BACKGROUND: Aging is the result of several mechanisms which operate simultaneously. Among them, glycation is of particular interest because it is a reaction which affects slowly renewing tissues and macromolecules with elevated half-life, like the dermis, a skin compartment highly affected by aging. Glycation produces crosslinks between macromolecules thereby providing an explanation for the increased age-related stiffness of the skin. Glycation products, also called AGEs (advanced glycation end products), accumulate primarily in extracellular matrix molecules like collagen or elastin. METHODS: In order to reproduce this phenomenon in vitro we have created a model of reconstructed skin modified by glycation of the collagen used to fabricate the dermal compartment. RESULTS: This system allowed us to uncover biological modifications of dermal markers, and more surprisingly epidermal markers, as well as an increase of metalloproteinases responsible for degradation of the dermal matrix. Consequently, the imbalance between synthesis and degradation that results from glycation, may contribute to skin aging, as shown in this model. Moreover these modifications were shown to be prevented by the addition of aminoguanidine, a well-known inhibitor of glycation. CONCLUSIONS: Using this experimental approach our results taken together stress the importance and possibly central role of glycation in skin aging and the usefulness of the reconstructed skin as a model of physiological aging.
BACKGROUND: Aging is the result of several mechanisms which operate simultaneously. Among them, glycation is of particular interest because it is a reaction which affects slowly renewing tissues and macromolecules with elevated half-life, like the dermis, a skin compartment highly affected by aging. Glycation produces crosslinks between macromolecules thereby providing an explanation for the increased age-related stiffness of the skin. Glycation products, also called AGEs (advanced glycation end products), accumulate primarily in extracellular matrix molecules like collagen or elastin. METHODS: In order to reproduce this phenomenon in vitro we have created a model of reconstructed skin modified by glycation of the collagen used to fabricate the dermal compartment. RESULTS: This system allowed us to uncover biological modifications of dermal markers, and more surprisingly epidermal markers, as well as an increase of metalloproteinases responsible for degradation of the dermal matrix. Consequently, the imbalance between synthesis and degradation that results from glycation, may contribute to skin aging, as shown in this model. Moreover these modifications were shown to be prevented by the addition of aminoguanidine, a well-known inhibitor of glycation. CONCLUSIONS: Using this experimental approach our results taken together stress the importance and possibly central role of glycation in skin aging and the usefulness of the reconstructed skin as a model of physiological aging.
Authors: David R Sell; Wanjie Sun; Xiaoyu Gao; Christopher Strauch; John M Lachin; Patricia A Cleary; Saul Genuth; Vincent M Monnier Journal: Cardiovasc Diabetol Date: 2016-02-11 Impact factor: 9.951