Space radiation damage rescued by inhibition of key spaceflight associated miRNAs

J. Tyson McDonald; Jang Keun 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; Afshin Beheshti

doi:10.1038/s41467-024-48920-y

Space radiation damage rescued by inhibition of key spaceflight associated miRNAs

J. Tyson McDonald, Jang Keun 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 MeydanStephen 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, Afshin Beheshti

School of Medicine

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	4825
Journal	Nature communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-48920-y
State	Published - Dec 2024

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/s41467-024-48920-y

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McDonald, J. T., Kim, J. K., Farmerie, L., Johnson, M. L., Trovao, N. S., Arif, S., Siew, K., Tsoy, S., Bram, Y., Park, J., Overbey, E., Ryon, K., Haltom, J., Singh, U., Enguita, F. J., Zaksas, V., Guarnieri, J. W., Topper, M., Wallace, D. C., ... Beheshti, A. (2024). Space radiation damage rescued by inhibition of key spaceflight associated miRNAs. Nature communications, 15(1), Article 4825. https://doi.org/10.1038/s41467-024-48920-y

McDonald, JT, Kim, JK, Farmerie, L, Johnson, ML, Trovao, NS, Arif, S, Siew, K, Tsoy, S, Bram, Y, Park, J, Overbey, E, Ryon, K, Haltom, J, Singh, U, Enguita, FJ, Zaksas, V, Guarnieri, JW, Topper, M, Wallace, DC, Meydan, C, Baylin, S, Meller, R, Muratani, M, Porterfield, DM, Kaufman, B, Mori, MA, Walsh, SB, Sigaudo-Roussel, D, Mebarek, S, Bottini, M, Marquette, CA, Wurtele, ES, Schwartz, RE, Galeano, D, Mason, CE, Grabham, P & Beheshti, A 2024, 'Space radiation damage rescued by inhibition of key spaceflight associated miRNAs', Nature communications, vol. 15, no. 1, 4825. https://doi.org/10.1038/s41467-024-48920-y

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title = "Space radiation damage rescued by inhibition of key spaceflight associated miRNAs",

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.",

author = "McDonald, {J. Tyson} and Kim, {Jang Keun} and Lily Farmerie and Johnson, {Meghan L.} and Trovao, {Nidia S.} and Shehbeel Arif and Keith Siew and Sergey Tsoy and Yaron Bram and Jiwoon Park and Eliah Overbey and Krista Ryon and Jeffrey Haltom and Urminder Singh and Enguita, {Francisco J.} and Victoria Zaksas and Guarnieri, {Joseph W.} and Michael Topper and Wallace, {Douglas C.} and Cem Meydan and Stephen Baylin and Robert Meller and Masafumi Muratani and Porterfield, {D. Marshall} and Brett Kaufman and Mori, {Marcelo A.} and Walsh, {Stephen B.} and Dominique Sigaudo-Roussel and Saida Mebarek and Massimo Bottini and Marquette, {Christophe A.} and Wurtele, {Eve Syrkin} and Schwartz, {Robert E.} and Diego Galeano and Mason, {Christopher E.} and Peter Grabham and Afshin Beheshti",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = dec,

doi = "10.1038/s41467-024-48920-y",

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AU - McDonald, J. Tyson

AU - Kim, Jang Keun

AU - Farmerie, Lily

AU - Johnson, Meghan L.

AU - Trovao, Nidia S.

AU - Arif, Shehbeel

AU - Siew, Keith

AU - Tsoy, Sergey

AU - Bram, Yaron

AU - Park, Jiwoon

AU - Overbey, Eliah

AU - Ryon, Krista

AU - Haltom, Jeffrey

AU - Singh, Urminder

AU - Enguita, Francisco J.

AU - Zaksas, Victoria

AU - Guarnieri, Joseph W.

AU - Topper, Michael

AU - Wallace, Douglas C.

AU - Meydan, Cem

AU - Baylin, Stephen

AU - Meller, Robert

AU - Muratani, Masafumi

AU - Porterfield, D. Marshall

AU - Kaufman, Brett

AU - Mori, Marcelo A.

AU - Walsh, Stephen B.

AU - Sigaudo-Roussel, Dominique

AU - Mebarek, Saida

AU - Bottini, Massimo

AU - Marquette, Christophe A.

AU - Wurtele, Eve Syrkin

AU - Schwartz, Robert E.

AU - Galeano, Diego

AU - Mason, Christopher E.

AU - Grabham, Peter

AU - Beheshti, Afshin

PY - 2024/12

Y1 - 2024/12

N2 - 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.

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VL - 15

JO - Nature communications

JF - Nature communications

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ER -

Space radiation damage rescued by inhibition of key spaceflight associated miRNAs

Abstract

ASJC Scopus subject areas

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