It is well-accepted that chronic UV exposure is one of the primary drivers for changes in the structure and function of skin that can be visualized as increased fine lines and wrinkles, altered pigmentation, and physical property changes. These changes, particularly in facial skin, can be detected at the structural, cellular, and molecular levels. Biophysical changes caused by ROS include protein degeneration that impacts structure and function as evidenced by cross-linking and glycation of ECM proteins including collagen and elastin [31]
and lipid peroxidation. In addition, there is an unbalancing of the cellular redox status which in turn can impact the expression of stress response genes.
In general, there is a marked decrease in the levels of new collagen synthesized in the papillary layers, which reside closer to the surface and presumably sustain more UV damage than the underlying reticular layers [32]. The effect on net collagen is exaggerated by an increase in the expression levels of MMPs, including MMP-1, MMP-3, and MMP-9. The elevation of MMP protein levels in turn leads to a steady degradation of existing collagen fibril networks. This overall thinning process of the dermis is thought to lead to the sagging and furrowing of skin, causing wrinkles [33]. The degeneration and gross alterations in the elastin fiber network, referred to as elastosis, produce a thickened mass that is presumed to impact the skin’s elastic properties, rendering it less resilient in comparison to nonphotodamaged skin. However, it is unclear whether any newly synthesized elastin by fibroblasts leads to functionally relevant elastin, as can be measured by restoration of skin’s elasticity. To date, this does not appear to be the case. Levels of GAGs, another major EMC component, are elevated in the upper dermis [34]. The increase in GAGs are thought to occur in response to UV-induced damage to collagen, the likely function of GAG being to protect collagen from potential degradation by endogenous proteases. However, excessive levels are probably deleterious to the visible appearance of skin. In vitro cell culture experiments [35] indicate that the addition of GAGs inhibits collagen bundle assembly and thus would be expected to interfere with the dermal repair processes. The combination of these various cutaneous changes in skin contributes to the appearance of fine lines and wrinkles. The overall decrease in collagen content in skin, elevated levels of aberrantly cross-linked collagen, and increased GAG levels lead to the strong appearance of fine lines and wrinkles in human facial skin.
At the molecular level, it has been proposed that the generation of ROS inside the skin leads to the activation of specific signaling pathways that are induced [29]. Upon UV exposure, several cytokine and growth factor signaling pathways are activated, including EGF, TNFa, PDGF, and IL-1 and activate a MAP kinase-mediated cascade of signal transduction. In addition, UV irradiation of cells can lead to an increase in hydrogen peroxide production, which in turn may further stimulate or enhance the signaling pathways, particularly the G-protein-coupled protein-kinase-mediated ones. Upon transduction to the nucleus, there is further activation of the AP-1 transcription factor, which in turn regulates several stress response genes as well as collagen synthesis. Of particular relevance is type I collagen and the MMP family. However, there is a divergence of regulation in that UV-induced AP-1 upregulates MMP expression but suppresses type I collagen (both COL1A1 and COL1A2) gene expression. The overall mechanism of UV-generated ROS and hydrogen peroxide is not currently understood. However, the net result on alterations in gene expression patterns strongly supports the lowered responsiveness of damaged keratinocytes and fibroblasts to the environmental insult and the skin’s ability to repair itself. This is further compounded in aged skin in contrast to younger-aged skin.
UV exposure can also cause hyperpigmentation of the skin, which is observed as a darkening of an area of skin caused by increased concentrations of melanin [36], which in turn acts as a natural sun screen to help protect the skin from further damage [37]. This phenomenon can also be elicited by aging and skin injury and results in the appearance of age spots, also known as lentigines. Age spots are harmless, flat, brown discolorations of the skin that usually appear on sun-exposed areas of the hands, neck, and face of people older than 40 years of age. However, pigmented lesions can also be the hallmark for early stages of melanoma. Long-term chronic exposure to UV damage has clearly been connected not only to premature aging and skin discoloration but is also one of the primary inducers of this deadly form of cancer.