In space, cells sustain strong modifications of their mechanical environment. Mechanosensitive molecules at the cell membrane regulate mechanotransduction pathways that induce adaptive responses through the regulation of gene expression, post-translational modifications, protein interactions or intracellular trafficking, among others. In the current study, human osteoblastic cells were cultured on the ISS in microgravity and at 1 g in a centrifuge, as onboard controls. RNAseq analyses showed that microgravity inhibits cell proliferation and DNA repair, stimulates inflammatory pathways and induces ferroptosis and senescence, two pathways related to ageing. Morphological hallmarks of senescence, such as reduced nuclear size and changes in chromatin architecture, proliferation marker distribution, tubulin acetylation and lysosomal transport were identified by immunofluorescence microscopy, reinforcing the hypothesis of induction of cell senescence in microgravity during space flight. These processes could be attributed, at least in part, to the regulation of YAP1 and its downstream effectors NUPR1 and CKAP2L.

在太空中，细胞的机械环境持续发生强烈变化。细胞膜上的机械敏感分子调节机械转导途径，通过调节基因表达、翻译后修饰、蛋白质相互作用或细胞内运输等诱导适应性反应。在当前的研究中，人类成骨细胞在国际空间站上以微重力和 1 g 离心力培养，作为机载对照。 RNAseq 分析表明，微重力抑制细胞增殖和 DNA 修复、刺激炎症途径并诱导铁死亡和衰老（这两种途径与衰老相关）。通过免疫荧光显微镜鉴定了衰老的形态学特征，例如核尺寸减小和染色质结构的变化、增殖标记物分布、微管蛋白乙酰化和溶酶体运输，这强化了太空飞行期间微重力下诱导细胞衰老的假设。这些过程至少部分归因于 YAP1 及其下游效应器 NUPR1 和 CKAP2L 的调节。