Mitochondria originated millions of years ago, likely when a eukaryotic cell incorporated a bacterium. Thus, mitochondrial DNA strands are 200,000× smaller than those from a cell’s nucleus. Depending on cell type, thousands of mitochondria can reside within the walls of one human cell. The scientific community long has considered these organelles to be cellular “energy factories.” But their centrality to human health and disease only now has come to light.

In a breakthrough study published in Cell (1), biologists collaborated with scientists from the US National Aeronautics and Space Administration (NASA) to analyze the largest collection to date of biomedical data from astronauts. As lead author Afshin Beheshti (bioinformatician and principal investigator at KBR) later reflected, da Silveira et al. sought to understand negative effects of spaceflight on human physiology (2). They stumbled upon “a universal mechanism that explains the kinds of changes [that occur] to the body in space” but found it “in a place [that] we didn’t expect.” In space, “everything gets thrown out of whack, and it all starts with the mitochondria.”

The study proposes that “mitochondrial dysregulation is driving spaceflight health risks.” Researchers analyzed biomedical profiles from 59 astronauts and data from NASA’s GeneLab repository (3), which houses results from hundreds of experiments performed in space. “Overall pathway analyses on the multiomics data sets showed significant enrichment for mitochondrial processes, as well as innate immunity, chronic inflammation, cell cycle, circadian rhythm, and olfactory functions.” Data from the NASA Twins Study (4) helped to confirm several of the study’s principal findings. For instance, “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 Twins Study data, indicating mitochondrial stress as a consistent phenotype of spaceflight.”

Mitochondrial Dysfunction on the Ground
Unfortunately, mitochondrial dysregulation occurs on Earth as well. Roughly one in 5,000 people bears genetic defects that can result in mitochondrial dysfunction and life-threatening illnesses. Far more people experience dysfunction because of aging, lifestyle choices, exposure to toxins, drug side effects, and disease. Mitochondrial dysregulation correlates strongly with several diseases, including cardiovascular disease, diabetes, obesity, liver disease, cancer, neurological dysfunction, and immune and inflammatory disorders — and with increases in comorbidity and mortality across those conditions.

It’s not surprising that the study identified mitochondrial dysfunction in astronauts. It is surprising, however, that a group of astronauts — in peak physical condition and supported by healthy diets and regular exercise — developed dysfunction so quickly when, on the ground, patients experience such problems after many years and often because of unhealthy lifestyles. Mitochondria are just that important to human biology and health. Could it be that space’s lack of gravity produces physiological effects that resemble those incited by a sedentary lifestyle, a known contributor to mitochondrial dysfunction?

Mitochondrial Science Meets Medicine
Considering the growing evidence of mitochondrial dysfunction’s significant impact on human health and longevity, researchers are beginning to study how mitochondria function in a healthy subject, how they become impaired, and what can be done to prevent or correct their dysfunction. Among those researchers are the founders of CohBar, Inc. The CohBar team has spent two decades exploring mitochondrial genetics and biology, discovering new mitochondrial genes and mechanisms, and identifying opportunities for treating unmet medical needs. Expanding on breakthrough discoveries, our scientists also have been developing a number of mitochondria-based peptide therapeutics with significant potential to address diseases associated with mitochondrial dysfunction — on the ground and in space.

References
1 da Silveira WA, et al. Comprehensive Multiomics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact. Cell 183(5) 2020: 1185–1201; https://doi.org/10.1016/j.cell.2020.11.002.

2 Taveres F. Mitochondrial Changes Key to Health Problems in Space. National Aeronautics and Space Administration, Ames Research Center: Santa Clara, CA, 2 March 2021; https://www.nasa.gov/feature/ames/mitochondria-cell-science.

3 GeneLab: Open Science for Life in Space. National Aeronautics and Space Administration Ames Research Center: Washington, DC, 2021; https://genelab.nasa.gov.

4 Human Research Program. National Aeronautics and Space Administration Ames Research Center: Washington, DC, 2021; https://www.nasa.gov/twins-study.

When this article was written, Steven B. Engle was chief executive officer and director of CohBar, Inc., a clinical-stage biotechnology company developing mitochondria-based peptide therapeutics to treat chronic diseases and extend healthy lifespans; https://www.cohbar.com.