Mechanopharmacology of cellular microenvironment stiffness: Therapeutic strategies for age-related diseases

Ageing brings about various biochemical, structural and mechanical alterations within tissues, profoundly impacting cellular behaviour and function. One of the hallmark changes observed with ageing is an increase in cellular microenvironment stiffness, a biomechanical property influenced by intrinsic factors within the cell and extrinsic factors from the surrounding extracellular matrix (ECM). This shift in ECM stiffness has been implicated in the development and progression of several age-related diseases, but the exact molecular mechanisms underlying different organ tissues remain to be fully elucidated. This review examines the lung and ovaries, two organ tissues with distinct functions but interconnected by similar timing of changes in ECM stiffness with age. We discuss common pathways and factors that drive changes in the ECM stiffness of these organs. Such insights may pave the way for innovative treatments addressing the root causes of age-related diseases, ultimately enhancing the ageing population's health span and quality of life. LINKED ARTICLES: This article is part of a themed issue Mechanopharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v183.4/issuetoc.