- Protein homeostasis (proteostasis) networks are dynamic throughout the lifespan of an organism. During Caenorhabditis elegans adulthood, the maintenance of metastable proteins and the activation of stress responses are inversely associated with germline stem cell proliferation. Here, we employed the thymidylate synthase inhibitor 5-fluoro-2'-deoxyuridine (FUdR) to chemically inhibit reproduction, thus allowing for examination of the interplay between reproduction and somatic proteostasis. We found that treatment with FUdR modulates proteostasis decline both before and after reproduction onset, such that effective induction of the heat shock response was maintained during adulthood and that metastable temperature-sensitive mutant phenotypes were rescued under restrictive conditions. However, FUdR treatment also improved the folding capacity of germline- and gonadogenesis-defective mutants, suggesting that proteostasis modulation by FUdR is independent of germline stem cell proliferation or inhibition of reproduction. Our data, therefore, indicate that FUdR converges on alternative regulatory signals that modulate C. elegans proteostasis capacity during development and adulthood.