Four glial cells regulate ER stress resistance and longevity via neuropeptide signaling in C. elegans

Science. 2020 Jan 24;367(6476):436-440. doi: 10.1126/science.aaz6896.


The ability of the nervous system to sense cellular stress and coordinate protein homeostasis is essential for organismal health. Unfortunately, stress responses that mitigate disturbances in proteostasis, such as the unfolded protein response of the endoplasmic reticulum (UPRER), become defunct with age. In this work, we expressed the constitutively active UPRER transcription factor, XBP-1s, in a subset of astrocyte-like glia, which extended the life span in Caenorhabditis elegans Glial XBP-1s initiated a robust cell nonautonomous activation of the UPRER in distal cells and rendered animals more resistant to protein aggregation and chronic ER stress. Mutants deficient in neuropeptide processing and secretion suppressed glial cell nonautonomous induction of the UPRER and life-span extension. Thus, astrocyte-like glial cells play a role in regulating organismal ER stress resistance and longevity.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / physiology
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology
  • Endoplasmic Reticulum Stress / physiology*
  • Longevity*
  • Mutation
  • Neuroglia / physiology*
  • Neuropeptides / physiology*
  • Protein Aggregates / physiology
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / physiology


  • ATF-6 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Neuropeptides
  • Protein Aggregates
  • Transcription Factors
  • XBP-1 protein, C elegans