A new analysis led by scientists at the Buck Institute for Research on Aging uses blood samples from that mission to position spaceflight as a model system for studying biological aging and cellular resilience, and to explore how extreme environmental stressors reshape the molecular signatures of age.
Astronauts are exposed simultaneously to microgravity, ionizing radiation, disrupted circadian rhythms and social isolation, a combination of stressors that is difficult to reproduce on Earth and that provides a natural testbed for aging biology.
Working with collaborators at Weill Cornell Medicine in New York and King Faisal Specialist Hospital and Research Centre in Jeddah, Saudi Arabia, the Buck team developed an epigenetic age acceleration metric, or EAA, that combines information from multiple DNA methylation based clocks to estimate how those stressors alter biological age over time.
Using serial blood draws collected before flight, in flight and after landing, the researchers report that average epigenetic age acceleration rose by 1.91 years by flight day 7 for the Axiom 2 crew, indicating a rapid age associated response at the molecular level during the mission.
After the astronauts returned to Earth, biological age estimates declined in all four crew members, with older astronauts returning to their preflight epigenetic age and younger astronauts showing a biological age that dipped below baseline values.
The findings suggest that the biological impact of short term spaceflight on epigenetic aging is largely reversible and that human physiology may harbour intrinsic rejuvenation mechanisms that counteract the age accelerating effects of space related stress.
"These results point to the exciting possibility that humans have intrinsic rejuvenation factors that can counter these age accelerating stressors," said senior author David Furman, PhD, an associate professor at the Buck Institute and director of its AI and Bioinformatics Core.
The investigators applied 32 DNA methylation based aging clocks to the samples and then examined how changes in immune cell composition might explain the observed shifts in epigenetic age acceleration over the course of the mission.
They found that alterations in immune cell populations accounted for a substantial fraction of the apparent age acceleration, with regulatory T cells and naive CD4 T cells showing prominent changes in response to spaceflight.
Even after adjusting the models for immune cell composition, several chronological age predictors still indicated accelerated aging signatures in flight, pointing to epigenetic effects that go beyond changes in circulating cell types.
According to the authors, the pattern supports the view that spaceflight induces rapid but reversible epigenetic remodeling in blood cells, and that some of these changes reflect processes that are partially distinct from simple immune cell redistribution.
Furman and colleagues argue that commercial and governmental space missions now offer a platform for testing geroprotective interventions, using molecular clocks and immune readouts to track how candidate countermeasures influence aging biology in real time.
In parallel with the human study, Furmans group is modeling aspects of microgravity in the laboratory using organoids derived from heart, brain and immune cells to dissect tissue specific responses to simulated spaceflight conditions.
The lab has developed and patented technology to recapitulate elements of microgravity in vitro and this intellectual property has been licensed to a spin off company that is building tools and assays for both drug discovery and consumer facing interventions in the aging process.
The researchers note that the work builds on a growing body of evidence tying immune system status, epigenetic regulation and environmental stress exposure to trajectories of health span and lifespan in humans.
The new results, published in the journal Aging Cell, are presented in a paper titled "Astronauts as a Human Aging Model: Epigenetic Age Responses to Space Exposure," which details the data from Axiom 2 as a proof of concept for future space based aging research.
Coauthors on the study include Christopher Mason, JangKeun Kim, Jeremy Wain Hirschberg and Eliah G Overbey from the Department of Physiology and Biophysics at Weill Cornell Medicine in New York, and Bader Shirah from the Department of Neuroscience at King Faisal Specialist Hospital and Research Centre in Jeddah, Saudi Arabia.
The authors disclose that Furman is a co founder of Cosmica Biosciences, a company focused on aging related technologies, while the remaining coauthors report no competing interests.
Research Report:Astronauts as a Human Aging Model: Epigenetic Age Responses to Space Exposure
Related Links
Buck Institute for Research on Aging
Space Medicine Technology and Systems
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