Stratified longitudinal transcriptomic analysis indicates age-associated mitochondrial dysfunction and immune response in astronauts aboard the ISS

Exposure to the space environment poses significant challenges to human physiological systems, including the immune system. Sex and age significantly influence immune function. Therefore, this study aimed to investigate the effects of age and sex on spaceflight-associated gene expression. Blood samples were collected between 75 and 210 days in space. At the time of launch, the ISS astronauts were 34–61 years old. Transcriptomic analyses were performed using peripheral blood mononuclear cells (PBMCs) isolated from ten crewmembers. Principal component analysis showed an age-dependent response to the in-flight environment, with no clear sex-related effect. The number of differentially expressed genes (DEGs) was also associated with mission duration, with more dysregulated genes observed in younger crewmembers and during longer-duration space missions. Similarly, cellular pathway analysis indicated that younger astronauts experienced more severe mitochondrial dysfunction. Our results suggest that spaceflight-associated gene expression changes were more pronounced in younger astronauts than in older astronauts. Whether this heightened response is beneficial or detrimental remains to be investigated.