Figure 3.

The effects of UV exposure combined with AGEs on the skin. A dotted line with an arrow indicates an induced effect; a dotted line with a diamond shape indicates a suppressive effect. AGEs in the skin are endogenously generated or exogenously ingested, including CML, CEL, pentosidine, and glucosepane, etc. Collagen is more likely to be glycated due to the slow turnover rate. On the one hand, AGEs act directly on cells, leading to a decrease in cell function by activating inflammatory signaling pathways and oxidative stress through cell surface receptors, as well as by modifying cell membranes and intracellular molecules, resulting in skin problems, such as dullness, pigmentation, and wrinkles. On the other hand, AGEs crosslink with collagen and elastin in ECM and promote the secretion of melanin, causing skin problems, such as macula and loss of elasticity. In addition, UV exposure can exacerbate skin glycation by promoting the generation of AGEs, exacerbate oxidative stress, and reduce epidermal GLO-2 production, leading to the accumulation of AGEs. AGEs can be degraded by proteases through receptor-mediated fibroblast endocytosis; the glyoxalase system can detoxify the reactive precursors of AGEs; sRAGE can competitively bind to AGEs with RAGE.