Lansweers Ivana, van Rijthoven Sharon, van Loon Jack J W A
Faculty of Medicine, Utrecht University, Universiteitsweg 98, Utrecht 3584 CG, the Netherlands.
Faculty of Mechanical Engineering, Delft University of Technology, Mekelweg 2, Delft 2628 CD, the Netherlands; Department Oral & Maxillofacial Surgery/Pathology, Amsterdam Movement Sciences & Amsterdam Bone Center (ABC), Amsterdam University Medical Center location Vrije Universiteit Amsterdam & Academic Center for Dentistry Amsterdam (ACTA), Gustav Mahlerlaan 3004, Amsterdam 1081 LA, the Netherlands.
Mech Ageing Dev. 2025 Apr;224:112028. doi: 10.1016/j.mad.2025.112028. Epub 2025 Jan 14.
The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex plays a crucial role in connecting the nuclear envelope to the cytoskeleton, providing structural support to the nucleus and facilitating mechanical signaling between the extracellular environment and the nucleus. Research in mechanobiology onboard the International Space Station (ISS) and in simulated microgravity (SMG) highlight the importance of gravity in functional mechanotransduction. Although the altered gravity research regarding mechanobiology has been greatly focused on the cytoskeleton and the extracellular matrix (ECM), recent research demonstrates that SMG also induces changes in nuclear mechanics and gene expression patterns, which have been shown to be LINC complex dependent. Additionally, dysregulation of the LINC complex disrupts nuclear integrity which leads to nuclear shape abnormalities in both Hutchinson-Gilford Progeria Syndrome (HGPS) and aged cells, which highlights the significance of the LINC complex and related proteins in ageing and age-related disorders. Interestingly, as the effects of spaceflight closely resemble those found in the elderly, the microgravity environment seems to induce an accelerated ageing phenotype in astronauts. Therefore, this review will explore the role of the LINC complex and related proteins in ageing and in microgravity, to further elucidate the interplay between loss of gravitational loading and ageing.
核骨架与细胞骨架连接复合体（LINC复合体）在将核膜与细胞骨架连接起来的过程中起着关键作用，为细胞核提供结构支撑，并促进细胞外环境与细胞核之间的机械信号传导。国际空间站（ISS）上以及模拟微重力（SMG）环境下的力学生物学研究突出了重力在功能性机械转导中的重要性。尽管关于力学生物学的重力改变研究主要集中在细胞骨架和细胞外基质（ECM）上，但最近的研究表明，模拟微重力也会诱导核力学和基因表达模式的变化，且这些变化已被证明依赖于LINC复合体。此外，LINC复合体的失调会破坏核完整性，导致早老症（HGPS）和衰老细胞中出现核形态异常，这凸显了LINC复合体及相关蛋白在衰老和与年龄相关疾病中的重要性。有趣的是，由于太空飞行的影响与老年人的情况极为相似，微重力环境似乎会在宇航员中诱导出加速衰老的表型。因此，本综述将探讨LINC复合体及相关蛋白在衰老和微重力中的作用，以进一步阐明重力负荷丧失与衰老之间的相互作用。
