Abstract
As human space exploration accelerates, understanding the organism-wide molecular effects of longer spaceflight in mammals becomes increasingly critical. Non-coding RNAs like miRNAs are key to regulating this landscape. We thus analyze 686 small RNA samples of female mice from 13 solid organs at 3 and 8 months of age, after at least 3 weeks on the International Space Station and compare them to earth-bound controls. We observe significant spaceflight effects in systemic tissue remodeling pathways along the Fat-Liver-Pancreas axis and in heart, brain, spleen and thymus. The MIR-17/92 and MIR-1/133 families drive distinct molecular changes through specific gene targeting. Age-dependent changes, smaller in magnitude compared to age-independent changes, primarily involve tissue remodeling through MIR-8, MIR-154 and MIR-15 families in mesenteric adipose tissue, pancreas, and diaphragm. Our findings provide evidence on how spaceflight regulates mammalian gene expression in preparation for interplanetary spaceflight.
Data availability
The raw and processed miRNA data generated in this study have been deposited in the GEO database under accession code GSE294046. The raw and processed mRNA data generated in this study have been deposited in the GEO database under accession code GSE295428. Furthermore, the mRNA and miRNA data have been deposited in the NASE OSDR database under accessions OSD-904, OSD-905, OSD-906, OSD-907, OSD-908, OSD-909, OSD-910, OSD-911, OSD-912, OSD-913, OSD-914, OSD-915, OSD-916. Source data are provided with this paper.
Code availability
The code used to create the figures (based on count data or the provided Supplementary Data) is available from GitHub83.
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Acknowledgements
We thank all members of the Wyss-Coray and Meese labs, as well as the Keller lab, for their feedback and support. This study is partially funded by the Michael J. Fox Foundation and the Schaller-Nikolich Foundation. We acknowledge funding from the Deutsche Forschungsgemeinschaft (DFG, project number 469073465: Compute- und Storage Cluster). For the Development of the software pipeline used to process the single-cell data, we are supported by funds from the EU (Project 101057548-EPIVINF).
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F.G., S.R., A.E., and A.K. performed computational analysis and/or primary data processing. F.G., S.R., A.E., V.W., N.S., V.K., and A.K. wrote the manuscript with input from all authors. F.K., L.S., V.F., E.M., N.S., S.Q., T.W.-C. and A.K. organized the study. A.R., N.S., and K.C. were involved in sample collection. V.W., N.L., and M.K. performed the Sequencing preparation and the Sequencing.
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Grandke, F., Rishik, S., Wagner, V. et al. MiRNAs shape mouse age-independent tissue adaptation to spaceflight via ECM and developmental pathways. Nat Commun (2026). https://doi.org/10.1038/s41467-026-68737-1
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DOI: https://doi.org/10.1038/s41467-026-68737-1
