Genome and Clonal Hematopoiesis Stability Contrasts with Immune, cfDNA, mitochondrial, and telomere length changes to Short Duration Spaceflight

Abstract The I4 mission, the first all-civilian orbital flight mission, investigated the physiological effects of short duration spaceflight through a multi-omic approach. We analyzed telomere length, clonal hematopoiesis of indeterminate potential (CHIP), whole genome stability, cell-free DNA (cfDNA) cell lysis, and immune cell gene expression. Our results revealed telomere length dynamics similar to those observed in the NASA Twins Study and in astronauts spending 6 months on the ISS, with lengthening in space and shortening upon return to Earth. Our cell-type of origin analysis of cfDNA fragments revealed an increased presence of innate and adaptive immune cell signatures that persisted over a month after return to earth. No significant relationship between spaceflight and CHIP-related or whole genome abnormalities were observed. Longitudinal mitochondrial, ribosomal and immune function gene expression changes occurred across both adaptive and innate immune cells, suggesting adaptations to the space environment can extend months after return from spaceflight and alter immune function. Our findings provide valuable insights into the physiological consequences of short duration spaceflight and will serve as a reference point for future space tourism, low Earth-orbit (LEO) missions, and deep-space exploration.