Cellular senescence, which is triggered by various stressors, manifests as irreversible cell cycle arrest, resulting in the disruption of multiple nuclear condensates. One of the affected structures is the nucleolus, whose tripartite layout, separated into distinct liquid phases, allows for the stepwise progression of ribosome biogenesis. The dynamic properties of dense fibrillar components, a sub-nucleolar phase, are crucial for mediating pre-rRNA processing. However, the mechanistic link between the material properties of dense fibrillar components and cellular senescence remains unclear. We established a significant association between cellular senescence and alterations in nucleolar materiality and characteristics, including the number, size, and sphericity of individual subphases of the nucleolus. Senescent cells exhibit reduced fibrillarin dynamics, aberrant accumulation of high-order protein assemblies, such as oligomers and fibrils, and increased dense fibrillar component density. Intriguingly, the addition of RNA-interacting entities mirrored the diminished diffusion of fibrillarin in the nucleolus during cellular senescence. Thus, our findings contribute to a broader understanding of the intricate changes in the materiality of the nucleolus associated with cellular senescence and shed light on nucleolar dynamics in the context of aging and cellular stress.

中文翻译：

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细胞衰老下核仁致密纤维成分的动态性降低和高阶蛋白质组装增加


由各种应激源引发的细胞衰老表现为不可逆的细胞周期停滞，导致多个核凝聚体的破坏。受影响的结构之一是核仁，其三部分布局，分为不同的液相，允许核糖体生物发生的逐步进行。致密纤维成分（亚核仁相）的动态特性对于介导前 rRNA 加工至关重要。然而，致密纤维成分的材料特性与细胞衰老之间的机制联系仍不清楚。我们建立了细胞衰老与核仁物质和特征（包括核仁各个亚相的数量、大小和球形度）的改变之间的显着关联。衰老细胞表现出原纤维蛋白动力学降低、高阶蛋白质组装体（例如寡聚物和原纤维）的异常积累以及致密原纤维成分密度增加。有趣的是，RNA相互作用实体的添加反映了细胞衰老过程中原纤维蛋白在核仁中扩散的减少。因此，我们的研究结果有助于更广泛地理解与细胞衰老相关的核仁物质性的复杂变化，并揭示衰老和细胞应激背景下的核仁动力学。