Challenges of Health Issues in a Space Environment: A Nutritional Approach

Abstract

Space environments, characterized by microgravity and cosmic radiation, induce rapid aging-like physiological changes in humans. Central to these changes are mitochondrial dysfunction and ATP depletion, which share molecular features with terrestrial aging. This study proposes a novel paradigm viewing aging as an “energy deficit” process, driven by chronic hypoxia, HIF-1α stabilization, and suppression of aerobic metabolism. To address this, we focused on high-altitude populations adapted to hypoxic conditions and identified kaempferol (KMP), a flavonoid abundant in their traditional diet. In vitro assays, animal models, and clinical trials showed that KMP consistently promoted ATP production by facilitating HIF-1α degradation and restoring mitochondrial oxidative phosphorylation. Furthermore, studies using animals and organoids under simulated space conditions demonstrated that KMP mitigates tissue atrophy and functional decline. These findings suggest that KMP would be a promising nutritional supplement for maintaining health in space and also on Earth. Future directions include astronaut trials and precision nutrition approaches, aiming to establish a paradigm that redefines health and aging through the lens of cellular energy. Such insights may contribute to the development of countermeasures for space missions, improvement of longevity strategies, and guiding nutritional interventions for age-related disorders. Ultimately, this work bridges space medicine and global health, offering a foundation for sustainable strategies to address aging and chronic disease worldwide.