Collagen glycation triggers the formation

Reprints: H . Pagcon Glycation products acctmlulate during the aging of many slowly renewing tissues, including skin . We have deyeloped an in vitro model of chronologie aging of skin based on reconstructed skin modified by artificially glycating the collagen used to prepare the dermal compart-ment. The morphology of the modified skin is close to the morphology usually observed except that the dermis is altered in ils fibrillar structure . Moreover, the analysis of skin markers revealed several unexpected biological and morphological modifications, which reflect in vivo aging and could be related to glycation per se . These include the activation of fibroblasts, increase of matrix molecules (collagen type 111 and collagen type IV) and metalloproteinase production (MMP1, MMP2 and MMP9), thickening of the basement membrane zone, and more strikingly, the modification of u6 and (31 integrin patterns especially in epidermis, in a way closely resembling aged skia in vivo . We also found that these effects could be related to the production of putative diffusible factors by the dermal fibroblasts activated by glycation . Finally, we show that ail these effects are likely to be glycation specific since they could be inhibited by aminoguanidine, a well-known glycation inhibitor. We conclude that the reconstructed skin model modified by glycation of the collagen closely mimics chronologie aging of skin in vivo . Taken together, these results strengthen the importance of glycation reactions in skin aging .