Newswise – (New York, NY – August 31, 2022) – Astronauts are at higher risk of developing mutations, possibly related to spaceflight, that may increase the risk of developing cancer and heart disease during their lifetime, according to an unpublished study from the Icahn School of Medicine at Mount Sinai .
A team of researchers took blood samples from National Aeronautics and Space Administration (NASA) astronauts who flew space shuttle missions between 1998 and 2001. They found mutations in DNA, called somatic mutations, in the blood-forming system (hematopoietic stem cells) in all 14 astronauts studied. Their findings, published in the August issue of Nature Communication Biologysuggest that spaceflight may be associated with these mutations and highlight the importance of continued blood screening of astronauts throughout their careers and during retirement to monitor their health.
Somatic mutations are mutations that occur after a person is conceived and in cells other than sperm or egg, meaning they cannot be passed on to offspring. The mutations identified in this study were characterized by the overrepresentation of blood cells from a single clone, a process called clonal hematopoiesis (CH). These mutations are frequently caused by environmental factors, such as exposure to ultraviolet rays or certain chemicals, and may be the result of cancer chemotherapy or radiation therapy. There are few signs or symptoms associated with CH; most patients are identified after genetic testing of their blood for other diseases. Although CH is not necessarily an indicator of disease, it is associated with a higher risk of cardiovascular disease and blood cancer.
“Astronauts work in an extreme environment where many factors can lead to somatic mutations, including space radiation, which means that there is a risk that these mutations will turn into clonal hematopoiesis. Considering the growing interest in commercial spaceflight and deep space exploration, and the potential health risks from exposure to various harmful factors associated with repeated or long duration exploration space missions , like a trip to Mars, we decided to explore, retrospectively, somatic mutation in the cohort of 14 astronauts,” said study lead author David Goukassian, MD, professor of medicine (cardiology) at the Icahn Mount Sinai Cardiovascular Research Institute.
Study subjects were astronauts who flew relatively short space shuttle missions (median 12 days) between 1998 and 2001. Their median age was approximately 42; about 85% were men and six of the 14 were on their first mission. The researchers took whole blood samples from the astronauts 10 days before their flight and on the day of landing, and white blood cells just three days after landing. The samples were stored at -80°C for approximately 20 years.
Using DNA sequencing followed by extensive bioinformatics analyses, the researchers identified 34 mutations in 17 CH driver genes. The most common mutations occurred in TP53, a gene that produces a tumor suppressor protein, and DNMT3A, one of the most frequently mutated genes in acute myeloid leukemia. However, the frequency of somatic mutations in the genes the researchers assessed was less than two percent, the technical threshold for somatic mutations in hematopoietic stem cells to be considered clonal hematopoiesis of undetermined potential (CHIP). CHIP is more common in the elderly and is associated with an increased risk of developing cardiovascular disease and hematological and solid cancer.
“Although the clonal hematopoiesis we observed was of a relatively small size, the fact that we observed these mutations was surprising given the relatively young age and health of these astronauts. The presence of these mutations does not necessarily mean that astronauts will develop cardiovascular disease or cancer, but there is a risk that over time this may occur due to continued and prolonged exposure to the extreme environment of deep space” , said Dr. Goukassian. . “Through this study, we have shown that we can determine the susceptibility of individual astronauts to developing a work-related disease without any implications that may affect their ability to do their job. Indeed, our studies demonstrate the importance of early and ongoing screening to assess this susceptibility.Our recommendation is that NASA and its medical team examine astronauts for somatic mutations and eventual clonal expansion, or regression, every three to five years, and, no less important, into their retirement years when somatic mutations can develop clonally and become CHIP . .”
The team’s research follows previous studies that used the same samples to identify predictive biomarkers in exosomes – small, microscopic lipid-coated vesicles of nucleic acids, proteins, lipids and metabolites that form in the cells of the human body and are then released into the blood. circulation, thus carrying information from their cells of origin that reflects their intercellular condition. This characteristic of exosomes can qualify them as great biomarkers of health and/or disease, as well as the transfer of information from one cell to another over great distances in the body. When they treated human heart cells with astronaut-derived exosomes, the researchers found that the exosomes affected the biology of the vitamin D receptor, which plays a key role in bone, heart and muscle health. skeletal. They also assessed the impact of spaceflight on mitochondrial DNA, the genome of small organelles that supply cells with energy. In this study, the team found that the amount of cell-free mitochondrial DNA circulating in astronauts’ blood was two to 350 times higher than normal, which can lead to oxidative damage and inflammation elsewhere in the body.
“Through these studies, we have demonstrated the potential for assessing the health risk of spaceflight in astronauts. What is important now is to conduct well-controlled retrospective and prospective longitudinal studies involving a large number of astronauts to see how that risk changes with continued exposure, and then compare that data to their clinical symptoms, imaging, and lab results. This will allow us to make informed predictions about who is most likely to to develop a disease based on the phenomena we observe and to open the door to individualized precision medicine approaches for early intervention and prevention,” said Dr. Goukassian.
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