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Age‐related Structural Changes that Occur in Human Skin

During the last decade, substantial progress has been made towards understanding underlying mechanisms of human skin aging. This understanding provides the basis for current use and new development of anti‐aging treatments. The bulk of human skin is the collagenous extracellular matrix, which comprises the dermis and confers strength and resiliency. A major feature of aged skin is fragmentation of collagen fibrils within the dermis. Fragmentation results from the actions of specific enzymes (matrix metalloproteinases), and impairs both the mechanical stability of the skin and the function of cells within the skin. Fibroblasts within the dermal compartment of skin produce and organize the collagen extracellular matrix. Their function is largely dependent on attachment to collagen fibrils. This attachment allows fibroblasts to stretch and achieve optimal mechanical tension. Stretch is critical for normal balanced production of collagen and collagen‐degrading enzymes. Age‐dependent fragmentation of collagen fibrils results in loss of attachment sites, thereby causing fibroblasts collapse. Reduced mechanical tension leads to down‐regulation of the TGF‐beta signal transduction pathway. This decreased responsiveness to TGF‐beta promotes fibroblasts to produce high levels of collagen–degrading enzymes, while simultaneously reducing collagen biosynthesis. This imbalance advances further degradation of the dermal extracellular matrix, in a self‐perpetuating manner. Clinically‐proven treatments for aged skin, such as topical retinoic acid, CO2 laser resurfacing, and intradermal injection of cross‐linked hyaluronic acid stimulate production of new undamaged collagen. Attachment of fibroblasts to this new collagen allows stretch, which in turn balances collagen production/degradation and thereby improves the health of aged skin.