Novel elasticity and tightness enhancing peptide

The synergistic effects of chronological ageing, photoageing, environmental factors, and hormonal deficiency, cause skin quality deterioration with age. Hormonal ageing of skin due to oestrogen loss during the menopause is thought to include atrophy, elasticity loss and decreased sebaceous secretions, and collagen and water content.2 Intrinsically, aged skin shows characteristic fine wrinkling and appears smooth.3 Especially from the age of 40 years, synthesis and turnover of new components by fibroblasts slow, and enzyme action on fibres increases, implying skin elasticity loss and a less supple and more hardened collagen. On the other hand, solar radiation is the main cause of extrinsic ageing, but some other causes, such as air pollution, are also very important.4 Severe photoageing presents increased proteolytic activation and shows abnormal extracellular matrix (ECM) turnover. The consequence is an acceleration of collagen and elastic fibres degradation in the dermis, resulting in loss of the skin’s ability to resist stretching.5 Typically, sun-exposed skin appears papular, coarse, roughened, and deeply wrinkled with marked loss of elasticity and recoil.6

Mechanics of skin elasticity

Elastic fibres are responsible for the normal resilience of the skin. When elastic fibres suffer elongation, their immediate tendency is to return to their initial position with an elastic behaviour (Fig. 1). This elasticity decreases with time for different reasons, such as natural ageing or several other factors that accelerate or modify the natural process.4 Skin elasticity is a mechanical property which is influenced by elastin, a protein in the skin which, together with collagen and glycosaminoglycans, make up the connective tissue. Protein fibres are arranged to form a network submerged in a gel matrix of water and glycosaminoglycans. Fibroblasts are included in this structure and are responsible for synthesising the other components. The protein network gives the tissue its physical properties, such as rigidity and elasticity, elastin being fundamental in the latter parameter.4 The connective tissue of the skin is composed mostly of collagen which is the most abundant protein in the skin. Collagen makes up 70%-80% of the dry weight of the skin and gives the dermis its mechanical and structural integrity.6 The various collagens and the structures they form all serve the same purpose, to help tissues withstand stretching.7 One of the most important is type I collagen, which is the most abundant collagen in the human body, representing 80%-85% of the dermal collagen. Type I collagen fibrils have a great tensile strength and elastic resistance.1,6 Elastic fibres are insoluble structural elements of connective tissue that have a central core of amorphous, hydrophobic cross-linked elastin surrounded by fibrillar structures with a regular diameter of 10 nm-12 nm (Fig. 2). Elastin is a wellcharacterised connective tissue protein and is the major component of the elastic fibres. Although elastin is found in smaller amounts than collagen in the dermis, it is crucial for skin elasticity. During early embryonic development, most of the elastic fibres consist of microfibrils, which form a microfibrillar skeleton upon which elastin is deposited. In mature, fully developed elastic tissue, well over 90% of the total content consists of elastin.3,6 Natural aged skin shows general atrophy of the ECM with reduced elastin and disintegration of elastic fibres.3 There is also a reduction in the amount of peripheral microfibrils. The fibre surface becomes irregular and granular, microfibrils become thicker, and there is a decrease in the amount of glycosaminoglycans and fibroblasts.4 A major feature of aged skin is also reduced collagen synthesis and increased degradation, resulting in connective tissue damage, and loss of the skin’s three-dimensional integrity.8 The chronological ageing process and environmental insults contribute to the generation of ROS (Reactive Oxygen Species) that stimulate the inflammatory process in the skin, activating the transcription factors that regulate the proteolytic degradation of the ECM. In response to UV-induced production of pro-inflammatory cytokines, phagocytic cells such as neutrophils and monocytes infiltrate the skin from capillaries. In addition to keratinocytes, the phagocytic
cells themselves secrete cytokines that further enhance recruitment of inflammatory cells. Furthermore, neutrophils release elastases and other proteases that can cause further inflammation, and activation of matrix metalloproteases (MMP) which are known for degrading collagen fibres.5 Damage to connective tissues is a major complication of the inflammatory response. Elastic fibres are degraded by several types of enzymes, such as neutrophil elastase released during neutrophil infiltration of the epidermis, MMP-12 derived from macrophages, and skin fibroblast elastase produced by fibroblasts.5,9 Ultraviolet radiation induces both neutrophil elastase and skin fibroblast elastase. Neutrophil elastase is able to rapidly degrade intact microfibrils and its inhibition has been shown to prevent UV-induced wrinkle formation in skin. The secretion and activation of skin fibroblast elastase is thought to be responsible for the degeneration of the three-dimensional structure of elastic fibres during the formation of wrinkles.3,5,9 Inflammation, UV irradiation and the normal process of ageing can activate MMPs leading to increased matrix degradation. MMPs are a group of zinc-dependent endopeptidases capable of degrading ECM components and are involved in the turnover and remodelling of the dermis.5 Human macrophage metalloelastase (HME, MMP-12) is the most active MMP against elastin on a molar basis and has broad substrate specificity, being able to degrade also type IV collagen which is the most abundant structural component of basement membranes.10 On the other hand, MMP-1 initiates cleavage of fibrillar collagen types I and III in the dermis, which is then further degraded by MMP-2 and MMP-9.5 An increase of elastases activity and a slow elastogenesis result in elasticity loss which is reflected in a sagging, soft and wrinkled skin.