Spaceflight was also found to be linked to DNA mutations.
A groundbreaking study from the Icahn School of Medicine at Mount Sinai found that astronauts are more likely to develop mutations, potentially connected to spaceflight, that raise astronaut’s lifelong risk of acquiring cancer and heart disease.
Researchers took blood samples from astronauts who served on space shuttle missions between 1998 and 2001 for the National Aeronautics and Space Administration (NASA). All 14 astronauts were found to have DNA alterations, or somatic mutations, in the blood-forming system (hematopoietic stem cells). Their research, which was recently published in the journal Communications Biology, raises the possibility that these mutations may be brought on by spaceflight and highlights the importance of routine blood testing for astronauts throughout their careers and during retirement to keep an eye on their health.
Somatic mutations are mutations that occur after conception and in cells other than sperm or egg cells, meaning they cannot be passed on to children. The mutations uncovered in this study were characterized by an excess of blood cells produced from a single clone, a process known as clonal hematopoiesis (CH). Such mutations are commonly brought on by environmental causes, such as exposure to UV radiation or certain chemicals, and may develop as a consequence of chemotherapy or radiation treatment for cancer. There are few symptoms or signs of CH; most individuals are identified via genetic testing of their blood for other disorders. Although CH is not always a sign of disease, it is linked to an increased risk of blood cancer and cardiovascular disease.
“Astronauts work in an extreme environment where many factors can result in somatic mutations, most importantly space radiation, which means there is a risk that these mutations could develop into clonal hematopoiesis. Given the growing interest in both commercial spaceflights and deep space exploration, and the potential health risks of exposure to various harmful factors that are associated with repeated or long-duration exploration space missions, such as a trip to Mars, we decided to explore, retrospectively, somatic mutation in the cohort of 14 astronauts,” said the study’s lead author David Goukassian, MD, Professor of Medicine (Cardiology) with the Cardiovascular Research Institute at Icahn Mount Sinai.
The study subjects were astronauts who flew relatively short (median 12 days) space shuttle missions between 1998 and 2001. Their median age was approximately 42 years old; roughly 85 percent were male, and six of the 14 were on their first mission. The researchers collected whole blood samples from the astronauts 10 days before their flight and on the day of landing, and white blood cells only three days after landing. The samples were stored at -80ºC for approximately 20 years.
Using DNA sequencing followed by extensive bioinformatics analyses, researchers identified 34 mutations in 17 CH-driver genes. The most frequent mutations occurred in TP53, a gene that produces a tumor-suppressing protein, and DNMT3A, one of the most frequently mutated genes in acute myeloid leukemia. However, the frequency of the somatic mutations in the genes that the researchers assessed 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 individuals and is associated with an increased risk of developing cardiovascular disease and both hematologic and solid cancer.
“Although the clonal hematopoiesis we observed was of 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 the risk that, over time, this could happen through ongoing and prolonged exposure to the extreme environment of deep space,” Dr. Goukassian said. “Through this study, we have shown that we can determine the individual susceptibility of astronauts to develop disease related to their work without any implications that can affect their ability to do their work. Indeed, our studies demonstrate the importance of early and ongoing screening to assess that susceptibility. Our recommendation is that NASA, and its medical team, screen astronauts for somatic mutations and possible clonal expansion, or regression, every three to five years, and, not less importantly, well into their retirement years when somatic mutations may expand clonally and become CHIP.”
The team’s research follows previous studies that used the same samples to identify predictive biomarkers in exosomes—small lipid-layered microscopic vesicles of nucleic acids, proteins, lipids, and metabolites that form within the cells of the human body and are subsequently released into the blood circulation, hence carrying the information from their cells of origin that reflects their intercellular condition. This feature of exosomes may qualify them as great biomarkers of health and/or disease, as well as transfer information from one cell to another at a great distance in the body. When they treated human heart cells with exosomes derived from astronauts, 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 assessed the impact of space flight on mitochondrial DNA—the genome of small organelles that supply energy to cells. In that study, the team found that the amount of cell-free mitochondrial DNA circulating in the blood of astronauts was two to 350 times higher than normal, which may lead to oxidative damage and inflammation elsewhere in the body.
“Through these studies, we have demonstrated the potential to assess the health risk of space flight among astronauts. What is important now is to conduct longitudinal retrospective and well-controlled prospective studies involving a large number of astronauts to see how that risk evolves based on continued exposure and then compare that data against their clinical symptoms, imaging, and lab results. That will enable us to make informed predictions as to which individuals are more likely to develop disease based on the phenomena we are seeing and open the door to individualized precision medicine approaches to early intervention and prevention,” said Dr. Goukassian.
Reference: “Retrospective analysis of somatic mutations and clonal hematopoiesis in astronauts” by Agnieszka Brojakowska, Anupreet Kour, Mark Charles Thel, Eunbee Park, Malik Bisserier, Venkata Naga Srikanth Garikipati, Lahouaria Hadri, Paul J. Mills, Kenneth Walsh and David A. Goukassian, 17 August 2022, Communications Biology.
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