The loss of a ClC anion channel increases life span, health span, and stress resistance by alkalinizing a pair of glial cells in C. elegans

IF 12.5 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2025-10-08 DOI:10.1126/sciadv.ady1027

Lei Wang, Enrique I. Oliver, Dario L. D’Urso, Bianca Graziano, Laura Bianchi

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Abstract

Aging depends on genetic and environmental factors, but the specific cell types and mechanisms that coordinate aging of the entire organism are not yet fully understood. Glial cells regulate ionic homeostasis, which is essential for neuronal function and survival. Here, we investigated the role of glial ion channel CLH-1, which is a glial pH regulator, in aging. We found that loss of clh-1 extends life span, improves stress resistance, reduces neuronal damage, and extends health span. These effects are linked to protective pathways, including those for oxidative stress and autophagy, and depend on the DAF-16/FoxO transcription factor. Notably, by knocking down and overexpressing the carbonic anhydrase cah-4, we show that it is the glial alkalinization caused by loss of clh-1 that mediates these protective effects. This work highlights the crucial role of glial pH in regulating life span and health span.

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通过碱化秀丽隐杆线虫的一对胶质细胞，ClC阴离子通道的缺失增加了寿命、健康寿命和抗逆性

衰老取决于遗传和环境因素，但协调整个生物体衰老的特定细胞类型和机制尚未完全了解。神经胶质细胞调节离子稳态，这对神经元的功能和存活至关重要。在这里，我们研究了胶质离子通道CLH-1在衰老中的作用，CLH-1是一种胶质pH调节剂。我们发现clh-1的缺失延长了寿命，提高了抗应激能力，减少了神经元损伤，延长了健康寿命。这些作用与保护途径有关，包括氧化应激和自噬，并依赖于DAF-16/FoxO转录因子。值得注意的是，通过敲除和过表达碳酸酐酶cah-4，我们表明是clh-1缺失引起的胶质碱化介导了这些保护作用。这项工作强调了神经胶质pH值在调节寿命和健康寿命中的重要作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.