance. Results show that lowering expression of this translation factor enhanced thermotolerance, but only after prolonged attenuation, the timing of which corresponded to increased transcription of heat-shock factor transcriptional targets. Results indicate that restricting overall translation through eIF4G/IFG-1 enhances ER and cytoplasmic proteostasis through a mechanism that relies heavily on hsf-1.
authors.affiliation: MDI Biological Laboratory, Davis Center for Regenerative Biology and Medicine, 159 Old Bar Harbor Road, Salisbury Cove, ME, 04672, USA.
authors.forename: Amber C
authors.initials: AC
authors.lastname: Howard
authors.affiliation: MDI Biological Laboratory, Davis Center for Regenerative Biology and Medicine, 159 Old Bar Harbor Road, Salisbury Cove, ME, 04672, USA.
authors.forename: Jarod
authors.initials: J
authors.lastname: Rollins
authors.affiliation: MDI Biological Laboratory, Davis Center for Regenerative Biology and Medicine, 159 Old Bar Harbor Road, Salisbury Cove, ME, 04672, USA.
authors.forename: Santina
authors.initials: S
authors.lastname: Snow
authors.affiliation: The Jackson Laboratory, 600 Main Street, Bar Harbor, ME, 04609, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Castor
authors.affiliation: MDI Biological Laboratory, Davis Center for Regenerative Biology and Medicine, 159 Old Bar Harbor Road, Salisbury Cove, ME, 04672, USA.
authors.forename: Aric N
authors.initials: AN
authors.lastname: Rogers
keywords: 
  Caenorhabditis elegans
  ; 
  ifg-1
  ; eIF4G; healthspan; lifespan; proteostasis