Features

Erasing the Signs of Aging

Silab researchers explain how by acting on the endogenous hyaluronic acid pathway.

By: Brigitte Closs

Silab R&D, Saint-Viance, France

By: Buranger Tassy

Silab R&D, Saint-Viance, France

By: David Boudier

Silab R&D, Saint-Viance, France

By: Geraldine Bon

Silab R&D, Saint-Viance, France

By: Isabelle Cruz

Silab R&D, Saint-Viance, France

By: Jenny Laumonier

Silab R&D, Saint-Viance, France

By: Karine Perrinet

Silab R&D, Saint-Viance, France

By: Pauline Rouaud-Tinguely

Silab R&D, Saint-Viance, France

By: Sylvain Mazalrey

Silab R&D, Saint-Viance, France

Hyaluronic acid is the most abundant skin component and, in conjunction with collagen and elastin, constitutes the dermal support tissue. Due to its high hygroscopic capacity, it has the ability to capture and bind a significant quantity of water.1 In the form of a hydrated gel, it replenishes interstitial spaces between the fibrillar components of the extracellular matrix, thus guaranteeing skin hydration as well as the maintenance of its suppleness.2-4 Hyaluronic acid is a non-sulfated glycosaminoglycan with rapid metabolic turnover. Its synthesis is ensured by hyaluronan synthases (HAS1, HAS2 and HAS3) and its degradation by hyaluronidases (HYAL).5 Among the enzymes involved in its synthesis, HAS2 is the only one resulting in high molecular weight hyaluronic acid production in the depth of the skin.

In the course of aging, the dermal content of hyaluronic acid diminishes, due to the reduced expression of its synthesis enzymes by dermal fibroblasts.6 These age-related metabolic changes directly affect the skin’s water content and therefore promote the loss of its elasticity and the appearance of wrinkles.7-8 This explains why boosting the presence of hyaluronic acid to take up and retain water in the skin is an essential factor for the efficacy of skin-moisturizing and/or anti-aging concepts.

Among products on the market, the topical application of hyaluronic acid is one of the approaches currently used in cosmetics. Their effectiveness is nevertheless closely linked to the sizes, structures and origins of hyaluronic acid applied to the skin.

The logical strategy would therefore be to simply boost the skin’s natural capacities to make up the shortfall of its intrinsic hyaluronic acid content. In line with this objective, Silab has developed an exclusive natural active ingredient, Prohyal+ (INCI: Yeast extract). This active ingredient is obtained from the yeast Metschnikowia agaves, a microorganism found in the Mexican blue agave ecosystem.9 Just as the agave has developed an efficient strategy to retain water in a very arid environment, YE is a biomimetic active ingredient that reactivates the natural mechanisms of hyaluronic acid synthesis in order to take up and retain water in the skin. This efficacy was evaluated in vitro and in vivo and was compared to reference molecules.

Increasing HA Production
Tested at 2% in normal human fibroblasts, YE significantly stimulates the synthesis of hyaluronic acid by 237% (ELISA assay, Figure 1A). This effect is similar to that obtained with the reference molecule TGF-β at the dose of 10ng/mL.10

In order to determine the mechanism of action of YE, the expression of mRNA coding for HAS2, the essential enzyme for the natural production of hyaluronic acid,11 was assayed by quantitative PCR in these same normal human fibroblasts. Tested at 2%, YE significantly increases HAS2 expression by 651% compared to non-treated normal human fibroblasts. This effect is similar to that obtained with the TGF-β at a dose of 10ng/mL.

By increasing the expression of the HAS2 synthesis, YE boosts the endogenous production of hyaluronic acid.

Skin Hydrated In-Depth
The hydrating effect of YE at 3% was determined using a Moisturemeter-D and comparing it to the effect of the hyaluronic acid reference molecule at the same concentration (0.13% dry weight). This study involved applying one of the study products to each half of the face. Products were randomly assigned to 30 volunteers distributed as follows:

  • Placebo: 20 volunteers, mean age 58 ± 6 years;
  • YE: 20 volunteers, mean age 59 ± 5 years; and
  • Hyaluronic acid: 20 volunteers, mean age 59 ± 6 years.
After 28 days of twice daily applications and in comparison to the placebo, YE formulated in an emulsion at 3% (0.13% dry weight) significantly improves hydration of the skin by +6.5% (P=0.0081). This efficacy tends to be higher than that of hyaluronic acid, the market reference molecule tested in the same conditions.

