Reaction of glycation and human skin: the effects on the skin and its components, reconstructed skin as a model

Abstract

Skin is affected by the aging process and numerous modifications are observed. In human, with time the skin becomes drier, thinner, spots appear, elasticity decreases and stiffening increases, together with the appearance of wrinkles. These observations result from the overlapping of an intrinsic chronological aging (individual, genetic) and of an extrinsic aging (dependent on external factors like UV, pollution and lifestyle). One of the causes of aging is the appearance of the Advanced Glycosylation End Products (AGEs) during life. The glycation reaction results from a non-enzymatic reaction between a sugar and a free amine group of Lys, Arg amino acids in proteins. This reaction does not occur only in the skin, indeed, AGEs are also found in the kidney, lens, vessels, etc. These products are also responsible, because of their localization, of some pathologies related to diabetes. AGEs provoke biological modifications implying an activation of molecules synthesis (extracellular matrix, cytokines) and enzyme activation of matrix degradation (metalloproteinases). The UV effect on AGEs (like pentosidine) generates reactive oxygen species (ROS) in the extracellular matrix which could lead to additional deleterious effects. Molecules are described in the literature as inhibitors to this irreversible reaction i.e. aminoguanidine. To understand the consequences of the glycation in the skin, a system of reconstructed skin was developed with a collagen modified by glycation for the dermal component. In this system we observed that dermis and epidermis are both modified due to glycation (macromolecules synthesis, cytokines, metalloproteinases) and it is possible to test inhibitors of this reaction. In conclusion, in skin, glycation is involved in a very complex aging process and simultaneously affect, directly and indirectly, certain cells, their synthesis and the organization of the matrix.