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

Willian A da Silveira1, Hossein Fazelinia2, Sara Brin Rosenthal3, Evagelia C Laiakis4, Man S Kim2, Cem Meydan5, Yared Kidane6, Komal S Rathi2, Scott M Smith7, Benjamin Stear2, Yue Ying2, Yuanchao Zhang2, Jonathan Foox5, Susana Zanello8, Brian Crucian7, Dong Wang9, Adrienne Nugent10, Helio A Costa11, Sara R Zwart12, Sonja Schrepfer9, R A Leo Elworth13, Nicolae Sapoval13, Todd Treangen13, Matthew MacKay5, Nandan S Gokhale14, Stacy M Horner14, Larry N Singh15, Douglas C Wallace16, Jeffrey S Willey17, Jonathan C Schisler18, Robert Meller19, J Tyson McDonald4, Kathleen M Fisch3, Gary Hardiman20, Deanne Taylor21, Christopher E Mason5, Sylvain V Costes22, Afshin Beheshti23

  1. Queens University Belfast, Belfast BT9 5DL, UK.
  2. The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  3. University of California San Diego, La Jolla, CA 92093, USA.
  4. Georgetown University Medical Center, Washington D.C. 20057, USA.
  5. Weill Cornell Medical College, New York, NY 10065, USA.
  6. Texas Scottish Rite Hospital for Children, Dallas, TX 75219, USA.
  7. NASA Johnson Space Center, Houston, TX 77058, USA.
  8. imec USA, Kissimmee, FL 34744, USA.
  9. University of California San Francisco, San Francisco, CA 94115, USA.
  10. Hampton University, Hampton, VA 23669, USA.
  11. Stanford University, Stanford, CA 94305, USA.
  12. University of Texas Medical Branch, Galveston, TX 77555, USA.
  13. Rice University, Houston, TX 77005, USA.
  14. Duke University Medical Center, Durham, NC 27710, USA.
  15. Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  16. Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  17. Wake Forest School of Medicine, Winston-Salem, NC 27101, USA.
  18. The University of North Carolina at Chapel Hill, NC 27599, USA.
  19. Morehouse School of Medicine, Atlanta, GA 30310, USA.
  20. Queens University Belfast, Belfast BT9 5DL, UK; Medical University of South Carolina, Charleston, SC 29425, USA.
  21. The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  22. NASA Ames Research Center, Moffett Field, CA 94035, USA.
  23. KBR, NASA Ames Research Center, Moffett Field, CA 94035, USA. Electronic address: afshin.beheshti@nasa.gov.

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.

Presented By Willian A da Silveira | ORCID iD

Cell & Developmental Bio, Genomics, Metabolism, MedicineNicholas Liao2020-11 (Nov)