title: In vivo topical application of acetyl aspartic acid increases fibrillin-1 and collagen IV deposition leading to a significant improvement of skin firmness.
abstract: OBJECTIVE
  Acetyl aspartic acid (A-A-A) was discovered through gene array analysis with corresponding Cmap analysis. We found that A-A-A increased keratinocyte regeneration, inhibited dermal matrix metalloprotease (MMP) expression and relieved fibroblast stiffness through reduction of the fibroblast stiffness marker F-actin. Dermal absorption studies showed successful delivery to both the epidermal and dermal regions, and in-use trial demonstrated that 1% A-A-A was well tolerated. In this study, the aim was to investigate whether A-A-A could stimulate the synthesis of extracellular matrix supporting proteins in vivo and thereby improving the viscoelastic properties of human skin by conducting a dual histological and biophysical clinical study.
  
  
  METHODS
  Two separate double-blind vehicle-controlled in vivo studies were conducted using a 1% A-A-A containing oil-in-water (o/w) emulsion. In the histological study, 16 female volunteers (>55 years of age) exhibiting photodamaged skin on their forearm were included, investigating the effect of a 12-day treatment of A-A-A on collagen IV (COLIV) and fibrillin-1. In a subsequent pilot study, 0.1% retinol was used for comparison to A-A-A (1%). The biomechanical properties of the skin were assessed in a panel of 16 women (>45 years of age) using the standard Cutometer MPA580 after topical application of the test products for 28 days. The use of multiple suction enabled the assessment of F4, an area parameter specifically representing skin firmness.
  
  
  RESULTS
  Twelve-day topical application of 1% A-A-A significantly increased COLIV and fibrillin with 13% and 6%, respectively, compared to vehicle. 1% A-A-A and 0.1% retinol were found to significantly reduce F4 after 28 days of treatment by 15.8% and 14.7%, respectively, in the pilot Cutometer study. No significant difference was found between retinol and A-A-A. However, only A-A-A exhibited a significant effect vs. vehicle on skin firmness which indicated the incremental benefit of A-A-A as a skin-firming active ingredient.
  
  
  CONCLUSIONS
  In this study, we showed the in vivo efficacy of 1% A-A-A both on a protein level (fibrillin and collagen IV) and on a clinical end point, specifically skin firmness, providing proof that, acetyl aspartic acid has a strong potential as an anti-ageing 'cosmeceutical' ingredient answering the needs of our key consumer base.
authors.affiliation: Oriflame Skin Research Institute, Mäster Samuelsgatan 56, Stockholm, 11121, Sweden.
authors.forename: J M
authors.initials: JM
authors.lastname: Gillbro
authors.affiliation: Oriflame R&D Ltd, Bray Business Park, Kilruddery, Bray, Co Wicklow, Ireland.
authors.forename: E
authors.initials: E
authors.lastname: Merinville
authors.affiliation: Oriflame R&D Ltd, Bray Business Park, Kilruddery, Bray, Co Wicklow, Ireland.
authors.forename: K
authors.initials: K
authors.lastname: Cattley
authors.affiliation: Oriflame Skin Research Institute, Mäster Samuelsgatan 56, Stockholm, 11121, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Al-Bader
authors.affiliation: Department of Medical Sciences, Dermatology and Venereology, Uppsala University, Uppsala, 751 85, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Hagforsen
authors.affiliation: Oriflame Skin Research Institute, Mäster Samuelsgatan 56, Stockholm, 11121, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Nilsson
authors.affiliation: Oriflame Skin Research Institute, Mäster Samuelsgatan 56, Stockholm, 11121, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Mavon
mesh_terms: D000287:Administration, Topical; D000368:Aged; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D002853:Chromatography, Liquid; D024141:Collagen Type IV / Q000378:metabolism*; D000071838:Fibrillin-1; D000071837:Fibrillins; D006801:Humans; D066298:In Vitro Techniques; D008840:Microfilament Proteins / Q000378:metabolism*; D008875:Middle Aged; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption; D021241:Spectrometry, Mass, Electrospray Ionization; D054392:Adipokines
chemical_list: D001224:Aspartic Acid; D024141:Collagen Type IV; D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines
keywords: Cutometer; ageing; collagen IV; cosmeceutical; extracellular matrix; fibrillin-1; photoageing