Reversing signs of ageing in mature skin

It is clear that skin continuously suffers aggressions like photoageing, environmental factors, chronological ageing and hormonal deficiency, which end up in skin deep alterations including a loss of elasticity and firmness, an increase of flaccidity and sagginess, and a thicker and atrophic skin.1 Skin elasticity is a basic mechanical property mainly depending on elastin, protein forming the connective tissue together with collagen and glycosaminoglycans. Elastin is important for skin because it is responsible for its capacity to resist stretching and keep firmness under pressure, avoiding noticeable signs like sagginess. Collagen is the most abundant protein in the Extracellular matrix (ECM) and also another key compound for the adequate functioning of skin, providing compactness and support. Both elastin and collagen fibres are altered by photoageing and chronologic ageing, generating the atrophy of the ECM, a loss of 3D-skin integrity and undesired visible effects like wrinkles.2 From the 40s onwards, there is a slower turnover and synthesis of new components of the ECM and a superior enzyme proteolytic degradation of collagen and elastin fibres, which negatively affects skin conditions. Matrix metalloproteinases (MMP) plus other specific enzymes like collagenases, neutrophil elastases and skin fibroblast elastases degrade these important compounds as well as other connective tissue proteins.3 Additionally, sun exposure contributes to these skin alterations as it is the main environmental agent causing extrinsic ageing. Therefore, the ECM is deeply altered through ageing and this affects the dermoepidermal junction line (DEJ) as well, bi-layer basement membrane in charge of supporting the epidermis and ensuring an adequate communication between epidermal and dermal cells. The DEJ reticular lamina is in direct contact with the ECM and the above DEJ basal lamina contains high levels of type IV collagen, proteoglycans and laminin that offer structural support and bio-adhesive properties for cell attachment. As these proteins are degraded when ageing, the outcome is a flatter DEJ and a lower skin resistance. As mentioned above, laminin is another necessary compound for the skin, being the second most abundant protein in the ECM in terms of quantity and being involved in cell proliferation, migration and adhesion. Several features of the DEJ become altered with time like the decrease in the anchoring ability of keratinocytes and in the synthesis of laminin-5. These changes induce a contact reduction between dermis and epidermis that, in turn, leads to skin elasticity loss and sagginess. On the other hand, collagen also interacts with the proteoglycan decorin, which in turn influences collagen fibrillogenesis by regulating excessive bundle-like aggregation of collagen. As a result of the progressive reduction of this functional proteoglycan through ageing, collagen fibres get disrupted and skin tensile strength is reduced. To minimise the ageing effects and help mature skin become and look younger, Lipotec developed three peptides to enhance rejuvenation and reduce undesired effects. Relistase is a tetrapeptide (acetylarginyltryptophyl diphenylglycine) that enhances skin elasticity and tightness. Serilesine is a hexapeptide (hexapeptide-10) which promotes cell adhesion and proliferation, retaining many of the characteristics of the laminin-1 native protein (sequence from its alpha chain). Finally, Decorinyl (liposomal system with tripeptide-10 citrulline) contains a mimic tetrapeptide of the binding sequences of decorin, which targets collagen fibre organisation, ensures uniformity of fibril diameter and increases cutaneous suppleness thanks to a better cohesion of collagen fibres. The beneficial properties of these three peptides were proved in several in vitro and in vivo tests, which showed the excellent anti-ageing effects by improving overall conditions of mature skin.

Materials and methods

Inhibition of human neutrophil elastase