The Heat Shock Response (HSR) is an essential, highly conserved stress pathway that maintains protein homeostasis (proteostasis) by resolving misfolded proteins and detrimental protein aggregates. Recent studies in C. elegans have demonstrated that chromatin remodeling during the transition from larva to adulthood causes an abrupt decline in the heat shock response. To further our knowledge as to which chromatin remodeling factors may influence the HSR in an age-dependent manner, we have performed an RNAi sub-library screen of 62 chromatin remodeling factors across the larval stages to adulthood in C. elegans. Initiating RNAi at L1, we utilized a worm strain carrying the heat-inducible transcriptional reporter phsp-16.2::GFP and the constitutive RFP construct pdop-3::RFP. We then treated the worms with or without heat shock at the L4/YA stage or 24 hours later during active reproduction. The regulators we identified to either positively or negatively influence the HSR in an age-dependent manner include Nucleosome Remodeling Factor (NURF) complex members, SWI/SNF family genes, and histone deacetylases. Of these hits, PYP-1, an inorganic pyrophosphatase and member of the NuRF complex, stood out as our strongest hit. PYP-1 negatively regulates the HSR only after the onset of reproduction. After this transition, pyp-1 knockdown causes activation of both hsp-70 and hsp-16.2 transcriptional reporter animals during both non-stress and stress conditions. While pyp-1 RNAi does not affect overall juvenile development and lifespan, it completely eliminates reproduction. This uncoupling of stress activation, reproduction, and lifespan by pyp-1 knockdown appears to be a unique physiological feature, since cell physiological changes that activate stress responses typically trade-off reproduction and yield increased cell survival and longevity. We are interested in further characterizing PYP-1 function during the transition to adulthood as a way to epigenetically regulate the heat shock response upon aging and we are interested the mechanism in the uncoupling of longevity, reproduction, and development.