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

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 (UPR), become defunct with age. In this work, we expressed the constitutively active UPR transcription factor, XBP-1s, in a subset of astrocyte-like glia, which extended the life span in Glial XBP-1s initiated a robust cell nonautonomous activation of the UPR 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 UPR and life-span extension. Thus, astrocyte-like glial cells play a role in regulating organismal ER stress resistance and longevity.