Extrinsic skin agingL98.8

Structural epidermal and dermal changes of the skin induced by artificial and/or natural UV radiation. Characteristic of photoaged skin is actinic elastosis in the border area between papillary and dermal dermis (see also cutis rhomboidalis nuchae, elastoidosis cutanea nodularis et cystica), as well as differently pronounced epidermal changes (epithelial atrophy; different degrees of keratosis actinica).

The two main components of the dermal extracellular matrix (collagen and elastin) determine the elasticity and firmness of human skin. The extracellular matrix consists of 85-90% collagen type 1, which is formed by dermal fibroblasts. In young skin, a network of elastic fibers is found that extends continuously from the dermo-epidermal junction zone to the deep dermis and consists of thick elastin-rich fibers in the reticular dermis. In the lower parts of the papillary dermis there is a network of fine fibres with reduced elastin content. In the upper papillary dermis there is a network of fine microfilled bundles which contain no elastin. UV rays induce different degrees of damage to the dermal matrix structure, histologically known as elastosis (see Elastosis actinica).
The following pathomechanisms of light aging are discussed:

• Inhibitory effect of UV rays on the synthesis of collagen fibres and/or accelerated degradation of collagen fibres: In particular UVB leads in vitro to a temporary disturbance of pro-collagen-1 synthesis in human fibroblasts. In addition, UVB and UVA induce in vitro and in vivo the formation of metalloproteinases capable of proteolytically degrading collagen fibres. Among other things, UVB leads to the increased transcription and finally expression of matrix metalloproteinase-1 (MMP-1) in epidermal keratinocytes by activating the transcription factor AP-1, a consequence of the activation of matrix metalloproteinases.
• It has been shown that the acrylic hydrocarbon receptor (AhR), also called dioxin receptor, plays a central role in the initiation of internal signalling cascades. In epidermal keratinocytes, UVB irradiation leads to the formation of different signalling cascades. Photoproducts of tryptophan, natural ligands of the AhR.
• UVA can induce MMP-1 expression in dermal fibroblasts and keratinocytes directly or indirectly through paracrine mechanisms. The direct activation is mainly mediated by the generation of reactive oxygen species, especially singlet oxygen. The consequence of the increased MMP-1 expression is the reduction of fibrillin-1, which is formed by epidermal keratinocytes and is the essential component of the microfilar bundles in the upper papillary dermis.
• IR radiation (infrared), especially IRA radiation (780-1600nm), also leads to actinic damage of the skin (Lademann J et al. 2018). IR radiation increases the temperature in the skin; this leads to an increase in free radicals.
• Neovascularization: Vascular neovascularization is caused by growth factors such as FGF, TGF-ß and PDGF, vascular endothelial growth factors and angiopoietins. Natural inhibitors of angiogenesis include thrombospondins, which are deposited along the basement membrane and prevent the formation of vessels in the epidermis (studies with transgenic mice overexpressing thrombospondin-1 show a lack of increase in dermal vascularization and also wrinkling after UV exposure). Reduced expression of angiogenesis inhibitors therefore leads to premature light aging.
• Increase in the number of dermal fibroblasts and mast cells as well as histiocytes and other mononuclear cells (in contrast to intrinsically aged skin) as an indication of chronic inflammation (heliodermatitis or dermatoheliosis).
• Accumulation of oxidatively modified proteins in intrinsically and extrinsically aged skin, especially UVA and UVB reduce the activity of proteasome peptidases (protein degrading system).
• Mitochondrial DNA mutations in UV-exposed skin lead to a disturbance of oxidative phosphorylation and thus to increased formation of reactive oxygen species, which in turn lead to mitochondrial DNA mutations (in vitro and in vivo). As a result, genes involved in the pathogenesis of photo-aging (e.g. metalloproteinases) were also expressed more strongly. Once induced, the mutations persisted even after the end of the repetitive UV exposure and even increased in some of the vitiosus circles described above.
• Damage of chromophores: UVB induces photoproducts in the cellular DNA between adjacent pyrimidine bases, mainly cyclobutane pyrimidine dimers, which may be responsible for damage of dermal repair mechanisms in the DNA (topical application of DNA repair enzyme containing liposomes leads to significant inhibition of UVB induction of MMP-1 in the epidermis).

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