Spaceflight accelerates human stem cell getting older, UC San Diego researchers discover

Researchers from University of California San Diego Sanford Stem Cell Institute have found that spaceflight accelerates the getting older of human hematopoietic stem and progenitor cells (HSPCs), that are important for blood and immune system well being. In a research revealed in Cell Stem Cell, the group used automated synthetic intelligence (AI)-driven stem cell-tracking nanobioreactor methods in 4 SpaceX Commercial Resupply Services missions to the International Space Station (ISS) to trace stem cell modifications in actual time. The findings present that the cells misplaced a few of their capacity to make wholesome new cells, turned extra liable to DNA injury and confirmed indicators of sooner getting older on the ends of their chromosomes after spaceflight — all indicators of accelerated getting older.

“Space is the ultimate stress test for the human body,” stated Catriona Jamieson, M.D., Ph.D., director of the Sanford Stem Cell Institute and professor of medication at UC San Diego School of Medicine. “These findings are critically necessary as a result of they present that the stressors of area — like microgravity and cosmic galactic radiation — can speed up the molecular getting older of blood stem cells. Understanding these modifications not solely informs how we shield astronauts throughout long-duration missions but additionally helps us mannequin human getting older and ailments like most cancers right here on Earth. This is important data as we enter a brand new period of business area journey and analysis in low earth orbit.”

Previous NASA research have proven that spaceflight can have an effect on immune operate and telomere size. One such research — the NASA Twins Study — was a landmark, year-long experiment (2015-2016) the place astronaut Scott Kelly spent 340 days aboard the ISS whereas his similar twin, Mark Kelly, remained on Earth. The research tracked modifications throughout genetics, physiology, cognition and the microbiome and located altered gene expression, shifts in telomere size and modifications within the intestine microbiome. However, many of those modifications reversed or returned to regular after astronaut Kelly returned to Earth. The research did establish some persistent modifications, equivalent to elevated numbers of quick telomeres and disruptions in gene expression, which could possibly be related for longer area missions.

This UC San Diego-led research builds on the findings of the Twins Study and the seminal work of the Space Omics and Medical Atlas group which revealed 44 scientific papers on aerospace drugs and area biology in Nature. By focusing particularly on HSPCs, the research supplied an in depth mechanistic take a look at how area triggers molecular getting older, one thing the Twins Study hinted at however couldn’t totally discover on the mobile degree.

To conduct the research, researchers — together with Space Tango — developed a novel “nanobioreactor” platform — miniaturized 3D biosensing methods that allowed human stem cells to be cultured in area and monitored with AI-powered imaging instruments.

The research’s findings:

• Human HSPCs uncovered to 32 to 45 days of spaceflight confirmed hallmark options of getting older. Researchers noticed that spaceflight triggers a spread of modifications in blood-forming stem cells that intently resemble what occurs to those cells as we age. The cells turned extra lively than regular, burning by means of their reserves and dropping the flexibility to relaxation and get well — a key trait that enables stem cells to regenerate over time.
• Their capacity to make wholesome new cells declined, whereas indicators of molecular wear-and-tear, like DNA injury and shorter chromosome ends (telomeres), turned extra pronounced.
• The cells additionally confirmed indicators of irritation and stress inside their mitochondria — the cell’s power producers — and started activating hidden sections of the genome which might be usually stored quiet to keep up stability. These stress responses can impair immune operate and enhance the danger of ailments.

Notably, when these space-exposed cells had been later positioned in a younger, wholesome atmosphere, among the injury started to reverse, suggesting it could be potential to rejuvenate getting older cells with the appropriate interventions.

These findings have implications not only for astronaut well being, but additionally for understanding the mechanisms of getting older and age-related ailments like most cancers on Earth. They underscore the necessity for brand new countermeasures to guard stem cell operate throughout prolonged area missions and help the event of organic markers to detect stress-induced getting older early.

“We’re excited this breakthrough work is being published to the wider scientific and space communities,” stated 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 analysis group plans to increase this work with extra ISS missions and astronaut-based research, specializing in real-time monitoring of molecular modifications and potential pharmaceutical or genetic countermeasures to guard human well being in area and past. To date, the SSCI has carried out 17 missions to the ISS.

“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.”

Link to full study.

Additional co-authors on the research embody: Jessica Pham, Jane Isquith, Larisa Balaian, Shuvro P. Nandi, Claire Engstrom, Karla Mack, Inge van der Werf, Patrick Chang, Jana Stoudemire, Luisa Ladel, Emma Klacking, Antonio Ruiz, Daisy Chilin-Fuentes, Jenna Sneifer, Alysson R. Muotri, Thomas Whisenant and Ludmil B. Alexandrov from UC San Diego. David Mays, Paul Gamble, Shelby Giza, Jiya Janowitz, Trevor Nienaber and Twyman Clements from Space Tango. Tejaswini Mishra and Michael P. Snyder from Stanford University School of Medicine. Anna A. Khachatrian from Scripps Health. Elsa Molina and Sheldon R. Morris from The Salk Institute for Biological Studies.

The research was funded, partially, by NASA (NRA NNJ13ZBG001N) to UC San Diego Sanford ISSCOR Center; NCI (R01CA205944); NIH/NIDDK (R01DK114468-01); NIH NCI CCSG p30CA023100; NIH NCI CCSG: P30 CA01495; NIH NIA San Diego Nathan Shock Center (P30 AG068635); The Chapman Foundation and the Helmsley Charitable Trust; LLS Blood Cancer Discoveries; Sanford Stem Cell Institute; Koman Family Foundation; JM Foundation and Moores Family Foundation.

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