Astronauts as a Human Aging Model: Epigenetic Age Responses to Space Exposure.

Spaceflight exposes astronauts to a combination of environmental stressors such as microgravity, ionizing radiation, circadian disruption, and social isolation that induce phenotypes of aging. However, whether these exposures accelerate biological aging remains unclear. In this exploratory study, we assessed 32 DNA methylation-based biological age metrics in 4 astronauts during the Axiom-2 mission at pre-flight, in-flight (day 4 and 7), and post-flight (return days 1 and 7). On average, Epigenetic Age Acceleration increased 1.91 years by flight day 7. Upon return to Earth, biological age decreased in all crew members, with older astronauts returning to pre-flight estimates and younger astronauts showing a biological age significantly lower than pre-flight levels. We found that shifts in immune cell composition, specifically regulatory and naïve CD4 T-cells, accounted for a significant portion of the observed age acceleration in several clock models. However, even after adjusting for cell composition, chronological age and mortality-based predictors showed acceleration during spaceflight. These findings suggest that spaceflight induces rapid, yet reversible, epigenetic changes associated with aging, positioning spaceflight as a platform to study human aging mechanisms and test geroprotective interventions.