Glia as Regulators of Mitochondrial Stress Resistance and Aging
The integrity of the proteome within cells is of highest importance, as loss of protein homeostasis may lead to cellular dysfunction. Several protective cellular pathways have evolved to protect the integrity of proteins within the cell, and their activity was previously shown to decrease with age. One such prominent protective pathway is the Unfolded Protein Response (UPR) of the mitochondria, a pathway that is activated when proteins become misfolded or unfolded within this organelle. In this project, I am studying how glial cells are capable of regulating longevity and stress resistance. Glia are non-neuronal cells, that were classically thought to act only as a support and protection network for neurons. I find that mitochondrial stress specifically in glia is able of eliciting distal activation of the mitochondrial UPR. I aim to uncover the signaling pathways capable of extending lifespan, by defining the crosstalk of between glia and neurons, uncovering the molecular pathways involved in the secretion of the glial stress signal, and exploring the response in other tissues using tissue-specific RNA-sequencing methods. At the culmination of this study, I will identify the molecular pathways involved in the signaling between glia and the rest of the body, and uncover the signaling molecule(s) – the glial secreted stress molecule. Furthermore, I will discover what are the molecular effects of this glial signal, allowing a deeper understanding of the biology of aging at the cellular level.