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 (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 aging Science, this issue p. 436; see also p. 365 Organismal protein homeostasis and longevity in nematodes are coordinated by a subtype of glia. 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.

中文翻译：

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四种神经胶质细胞通过秀丽隐杆线虫中的神经肽信号传导调节内质网应激抗性和寿命

消除生活中的压力 在模型生物秀丽隐杆线虫（一种蛔虫）中，已经表明神经元可以将蛋白质稳态传递到外周以影响衰老。弗雷克斯等人。现在已经鉴定出星形胶质细胞样胶质细胞，它们也作为全身蛋白质稳态和衰老的中央调节剂（参见 Miklas 和 Brunet 的观点）。他们发现，线虫的寿命可以通过在特定的神经胶质细胞亚群中表达组成性活性版本的转录因子 XBP-1s 来延长，XBP-1s 介导内质网 (UPRER) 的未折叠蛋白反应。神经胶质 XBP-1s 启动远端肠细胞中 UPRER 的诱导，这使得蠕虫对慢性 ER 应激更具抵抗力。神经肽信号是神经胶质介导的寿命和外周 UPRER 诱导所必需的，这表明与神经元 XBP-1 启动的机制不同。因此，在这个衰老的动物模型中，仅仅四个细胞就可以控制机体生理和衰老科学，本期第 436; 另见第。365 线虫的生物体蛋白质稳态和寿命由神经胶质亚型协调。神经系统感知细胞压力和协调蛋白质稳态的能力对于机体健康至关重要。不幸的是，减轻蛋白质稳态紊乱的应激反应，例如内质网 (UPRER) 的未折叠蛋白反应，随着年龄的增长而失效。在这项工作中，我们在星形胶质细胞样胶质细胞亚群中表达了组成型活性的 UPRER 转录因子 XBP-1s，这延长了秀丽隐杆线虫的寿命。神经胶质 XBP-1s 启动了远端细胞中 UPRER 的强大细胞非自主激活，并使动物对蛋白质聚集和慢性 ER 应激更具抵抗力。神经肽加工和分泌缺陷的突变体抑制了神经胶质细胞对 UPRER 的非自主诱导和寿命延长。因此，星形胶质细胞样胶质细胞在调节机体内质网应激抵抗和长寿方面发挥作用。