Abstract
Intrinsic or photo-induced skin aging mainly affects the structural organization of collagen and elastin fibers, the remodeling of which involves proteases such as matrix metalloproteinases (MMPs). Indeed, senescent fibroblasts are characterized by high MMP secretion levels. MMPs display several types of regulation, of which epigenetic modifications may be influenced by the cell environment itself. In addition, amplified oxidative stress following ultraviolet exposure drives MMP expression, leading to transregulation between the dermis and epidermis. Subsequently, the importance of neutrophil elastase in solar elastosis generates a feedback loop, in which elastolysis can mediate collagenolysis through the generation of elastin-derived peptides. Disorganization of dermal collagen and elastin fibers in aged dermis may release peptides containing a GxxPG motif; these are named elastokines as they induce biological effects in a similar way to cytokines. These peptides may have a crucial role in skin inflammaging through the liberation of proinflammatory cytokines, thus leaving the elderly highly susceptible to diseases such as skin cancers, as well as inflammatory and autoimmune diseases.
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