The role of the LINC complex in ageing and microgravity

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.