title: The use of gene arrays and corresponding connectivity mapping (Cmap) to identify novel anti-ageing ingredients.
abstract: OBJECTIVE
  The need for effective 'anti-ageing' treatments, in particular for the management of photodamaged skin, prompted us to develop a novel method to identify new active ingredients. The model utilized a gene profiling study with corresponding connectivity mapping (Cmap) to identify novel anti-ageing compounds using all-trans retinoic acid (RA) as the lead compound due to its beneficial effect on photodamaged skin and skin firmness.
  
  
  METHODS
  A vehicle-controlled clinical study including nine healthy Caucasian female volunteers aged 57 ± 7 (mean ± SEM) exhibiting photodamage on their lower outer forearms was conducted. The volunteers applied RA once daily on photodamaged skin for 7 days, and biopsies were subjected to Affymetrix gene arrays. Connectivity mapping (Cmap), examining hundreds of gene expression profiles, was run on the gene signature of RA-treated photodamaged skin to identify small bioactive compounds.
  
  
  RESULTS
  Affymetrix gene array identified 19 genes significantly differentially expressed after application of RA. Corresponding Cmap analysis revealed six natural bioactive compounds including N-acetyl aspartic acid (A-A-A) showing similar activity to RA on the differentially expressed genes identified.
  
  
  CONCLUSIONS
  Based on RA mimicking gene array activity, potential use within skincare on molecular size, safety assessment and sourcing, we identified the natural amino acid, A-A-A as a potential candidate to treat ageing skin.
authors.affiliation: Oriflame Skin Research Institute, Mäster Samuelsgatan 56, Stockholm, 11121, Sweden.
authors.forename: J M
authors.initials: JM
authors.lastname: Gillbro
authors.affiliation: Bray Business Park, Kilruddery, Oriflame R&D Ltd, Bray, Co Wicklow, Ireland.
authors.forename: E
authors.initials: E
authors.lastname: Merinville
authors.affiliation: ParkCell AB, Uppsala Science Park, Uppsala, SE, 75183, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Olsson
authors.affiliation: Oriflame Skin Research Institute, Mäster Samuelsgatan 56, Stockholm, 11121, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Al-Bader
authors.affiliation: Oriflame Skin Research Institute, Mäster Samuelsgatan 56, Stockholm, 11121, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Klack
authors.affiliation: Oriflame Skin Research Institute, Mäster Samuelsgatan 56, Stockholm, 11121, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Visdal-Johnsen
authors.affiliation: Oriflame Skin Research Institute, Mäster Samuelsgatan 56, Stockholm, 11121, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Mavon
mesh_terms: D000368:Aged; D001224:Aspartic Acid / Q000494:pharmacology; D005260:Female; D006801:Humans; D008875:Middle Aged; D014677:Pharmaceutical Vehicles; D015595:Skin Aging / Q000187:drug effects*; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D014677:Pharmaceutical Vehicles; D001224:Aspartic Acid; D014212:Tretinoin
keywords: acetyl aspartic acid (A-A-A); connectivity mapping (Cmap); gene array; retinoic acid; retinoids