Stanford scientists help parse molecular changes in astronauts

Stanford scientists and their collaborators found markers of immune-related stress and other molecular changes in the body of NASA astronaut Scott Kelly.

- By Hanae Armitage

Michael Snyder

A new NASA-led study comparing the biology of twin astronauts Scott and Mark Kelly details the range of immune and molecular stresses outer space imposes on the human body. 

Among the 26 institutions that collaborated with NASA to conduct the analyses, the School of Medicine led an effort to characterize the twins at the molecular level, focusing on protein production, immune response, metabolism and the efficacy of vaccines in space.

Details of the study were published April 11 in Science. Michael Snyder, PhD, professor and chair of genetics and the Stanford W. Ascherman, MD, FACS, Professor in Genetics, and Emmanuel Mignot, MD, PhD, professor of psychiatry and behavioral sciences and the Craig Reynolds Professor in Sleep Medicine, are two of the senior authors of the study.

A stressful situation

Snyder and a team of researchers characterized the molecular shifts in both Scott Kelly, the brother who travel to space and lived on the International Space Station for a year, and Mark Kelly, his twin, who remained on the ground. In particular, the researchers focused on immune-, metabolic- and protein production-related stresses imposed by space capsule launch, zero gravity and re-entry to Earth. Blood samples from Scott taken when he was in space showed heightened levels of immune-related molecules called cytokines, which flag inflammation and bodily stress.

“We looked at a panel of 62 cytokines and saw that 50 of them were changing in some manner associated with flight, about half of which were elevated,” said Tejaswini Mishra, PhD, a postdoctoral scholar at Stanford and one of the study’s lead authors. The overall takeaway, she said, is that the immune system is revved up under the stressors of space flight. 

Astronauts on the station periodically sent frozen vials of blood back to Earth via unmanned spacecraft. Blood samples taken at different time points revealed that Scott Kelly’s cytokine-spike pattern was not uniform: Levels of some cytokines rose before takeoff, some rose while in space and some rose upon return to Earth. Six months after Scott Kelly’s return to Earth, the majority of his cytokine levels were back to normal.

Intriguing associations

Although it’s still unclear exactly how cytokine fluctuation tracked with Scott Kelly’s overall health, Snyder’s team did find intriguing associations. These connections, while interesting, are only associations at this point, and more extensive studies will be needed to understand exactly how space flight changes human health. 

Emmanuel Mignot

Despite the dips and spikes in inflammatory markers, Mignot, who was responsible for assessing the efficacy of vaccines in space, said that Scott Kelly’s body handled the flu vaccination no differently than his brother’s body back on Earth. 

“The challenges of keeping our immune system up to date and heathy during space travel are likely to become critical,” Mignot said. “Our studies show that vaccination in space is feasible and effective.”

All of this data, Snyder said, will begin to help “work out the circuitry of the immune system in response to this unusual environment.”

Outside the immune system, Snyder and Mishra saw a change in the ratio of two particular proteins known as apoB and apoA-1. Studies within the past decade have suggested that the apoB to apoA-1 ratio can predict cardiovascular disease even more accurately than cholesterol levels. According to these studies, a decreased apoB to apoA-1 ratio predicts a lower risk of cardiovascular disease. When analyzing Scott Kelly’s protein-production levels after a year in space, Snyder and Mishra saw that his ratio of apoB to apoA-1 had increased. While that doesn’t directly equate to an increase in heart disease risk, Mishra said, it’s a potential factor to watch for in future studies of the effects of long-term space exposure on humans.

Ling Lin, MD, PhD, a research associate at Stanford, and Brian Piening, PhD, a former postdoctoral scholar at Stanford, are also lead authors of the study.

The study was supported by NASA, the National Institutes of Health, the National Science Foundation, the German Aerospace Center, the Vallee Foundation, the WorldQuant Foundation, the Pershing Square Sohn Cancer Research Alliance and the Bill and Melinda Gates Foundation.

About Stanford Medicine

Stanford Medicine is an integrated academic health system comprising the Stanford School of Medicine and adult and pediatric health care delivery systems. Together, they harness the full potential of biomedicine through collaborative research, education and clinical care for patients. For more information, please visit med.stanford.edu.

2023 ISSUE 3

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