Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact

Willian A da Silveira; Hossein Fazelinia; Sara Brin Rosenthal; Evagelia C Laiakis; Man S Kim; Cem Meydan; Yared Kidane; Komal S Rathi; Scott M Smith; Benjamin Stear; Yue Ying; Yuanchao Zhang; Jonathan Foox; Susana Zanello; Brian Crucian; Dong Wang; Adrienne Nugent; Helio A Costa; Sara R Zwart; Sonja Schrepfer; R A Leo Elworth; Nicolae Sapoval; Todd Treangen; Matthew MacKay; Nandan S Gokhale; Stacy M Horner; Larry N Singh; Douglas C Wallace; Jeffrey S Willey; Jonathan C Schisler; Robert Meller; J Tyson McDonald; Kathleen M Fisch; Gary Hardiman; Deanne Taylor; Christopher E Mason; Sylvain V Costes; Afshin Beheshti

doi:10.1016/j.cell.2020.11.002

Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact

Willian A da Silveira, Hossein Fazelinia, Sara Brin Rosenthal, Evagelia C Laiakis, Man S Kim, Cem Meydan, Yared Kidane, Komal S Rathi, Scott M Smith, Benjamin Stear, Yue Ying, Yuanchao Zhang, Jonathan Foox, Susana Zanello, Brian Crucian, Dong Wang, Adrienne Nugent, Helio A Costa, Sara R Zwart, Sonja SchrepferR A Leo Elworth, Nicolae Sapoval, Todd Treangen, Matthew MacKay, Nandan S Gokhale, Stacy M Horner, Larry N Singh, Douglas C Wallace, Jeffrey S Willey, Jonathan C Schisler, Robert Meller, J Tyson McDonald, Kathleen M Fisch, Gary Hardiman, Deanne Taylor, Christopher E Mason, Sylvain V Costes, Afshin Beheshti

School of Biological Sciences

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Abstract

Spaceflight is known to impose changes on human physiology with unknown molecular etiologies. To reveal these causes, we used a multi-omics, systems biology analytical approach using biomedical profiles from fifty-nine astronauts and data from NASA's GeneLab derived from hundreds of samples flown in space to determine transcriptomic, proteomic, metabolomic, and epigenetic responses to spaceflight. Overall pathway analyses on the multi-omics datasets showed significant enrichment for mitochondrial processes, as well as innate immunity, chronic inflammation, cell cycle, circadian rhythm, and olfactory functions. Importantly, NASA's Twin Study provided a platform to confirm several of our principal findings. Evidence of altered mitochondrial function and DNA damage was also found in the urine and blood metabolic data compiled from the astronaut cohort and NASA Twin Study data, indicating mitochondrial stress as a consistent phenotype of spaceflight.

Original language	English
Pages (from-to)	1185-1201
Number of pages	7
Journal	Cell
Volume	183
Issue number	5
DOIs	https://doi.org/10.1016/j.cell.2020.11.002
Publication status	Published - 25 Nov 2020

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Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact
Copyright 2020 Elsevier. This manuscript is distributed under a Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits distribution and reproduction for non-commercial purposes, provided the author and source are cited
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da Silveira, W. A., Fazelinia, H., Rosenthal, S. B., Laiakis, E. C., Kim, M. S., Meydan, C., Kidane, Y., Rathi, K. S., Smith, S. M., Stear, B., Ying, Y., Zhang, Y., Foox, J., Zanello, S., Crucian, B., Wang, D., Nugent, A., Costa, H. A., Zwart, S. R., ... Beheshti, A. (2020). Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact. Cell, 183(5), 1185-1201. https://doi.org/10.1016/j.cell.2020.11.002

@article{6178686802e24c2f8a35a5451233819b,

title = "Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact",

abstract = "Spaceflight is known to impose changes on human physiology with unknown molecular etiologies. To reveal these causes, we used a multi-omics, systems biology analytical approach using biomedical profiles from fifty-nine astronauts and data from NASA's GeneLab derived from hundreds of samples flown in space to determine transcriptomic, proteomic, metabolomic, and epigenetic responses to spaceflight. Overall pathway analyses on the multi-omics datasets showed significant enrichment for mitochondrial processes, as well as innate immunity, chronic inflammation, cell cycle, circadian rhythm, and olfactory functions. Importantly, NASA's Twin Study provided a platform to confirm several of our principal findings. Evidence of altered mitochondrial function and DNA damage was also found in the urine and blood metabolic data compiled from the astronaut cohort and NASA Twin Study data, indicating mitochondrial stress as a consistent phenotype of spaceflight.",

