title: Molecular characterization of glycation-associated skin ageing: an alternative skin model to study in vitro antiglycation activity of topical cosmeceutical and pharmaceutical formulations.
abstract: BACKGROUND
  Glycation is a nonenzymatic reaction that cross-links a sugar molecule and protein macromolecule to form advanced glycation products (AGEs) that are associated with various age-related disorders; thus glycation plays an important role in skin chronological ageing.
  
  
  OBJECTIVE
  To develop a novel in vitro skin glycation model as a screening tool for topical formulations with antiglycation properties and to further characterize, at the molecular level, the glycation stress-driven skin ageing mechanism.
  
  
  METHODS
  The glycation model was developed using human reconstituted full-thickness skin; the presence of Nε-(carboxymethyl) lysine (CML) was used as evidence of the degree of glycation. Topical application of emulsion containing a well-known antiglycation compound (aminoguanidine) was used to verify the sensitivity and robustness of the model. Cytokine immunoassay, quantitative real-time polymerase chain reaction and histological analysis were further implemented to characterize the molecular mechanisms of skin ageing in the skin glycation model.
  
  
  RESULTS
  Transcriptomic and cytokine profiling analyses in the skin glycation model demonstrated multiple biological changes, including extracellular matrix catabolism, skin barrier function impairment, oxidative stress and subsequently the inflammatory response. Darkness and yellowness of skin tone observed in the in vitro skin glycation model correlated well with the degree of glycation stress.
  
  
  CONCLUSIONS
  The newly developed skin glycation model in this study has provided a new technological dimension in screening antiglycation properties of topical pharmaceutical or cosmeceutical formulations. This study concomitantly provides insights into skin ageing mechanisms driven by glycation stress, which could be useful in formulating skin antiageing therapy in future studies.
authors.affiliation: Wipro Skin Research and Innovation Centre, No. 7, Persiaran Subang Permai, Taman Perindustrian Subang, 47610, Subang Jaya, Selangor, Malaysia.
authors.forename: K H
authors.identifier: http://orcid.org/0000-0002-3032-4060
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Wipro Skin Research and Innovation Centre, No. 7, Persiaran Subang Permai, Taman Perindustrian Subang, 47610, Subang Jaya, Selangor, Malaysia.
authors.forename: Y P
authors.initials: YP
authors.lastname: Ng
authors.affiliation: Department of Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.
authors.forename: P S
authors.initials: PS
authors.lastname: Cheah
authors.affiliation: Wipro Skin Research and Innovation Centre, No. 7, Persiaran Subang Permai, Taman Perindustrian Subang, 47610, Subang Jaya, Selangor, Malaysia.
authors.forename: C K
authors.initials: CK
authors.lastname: Lim
authors.affiliation: Wipro Skin Research and Innovation Centre, No. 7, Persiaran Subang Permai, Taman Perindustrian Subang, 47610, Subang Jaya, Selangor, Malaysia.
authors.forename: M S
authors.initials: MS
authors.lastname: Toh
mesh_terms: D000279:Administration, Cutaneous; D002478:Cells, Cultured; D000068937:Cosmeceuticals / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D003872:Dermatitis / Q000503:physiopathology; D006031:Glycosylation; D006037:Glyoxal / Q000494:pharmacology; D006146:Guanidines / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008954:Models, Biological; D015595:Skin Aging / Q000187:drug effects*; D059467:Transcriptome
chemical_list: D000068937:Cosmeceuticals; D006146:Guanidines; C067242:N(epsilon)-(carboxymethyl)hydroxylysine; C070130:diaminoguanidine; D006037:Glyoxal; D008239:Lysine