Glia in Aging

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.

Grant Number: 5R21AG087451-02
NIH Institute/Center: NIH
Principal Investigator: Laura Bianchi