Researchers find that spaceflight may be associated with DNA mutations and increased risk of developing heart disease and cancer

Astronauts are at increased risk of developing mutations, possibly related to spaceflight, that can increase the risk of developing cancer and heart disease later in life, according to a groundbreaking study from the Icahn School of Medicine at Mount Sinai. .

A team of researchers collected blood samples from National Aeronautics and Space Administration (NASA) astronauts who flew on space shuttle missions between 1998 and 2001. They discovered DNA mutations, known as somatic mutations, in the formation system of blood (hematopoietic stem cells) in all 14 astronauts studied. Their findings, published in the August issue of Nature Communications Biologythey suggest that spaceflight could be associated with these mutations and emphasize the importance of continuous blood testing of astronauts throughout their careers and into retirement to monitor their health.

Somatic mutations are mutations that occur after a person is conceived and in cells that are not sperm or egg cells, meaning they cannot be passed on to offspring. The mutations identified in this study were characterized by overrepresentation of blood cells derived from a single clone, a process termed clonal hematopoiesis (CH). Such mutations are often caused by environmental factors, such as exposure to ultraviolet radiation 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 GH is not necessarily an indicator of disease, it is associated with an increased risk of cardiovascular disease and blood cancer.

“Astronauts work in an extreme environment where many factors can give rise to somatic mutations, especially space radiation, which means there is a risk that these mutations will develop into clonal hematopoiesis. Given the growing interest in both spaceflight such as in deep space exploration, and the potential health risks of exposure to various harmful factors that are associated with repeated or long-duration space exploration missions, such as a trip to Mars, we decided to explore, retrospectively, the mutation somatics in the cohort of 14 astronauts,” said the study author. lead author David Goukassian, MD, Professor of Medicine (Cardiology) at the Cardiovascular Research Institute at Icahn Mount Sinai.

The study subjects were astronauts who flew relatively short space shuttle missions (average 12 days) between 1998 and 2001. Their average age was about 42 years; about 85 percent were men, and six of the 14 were on their first assignment. The researchers collected 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 bioinformatic analysis, the researchers identified 34 mutations in 17 CH driver genes. The most frequent mutations occurred in TP53, a gene that makes 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 evaluated was less than two percent, the technical threshold for somatic mutations in hematopoietic stem cells to be considered clonal hematopoiesis of indeterminate potential (CHIP). CHIP is more common in older people and is associated with an increased risk of developing cardiovascular disease and hematologic and solid cancers.

“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 the astronauts will develop cardiovascular disease.” . or cancer, but there is a risk that, over time, this could happen due to continuous 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 work-related illnesses without any implication that could affect their ability to perform their jobs. In fact, our studies demonstrate the importance of early detection.” and continues to assess that susceptibility. Our recommendation is that NASA and its medical staff screen astronauts for somatic mutations and possible clonal expansion, or regression, every three to five years and, not least, well into their retirement years. retirement when somatic mutations can expand clonally and become CHIP.”

The team’s research follows previous studies that used the same samples to identify predictive biomarkers in exosomes — tiny, lipid-coated microscopic vesicles of nucleic acids, proteins, lipids, and metabolites that are formed inside the cells of the human body and then released into the body. blood circulation, so it carries the information of its cells of origin that reflects its intercellular condition. This characteristic of exosomes can qualify them as great biomarkers of health and/or disease, as well as transfer information from one cell to another over long 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 skeletal muscle health. They also evaluated the impact of spaceflight on mitochondrial DNA, the genome of tiny organelles that supply cells with energy. In that 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 shown the potential to assess the health risk of spaceflight among astronauts. What is important now is to conduct well-controlled retrospective longitudinal and prospective studies involving large numbers of astronauts to see how that risk evolves based on ongoing exposure and then compare that data to their clinical symptoms, imaging and lab results, and that will allow us to make informed predictions about which people are most likely to develop disease based on the phenomena we’re seeing and open up the door to precise individualized approaches to medicine for early intervention and prevention,” said Dr. Goukassian.

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