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Spaceflight presents unique environmental stressors, such as microgravity and radiation, that significantly affect biological systems at the molecular, cellular, and organismal levels. Female astronauts, in particular, face an increased risk of developing breast cancer due to exposure to ionizing radiation and other spaceflight-related factors. Age also plays a crucial role in the mammary gland’s response to these stressors, with younger organisms generally exhibiting more efficient response mechanisms than older ones. In this study, we utilized an ensemble of machine learning algorithms to analyze gene expression profiles from mammary tissue of young and old female mice exposed to spaceflight to predict age (old vs young) and condition (spaceflight vs ground control). Using the genes our ensemble identified as most predictive, we investigate the molecular pathways involved in spaceflight-related health risks, particularly in the context of breast cancer and cardiovascular health. We identified age-dependent differences in the gene expression profiles of spaceflight-exposed mice compared to ground control.

Specifically, younger mice exhibited enriched pathways related to cellular structure, while older mice showed activation of pathways involved in cortisol synthesis and muscle contraction. All mice responded to spaceflight with evidence of elevated lipid metabolic function. These findings highlight the critical role of age in modulating the response to spaceflight-induced stress and suggest that these molecular pathways may contribute to differential outcomes in tissue homeostasis, cardiovascular and metabolic disorders, and breast cancer susceptibility.