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Taking the stress out of life In the model organismCaenorhabditis elegans , a roundworm, it has been shown that neurons can communicate proteostasis to the periphery to affect aging. Frakeset 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 ofC. 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 (UPRER ), in a specific subset of glial cells. Glial XBP-1s initiates induction of the UPRER 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 UPRER , 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 agingScience , this issue p.436 ; see also p.365

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