The impact of senescence on the biomechanical characteristics of ageing skin

forthcoming

Skin ageing is characterized by structural changes in the extracellular matrix (ECM) that impair the mechanical properties of the tissue, such as elasticity and stiffness. A key driver of tissue and organismal ageing is cellular senescence, a state of irreversible cell-cycle arrest that triggers functional, metabolic and morphological changes. The accumulation of senescent fibroblasts in the dermis leads to impaired ECM remodelling and contributes to the mechanical decline associated with skin ageing. This project will explore how senescence influences the biomechanical characteristics of skin, focusing on changes in cell-ECM attachment. Building on my own prior observations that senescence is associated with increased cell-ECM attachment – evidenced by larger focal adhesions and elevated adhesion forces, I will extend this analysis across multiple tissues and establish it as a hallmark of senescence. Next, I will investigate the molecular mechanisms underlying enhanced senescent cell attachment by analysing surface proteomics, the composition of focal adhesions, and the role of mTORC1 hyperactivity. Alongside, I will develop a 3D hydrogel model mimicking aged dermal ECM to enable functional studies of senescent cells under physiologically relevant conditions. Lastly, I will assess potential treatments to promote cell migration and ECM remodelling in vitro. By integrating molecular, cellular, and biomechanical approaches, this project aims to deepen our understanding of skin ageing mechanisms, paving the way for novel therapeutic strategies to maintain skin health throughout the lifecourse.