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

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Friederike Grandke, Shusruto Rishik, Viktoria Wagner, Annika Engel, Nicole Ludwig, Kruti Calcuttawala, Fabian Kern, Verena Keller, Marcin Krawczyk, Louis Stodieck, Virginia Ferguson, Amanda Roberts, Eckart Meese, Nicholas Schaum, Steven Quake, Tony Wyss-Coray, Andreas Keller

Nat Commun. 2026 Feb 5;17(1):1387. doi: 10.1038/s41467-026-68737-1.

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 analyze 686 small RNA samples of female mice from 13 solid organs at 3 and 8 months of age, after at least 3 weeks on the International Space Station and compare them to earth-bound controls. We observe 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 involve tissue remodeling through MIR-8, MIR-154 and MIR-15 families in mesenteric adipose tissue, pancreas, and diaphragm. Our findings provide evidence on how spaceflight regulates mammalian gene expression in preparation for interplanetary spaceflight.

PMID:41644562 | PMC:PMC12876965 | DOI:10.1038/s41467-026-68737-1