Aging in Spaceflight, Oxidative Stress, and Microbiome Dysbiosis: A Comprehensive Review

The evolutionary theory of aging demonstrates that the force of natural selection declines with age in multicellular organisms. Two population genetic mechanisms are consistent with the evolutionary theory: mutation accumulation and antagonistic pleiotropy. These in turn account for the physiological, cellular, and molecular mechanisms associated with aging. Spaceflight provides an opportunity to examine how organisms physiologically acclimate to environmental conditions. Mitochondria and the gut microbiome are central regulators of host metabolism, redox homeostasis, immune function, and physiological resilience, and both are impacted by host adaptations and acclimations. Mitochondrial dysfunction and oxidative stress have consequently emerged as important candidate mechanisms linking biological aging and spaceflight-associated physiological change. This review examines evidence surrounding mitochondrial dysfunction, oxidative stress, and gut microbiome dysbiosis across humans, mice, and fruit flies under spaceflight and corresponding terrestrial control conditions. This review reports further on the progression of theory and recent evidence from spaceflight missions for how biomarker genes most associated with mutation accumulation and antagonistic pleiotropy appear to have a core role in natural aging and extreme physiological acclimation.