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A year-long human spaceflight reveals circulating biomarkers

A team of researchers have profiled cfDNA isolated from plasma of an astronaut during a year-long mission on the International Space Station (ISS), identifying potential circulating biomarkers for physiological stress or immune responses related to spaceflight.

cfDNA and exosomes

There are a wide range of physiological effects that impact the body during prolonged stay in microgravity. These include, headward fluid shift, muscle atrophy and decreased bone density. Plans to go to the Moon and Mars are already in motion. These missions may span 30 months with almost no clinical infrastructure for medical monitoring or treatment. However, the data on physiological changes of long-term missions (>6 months) is limited.

The NASA Twins study enabled the interrogation of the impact prolonged spaceflight has on human biology and cell-to-cell variations in the immune system. Nonetheless, there has never been a study that has analysed the impact of spaceflight on cell-free DNA (cfDNA). Analysis of cfDNA can provide molecular signatures that are informative of human health and disease. cfDNA is also extremely dynamic and responsive, providing a strong indicator of DNA damage and tumour growth in distal tissues, immune response or infection and RNA regulatory changes.

Exosomes are nano-sized vesicles derived from perinuclear luminal membranes. They act as vehicles for horizontal transfer of information through their cargo, e.g. proteins and DNA. Additionally, they are powerful mediators of responses to environmental stimuli. This is because external and physiological stress can impact cargo release. Exosomes are critical components of liquid biopsies as they are highly abundant in plasma. Importantly, analysis of their content can complement the information obtained from cfDNA. However, there is currently no information about exosomes in astronauts.

Circulating biomarkers

In a recent study, published as preprint in bioRxiv, researchers profiled cfDNA isolated from plasma samples before, during and after a one-year mission on the ISS. They obtained these samples during the NASA Twins study. The team evaluated the utility of cfDNA as a means to monitor physiological problems during extended missions into space. Moreover, they also profiled the exosomes of both astronauts after the mission. They specifically focussed on quantitative measures, such as the levels of mitochondrial DNA and cfDNA fragment length.

The team found a significant increase in the proportion of cell-free mitochondrial DNA inflight, suggesting that cf-mtDNA is a potential biomarker for space flight-associated stress. Furthermore, analysis of exosomes isolated from post-flight plasma revealed a 30-fold increase in circulating exosomes. Additionally, they found distinct exosomal protein cargo, including brain-derived peptides, between the twins and all known controls.

This study provides the first longitudinal analysis of astronaut cfDNA during spaceflight. These findings support cf-mtDNA as a novel biomarker of physiological stress or immune responses related to microgravity, radiation exposure and other unique environmental conditions during prolonged spaceflight. Overall, experts can use this data and methods in planning for future types of astronaut health monitoring. Most importantly, these non-invasive molecular tools may be key for tracking the impact of stress and spaceflight during future missions.

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Biomarkers / cf-DNA / Space / Telomeres