Longitudinal transcriptomic and epigenetic analysis in astronauts reveals dynamic immune response to spaceflight

The space industry has made significant strides in recent years, leading to an era of commercial spaceflight. Meanwhile, understanding the molecular responses to spaceflight becomes crucial for astronaut safety in harsh space conditions. To this end, we conducted a study to examine the transcriptomic and epigenetic changes in two astronauts' blood samples at three timepoints: two weeks before spaceflight (T0), 24 hours after spaceflight (T2), and three months after spaceflight (T3). Transcriptomic analysis pinpointed two gene clusters with opposing transient expression trends post-flight (T2) which was normalized at T3: one upregulated and the other downregulated. Pathway analysis of these gene clusters showed enrichment in the protein modification, cell cycle, and regulation of autophagy pathways, suggesting autophagy’s role in monocyte differentiation. Epigenetic analysis identified four methylation patterns that showed transient and persistent changes immediately after the spaceflight, enriched in the nervous system development and cell apoptosis pathways. Methylation changes at specific regions implicated genes associated with bone disorders, including FBLIM1, IHH, and SCAMP2. Further, eQTM analysis suggested a link between RNA transcriptional activity and DNA methylation through a transcriptional regulator ZNF684. In conclusion, our longitudinal study offers a detailed perspective of spaceflight’s physiological effects on human biology, revealing both significant short-term transcriptional and methylation and profound long-term methylation impacts on bodily functions. Samples for this study were collected at three timepoints: T0 = within two weeks before the flight (Pre-Flight), T2= within two weeks after the flight (Post-Landing), and T3= 3 months after the flight (3 months follow up).