As NASA and other space agencies set their sights on longer and more ambitious missions to the Moon, Mars, and beyond, understanding and mitigating CO2-driven oxidative stress becomes paramount. (Credit: NASA Ames Research Center)

While DNA damage caused by space radiation exposure has long been recognized as a major threat to astronaut health, a recent study published in Redox Biology (Stolc et al., 2024) reveals an unexpected culprit in the atmosphere of the International Space Station (ISS) itself: elevated carbon dioxide (CO2) levels. In this study, mice were sent into space where they spent 5–6 week aboard the ISS.

On the ISS, the mice were exposed to CO2 levels approximately 10 times higher than those on the ground. On return to Earth, tissue samples from the experimental animals were analyzed for somatic mutations — DNA damage in the form of single base changes that can alter the amino acids sequence of the proteins encoded by the DNA. These mutations, particularly prevalent in metabolically active tissues like the liver and eyes, were traced to oxidative stress induced by the elevated CO2 levels that are a consequence of the closed-loop life support system of the ISS.1

This discovery, enabled by high-performance computing (HPC), has profound implications for long-duration space missions, and highlights the importance of advanced computational tools in deciphering complex medical risks, as discussed in a previous article “Deciphering Medical Risk with High-Performance Computing,” published in Medical Design Briefs in March 2021.2

Delving Deeper into the Mechanism

Within cells, CO2 can disrupt the delicate balance of reactive oxygen species (ROS), a family of chemically reactive molecules produced by cellular metabolism. While some ROS molecules are necessary for normal physiological processes, excessive ROS can overwhelm a cell’s antioxidant defenses, leading to DNA damage. To analyze the vast amounts of genomic data generated by this study, researchers utilized a sophisticated genomics analysis software suite, developed at NASA Ames Research Center.

This software is designed to exploit the efficiency of computer systems with parallel processing capability, ranging from the NASA Ames Supercomputer to high-end desktop computers with graphics processing unit (GPU), increasing the speed and efficiency of data processing. By harnessing these tools, the study team scientists were able to perform the computationally intensive analysis needed to determine the somatic mutation patterns in a fraction of the time it would have taken using traditional CPUbased methods.

Using these tools, a high frequency of guanine-to-adenine conversions was seen in the RNA of the experimental mice. Guanine-to-adenine conversion is a hallmark of oxidative stress-induced DNA damage. High-performance computational tools were essential for identifying these mutation patterns. By analyzing the genomic data, we were able pinpoint specific genetic vulnerabilities in the mice. In the future, we may be able to develop novel therapeutic agents targeted to these specific sites in the genome, to prevent genetic damage from taking place.

Implications for Space Exploration and Terrestrial Medicine

This groundbreaking research has implications that extend beyond the confines of space travel. Understanding the link between CO2 and oxidative stress could be relevant to terrestrial medicine, such as in patients with respiratory diseases who experience chronically elevated carbon dioxide levels. Closed environments like submarines and hyperbaric oxygen therapy chambers are relevant, too, since elevated CO2 levels may rise in these closed structures. This study underscores the need for careful monitoring and management of CO2 levels in these settings, to minimize potential risk to humans.

Looking Ahead: Mitigating the Risks

As NASA and other space agencies set their sights on longer and more ambitious missions to the Moon, Mars, and beyond, understanding and mitigating CO2-driven oxidative stress becomes paramount. This research paves the way for the development of innovative countermeasures, such as:

  • Advanced CO2 Removal Systems: Development of improved methods of CO2 removal and air purification technologies on spacecraft.

  • ROS-reducing Supplements: Identification of dietary supplements or medications that boost the body’s natural antioxidant defenses.

  • Metabolic Suppression: If environments with elevated CO2 cannot be avoided, methods of inducing metabolic suppression (synthetic torpor), to protect astronauts on long-duration missions, may be warranted. Inspired by the natural survival strategies of hibernating animals, this concept involves inducing a reversible state of reduced metabolic activity, to minimize the detrimental effects of prolonged exposure to elevated CO2 levels, microgravity, radiation, and other spaceflight stressors. Ongoing research is exploring the feasibility and safety of inducing torpor in humans for space travel, with promising preliminary results.3

This study demonstrates the power of sophisticated computational tools — specialized software and specialized computers — for unraveling complex biological processes. As we push the boundaries of human exploration, the synergy between computational approaches and biological research will continue to drive innovation, to support the health and safety of astronauts in the extreme environment of space.

This work was supported by the NASA Human Research Program (HRP) and the Biological and Physical Sciences (BPS) Division.

References

  1. Stolc, V., Karhanek, M., Freund, F., Griko, Y., Loftus, D. J., and Ohayon, M. M. (2024). Metabolic stress in space: ROS-induced mutations in mice hint at a new path to cancer. Redox Biology, 103398.
  2. Stolc, V., Karhanek, M., Loftus, D. J (2021) Deciphering Medical Risk with High-Performance Computing. Medical Design Briefs, Mar 25, 2021.
  3. Griko, Y., Loftus, D. J., & Stolc, V. (2024). Metabolic suppression: A promising solution to unlock the future of space travel. Journal of Tourism & Hospitality, Vol. 12, Issue 6 (2023). DOI: 10.35248/2167-0269.24.12.537

This article was written by Viktor Stolc, Miloslav Karhanek, Yuri Griko, David J. Loftus NASA Ames Research Center, Mountain View, CA. For more information, contact This email address is being protected from spambots. You need JavaScript enabled to view it. or visit here  .

Topics:
Aerospace Computers Diagnostics Medical

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