Jul. 02, 2020

The science behind Nomige

Nerd alert!

In this blog we go deeper into the scientific fundamentals on which the concept of Nomige is built. It gives an overview of the published literature in regenerated peer-reviewed journals, as can be found on MEDLINE and PubMed.

INTRODUCTION

As everyone ages, scientists try to understand the molecular and physiological events involved in the skin aging process. Skin changes are one of the most visible signs of aging and have been given more attention in a society that values youth and beauty (1). The term "perceived age" refers to the age a person is estimated to have, how this person looks, in relation to his or her chronological age. This concept has implications that go beyond aesthetics: perceived age is a robust biomarker of aging that predicts survival in certain groups of patients (2) and correlates with important functional and molecular aging phenotypes (3).

Research on same-sex twins suggests that up to 60% of the variation in perceived age is influenced by genetics , while the remaining 40% can be explained by non-genetic factors (3,4). Among the latter, smoking, pollution and sun exposure are the environmental factors of major importance for premature skin aging (5).

Ethnicity and gender are clear evidence of genetic influence on skin aging . Wrinkles in Asians tend to appear later and less 'severe' than in white people (6), while another study shows that skin dryness is higher in African-American and Caucasian women (7). The most explicit difference between ethnic groups is that people with darker skin tones tend to retain younger skin characteristics (8). Physiological differences between men and women also point to the role of genetics in skin aging. For example, male skin is more susceptible to harmful external influences, especially ultraviolet light (9).

The combination of intrinsic (from the inside) and extrinsic (from the outside) factors are ultimately responsible for accelerated skin aging. Significant changes in biological processes driving skin aging are oxidative stress (10), lack of elasticity and reduced hydration (11). Oxidative damage can occur, for example, as a result of exposure to the sun and the formation of free radicals. These have a negative impact on skin firmness. And due to a lack of lipids that are part of the skin structure, the skin experiences severe water loss ( dehydration ) , making wrinkles much more visible.

Sequencing of the human genome and subsequent developments in genomics have yielded new instruments with which these factors can be investigated at a molecular level (12). Single nucleotide polymorphisms (SNPs) are mutations or genetic variations that occur when individual bases in genes are altered or removed, which can result in an amino acid change at a specific position and a change in phenotype . Numerous physiological conditions are correlated with the occurrence of SNPs in specific genes in a human genome.

SNPs are also associated with skin functions. Han et al. identified novel SNPs associated with skin pigmentation and hair color (13). A genome-wide association study also demonstrated the role of STXBP5L gene variants in photoaging or the association of mutations in genes coding for antioxidant response with a predisposition to higher oxidative stress (14).

CHARACTERIZATION OF SKIN AGING AT THE GENE AND PROTEIN LEVEL

An older skin is characterized by mainly dehydration, loss of elasticity and increased oxidative damage (10,11). These three main skin properties have been selected because they are strongly related to known metabolic pathways and because many other visible skin properties such as wrinkle lengthening and depth can be attributed to one of these three (in this case, wrinkles can be attributed to loss of elasticity and collagen metabolism).

Through an extensive literature review, we found genes that code for proteins involved in skin hydration, skin elasticity and antioxidant capacity of the skin. We then further identified which proteins have SNPs in their genes that affect (in a negative way) the corresponding expression or functionality of the protein product. The following proteins were selected: matrix metalloproteinase-1 (MMP-1) (15), superoxide dismutase II (16,17), glutathione peroxidase (18), matrix metalloproteinase-3 ((MMP-3) (19), fillagrin ( 20) and aquaporin-3 (21).

The MMP genes

Trapped between the epidermis and the hypodermis is the dermis. The dermis contains blood vessels that nourish the skin, and structural proteins such as collagen that strengthen the skin. As we age, the production of collagen decreases. However, in some people with an SNP in MMP-1 or MMP-3 , collagen is broken down faster than others because the mutation in these genes causes an increased expression of MMP (15,17).

Scientific research on dermagenetics suggests that different skin care needs depend on that person's polymorphism (22). Skin care products for people with higher collagen loss should be more concentrated in collagen strengthening ingredients and active substances that help reduce the action of MMP enzymes (23, 24, 25).

Antioxidants

Free radicals are highly reactive molecules that can damage any structure in our body. They are created by factors such as pollution, smoking, exposure to the sun, etc. Skin damage caused by free radicals can occur in various forms, such as changes in skin color (broken blood vessels and dark spots), wrinkles & aging due to collagen and elastin damage.

