Four glial cells regulate ER stress resistance and longevity via neuropeptide signaling in <i>C. elegans</i>
Ashley E. Frakes, Melissa G. Metcalf, Sarah U. Tronnes, Raz Bar‐Ziv, Jenni Durieux, Holly K. Gildea, Nazineen Kandahari, Samira Monshietehadi, Andrew Dillin
Abstract
Taking the stress out of life In the model organism Caenorhabditis elegans , a roundworm, it has been shown that neurons can communicate proteostasis to the periphery to affect aging. Frakes et al. have now identified astrocytelike glial cells that also act as central regulators of systemic protein homeostasis and aging (see the Perspective by Miklas and Brunet). They found that the life span of C. elegans can be extended by expression of a constitutively active version of the transcription factor XBP-1s, which mediates the unfolded protein response of the endoplasmic reticulum (UPR ER ), in a specific subset of glial cells. Glial XBP-1s initiates induction of the UPR ER in distal intestinal cells, which makes the worms more resistant to chronic ER stress. Neuropeptide signaling was required for glial-mediated longevity and induction of the peripheral UPR ER , suggesting a distinct mechanism from that initiated by neuronal XBP-1s. Thus, in this animal model of aging, a mere four cells can control organismal physiology and aging Science , this issue p. 436 ; see also p. 365