ABSTRACT Because of the increase in life expectancy, a larger fraction of the population is now elderly and afflicted by age- related diseases with a huge cost for the health care system. Understanding the process of aging is thus imperative to help with the identification of strategies for healthier and more graceful aging. Exciting new studies in the pioneering organism C. elegans show that glia, a previously unsuspected cell type, communicate long distance to other cells to control stress response and aging. Furthermore, gene expression analysis in mice and humans show that glial genes undergo larger changes in expression, as compared to neuronal genes, during aging. Taken together, these data support the idea that glia may govern aging across species. However, the understanding of the function of glia in aging is in its infancy. Our lab has dedicated the past 17 years to the study of glia in C. elegans and thus is perfectly positioned to significantly contribute to this exciting new area of research. In our studies, we have identified the Cl-/HCO3- permeable channel clh-1 as a major contributor of ionic homeostasis in the worm nervous system. We have published that clh-1, by controlling Cl- and HCO3-, regulates pH and GABA signaling in the nervous system. We have now unexpectedly discovered that knockout of clh-1 extends lifespan and increases stress resistance. Our preliminary data support that the stress response transcription factor daf-16/FOXO is needed for clh-1 mediated changes in lifespan. In this exploratory application, we will leverage the power of C. elegans genetics and the imaging and solutes supplementation methods we have developed in the last 17 years to begin deciphering how the glial ion channel clh-1 controls organismal aging. Our specific aims are: 1. To establish what function of glial clh-1 influences aging, and 2. To identify tissues and pathways regulated by glial clh-1 in aging. This work will lay the foundation for future studies on the role of glial clh-1 and glia in general in aging and stress response. Ultimately, our work will advance our understanding of the role of glia in organismal aging, potentially suggest novel targets for the treatment of age- related disease, and even help identify strategies to improve our quality of life in old age.