Anti-Wrinkle Performance
The anti-wrinkle effect of YE formulated in an emulsion at 3% (0.13% dry weight) was studied vs. placebo in vivo on the crow’s feet by fringe projection. The effect of hyaluronic acid, the reference molecule formulated in an emulsion at 0.13% (dry weight), was also tested in the same conditions. 3D acquisitions were analyzed in the same panel as above, before and after 28 days of twice daily treatment.

In the conditions of this study, after 28 days of twice daily applications and in comparison to the placebo, YE formulated in an emulsion at 3% smoothes skin microrelief of the crow’s feet (Figure 2).
The study of the characteristic parameters of skin microrelief shows that YE also significantly decreases:
  • parameter Sq by 6.3% (P = 0.0238);
  • parameter Sa by 7.1% (P = 0.0184); and
  • volume of wrinkles by 14.2% (P = 0.0570).
In this study, the efficacy of YE tends to be greater than that of hyaluronic acid tested in the same conditions (Figure 3). These results demonstrate the anti-wrinkle performance of YE and the interest of using it in all anti-aging cosmetic skin care products.

Conclusion
In order to compensate the cutaneous deficit in hyaluronic acid that progresses with time and that accelerates skin dehydration and the appearance of wrinkles, Silab proposes a novel approach. By boosting the skin’s natural capacities to produce its own hyaluronic acid molecules, YE restores homeostasis of the skin. The skin is moisturized in depth, microrelief is smoothed and wrinkles are rapidly attenuated.

The active molecules of this exclusive natural ingredient are extracted from the biomass of the yeast Metschnikowia agaves whose production is traced and controlled in the new Silab’s production unit dedicated to biotechnologies.

Performance and natural origin are the basis of this novel concept that offers a new dimension to future hydrating and anti-aging cosmetic skin care products.

References
  1. Robert L. Hyaluronan, a truly “youthful” polysaccharide. Its medical applications. Pathol  Biol (Paris). 2015 Feb; 63(1):32–4.
  2. Oh J-H, Kim YK, Jung J-Y, Shin J, Chung JH. Changes in glycosaminoglycans and related proteoglycans in intrinsically aged human skin in vivo. Exp Dermatol. 2011 May 1; 20(5):454–6.
  3. Verdier-Sévrain S, Bonté F. Skin hydration: a review on its molecular mechanisms. J Cosmet Dermatol. 2007 Jun; 6(2):75–82.
  4. Rawlings AV, Harding CR. Moisturization and skin barrier function. Dermatol Ther. 2004; 17 Suppl 1:43–8.
  5. Itano N, Kimata K. Mammalian hyaluronan synthases. IUBMB Life. 2002 Oct; 54(4):195–9.
  6. Tzellos TG, Sinopidis X, Kyrgidis A, Vahtsevanos K, Triaridis S, Printza A, et al. Differential hyaluronan homeostasis and expression of proteoglycans in juvenile and adult human skin. J Dermatol Sci. 2011 Jan; 61(1):69–72.
  7. Waller JM, Maibach HI. Age and skin structure and function, a quantitative approach (II): protein, glycosaminoglycan, water, and lipid content and structure. Skin Res Technol Off J Int Soc Bioeng Skin ISBS Int Soc Digit Imaging Skin ISDIS Int Soc Skin Imaging ISSI. 2006 Aug; 12(3):145–54.
  8. Oh J-H, Kim YK, Jung J-Y, Shin J, Kim KH, Cho KH, et al. Intrinsic aging- and photoaging-dependent level changes of glycosaminoglycans and their correlation with water content in human skin. J Dermatol Sci. 2011 Jun; 62(3):192–201.
  9. Lachance MA. Yeast communities in a natural tequila fermentation. Antonie Van Leeuwenhoek. 1995 Aug; 68(2):151–60.
  10. Redini F, Galera P, Mauviel A, Loyau G, Pujol JP. Transforming growth factor beta stimulates collagen and glycosaminoglycan biosynthesis in cultured rabbit articular chondrocytes. FEBS Lett. 1988 Jul 4; 234(1):172–6.
  11. Triggs-Raine B, Natowicz MR. Biology of hyaluronan: Insights from genetic disorders of hyaluronan metabolism. World J Biol Chem. 2015 Aug 26; 6(3):110–20.  

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