Discoveries made in the nematode Caenorhabditis elegans revealed that aging is under genetic control. Since these transformative initial studies, C. elegans has become a premier model system for aging research. Critically, the genes, pathways, and processes that have fundamental roles in organismal aging are deeply conserved throughout evolution. This conservation has led to a wealth of knowledge regarding both the processes that influence aging and the identification of molecular and cellular hallmarks that play a causative role in the physiological decline of organisms. One key feature of age-associated decline is the failure of mechanisms that maintain proper function of the proteome (proteostasis). Here we highlight components of the proteostatic network that act to maintain the proteome and how this network integrates into major longevity signaling pathways. We focus in depth on the heat shock transcription factor 1 (HSF1), the central regulator of gene expression for proteins that maintain the cytosolic and nuclear proteomes, and a key effector of longevity signals.

SummaryDividing cells often move apically within epithelial tissue layers, likely to escape the spatial confinement of their neighbors. Because of this movement, daughter cells may be born displaced from the tissue layer. Reintegration of these displaced cells helps support tissue growth and maintain tissue architecture. In theDrosophilafollicular epithelium, reintegration relies on the immunoglobulin-superfamily cell-adhesion molecules (IgCAMs) Neuroglian and Fasciclin 2, which line cell-cell borders1. These molecules have been described in epithelia, but are well-studied for their roles in neural development2–8. We show here that reintegration works in the same way as IgCAM-mediated axon growth and pathfinding; it relies not only on extracellular adhesion but also mechanical coupling between IgCAMs and the lateral Spectrin-Based Membrane Skeleton. Our work indicates that reintegration is mediated by a distinct epithelial cell-cell junction that is compositionally and functionally equivalent to junctions made between axons.