biostudies-literatureCelen INIH NIGMS IDeA ProgramSigma XiNASADelaware INBREDelaware EPSCoRNIGMS NIH HHS270https://www.ebi.ac.uk/biostudies/studies/S-EPMC9856674biostudies-literatureUnknown12(2)Given the growing interest in human exploration of space, it is crucial to identify the effects of space conditions on biological processes. Here, we analyze the transcriptomic response of <i>Caenorhabditis elegans</i> to simulated microgravity and observe the maintained transcriptomic response after returning to ground conditions for four, eight, and twelve days. We show that 75% of the simulated microgravity-induced changes on gene expression persist after returning to ground conditions for four days while most of these changes are reverted after twelve days. Our results from integrative RNA-seq and mass spectrometry analyses suggest that simulated microgravity affects longevity-regulating insulin/IGF-1 and sphingolipid signaling pathways. Finally, we identified 118 genes that are commonly differentially expressed in simulated microgravity- and space-exposed worms. Overall, this work provides insight into the effect of microgravity on biological systems during and after exposure.CellsTranscriptomic Signature of the Simulated Microgravity Response in <i>Caenorhabditis elegans</i> and Comparison to Spaceflight Experiments.PMC9856674G2016100191301836,NSF EPS-0814251NIH/NIGMS GM103446P20 GM103446NNX10AN63H#P20 GM103446NNX12AR59GNNX13AM08GNSF IIA-1330446Celen IJayasinghe ADoh JHSabanayagam CRfalseTranscriptomic Signature of the Simulated Microgravity Response in <i>Caenorhabditis elegans</i> and Comparison to Spaceflight Experiments.Given the growing interest in human exploration of space, it is crucial to identify the effects of space conditions on biological processes. Here, we analyze the transcriptomic response of <i>Caenorhabditis elegans</i> to simulated microgravity and observe the maintained transcriptomic response after returning to ground conditions for four, eight, and twelve days. We show that 75% of the simulated microgravity-induced changes on gene expression persist after returning to ground conditions for four days while most of these changes are reverted after twelve days. Our results from integrative RNA-seq and mass spectrometry analyses suggest that simulated microgravity affects longevity-regulating insulin/IGF-1 and sphingolipid signaling pathways. Finally, we identified 118 genes that are commonly differentially expressed in simulated microgravity- and space-exposed worms. Overall, this work provides insight into the effect of microgravity on biological systems during and after exposure.2023-01-01T00:00:00Z2023 Jan2026-04-08T11:24:35.028Z2025-02-19T04:45:51.287ZS-EPMC98566743667220510.3390/cells12020270