Space radiation damage rescued by inhibition of key spaceflight associated miRNAs

J. Tyson McDonald, JangKeun Kim, Lily Farmerie, Meghan L. Johnson, Nidia S. Trovao, Shehbeel Arif, Keith Siew, Sergey Tsoy, Yaron Bram, Jiwoon Park, Eliah Overbey, Krista Ryon, Jeffrey Haltom, Urminder Singh, Francisco J. Enguita, Victoria Zaksas, Joseph W. Guarnieri, Michael Topper, Douglas C. Wallace, Cem Meydan, Stephen Baylin, Robert Meller, Masafumi Muratani, D. Marshall Porterfield, Brett Kaufman, Marcelo A. Mori, Stephen B. Walsh, Dominique Sigaudo-Roussel, Saida Mebarek, Massimo Bottini, Christophe A. Marquette, Eve Syrkin Wurtele, Robert E. Schwartz, Diego Galeano, Christopher E. Mason, Peter Grabham () and Afshin Beheshti ()
Additional contact information
J. Tyson McDonald: Georgetown University School of Medicine
JangKeun Kim: Biophysics and Systems Biology and the WorldQuant Initiative, Weill Cornell Medicine
Lily Farmerie: Vascular Medicine Institute at the University of Pittsburgh Department of Medicine
Meghan L. Johnson: Vascular Medicine Institute at the University of Pittsburgh Department of Medicine
Nidia S. Trovao: Fogarty International Center, National Institutes of Health
Shehbeel Arif: Children’s Hospital of Philadelphia
Keith Siew: University College London
Sergey Tsoy: Weill Cornell Medicine
Yaron Bram: Weill Cornell Medicine
Jiwoon Park: Biophysics and Systems Biology and the WorldQuant Initiative, Weill Cornell Medicine
Eliah Overbey: Biophysics and Systems Biology and the WorldQuant Initiative, Weill Cornell Medicine
Krista Ryon: Biophysics and Systems Biology and the WorldQuant Initiative, Weill Cornell Medicine
Jeffrey Haltom: The Children’s Hospital of Philadelphia
Urminder Singh: Iowa State University
Francisco J. Enguita: Universidade de Lisboa
Victoria Zaksas: University of Chicago
Joseph W. Guarnieri: The Children’s Hospital of Philadelphia
Michael Topper: The Johns Hopkins Medical Institutions
Douglas C. Wallace: The Children’s Hospital of Philadelphia
Cem Meydan: Biophysics and Systems Biology and the WorldQuant Initiative, Weill Cornell Medicine
Stephen Baylin: The Johns Hopkins Medical Institutions
Robert Meller: Morehouse School of Medicine
Masafumi Muratani: University of Tsukuba
D. Marshall Porterfield: Purdue University
Brett Kaufman: Vascular Medicine Institute at the University of Pittsburgh Department of Medicine
Marcelo A. Mori: Universidade Estadual de Campinas
Stephen B. Walsh: University College London
Dominique Sigaudo-Roussel: Université Claude Bernard Lyon 1
Saida Mebarek: Université Claude Bernard Lyon 1
Massimo Bottini: University of Rome Tor Vergata
Christophe A. Marquette: Université Claude Bernard Lyon 1
Eve Syrkin Wurtele: Iowa State University
Robert E. Schwartz: Weill Cornell Medicine
Diego Galeano: Universidad Nacional de Asunción
Christopher E. Mason: Biophysics and Systems Biology and the WorldQuant Initiative, Weill Cornell Medicine
Peter Grabham: Columbia University
Afshin Beheshti: Broad Institute of MIT and Harvard

Nature Communications, 2024, vol. 15, issue 1, 1-23

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-48920-y

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