RESUMO
Purpose: Personalized approaches in dermatology are designed to match the specific requirements based on the individual genetic makeup. One major factor accounting for the differences in skin phenotypes is single nucleotide polymorphism (SNP) within several genes with diverse roles that extend beyond skin tone and pigmentation. Therefore, the cellular sensitivities to the environmental stress and damage linked to extrinsic aging could also underlie the individual characteristics of the skin and dictate the unique skin care requirements. This study aimed to identify the likely biomarkers and molecular signatures expressed in skin cells of different ethnic backgrounds, which could aid further the design of personalized skin products based on specific demands. Methods: Using data mining and in-silico modeling, the association of SNP-affected genes with three major skin types of European, Asian and African origin was analyzed and compared within the structure-function gene interaction networks. Cultured dermal fibroblasts were subsequently subjected to ultraviolet radiation and oxidative stress and analyzed for DNA damage and senescent markers. The protective applications of two cosmetic ingredients, Resveratrol and Quercetin, were validated in both cellular and in-silico models. Results: Each skin type was characterized by the presence of SNPs in the genes controlling facultative and constitutive pigmentation, which could also underlie the major differences in responses to photodamage, such as oxidative stress, inflammation, and barrier homeostasis. Skin-type-specific dermal fibroblasts cultured in-vitro demonstrated distinctive sensitivities to ultraviolet radiation and oxidative stress, which could be modulated further by the bioactive compounds with the predicted capacities to interact with some of the genes in the in-silico models. Conclusion: Evaluation of the SNP-affected gene networks and likely sensitivities of skin cells, defined as low threshold levels to extrinsic stress factors, can provide a valuable tool for the design and formulation of personalized skin products that match more accurately diverse ethnic backgrounds.
RESUMO
Human skin demonstrates a striking variation in tone and color that is evident among multiple demographic populations. Such characteristics are determined predominantly by the expression of the genes controlling the quantity and quality of melanin, which can alter significantly due to the presence of small nucleotide polymorphism affecting various steps of the melanogenesis process and generally linked to the lighter skin phenotypes. Genetically determined, constitutive skin color is additionally complemented by the facultative melanogenesis and tanning responses; with high levels of melanin and melanogenic factors broadly recognized to have a protective effect against the UVR-induced molecular damage in darker skin. Long-term sun exposure, together with a genetic makeup responsible for the ability to tan or the activity of constitutive melanogenic factors, triggers defects in pigmentation across all ethnic skin types. However, sun exposure also has well documented beneficial effects that manifest at both skin homeostasis and the systemic level, such as synthesis of vitamin D, which is thought to be less efficient in the presence of high levels of melanin or potentially linked to the polymorphism in the genes responsible for skin darkening triggered by UVR. In this review, we discuss melanogenesis in a context of constitutive pigmentation, defined by gene polymorphism in ethnic skin types, and facultative pigmentation that is not only associated with the capacity to protect the skin against photo-damage but could also have an impact on vitamin D synthesis through gene polymorphism. Modulating the activities of melanogenic genes, with the focus on the markers specifically altered by polymorphism combined with differential requirements of sun exposure in ethnic skin types, could enhance the applications of already existing skin brightening factors and provide a novel approach toward improved skin tone and health in personalized skincare.