Updated project metadata. In this study, we utilize high-content microscopy screening and quantitative proteomics to establish a function of nuclear Hsp104 during aging. We find that the cytosolic-nuclear partitioning of Hsp104 is critical to maintain nuclear proteostasis in quiescent cells. Whereas high global translation rates in rapidly growing cells constrain Hsp104 to the cytosol, a decrease in protein biosynthesis re-directs the disaggregase to the nucleus dependent on a specific C-terminal motif. Nuclear Hsp104 interacts with latent eIF2 translation initiation subcomplexes and suppresses protein aggregation. This protects the dormant translation machinery from age-induced damage, enabling the rapid resumption of protein synthesis upon re-entry into the cell cycle. In this project two separate IP-MS experiments are included, KGSBVK (IP-MS, 9 samples) and GMCAVK (UV-inducible crosslinking IP-MS, 12 samples).