Space travel puts mitochondria’s central role in the spotlight

The scientific community has long validated the significance of mitochondria as our cell’s “energy factories.” Now, though, the much more central role that these membrane-bound cell organelles play in health and disease has come into focus with NASA’s breakthrough Cell article

Steven B. Engle, Chief Executive Officer and Director, CohBar Inc., explains: "This study, a collaboration between NASA and leading researchers, analysed the largest currently available cohort of astronaut biomedical data to better understand the negative effects of spaceflight on human physiology and health."1

“We've found a universal mechanism that explains the kinds of changes we see to the body in space … and in a place we didn’t expect,” adds Afshin Beheshti, the paper’s lead author and a researcher with KBR, which provides contract support to NASA's Ames Research Center in California's Silicon Valley.2,3

“Everything gets thrown out of whack and it all starts with the mitochondria.”

“Mitochondrial dysregulation promotes spaceflight health risks,” note the researchers, who examined the biomedical profiles of 59 astronauts and data from NASA’s GeneLab (derived from hundreds of samples flown in space).

Overall pathway analyses on the multiomic datasets showed the significant enrichment of mitochondrial processes, as well as innate immunity, chronic inflammation, cell cycle, circadian rhythm and olfactory functions.

Steven Engle

Importantly, NASA’s Twin Study provided a platform to confirm several of the principal findings.4 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.

Mitochondrial dysfunction on the ground.

Unfortunately, mitochondrial dysregulation doesn’t only occur in space. An estimated one in 5000 people have genetic defects that can result in mitochondrial dysfunction and life-threatening illnesses … but a far greater population develops it during their lifetime from ageing, lifestyle behaviours, toxins, drug side-effects or other diseases.

Mitochondrial dysfunction is strongly associated with a wide range of highly prevalent diseases, including diabetes, cardiovascular disease, obesity, liver disease, cancer, neurological diseases and immune and inflammatory disorders, as well as increased comorbidity and mortality.

And, in turn, these conditions are responsible for the majority of annual deaths, excluding accidents. As such, it’s not surprising that, once the study identified mitochondrial dysfunction in its astronaut subjects, so many of their body’s Earth-normal functions and their health would also be impaired.

Given that mitochondria are critical to both human biology and a healthy lifespan, it’s possibly more surprising that a group of astronauts, in peak physical condition with a healthy diet and regular exercise, would all develop dysfunction so quickly.

It typically takes many years and an unhealthy lifestyle on the ground! Perhaps the lack of gravity in space has an effect similar to that of a sedentary lifestyle on the ground, a known contributor to mitochondrial dysfunction.

Mitochondrial science and medicine.

It’s also not unexpected that, given the increasing awareness of the enormous impact of mitochondrial dysfunction on health and lifespan, leading research scientists have been increasingly focused on mitochondria to better understand how they perform their much more complex and central role in healthy people, how they become dysfunctional and what can be done to prevent or correct the dysfunction.

CohBar, for instance, has spent the past two decades exploring mitochondrial genetics and biology, discovering new mitochondrial genes and mechanisms, and identifying opportunities for therapeutic drugs to address the huge unmet medical need.

Expanding on their breakthrough discoveries, the company has been identifying and developing a growing number of mitochondria-based therapeutics that offer significant potential to address diseases associated with mitochondrial dysfunction both on the ground and, perhaps, in space as well.

To cite a recent example, new preclinical data have been obtained that confirm the efficacy of CohBar’s apelin agonist peptides in a preclinical model of acute respiratory distress syndrome (ARDS).

Supporting previous results showing that CB5064 Analogs reduce fluid accumulation and proinflammatory cytokine secretion, the company believes the apelin agonists may be able to treat COVID-19-associated ARDS, as well as ARDS patients in general, of which there are approximately three million globally.5

In the preclinical study, acute lung injury was induced in mice by the administration of lipopolysaccharide (LPS), a bacterial toxin that produces similar symptoms to other causes of ARDS.

A single dose of CB5064 Analog was administered one hour prior to the LPS exposure and effects on lung weight and levels of proinflammatory cytokines were measured 4 hours after LPS exposure.

Compared with a placebo, treatment with CB5064 Analogs reduced both fluid accumulation in the lungs and the levels of key proinflammatory cytokines secreted into the lung fluid.

ARDS is a major unmet medical need with no approved therapeutics for this devastating condition. The data obtained from this study are therefore encouraging and support further advancement of the programme towards candidate selection for clinical testing.

References

  1. www.cell.com/cell/fulltext/S0092-8674(20)31461-6.
  2. www.nasa.gov/feature/ames/mitochondria-cell-science.
  3. www.kbr.com/en/markets/aerospace-defense/space.
  4. www.nasa.gov/feature/nasa-s-twins-study-results-published-in-science.
  5. www.longevity.technology/cohbar-announces-preclinical-collaboration-with-niaid.

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