author = "{da Silveira}, {Willian A} and Hossein Fazelinia and Rosenthal, {Sara Brin} and Laiakis, {Evagelia C} and Kim, {Man S} and Cem Meydan and Yared Kidane and Rathi, {Komal S} and Smith, {Scott M} and Benjamin Stear and Yue Ying and Yuanchao Zhang and Jonathan Foox and Susana Zanello and Brian Crucian and Dong Wang and Adrienne Nugent and Costa, {Helio A} and Zwart, {Sara R} and Sonja Schrepfer and Elworth, {R A Leo} and Nicolae Sapoval and Todd Treangen and Matthew MacKay and Gokhale, {Nandan S} and Horner, {Stacy M} and Singh, {Larry N} and Wallace, {Douglas C} and Willey, {Jeffrey S} and Schisler, {Jonathan C} and Robert Meller and McDonald, {J Tyson} and Fisch, {Kathleen M} and Gary Hardiman and Deanne Taylor and Mason, {Christopher E} and Costes, {Sylvain V} and Afshin Beheshti",

year = "2020",

month = nov,

day = "25",

doi = "10.1016/j.cell.2020.11.002",

language = "English",

volume = "183",

pages = "1185--1201",

journal = "Cell",

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da Silveira, WA, Fazelinia, H, Rosenthal, SB, Laiakis, EC, Kim, MS, Meydan, C, Kidane, Y, Rathi, KS, Smith, SM, Stear, B, Ying, Y, Zhang, Y, Foox, J, Zanello, S, Crucian, B, Wang, D, Nugent, A, Costa, HA, Zwart, SR, Schrepfer, S, Elworth, RAL, Sapoval, N, Treangen, T, MacKay, M, Gokhale, NS, Horner, SM, Singh, LN, Wallace, DC, Willey, JS, Schisler, JC, Meller, R, McDonald, JT, Fisch, KM, Hardiman, G, Taylor, D, Mason, CE, Costes, SV & Beheshti, A 2020, 'Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact', Cell, vol. 183, no. 5, pp. 1185-1201. https://doi.org/10.1016/j.cell.2020.11.002

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T1 - Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact

AU - da Silveira, Willian A

AU - Fazelinia, Hossein

AU - Rosenthal, Sara Brin

AU - Laiakis, Evagelia C

AU - Kim, Man S

AU - Meydan, Cem

AU - Kidane, Yared

AU - Rathi, Komal S

AU - Smith, Scott M

AU - Stear, Benjamin

AU - Ying, Yue

AU - Zhang, Yuanchao

AU - Foox, Jonathan

AU - Zanello, Susana

AU - Crucian, Brian

AU - Wang, Dong

AU - Nugent, Adrienne

AU - Costa, Helio A

AU - Zwart, Sara R

AU - Schrepfer, Sonja

AU - Elworth, R A Leo

AU - Sapoval, Nicolae

AU - Treangen, Todd

AU - MacKay, Matthew

AU - Gokhale, Nandan S

AU - Horner, Stacy M

AU - Singh, Larry N

AU - Wallace, Douglas C

AU - Willey, Jeffrey S

AU - Schisler, Jonathan C

AU - Meller, Robert

AU - McDonald, J Tyson

AU - Fisch, Kathleen M

AU - Hardiman, Gary

AU - Taylor, Deanne

AU - Mason, Christopher E

AU - Costes, Sylvain V

AU - Beheshti, Afshin

PY - 2020/11/25

Y1 - 2020/11/25

N2 - Spaceflight is known to impose changes on human physiology with unknown molecular etiologies. To reveal these causes, we used a multi-omics, systems biology analytical approach using biomedical profiles from fifty-nine astronauts and data from NASA's GeneLab derived from hundreds of samples flown in space to determine transcriptomic, proteomic, metabolomic, and epigenetic responses to spaceflight. Overall pathway analyses on the multi-omics datasets showed significant enrichment for mitochondrial processes, as well as innate immunity, chronic inflammation, cell cycle, circadian rhythm, and olfactory functions. Importantly, NASA's Twin Study provided a platform to confirm several of our principal findings. Evidence of altered mitochondrial function and DNA damage was also found in the urine and blood metabolic data compiled from the astronaut cohort and NASA Twin Study data, indicating mitochondrial stress as a consistent phenotype of spaceflight.

AB - Spaceflight is known to impose changes on human physiology with unknown molecular etiologies. To reveal these causes, we used a multi-omics, systems biology analytical approach using biomedical profiles from fifty-nine astronauts and data from NASA's GeneLab derived from hundreds of samples flown in space to determine transcriptomic, proteomic, metabolomic, and epigenetic responses to spaceflight. Overall pathway analyses on the multi-omics datasets showed significant enrichment for mitochondrial processes, as well as innate immunity, chronic inflammation, cell cycle, circadian rhythm, and olfactory functions. Importantly, NASA's Twin Study provided a platform to confirm several of our principal findings. Evidence of altered mitochondrial function and DNA damage was also found in the urine and blood metabolic data compiled from the astronaut cohort and NASA Twin Study data, indicating mitochondrial stress as a consistent phenotype of spaceflight.

U2 - 10.1016/j.cell.2020.11.002

DO - 10.1016/j.cell.2020.11.002

M3 - Article

C2 - 33242417

SN - 0092-8674

VL - 183

SP - 1185

EP - 1201

JO - Cell

JF - Cell

IS - 5

ER -

Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact

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