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MicroRNAs shape mouse age-independent tissue adaptation to spaceflight via ECM and developmental pathways

ABSTRACT: As human space exploration accelerates, understanding the organism-wide molecular effects of longer spaceflight in mammals becomes increasingly critical. Non-coding RNAs like miRNAs are key to regulating this landscape. We thus analyzed 686 small RNA samples of mice from 13 solid organs at 3 and 8 months of age, after at least 3 weeks on the ISS and compared them to earth-bound controls. We observed significant spaceflight effects in systemic tissue remodeling pathways along the Fat-Liver-Pancreas axis and in heart, brain, spleen and thymus. The MIR-17/92 and MIR-1/133 families drive distinct molecular changes through specific gene targeting. Age-dependent changes, smaller in magnitude compared to age-independent changes, primarily involved tissue remodeling through MIR-8, MIR-154 and MIR-15 families in MAT, pancreas, and diaphragm. Our findings provide evidence on how spaceflight regulates mammalian gene expression in preparation for interplanetary spaceflight.

ORGANISM(S): Mus musculus

PROVIDER: GSE294046 | GEO | 2025/12/18

REPOSITORIES: GEO

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Project description:Experimentation on the International Space Station has reached the stage where repeated and nuanced transcriptome studies are beginning to illuminate the structural and metabolic differences between plants grown in space compared to plants on the Earth. Genes that are important in setting up the spaceflight responses are being identified; their role in spaceflight physiological adaptation are increasingly understood, and the fact that different genotypes adapt differently is recognized. However, the basic question of whether these spaceflight responses are required for survival has yet to be posed, and the fundamental notion that spaceflight responses may be non-adaptive has yet to be explored. Therefore the experiments presented here were designed to ask if portions of the plant spaceflight response can be genetically removed without causing loss of spaceflight survival and without causing increased stress responses. The CARA experiment compared the spaceflight transcriptome responses of two Arabidopsis ecotypes, Col-0 and WS, as well as that of a PhyD mutant of Col-0. When grown with the ambient light of the ISS, phyD displayed a significantly reduced spaceflight transcriptome response compared to Col-0, suggesting that altering the activity of a single gene can actually improve spaceflight adaptation by reducing the transcriptome cost of physiological adaptation. The WS genotype showed and even simpler spaceflight transcriptome response in the ambient light of the ISS, more broadly indicating that the plant genotype can be manipulated to reduce the transcriptome cost of plant physiological adaptation to spaceflight and suggesting that genetic manipulation might further reduce, or perhaps eliminate the metabolic cost of spaceflight adaptation. When plants were germinated and then left in the dark on the ISS, the WS genotype actually mounted a larger transcriptome response than Col-0, suggesting that the in-space light environment affects physiological adaptation, which further implies that manipulating the local habitat can also substantially impact the metabolic cost of spaceflight adaptation.

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MicroRNAs shape mouse age-independent tissue adaptation to spaceflight via ECM and developmental pathways

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