Cell-free DNA (cfDNA) and Exosome Profiling from a Year-Long Human Spaceflight Reveals Circulating Biomarkers

Area of Science:

• Space Medicine
• Molecular Biology
• Biomarkers

Background:

• Liquid biopsies, including cell-free DNA (cfDNA) and exosomes, offer noninvasive health monitoring but are underutilized in astronaut populations.
• Understanding physiological changes during spaceflight is crucial for astronaut well-being and mission success.

Purpose of the Study:

• To longitudinally profile cfDNA characteristics and exosome cargo in an astronaut during a year-long space mission.
• To evaluate the potential of cfDNA and exosomes as biomarkers for physiological stress in astronauts.

Main Methods:

• Analysis of cfDNA fragment size, cellular deconvolution, and nucleosome positioning in an astronaut compared to an identical twin on Earth.
• Quantification and proteomic analysis of circulating exosomes in plasma before, during, and after spaceflight.
• Comparison with healthy donor samples to establish baseline variations.

Main Results:

• A significant increase in the proportion of cell-free mitochondrial DNA (cf-mtDNA) was observed during the spaceflight.
• Post-flight plasma revealed a 30-fold increase in circulating exosomes, containing astronaut-specific protein cargo, including brain-derived peptides.
• cfDNA and exosome profiles demonstrated significant alterations attributable to the spaceflight environment.

Conclusions:

• Longitudinal cfDNA and exosome profiling are valuable tools for astronaut health monitoring during long-duration space missions.
• Elevated cf-mtDNA levels may serve as a potential biomarker for physiological stress and immune responses in microgravity.
• Exosome cargo analysis provides insights into molecular changes and potential health risks associated with space travel.