Space flight produces an extreme environment with unique stressors, but little is known about how our body responds to these stresses. While there are many intractable limitations for in-flight space research, some can be overcome by utilizing gene knockout-disease model mice. Here, we report how deletion of Nrf2, a master regulator of stress defense pathways, affects the health of mice transported for a stay in the International Space Station (ISS). After 31 days in the ISS, all flight mice returned safely to Earth. Transcriptome and metabolome analyses revealed that the stresses of space travel evoked ageing-like changes of plasma metabolites and activated the Nrf2 signaling pathway. Especially, Nrf2 was found to be important for maintaining homeostasis of white adipose tissues. This study opens approaches for future space research utilizing murine gene knockout-disease models, and provides insights into mitigating space-induced stresses that limit the further exploration of space by humans.

太空飞行会产生一个具有独特压力源的极端环境，但我们的身体如何对这些压力做出反应却知之甚少。虽然飞行空间研究存在许多难以解决的局限性，但通过利用基因敲除疾病模型小鼠可以克服一些局限性。在这里，我们报告了压力防御途径的主要调节因子 Nrf2 的缺失如何影响运送到国际空间站 (ISS) 的小鼠的健康。在国际空间站停留 31 天后，所有飞行老鼠都安全返回地球。转录组和代谢组分析表明，太空旅行的压力会引起血浆代谢物的衰老样变化并激活 Nrf2 信号通路。特别是，发现 Nrf2 对于维持白色脂肪组织的稳态很重要。