MiRNAs 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 miRNAsarekeytoregulating 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 andcomparethem toearth-boundcontrols.Weobservesignificantspaceflight 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 find ings provide evidence on how spaceflight regulates mammalian gene expres sion in preparation for interplanetary spaceflight.