SpaceX Inspiration4 mission secretome profiling reveals the impact of spaceflight on human health

As space travel becomes more frequent with commercial missions like SpaceX’s Inspiration4, understanding the effects of spaceflight on human health is crucial. Recent research has taken a significant step in this direction by examining blood-based health markers from the Inspiration4 crew. By analyzing plasma proteins, metabolites, and extracellular vesicles/particles (EVPs), scientists at Weill Cornell Medicine have developed a detailed picture of how spaceflight affects the human body at a molecular level.

The “Spaceflight Secretome”

The researchers created “spaceflight secretome profiles” by profiling various biological components from the Inspiration4 crew. This analysis revealed notable changes in several key areas:

  1. Coagulation: This refers to the blood’s ability to form clots, which is essential for stopping bleeding and healing wounds. Spaceflight was found to affect this process.
  2. Oxidative Stress: This is a condition where there is an imbalance between free radicals (which can damage cells) and antioxidants (which protect cells). Increased oxidative stress can lead to various health issues.
  3. Brain-Enriched Proteins: These proteins are typically found in the brain and their presence in the blood suggests potential disruptions in brain function or the blood-brain barrier (BBB).

Changes in the proteomic profile of plasma and EVPs after 3-day spaceflight

Fig. 1

a Overview of study design, sample collection, and processing of plasma and EVP proteomics. b Venn diagram of proteins measured in plasma and EVP, before (left) and after (right) filtering, based on the coefficient of variance, low abundance, and number of not assessed (NAs). c Upset plot showing the overlap of differentially abundant proteins (adjusted p-value < 0.05, |logFC | >1) across the different comparisons performed in plasma and EVPs. Differential abundance analysis was performed with limma with the following model ~astronaut+flightSatus and p-values have been adjusted to control the false discovery rate d Boxplots of the scaled abundance of the 9 proteins differentially abundant in both plasma and EVPs. Where available, data represents n = 4 astronauts averaged at the indicated condition (preflight and long-term postflight). Plasma data is the average of two technical replicates, EVP data represents one technical replicate per astronaut and timepoint. Boxes show the quartiles of the dataset while the whiskers extend to show the rest of the distribution except for outliers. e Gene Ontology enrichment was performed using clusterProfiler::enrichGO() on differentially abundant proteins in plasma (adjusted p-value < 0.05, |logFC | >1) at R + 1 vs. Preflight. Biological processes (BP) were selected, and treeplot was used to organize significant pathways (adjusted p-value < 0.05) into biologically relevant clusters. f Gene Ontology enrichment was performed using clusterProfiler::enrichGO() on differentially abundant proteins in the EVPs (adjusted p-value < 0.05, |logFC | >1) at R + 1 vs. Preflight. Biological processes were selected, and treeplot was used to organize and cluster the significant pathways (adjusted p-value < 0.05) into biologically relevant clusters. Source data are provided as a Source Data file.

Recovery After Spaceflight

The study found that while more than 93% of the differentially abundant proteins (DAPs) in vesicles and metabolites returned to normal levels within six months after the flight, a significant portion (73%) of plasma DAPs remained altered post-flight. This indicates that some effects of spaceflight on the body persist longer than others, with plasma proteins showing the most prolonged changes.

Immune Cells and Spaceflight

Interestingly, the changes in proteomic profiles correlated more strongly with peripheral blood mononuclear cells (a type of immune cell) than with whole blood. This suggests that immune cells play a more significant role in the observed changes than red blood cells. Essentially, the immune system appears to be more affected by spaceflight, contributing more to the variations in the protein levels detected.

Insights from Spaceflight Mice

To understand why brain-enriched proteins were detected in the blood, the researchers also studied mice that had been in space. They discovered increases in a protein called PECAM-1, a marker associated with the integrity of the blood-brain barrier (BBB). This finding suggests that spaceflight can cause disruptions to the BBB, potentially allowing brain proteins to leak into the bloodstream.

Implications for Astronaut Health

These findings are significant because they highlight how even short-duration spaceflights can have substantial effects on human physiology. By identifying specific biomarkers—proteins and metabolites that change in response to spaceflight—scientists can better monitor astronaut health and develop targeted countermeasures to mitigate these effects. This research paves the way for improved health monitoring and safety measures for future space travelers.


As space travel becomes more accessible, understanding its impact on the human body is essential. The study of the SpaceX Inspiration4 crew provides valuable insights into how spaceflight affects coagulation, oxidative stress, and the blood-brain barrier, among other things. By identifying persistent changes in plasma proteins and the significant role of immune cells, this research helps us better understand the challenges astronauts face and how to protect their health on future missions.

Houerbi N, Kim J, Overbey EG, Batra R, Schweickart A, Patras L, Lucotti S, Ryon KA, Najjar D, Meydan C, Damle N, Chin C, Narayanan SA, Guarnieri JW, Widjaja G, Beheshti A, Tobias G, Vatter F, Hirschberg JW, Kleinman A, Afshin EE, MacKay M, Chen Q, Miller D, Gajadhar AS, Williamson L, Tandel P, Yang Q, Chu J, Benz R, Siddiqui A, Hornburg D, Gross S, Shirah B, Krumsiek J, Mateus J, Mao X, Matei I, Mason CE. (2024) Secretome profiling reveals acute changes in oxidative stress, brain homeostasis, and coagulation following short-duration spaceflight. Nat Commun 15(1):4862. [article]

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