title: Skin aging by glycation: lessons from the reconstructed skin model.
abstract: 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.forename: Hervé
authors.initials: H
authors.lastname: Pageon
authors.forename: Hélène
authors.initials: H
authors.lastname: Zucchi
authors.forename: Françoise
authors.initials: F
authors.lastname: Rousset
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Monnier
authors.forename: Daniel
authors.initials: D
authors.lastname: Asselineau
mesh_terms: D000818:Animals; D002417:Cattle; D018929:Cell Culture Techniques; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000737:chemistry / Q000378:metabolism*; D006031:Glycosylation / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D008954:Models, Biological; D015595:Skin Aging; D014466:Ultraviolet Rays
chemical_list: D017127:Glycation End Products, Advanced; D006146:Guanidines; D003094:Collagen; C004479:pimagedine