A good way to prevent these free radicals from damaging your body is to consume enough antioxidants through foods or supplements, but the reality is that the most potent antioxidants are found in your own body (26). The GPx-1 gene (encoding for Glutathione peroxidise) and the SOD2 gene (encoding for Superoxide-Dismutase2) are among the strongest antioxidants available in the human body. DNA variations modify (reduce) the production of these powerful natural antioxidants, weakening natural antioxidant capacity and making them more susceptible to external stress factors (27, 28). Topical supplementation of the respective actives therefore has a beneficial and proven effect on the skin (29, 30).

Hydration

Aquaporin-3 (AQP3) is a protein , encoded by the gene AQP3, that forms pores in the membrane of biological cells allowing water to flow into the cell faster than through diffusion through the membrane itself. Aquaporin-3 selectively transports water molecules and glycerol in and out of the cell , while preventing the passage of ions and other dissolved substances. AQP3 acts as a glycerol transporter in the skin and plays an important role in regulating the amount of glycerol in the stratum corneum (SC) and epidermis. Reduced AQP3-dependent glycerol transport, by genetic polymorphisms, appears to be responsible for reduced stratum corneum water content and elasticity (dry, inflexible skin), as well as reduced wound healing and epidermal biosynthesis (31). These deficiencies in AQP3 can be corrected by glycerol replacement delivered via topical applications.

Complex on chromosome 1q21, a dense cluster of genes coding for proteins involved in epidermal differentiation. Interestingly, the function of filaggrin changes throughout the layers of the epidermis. Filaggrin plays an integral role in maintaining skin hydration through SC integrity and the production of natural moisturizing factors (NMF). Certain mutations in FLG lead to lower numbers of ceramide 1, 4 and 7 (32), which are part of the intercellular lipid structure that holds the corneocytes together. Filaggrin deficiency thus results in a less compact skin structure and lowered levels of NMF and occurs in the presence of loss-of-function mutations of FLG (33, 34, 35).

An affected SC is reflected by an increase in transepidermal water loss and dehydration of the skin , as well as a decrease in levels of NMF, leading to a reduced ability to absorb and retain water at levels necessary for normal physiological function. Approximately 10% of people of European origin have one of two 'loss-of-function' mutations in FLG, referred to as R501X and 2282del436. And an improvement in skin structure and hydration degree can be captured by adding NMFs and skin's own lipids (ceramides, cholesterol, free fatty acids) to your daily skincare ritual (37,38).

PROOF OF CONCEPT: THE CLINICAL STUDY OF NOMIGE

These scientific foundations formed the final basis for the 'Nomige concept'. Nome develops personalized and tailor-made skincare . When selecting ingredients and formulating products, both the DNA (using DNA test) and the lifestyle (using questionnaire) of the customer are taken into account. This offers a more personal and effective approach than the classic off-the-shelf products.

As you can conclude from the above explanation, this concept has been supported by more than 10 years of scientific research . Yet this wasn't enough for Dr. Barbara Geussens! To show that Nomige is not a marketing gimmick, but is really based on science, Dr. Barbara Geusens has invested in a clinical study to show that customization for the skin works better. The study was officially published in ' The Journal of Clinical and Experimental Dermatology Research ', an open access, peer-reviewed, academic journal that publishes various aspects within the dermatology discipline.

The randomized, controlled, double-blinded split-face study of 24 women between the age of 30 and 65 showed, for instance, that Nomige guarantees a 5 times better anti-aging effect and shows a 7 times superior texture improving effect versus a standard product, as you can find on the shelves.

Read more about the clinical study on Nomige's website:

CONCLUSION

The use of genetic characteristics to identify individual skin care requirements opens the door to personalized treatments and products. With genotyping services becoming more and more affordable, this is being made more and more accessible to the general public. However, some caution must be exercised and it is important to remain critical, as less reliable services will undoubtedly appear on the market.

A clear privacy policy and description of the DNA analysis is a must. Be careful with parties claiming to need an individual's full DNA sequence as an aid to the design of a personalized skin care and anti-aging treatment. This seems unnecessary to us. That's why we stick to the genes & analyzes described above. However, there are suggestions for further research. These include the discovery of new proteins associated with skin aging, additional polymorphisms that modify their activity or expression, and epigenetic modifications of DNA that affect gene regulation. So, something for the future...

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