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Olga Koryakina, dermatovenerologist, master of medicine, expert in hardware and injection cosmetology, scientific director of SpaLand International , member of UADV, UALDVK, NOM, MAEKM, WOSIAM (Ukraine)<hr /> The mechanisms of aging are closely related to the functioning of the main cellular organelles: DNA, which is responsible for storing hereditary information, mitochondria, which provide energy to the cell; cell membrane that regulates the transmission of signals and the flow of substances into the cell. Today there are more than three hundred theories explaining the mechanisms of aging. They are mainly divided into two large groups: one part of the theories describes aging as a consequence of the influence of endogenous (internal) factors, the other focuses on the effect of exogenous (external) factors. Endogenous aging actually depends on a single factor – the information contained in DNA. Data accumulated over the past decades make it possible to present some aspects of the aging process in numbers:<ul><li style="text-align: justify;"> the concentration of collagen in the dermis, which provides the skin with strength, decreases by 1% annually upon reaching 30 years of age;</li><li style="text-align: justify;"> upon reaching 40 years of age, the skin thins by 1% annually;</li><li style="text-align: justify;"> skin cells are capable of regenerating from 10 to 100 thousand DNA mutations daily, but 2 hours of exposure to bright sun without protection generates up to 1 million mutations;</li><li style="text-align: justify;"> in just 15 minutes of exposure to bright sun, the reserves of antioxidants in the skin (primarily we are talking about vitamins C and E) are reduced by 70–90%, and it takes at least two hours to restore the balance;</li><li style="text-align: justify;"> 40% of proteins synthesized in the cell have errors in structure and are therefore utilized by special cellular mechanisms;</li><li style="text-align: justify;"> The total content of hyaluronic acid in the body is about 15 g, and 10 g of this is found in the skin. Every three days, all hyaluronic acid in the body is completely renewed, which is why its synthesis is so important: every failure threatens the skin with stress.</li></ul> In the age aspect, the skin is characterized by a strong deficiency of regenerative processes, burdened by accumulated and previously unresolved damage. HYDRATING THE SKIN IS THE WAY TO ITS HEALTH AND BEAUTY It is a generally accepted fact that the amount of moisture contained in cells and tissues is an indicator of their age status: the higher the percentage of moisture content, the younger the cell and tissue. The transfer of information from cell to cell, the transport of nutrients, and the functioning of enzymes are possible only with sufficient moisture content. Therefore, to ensure natural physiological needs, it is absolutely necessary to take care of skin hydration, regardless of age and gender. If we take into account that the conditions in which we live (polluted air, exhaust fumes, constant stress, smoking) do not contribute to improving the condition of the skin, then moisturizing it becomes simply an extremely important task. To this day, biorevitalization remains the most popular way to moisturize the face. The term biorevitalization was proposed in 2001 by A. Di Pietro, who initially defined biorevitalization as a method of intradermal injections of unmodified hyaluronic acid, allowing to achieve restoration of the physiological environment and normalization of metabolic processes in the dermis. At first, preparations based on hyaluronic acid were used for biorevitalization; later, vitamin complexes, microelements, amino acids, and peptides were added to them. Today, third generation drugs based on polynucleotides have been developed. Bioregeneration ⎼ is an innovative technique for rejuvenating and restoring the skin through the introduction of unique Twac preparations, in which hyaluronic acid is combined with polynucleotides. Third generation drugs based on polydeoxyribonucleotides (PDRN), which have a powerful regenerative and biostimulating effect; this is a unique patented formula that affects all parts of the aging mechanisms. LABORATORY RESEARCH During the tests, the complete harmlessness of the DNA-RNA complex and products based on it was proven. At the stage of preclinical studies of the possibilities of using the DNA-RNA complex in aesthetic medicine, its activity was studied in vitro in a test system, which is a long-living and continuous culture of human epidermal cells that preserves the main elements of the tissue, primarily keratinocytes and Langerhans cells. It was found that the complex significantly affects cell metabolism, increasing the rate of synthesis of intracellular proteins and DNA by 1.5–2.5 times, while the pronounced effect depends on the concentration of the complex. It has been proven that the identified stimulation effect extends through the immunocompetent cells of the epidermis to the entire immune system of the body as a whole. Immunohistochemical examination of epithelial tissue indicates that in patients before the use of DNA-RNA complexes, the frequency of CD20 antigen-positive cells (B cells) and CD56 antigen-positive cells (NK cells) averaged 7 and 12%, respectively. After the course of therapy, there was a significant decrease in the frequency of B and NK cells. Immunohistochemical verification of these cell types is not difficult. In connection with the data obtained, the results regarding changes in the expression of toll-like receptors (TLR4 and TLR9) in the epithelial tissues of women are interesting. Before treatment, the expression of both TLR4 and TLR9 was at a relatively low level, which is especially typical for the expression of toll-like receptors type 9. The use of DNA-RNA complexes led to a significant induction of cell expression of these types of receptors (p &lt; 0.5). It has been proven that toll-like receptors (TLRs) are the central link of innate immunity. It has been proven that the expression of certain types of TLRs differs in different tissues. All TLRs