The Skin Extracellular Matrix as a Target of Environmental Exposure: Molecular Mechanisms, Prevention and Repair
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 s
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The Skin Extracellular Matrix as a Target of Environmental Exposure: Molecular Mechanisms, Prevention and Repair Kieran T. Mellody, Mike Bell and Michael J. Sherratt
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.
Keywords Skin Ageing Extracellular matrix Sunscreens Anti-ageing formulations
Ultraviolet radiation
K.T. Mellody M.J. Sherratt (&) Centre for Tissue Injury and Repair, Institute of Inflammation and Repair, The University of Manchester, 1.529 Stopford Building, Oxford Road, Manchester M13 9PT, UK e-mail: [email protected] M. Bell Walgreens Boots Alliance, Thane Road, Nottingham, UK © Springer International Publishing Switzerland 2016 G.T. Wondrak (ed.), Skin Stress Response Pathways, DOI 10.1007/978-3-319-43157-4_5
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Introduction
Extracellular matrix (ECM) components perform key mechanical roles in the skin including resisting tensile (fibrillar collagens) and compressive (proteoglycans and hyaluronic acid) forces, and conferring elasticity (elastic fibres). With chronological age, and in particular with exposure to exogenous agents such as ultraviolet radiation (UVR), these components undergo architectural and structural remodelling which, in turn, is associated with the outward signs of ageing (wrinkles) and with increased skin stiffness and fragility (Agache et al. 1980; Baranoski 2000; Warren et al. 1991). Crucially, there is now a large and compelling body of evidence that highlights the important role played by ECM components in general and by elastic fibre components in particular in maintaining tissue homeostasis (Marastoni et al. 2008). As a consequence, it is likely that accumulated environmental damage to ECM components, by e
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