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Peptides Th e use of peptides in commercial products has signifi cantly risen in recent years. Known to play a role in wound-healing, naturally occurring peptides in the skin have been shown in vitro to: (1) stimulate the production of extracellular matrix components including collagen, elastin and fi bronectin and (2) decrease the production of dermal GAGs. 49, 50 Decreased dermal matrix components and increased dermal GAGs are hallmark features of aged skin, 51 the reversal of which has been hypothesized as a viable approach to anti-aging. With variations in amino acid sequence, number of amino acids and use of derivatives of these acids, there are limitless combinations of possible peptides. By testing the eff ect of multiple peptides on the synthesis of collagen in culture, scientists at the University of Tennessee 49, 50 narrowed the fi eld of possible amino acid combinations to a pentapeptide fragment of pro-collagen, KTTKS (lysine-threonine-threonine-lysineserine). Th is peptide retained 80% of the collagen-stimulating activity of the original, much larger 34–44 amino acid pro-collagen peptide from which it was derived. Because transdermal delivery of ionic peptides is likely to pose a signifi cant issue for delivery of bioactive peptide into the skin, a palmitoyl derivative 14 Fine Lines, Wrinkles & Texture: Research Update Collagen synthesis (% of control) 250 – 200 – 150 – 100 – 50 – 0 Control 4ppm pal-KTTKS In cell culture experiments, pal-KTTKS increases collagen synthesis. – – of KTTKS (pal-KTTKS) was used, which capitalizes on research conducted on peptides to improve transcutaneous delivery. 52 Consistent with the collagenstimulating eff ects of the underivatized KTTKS, pal-KTTKS promotes the production of collagen in organotypic cultures of human skin cells. 24 In addition, pal-KTTKS eff ectively reduces dermal GAGs at 1/10 th the dose of trans-retinoic acid (tRA). 53 Th e promotion of these eff ects in vitro are consistent with the antiaging strategy proposed above. Multiple clinical studies have demonstrated the signifi cant eff ect of formu lations containing pal-KTTKS on wrinkle reduction and facial appearance improvement. In one study, 54 60 subjects were treated for four months in a split-faced doubleblinded trial. Th e pal-KTTKS test product produced signifi cant % reduction in GAGs % change over 4 months 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 5 – 0 – -5 – -10 – -15 – -20 – -25 – -30 – -35 – -40 0.9ppm pal-KTTKS % change vs. To p< 0.01 % change vs. To p< 0.015 Wrinkle volume (μm 3 ) – 5 – 0 – -5 – -10 – -15 – -20 – -25 – -30 ¢ pal-KTTKS ¢ tRA control 10ppm tRA (*10ppm = 0.001%) In in vitro cell culture experiments, pal-KTTKS reduces GAGs comparably at 1/10 th the dose of tRA (10 ppm = 0.001%). ¢ pal-KTTKS ¢ Vehicle Wrinkle depth (μm) Moisturizer containing pal-KTTKS decreases both wrinkle volume and depth following 4 months of treatment. – improve ments versus the vehicle in wrinkle volume and wrinkle depth at two- and four-month time points. Results were based on quantitative image analysis of skin replicas. In another split-face double-blinded study of 92 subjects, 27 signifi cant
improvements were seen in wrinkle appearance (week 12 p=
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