Researchers from University of California San Diego Sanford Stem Cell Institute have discovered that spaceflight accelerates the aging of human hematopoietic stem and progenitor cells (HSPCs), which are vital for blood and immune system health.
The team used automated artificial intelligence (AI)-driven stem cell-tracking nanobioreactor systems to track stem cell changes in real time, during four SpaceX Commercial Resupply Services missions to the International Space Station (ISS). The findings showed that the cells lost some of their ability to make healthy new cells, became more prone to DNA damage, and showed signs of faster aging at the ends of their chromosomes after spaceflight—all signs of accelerated aging.
The findings have implications not just for astronaut health, but also for understanding the mechanisms of aging and age-related diseases, such as cancer, on Earth. The results also underscore the need for new countermeasures to protect stem cell function during extended space missions and support the development of biological markers to detect stress-induced aging early.
“Space is the ultimate stress test for the human body,” said research lead Catriona Jamieson, MD, PhD, director of the Sanford Stem Cell Institute and professor of medicine at UC San Diego School of Medicine. “These findings are critically important because they show that the stressors of space—like microgravity and cosmic galactic radiation—can accelerate the molecular aging of blood stem cells. Understanding these changes not only informs how we protect astronauts during long-duration missions but also helps us model human aging and diseases like cancer here on Earth. This is essential knowledge as we enter a new era of commercial space travel and research in low earth orbit.”
Jamieson is senior author of the team’s published paper in Cell Stem Cell. In their report, titled “Nanobioreactor detection of space-associated hematopoietic stem and progenitor cell aging,” the team concluded, “These short-duration spaceflight models of accelerated HSPC aging may provide insights into terrestrial human aging and age-related malignancies.
Previous NASA studies have shown that spaceflight can affect immune function and telomere length. “In the stressful environment of low-earth orbit (LEO), which has been increasingly used for scientific discovery and commercial manufacturing, fundamental physical phenomena shift, leading to changes in immune function, metabolic processes, and other physiological responses,” the authors explained.
One such study—the NASA Twins Study—was a landmark, year-long experiment (2015-2016) where astronaut Scott Kelly spent 340 days aboard the ISS while his identical twin, Mark Kelly, remained on Earth. The study tracked changes across genetics, physiology, cognition, and the microbiome and found altered gene expression, shifts in telomere length, and changes in the gut microbiome.
However, many of these changes reversed or returned to normal after astronaut Kelly returned to Earth. The study did identify some persistent changes, such as increased numbers of short telomeres and disruptions in gene expression, which could be relevant for longer space missions.
The newly reported UC San Diego-led study builds on the findings of the Twins Study and the seminal work of the Space Omics and Medical Atlas group, which published 44 scientific papers on aerospace medicine and space biology in Nature.
By focusing specifically on HSPCs, the study in Cell Stem Cell offers a detailed mechanistic look at how space triggers molecular aging, something the Twins Study hinted at but could not fully explore at the cellular level. “Few studies have investigated the combined stressors associated with the extreme environment of space on functional processes regulated at the HSPC level that will be vital for understanding the human-specific limitations of long-duration spaceflight,” Jameison and team noted.
To conduct their study, the researchers, including a team at Space Tango, developed a novel “nanobioreactor” platform—miniaturized 3D biosensing systems that allowed human stem cells to be cultured in space and monitored with AI-powered imaging tools. “To determine whether HSPC fitness is impaired and immune dysfunction derives from the loss of normal HSPC homeostasis in space compared with terrestrial environments, we developed a 3D biosensing nanobioreactor system that enables prolonged maintenance of human HSPCs,” they explained.
Their results showed that human HSPCs exposed to 32 to 45 days of spaceflight showed hallmark features of aging. Spaceflight was found to trigger a range of changes in blood-forming stem cells that closely resemble what happens to these cells as we age. The cells became more active than normal, burning through their reserves and losing the ability to rest and recover—a key trait that allows stem cells to regenerate over time.
The results showed that the ability of HSPCs in space to make healthy new cells declined, while signs of molecular wear-and-tear, such as DNA damage and shorter chromosome ends—telomeres—became more pronounced.
The cells also showed signs of inflammation and stress inside their mitochondria and began activating hidden sections of the genome that are normally kept quiet to maintain stability. These stress responses can impair immune function and increase the risk of diseases.
“…we observed inflammatory cytokine changes, mitochondrial DNA amplification, protein translation, and mitochondrial gene expression changes, which corroborated previous studies showing inflammatory cytokine and mitochondrial deregulation in longer-duration spaceflight,” the scientists reported.
“Together, these findings suggest a diminished capacity of HSPCs to maintain their function upon return from spaceflight, which is consistent with accelerated stem cell aging.”
Notably, when these space-exposed cells were later placed in a young, healthy environment, some of the damage began to reverse, suggesting it may be possible to rejuvenate aging cells with the right interventions. “Space-associated HSPC aging can be partially reversed on young stroma,” the scientists further stated.
“We’re excited this breakthrough work is being published to the wider scientific and space communities,” said Twyman Clements, president and co-founder of Space Tango. “Like many accomplishments, this one was a team effort bringing together the Integrated Space Stem Cell Orbital Research Center within SSCI, Space Tango, and others. Coupling Space Tango’s CubeLab capabilities, specifically the persistent microscopy, has enabled this work and will continue to do so in the future.”
The research team plans to extend their work with additional ISS missions and astronaut-based studies, focusing on real-time monitoring of molecular changes and potential pharmaceutical or genetic countermeasures to protect human health in space and beyond. To date, the SSCI has conducted 17 missions to the ISS.
The authors stated, “Together, our results reveal spaceflight-associated HSPC aging, thereby setting the stage for the development of countermeasures to enable long-duration human spaceflight and establish AI-driven technologies for predicting HSPC functional decline under conditions of macroenvironmental stress in space and terrestrially…Ultimately, these studies may provide guidance for therapeutic strategies to mitigate space-specific changes in the expanding space economy, as well as space-accelerated models of aging and age-related diseases, such as cancer.”
“Space experiments are so complex that they force you to do better science on the ground,” continued Jamieson. “Space research has accelerated technological advancements on Earth, making ground-based research easier and more relevant to human health. What we have learned about cancer from our studies in space is absolutely remarkable.”
In their paper the researchers suggested, “Moreover, the methods and findings from our study can help facilitate future studies to predict and understand the observed molecular changes for longer-duration or further destination spaceflight missions.”