The skin extracellular matrix as a target of environmental exposure: Molecular mechanisms, prevention and repair

Abstract

The dermal extracellular matrix (ECM) undergoes age-related remodelling which leads to wrinkle formation and increased tissue fragility. In healthy young individuals structural ECM assemblies, such as collagens and elastin, are ordered into larger scale structures (collagen fibril bundles and elastic fibres), which mediate the mechanical properties of the dermis. Equally important however, are the less abundant extracellular accessory molecules that regulate complex processes such as cell migration, wound healing and which also orchestrate complex ECM protein-to-protein interactions. These structures and molecular interactions are perturbed in extrinsically aged skin. Using bioinformatics alongside established molecular investigations opens up exciting new ways to understand skin ageing and may help to identify novel biomarkers. In this chapter we propose a mechanism whereby UVR-induced damage of key ECM molecules drives elastosis. We discuss how: i) the amino acid composition of proteins can be used to predict their susceptibility to damage by ultraviolet radiation (UVR) and ii) other environmental factors, such as smoking and air pollution may contribute towards premature skin ageing. Finally this chapter reviews the latest topical applications and systemic therapies that may be able to reverse the consequences of damage to the ECM in ageing.