Might the secret to making it through deep space lie in how our own cells take a nap or don’t?
A new generation of studies has found that in microgravity and the radiation-heavy environment of low Earth orbit, human hematopoietic stem and progenitor cells (HSPCs) act in ways that might speed up aging and stir long-dormant viral sequences built into our own DNA. The results, spearheaded by University of California San Diego Sanford Stem Cell Institute’s Catriona Jamieson and published in Cell Stem Cell, were based on four SpaceX Commercial Resupply Services missions to the International Space Station (ISS) between 2021 and 2023. Scientists used AI-powered nanobioreactor systems no bigger than a smartphone to monitor living human stem cells in real-time as they spent 32 to 45 days in space.
On the ground, these stem cells forming blood remained dormant about 80 percent of the time, maintaining their regenerative potential. In space, microgravity and cosmic radiation shocked them awake into a state of chronic activity. “The stem cells woke up, and they didn’t go back to sleep, and they became functionally exhausted,” Jamieson said. This hyperactivity burned through cellular energy reserves, degraded their ability to produce healthy new cells, and triggered hallmarks of accelerated aging including telomere shortening, mitochondrial stress, and DNA damage. Jamieson noted that in space, “your stem cells age ten times faster… than on the ground.”
The stress response went beyond ordinary genomic maintenance. Scientists found activation of repetitive DNA sequences typically referred to as the “dark genome” that make up more than half of human DNA and are largely remnants of ancient retroviruses. Under extreme stress, these normally silent sequences can switch on. “These are retroviruses that invaded our genomes thousands and thousands of years ago… They send the stem cells into a death spiral,” Jamieson said. This activation parallels cellular responses found in preleukemic diseases, the possibility of space-caused blood cancers looming.
The root mechanisms of damage agree with generations of radiation biology. Galactic cosmic rays (GCRs) heavy ions, helium nuclei, and high-energy protons are able to cause double-strand breaks in DNA, oxidative stress, and chromosomal damage. In the ISS environment, astronauts accrue about 50–100 millisieverts during six months, equivalent to hundreds of head CT scans. Deep space missions to Mars, for example, might see exposures as high as 870–1,200 mSv, well above the levels known to saturate DNA repair mechanisms. Investigations have established that high-LET particles like iron-56 not only directly damage DNA but also interfere with repair mechanisms, particularly when compounded by microgravity, which can repress expression of important DNA damage response genes.
The ISS studies verified that HSPCs exposed to spaceflight demonstrated decreased DNA repair capability and augmented genomic instability. This instability is not just an artifact of radiation; microgravity itself will alter chromatin structure, disrupt cell cycle checkpoints, and change mitochondrial redox balance, exacerbating radiation-induced oxidative damage. These combined stressors have the potential to establish a feedback loop of DNA damage, inflammatory signaling, and the triggering of endogenous retroviral elements.
These cellular changes have more general implications for astronaut immunity. HSPCs are the precursors of immune cells, and their depletion would make it more difficult for the body to react to infection or purge newly arising cancer cells. Similar studies on natural killer (NK) cells important for killing malignant or virally infected cells have demonstrated that sustained simulated microgravity drastically diminishes their cytotoxicity, especially against T-cell acute lymphoblastic leukemia lines. This would imply that in space, not only could the preleukemic mutations occur more easily, but the immune system’s capacity to suppress them would be weakened.
A glimmer of reversibility does exist, however. Early results show that when stem cells are returned to Earth, they can regain much of the function lost during space travel, although it might take a year or more. That window of recovery presents a possible avenue for countermeasures. Scientists are investigating pharmacological agents to inhibit dark genome activation, antioxidants to reduce mitochondrial stress, and even pre-flight screening of astronaut stem cell “avatars” in nanobioreactors to forecast individual resilience.
For the time being, the work highlights a stark truth: long-duration spaceflight is as much a challenge of spacecraft technology as it is of cellular longevity. The same stem cells that labor quietly to keep life ticking over on Earth could, under the otherworldly conditions of space, become over-worked, gene-shattered, and dogged by the viral apparitions of our evolutionary past.
