Trifluoroacetyl-Tripeptide-2 to Target Senescence for Anti-aging Benefits

Apr 1, 2012 | Contact Author | By: Estelle Loing, PhD, Unipex Innovations, Québec, Canada; Thiery Suere and Elisabeth Lamarque, Unipex Innovations, Ramonville St. Agne, France
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Title: Trifluoroacetyl-Tripeptide-2 to Target Senescence for Anti-aging Benefits
progerinx syndecanx MMPx synthetic tripeptidex
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Keywords: progerin | syndecan | MMP | synthetic tripeptide

Abstract: Recent work indicates that the biomarker progerin, in conjunction with dysfunctioning telomeres, triggers cellular senescence. In response, trifluoroacetyl-tripeptide-2, a synthetic tripeptide, was developed to decrease progerin production, thereby regulating biological mechanisms involved in the aging process and reducing the cosmetic effects of aging, which are explored here.

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E Loing, T Suere and E Lamarque, Trifluoroacetyl-tripeptide-2 to target senescence for anti-aging benefits, Cosm & Toil 127(4) 274-280 (Apr 2012)

Market Data

  • Smoking is a major contributor to skin discoloration, ECM breakdown, deep wrinkling, premature skin aging, poor wound-healing and the formation of abnormal skin growths.
  • Telangiectasias—small, dilated blood vessels near the skin’s surface—are a response to the body's need for more oxygen, stifled by smoking.
  • Exposure to the pollutants present in cigarettes accelerates the degradation of the ECM.
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The present study looks at the broader anti-aging properties of tripeptides by specifically examining the effects of trifluoroacetyl-tripeptide-2 (TT2) on ECM protection, on the synthesis of proteoglycans in cell-matrix interactions, and on the synthesis of progerin, a protein recently identified as a co-inducer of cellular senescence. This ingredient was chosen as the best candidate based on the in vitro screening of a library of materials built from peptides having known physiological activity.

In vitro studies were conducted to assess the ability of this tripeptide to inhibit MMP-1, MMP-3, MMP-9 and elastase, to stimulate syndecan-1 expression in human keratinocytes, and to reduce progerin synthesis in mature human normal fibroblasts. Two in vivo studies were conducted to confirm in vitro findings using cutometry and fringe projection profilometry techniques.

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This is an excerpt of an article from GCI Magazine. The full version can be found here.

 

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Figure 1. Inhibition of MMP-1 by TT2

Figure 1. Inhibition of MMP-1 by TT2

The tripeptide significantly inhibited MMP-1, MMP-3 and MMP-9 activities, in a dose-dependent manner, in comparison with the vehicle alone, which had no effect.

Figure 2. Inhibition of MMP-3 by TT2

Figure 2. Inhibition of MMP-3 by TT2

Inhibition of MMP-3 by TT2; ** = significantly different from the “buffer alone” (= 0) condition (p < 0.05; Student t-test)

Figure 3. Inhibition of MMP-9 by TT2

Figure 3. Inhibition of MMP-9 by TT2

Inhibition of MMP-9 by TT2; ** = significantly different from the “buffer alone” (= 0) condition (p < 0.05; Student t-test)

Figure 4. Anti-collagenase activity of TT2

Figure 4. Anti-collagenase activity of TT2

Anti-collagenase activity of TT2 in a skin slices model a) by image analysis (from left): buffer alone; + collagenase; and + collagenase + 0.05 ppm TT2; and b) quantification of the anti-collagenase activity of TT2; * = significantly different from the “collagenase” condition (p < 0.001; student t-test) by TT2

Figure 5. Anti-elastasease activity of TT2

Figure 5. Anti-elastasease activity of TT2

Anti-elastasease activity of TT2 in a skin slices model a) by image analysis (from left): buffer alone; + elastase; and + elastase + 0.05 ppm TT2; and b) quantification of the anti-elastase activity of TT2; * = significantly different from the “buffer alone” condition (p < 0.001; student t-test)

Figure 6. Effect of TT2 on syndecan-1 expression by keratinocytes

Figure 6. Effect of TT2 on syndecan-1 expression by keratinocytes

Effect of TT2 on syndecan-1 expression by keratinocytes, a) shown by immunolabelling of syndecan-1 synthesis by keratinocytes (from left): untreated keratinocytes and keratinocytes treated with 0.005 ppm TT2 ; and b) quantification of the syndecan-1 synthesis by keratinocytes by image analysis; ** = significantly different from the “buffer alone” condition (p < 0.05; student t-test)

Figure 7. Effect of TT2 on the progerin expression

Figure 7. Effect of TT2 on the progerin expression

Effect of TT2 on the progerin expression in fibroblasts issued from an aged subject; ** = significantly different from the control condition (p < 0.05; one way ANOVA + all pairwise multiple comparison procedures by Fisher LSD Method)

Figure 8. Effect of TT2 on the jawline volume of 10 healthy volunteers

Figure 8. Effect of TT2 on the jawline volume of 10 healthy volunteers

Figure 8. Effect of TT2 on the jawline volume of 10 healthy volunteers; * = significantly different from the T0 condition (p < 0.05; student t-test); # = significantly different from the placebo condition (p < 0.05; student t-test)

Figure 9. Effect of TT2 on cutaneous firmness, elasticity and visco-elasticity

Figure 9. Effect of TT2 on cutaneous firmness, elasticity and visco-elasticity

Effect of TT2 on cutaneous firmness, elasticity and visco-elasticity; * = significantly different from the T0 condition (*** p < 0.01 and * p < 0.1; student t-test)

Figure 10. Visualization of the anti-sagging and anti-wrinkle effect

Figure 10. Visualization of the anti-sagging and anti-wrinkle effect

Visualization of the anti-sagging and anti-wrinkle effect with 4 ppm TT2 a) before treatment, b) after 28 days of treatment and c) after 56 days of treatment

Footnotes [Loing 127(4)]

a Progeline (INCI: Trifluoroacetyl-tripeptide-2) is a product of Unipex, Quebec, Canada.

b The SEM575 cutometer is manufactured by Courage & Khazaka.

Formula 1. Test cream for clinical studies

Demineralized Water (aqua) qs to 100.00% w/w
Carbomer (Carbopol Ultrez-10, Lubrizol/Noveon) 0.15
Butylene Glycol 3.00
Phenoxyethanol (and) Methylparaben (and) Ethylparaben (and) Butylparaben (and) Propylparaben (and) Isobutylparaben 0.80
Glycerin 2.00
Hydrogenated Vegetable 2.00 Consistency Factor Glycerides (Cutina HVG, BASF) 5.00
Cetyl Alcohol (Lanette 16, BASF) 1.00
Sorbitan Oleate (Span 80, Sigma-Aldrich) 0.50
Caprylic/Capric Triglyceride (Labrafac CC, Alfa Chemicals) 5.00
Myristyl Myristate (Schercemol MM Ester, Lubrizol/Noveon) 3.00
Polysorbate 60 (Tween 60, Sigma-Aldrich) 2.00
Butyrospermum Parkii (Shea) Butter 1.00
Dimethicone (DM FLUID 350 CS, Shin-Etsu Silicone) 0.04
Fragrance (parfum) 0.02
Trifluoroacetyl Tripeptide-2 (TT2) 2.00
Sodium Hydroxide 0.66

 

      

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