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

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.