Aging in orbit: The twelve hallmarks as a bidirectional bridge between spaceflight-induced senescence and terrestrial geroscience

Abstract

Human spaceflight exposes crew members to a combination of environmental stressors – including microgravity, galactic cosmic radiation, circadian disruption, and prolonged confinement – that together induce multisystem physiological changes resembling terrestrial aging. In this narrative review, we examine how short- and medium-term spaceflight affects all twelve recognized hallmarks of aging. We conclude that the relationship between spaceflight biology and terrestrial geroscience is bidirectional. Aging research on Earth provides the interpretive framework that renders astronaut molecular data biologically meaningful, and spaceflight offers geroscience a compressed, partially reversible aging-like phenotype in healthy young subjects that has no direct terrestrial counterpart. The observation that space radiation induces qualitatively distinct senescent phenotypes amenable to senolytic clearance supports a translational framework in which geroprotective strategies may simultaneously serve astronaut health and promote healthy longevity in the broader aging population.