Support cells in the brain promote longevity

Glial cells in the brain use neuropeptides to communicate stress responses and longevity Aging is a multifaceted process that results in organismal decay. At the cellular level, protein homeostasis is a key system that becomes dysregulated with age, causing the accumulation of aberrant or unfolded proteins. In a youthful individual, unfolded proteins normally trigger the unfolded protein response (UPR), which upregulates the protein clearance machinery and returns cells to a homeostatic state. The UPR is typically induced in a cell-autonomous manner. But some cells communicate protein folding stress to distal cells. For example, neurons communicate activation of the UPR to peripheral tissues to promote longevity in the worm Caenorhabditis elegans ( 1 ). On page 436 of this issue, Frakes et al. ( 2 ) show that support cells in the brain called glial cells ( 3 ) can also initiate long-range activation of the endoplasmic reticulum UPR (UPR ER ) in distal cells to coordinate stress resistance and longevity in C. elegans and that this occurs through neuropeptide secretion.