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

## TL;DR

This study shows how miRNAs help mice adapt to spaceflight by changing gene activity in multiple organs, regardless of age.

## Contribution

The study identifies specific miRNA families that mediate spaceflight-induced tissue adaptations through extracellular matrix and developmental pathways.

## Key findings

- MiRNAs like MIR-17/92 and MIR-1/133 drive molecular changes in organs like liver, pancreas, heart, brain, spleen, and thymus during spaceflight.
- Age-independent changes are more prominent than age-dependent ones, with MIR-8, MIR-154, and MIR-15 families affecting mesenteric adipose tissue and pancreas.
- The findings highlight how miRNAs regulate mammalian gene expression in microgravity environments.

## 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.

Understanding the organism-wide molecular effects of spaceflight becomes increasingly critical as space exploration accelerates. Here, the authors show that miRNAs mediate microgravity-induced adaptations via extracellular matrix, DNA damage and developmental pathways, as shown by small RNA profiling in 13 organs of mice during and after spaceflight.