McDonald, J. TysonKim, JangKeunFarmerie, LilyJohnson, Meghan L.Trovao, Nidia S.Arif, ShehbeelSiew, KeithTsoy, SergeyBram, YaronPark, JiwoonOverbey, EliahRyon, KristaHaltom, JeffreySingh, UrminderEnguita, Francisco J.Zaksas, VictoriaGuarnieri, Joseph W.Topper, MichaelWallace, Douglas C.Meydan, CemBaylin, StephenMeller, RobertMuratani, MasafumiPorterfield, D. MarshallKaufman, BrettMori, Marcelo A.Walsh, Stephen B.Sigaudo-Roussel, DominiqueMebarek, SaidaBottini, MassimoMarquette, Christophe A.Wurtele, Eve SyrkinSchwartz, Robert E.Galeano, DiegoMason, Christopher E.Grabham, PeterBeheshti, Afshin2024-07-232024-07-232024Nat Commun. 2024 Jun 11;15(1):4825http://hdl.handle.net/10451/65410© The Author(s) 2024. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Our previous research revealed a key microRNA signature that is associated with spaceflight that can be used as a biomarker and to develop countermeasure treatments to mitigate the damage caused by space radiation. Here, we expand on this work to determine the biological factors rescued by the countermeasure treatment. We performed RNA-sequencing and transcriptomic analysis on 3D microvessel cell cultures exposed to simulated deep space radiation (0.5 Gy of Galactic Cosmic Radiation) with and without the antagonists to three microRNAs: miR-16-5p, miR-125b-5p, and let-7a-5p (i.e., antagomirs). Significant reduction of inflammation and DNA double strand breaks (DSBs) activity and rescue of mitochondria functions are observed after antagomir treatment. Using data from astronaut participants in the NASA Twin Study, Inspiration4, and JAXA missions, we reveal the genes and pathways implicated in the action of these antagomirs are altered in humans. Our findings indicate a countermeasure strategy that can potentially be utilized by astronauts in spaceflight missions to mitigate space radiation damage.engjournal article10.1038/s41467-024-48920-y2041-1723