Deep space exploration is firmly within reach, but health decline during extended spaceflight remains a key challenge. In this study, we performed comparative transcriptomic analysis of Caenorhabditis elegans responses to varying degrees of hypergravity and to two spaceflight experiments (ICE-FIRST and CERISE). We found that progressive hypergravitational load concomitantly increases the extent of differential gene regulation and that subtle changes in ∼1,000 genes are reproducibly observed during spaceflight-induced microgravity. Consequently, we deduce those genes that are concordantly regulated by altered gravity per se or that display inverted expression profiles during hypergravity versus microgravity. Through doing so, we identify several candidate targets with terrestrial roles in neuronal function and/or cellular metabolism, which are linked to regulation by daf-16/FOXO signaling. These data offer a strong foundation from which to expedite mechanistic understanding of spaceflight-induced maladaptation in higher organisms and, ultimately, promote future targeted therapeutic development.

深空探索是绝对可以实现的，但是长时间太空飞行期间健康状况下降仍然是关键挑战。在这项研究中，我们进行了秀丽隐杆线虫对不同程度的超重力反应以及对两个航天实验（ICE-FIRST和CERISE）的反应的转录组分析。我们发现，渐进式超重力负荷会同时增加差异基因调控的程度，并且在航天诱导的微重力作用下可重复观察到约1,000个基因的细微变化。因此，我们推论了那些受到重力改变本身一致调节的基因或在超重力与微重力之间显示反向表达谱。通过这样做，我们确定了几个在神经元功能和/或细胞代谢中具有陆地作用的候选靶标，这些靶标与daf-16 / FOXO信号的调控有关。这些数据为加快对高等生物中由航天引起的适应不良的机理的理解提供了坚实的基础，并最终促进了未来靶向治疗的发展。