Cosmetogenomics and the mechanisms of efficacy

And evidence because credible and sufficient proofs are a must-have to support claims all over the world. Let us see how genomics, proteomics and other recent claim substantiation technologies, gathered under the specific term of ‘cosmetogenomics’, represent a sophisticated solution to predict and validate performance of cosmetic active ingredients and/or finished products. A few definitions to start with: genomics, first, is the analysis of gene expression that can be achieved thanks to transcriptomics (study of RNA transcripts from genome), and/or proteomics (study of protein activity). A special focus of research into the genome is cosmetogenomics, which is the analysis of the modulation of gene activity induced by a cosmetic active ingredient (or a finished product). Depending on how cosmetic actives interact with the cell’s DNA, specific RNA molecules are produced. The sum of these molecules constitutes the transcriptome (studied by transcriptomics) and is the matrix for the proteins ultimately synthesised (studied by proteomics). The synthesised molecules - enzymes, carriers, collagen, elastin and others – take on a range of tasks which the cell’s metabolism supports and maintains. With the help of metabolomics the metabolic exchange is assigned to the transcriptomes and the proteomes. If the concerned metabolite is a lipid, then it goes to the field of lipidomics which analyses modifications of lipid structure and function. These methods have been used for some years now to research and develop cosmetic actives and also to evaluate them as well as finished products. Indeed, the results of such targeted studies clearly highlight the cell metabolism and the perceivable effects that are generated by the active ingredients (or the finished products). It sounds attractive that the underlying science has found a new way into the world of product efficacy, as it helps to support cosmetic claims. Cosmetogenomics helps to establish an extensive characterisation of new actives and enables the conception of new marketing claims.

 Active substances evaluated by cosmetogenomics

Sederma’s portfolio includes a whole range of different actives whose efficacy has been evaluated using cosmetogenomic methods. In the gene activation studies keratinocytes, fibroblasts and adipocyte cultures were used and a subsequent metabolomic study allowed the verification of the results obtained using transcriptomics. The anti-ageing active, Matrixyl 3000, is well-known for its anti-wrinkle action. It significantly reduces noticeable wrinkles, smoothes a rough skin surface and increases the skin’s elasticity and resilience. More recent data confirm a positive action on the structure of the papillary dermis which suffers particularly from the damaging effects of UVA radiation. Using this active substance, the defragmentation of the fibre network is reduced (see Fig. 1) and the new material matrix is formed. This action, observed in vivo, is supported by the gene activation profile. The activated gene phases code for molecules that are involved in the formation of new matrix proteins, and that stimulate cell renewal and cell anchoring. In particular the stage when the new cells are anchored into the surrounding matrix is very important for the subsequent functionality of the cell. If there is only an indication that the cell function is stimulated this still does not mean that efficacy can be perceived at a macroscopic level. The Nobel Prize for medicine in 2009 was given to three researchers who focused their work on the telomeres, i.e. the cells’ biological clock, and demonstrated their importance for the cell’s life cycle. Normal body cells die off after a specific period of time. The period of time depends on the length and condition of the telomeres. Skin cells are those most exposed to aggressive elements. The telomeres also suffer here. They become prematurely damaged and their lifetime is shortened. A protective and repair mechanism for this sensitive, yet key element of the cell’s genetic material has been demonstrated using the Renovage active substance in a gene expression study. A cell culture study carried out over several months showed a strengthening of the protective and maintenance function on the telomeres and the lifetime of the cells. In vivo, the activity showed itself in a generally more attractive skin quality. Parameters such as moisture content, micro-relief, pigment spots and redness, dilation of the pores and firmness, all showed significant improvement. Flawless skin with no unevenness or pigmentation problems is the wish of all consumers. The Chromocare active helps to produce a more even complexion by acting on the skin’s three chromophores – collagen, haemoglobin and melanin. Their formation is significantly influenced by inflammation processes in the skin. In the DNA array, valuable indications are obtained on the anti-inflammatory and antioxidative properties of two plant extracts which it contains, namely Siegesbeckia orientalis and Rabdosia rubescens. At the same time a positive action was observed on the matrix regeneration. Indeed, in vitro data from research into the cell metabolism confirm a reduction of melanin and haemoglobin (Fig. 2) and an increase in the matrix proteins, inflammation-caused redness decreased. The panel study finally confirmed the smoothing action on the complexion which produced a more even appearance. The active mechanism of Revidrate was very precisely defined using a gene activation profile in relation to keratinocytes. The profile showed that the synthesis of filaggrin – a basic molecule in the Natural Moisturising Factor (NMF) – was stimulated (Fig. 3). It was also seen that the enzymes needed for NMF formation actually increased. Because the keratinocyte maturity was stimulated so that the components of the intercellular substance and corneocyte cell casing were increased, an extensive range of action was produced: on the one hand the skin’s own moisture reservoir function was increased and on the other hand the skin’s mechanical and physical protective barriers were reinforced in order to optimise the moisture content. In application studies, it was shown that even some time after the use of the active cream was stopped the action continued. One week after the last application, the moisture level in the upper and deeper epidermis was still clearly higher than before the applications started. A very interesting indication of the synthesis performance of the keratinocytes has been supplied by the gene activation study on the Subliskin active substance. Only a few years ago it was known that hyaluronic acid is not only formed in the dermal fibroblasts but also in the keratinocytes, and helps to regulate the moisture level in the deeper layers of the epidermis. The glycokines of this active – which are by a special process biomimetically obtained oligosaccharides – are able to stimulate the hyaluronic acid production of the keratinocytes. Furthermore, the study confirms the results of the metabolomics with regard to the laminin-5 and collagen-IV stimulation. Both of these anchoring proteins are important binding elements between the dermis and the epidermis, and are essential for optimum maintenance of the outer skin layer. This confirms the findings of the volunteer study where in particular among people with thin, fragile skin the skin’s resistance was clearly increased. A gene activation profile can also be carried out on the adipocytes. For the slimming active, Phytosonic, interesting properties are found that reflect the extensive product efficacy. For an increase in lipid breakdown a continuous metabolic action in the mitochondria is required, and in which carnitine is involved. The genes which code for carnitine are clearly activated. The whole metabolism also requires a continuous energy supply. This function too is stimulated in the DNA array, as is the protection of cells from oxidative stress. Furthermore, a specific enzyme is activated which releases the adipocytes from its matrix, effectively isolates them and so prevents the lipids from bonding in place (Fig. 4). All of these actions were reproduced in vitro. In the application study the circumference of the upper thigh was on average reduced by 1 cm and the skin smoothing effect was noticed by the test volunteers.