are localized differently in cellular compartments. Thus, functionally active TLR4, which recognize pathogen-associated membrane complexes (PAMCs) of bacteria and cellular pathogens, are expressed on the cell surface, and after phagocytosis of the stimulus, they continue to be expressed on endosome membranes, where they receive an additional opportunity to interact with PAMCs after the destruction of the pathogen. In contrast, TLR9 is constitutively expressed in the endocytoplasmic reticulum and appears in endosomes after cell activation. Currently, two fundamentally different signaling pathways are described after the interaction of PAMP with TLRs: activation of the early anti-inflammatory response with the participation of TLR-2, TLR-4, TLR-5 and activation of the antiviral and late anti-inflammatory response with the participation of TLR-3, TLR-4 and TLR -9. It is noteworthy that TLR-4 is a unique receptor that is equally effectively involved in both pathways of cellular activation. Activation of the innate immune system causes the development of a complex of proinflammatory reactions regulated by cytokines, leading to the destruction and elimination of the pathogen. Then the activation of anti-inflammatory signals necessary to complete the inflammation occurs, which is necessary not only to return protective reactions to a normal homeostatic state, but also to prevent the development of hyperreactivity and damage to one’s own tissues. Activation of TLR not only leads to the synthesis of pro-inflammatory cytokines and induction of inflammation, but also causes increased production of anti-inflammatory cytokines IL-4, IL-10, IL-13. The need for adequate induction of anti-inflammatory cytokines and maintaining a balance between secreted pro- and antiproliferative cytokines is today a postulate of the immunology of aging. Studies have also shown that in patients, cells expressing TLR9 were detected at a low frequency. After a course of treatment with DNA-RNA complexes, the proportion of cells positive in the immunocytochemical reaction with monoclonal antibodies to toll-like receptors type 9 increased significantly (on average, more than three times). TLR9 is known to bind to nucleic acids containing CpG islands. Thus, the results obtained indicate that the DNA-RNA complex exhibits immunomodulatory properties in tissues and effectively stimulates the expression of toll-like receptors in cells. Numerous studies have proven that thanks to polynucleotides, the process of breakdown of enzymes contained in the intercellular space slows down, metabolism increases, and the protective functions of the skin in the fight against free radicals are enhanced. In addition, in vitro tests on fibroblasts damaged by UVB radiation and in vivo experiments on healthy volunteers confirmed the protective effect of polynucleotides against sun damage. Prolonged isosmotic hydration and action aimed at combating free radicals contribute to the renewal of the dermal matrix, which, in turn, stimulates the activity and regeneration of fibroblasts. By optimizing vital activity and synthesis, autologous fibroblasts restore the balance of the dermis, such as the amorphous dermis, due to its various elements (such as glycosaminoglycans, glycoproteins, fibronectin) or the fiber matrix (collagen, elastin and reticular fibrils), so the full course of treatment gives a long-lasting biorevitalization effect. PRACTICAL USE In the last few years, fillers have taken a leading position among facial rejuvenation products, but they are not able to help restore skin quality. I actively use these drugs in my practice. In the first clinical case, the patient underwent augmentation in the middle third of the face, with an emphasis on replenishing the volume in the medial fat accumulation. To restore the proportions of the face, the chin was adjusted and lip filling was performed. A drug was also used for bioreparation of the near-orbital area. The second patient underwent chin augmentation and boosterization of the lower third of the face and lips using a cannula, using a fan technique, with an emphasis on the areas of maximum tissue depression. Drugs used in these clinical examples:<ul><li style="text-align: justify;"> Twac eyes – eliminates puffiness and cyanosis in the eye area. Contains 0.2% polynucleotides and does not contain HA;</li><li style="text-align: justify;"> Twac 2.0 is a booster for the restoration of thin, aging, dry, atonic skin, to increase its tone and turgor, to tighten the skin after weight loss, to prevent premature aging, to prevent photoaging of young skin, as well as to induce repair processes after traumatic procedures;</li><li style="text-align: justify;"> Twac 3.0 is a booster used to replenish the deficiency of endogenous hyaluronic acid. The high viscosity of the drug determines its strengthening effect on the dermal matrix, restoration of supporting function and maintenance of tissue resistance to various mechanical damaging factors;</li><li style="text-align: justify;"> PhillexDeepPlus – filler for the correction of medium and deep wrinkles, deep glabellar wrinkles, marionette lines, nasolabial folds, nose correction, lip augmentation;</li><li style="text-align: justify;"> PhillexSub-Q plus - used for the correction of deep wrinkles, nasolabial wrinkles, chin wrinkles, for correction of the nose, cheekbone and cheek area.</li></ul> The correct sequence and combination of procedures are of interest due to their versatile impact on the factors and substrates of aging, achieving synergy with different methods and preventing side effects. Today, every cosmetologist has a sufficient number of professional tools, so the main tasks are professionalism and achieving a natural result. We, as specialists, are able to make subtle adjustments to the appearance, emphasizing individuality with the right choice of technologies used, thereby prolonging the youth of the patients who turn to us.<hr /> First published in <a href="https://afisha.bhub.com.ua/event/magazines/lne/les-nouvelles-esthetiques-2017-4-80grn" target="_blank">Les Nouvelles Esthetiques 2017/№4</a>

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