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Precision clinical medicine · 2024

Genome and clonal hematopoiesis stability contrasts with immune, cfDNA, mitochondrial, and telomere length changes during short duration spaceflight.

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Garcia-Medina J Sebastian, Sienkiewicz Karolina, Narayanan S Anand, Overbey Eliah G, Grigorev Kirill, Ryon Krista A, Burke Marissa, Proszynski Jacqueline, Tierney Braden, Schmidt Caleb M, Mencia-Trinchant Nuria, Klotz Remi, Ortiz Veronica, Foox Jonathan, Chin Christopher, Najjar Deena, Matei Irina, Chan Irenaeus, Cruchaga Carlos, Kleinman Ashley, Kim JangKeun, Lucaci Alexander, Loy Conor, Mzava Omary, De Vlaminck Iwijn, Singaraju Anvita, Taylor Lynn E, Schmidt Julian C, Schmidt Michael A, Blease Kelly, Moreno Juan, Boddicker Andrew, Zhao Junhua, Lajoie Bryan, Altomare Andrew, Kruglyak Semyon, Levy Shawn, Yu Min, Hassane Duane C, Bailey Susan M, Bolton Kelly, Mateus Jaime, Mason Christopher E

Аннотация

BACKGROUND: The Inspiration4 (I4) mission, the first all-civilian orbital flight mission, investigated the physiological effects of short-duration spaceflight through a multi-omic approach. Despite advances, there remains much to learn about human adaptation to spaceflight's unique challenges, including microgravity, immune system perturbations, and radiation exposure.

METHODS: To provide a detailed genetics analysis of the mission, we collected dried blood spots pre-, during, and post-flight for DNA extraction. Telomere length was measured by quantitative PCR, while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations. A robust bioinformatic pipeline was used for data analysis, including variant calling to assess mutational burden.

RESULT: Telomere elongation occurred during spaceflight and shortened after return to Earth. Cell-free DNA analysis revealed increased immune cell signatures post-flight. No significant clonal hematopoiesis of indeterminate potential (CHIP) or whole-genome instability was observed. The long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months post-flight.

CONCLUSION: Our findings provide valuable insights into the physiological consequences of short-duration spaceflight, with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to Earth. CHIP sequencing data will serve as a reference point for studying the early development of CHIP in astronauts, an understudied phenomenon as previous studies have focused on career astronauts. This study will serve as a reference point for future commercial and non-commercial spaceflight, low Earth orbit (LEO) missions, and deep-space exploration.

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

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