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

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. We sequenced 686 samples across 13 organs of young (3 months) and middle-aged (8 months) mice that were sent to the ISS (Flight). We compared them against mice living in standard conditions (Vivarium Ground Control) and mice living in an environment matched to ISS conditions (Habitat Ground Control). We euthanized mice at two time-points (matching timelines for controls and flight mice), one before returning to earth (TERM) and one after (LAR) in order to distinguish spaceflight-induced effects from the reentry-induced stress.

随着人类太空探索进程不断加速，解析哺乳动物长期太空飞行所引发的全生物体分子效应，其重要性与日俱增。以微小RNA（miRNAs）为代表的非编码RNA，是调控这一生物学过程的核心因子。本研究分析了来自13个实体器官的686份小鼠小RNA样本，这些小鼠在国际太空站（ISS）驻留至少3周后，分别于3月龄和8月龄时被采样，并与地面对照组进行对比。研究团队观测到，在脂肪-肝脏-胰腺轴相关的全身组织重塑通路，以及心脏、大脑、脾脏与胸腺中，存在显著的太空飞行诱导效应。MIR-17/92与MIR-1/133家族可通过特异性基因靶向，引发不同的分子变化。相较于非年龄依赖性变化，幅度更小的年龄依赖性变化，主要通过脂肪组织（MAT）、胰腺与膈肌中的MIR-8、MIR-154及MIR-15家族介导组织重塑过程。本研究结果为太空飞行如何调控哺乳动物基因表达以适配星际太空飞行提供了实证依据。本研究对两类小鼠的13个器官共计686份样本进行了测序：一类为被送往国际太空站（ISS）的飞行组（Flight）小鼠，涵盖3月龄（青年）与8月龄（中年）两个年龄段；另一类为地面对照小鼠，分别饲养于标准环境的Vivarium Ground Control组，以及与国际太空站环境匹配的Habitat Ground Control组。为区分太空飞行诱导的效应与重返地球引发的应激反应，研究人员在两个时间点对小鼠实施安乐死：其一为返回地球前（TERM组），其二为返回地球后（LAR组），两个时间点均与对照组及飞行组的时间线保持一致。