AUTHOR: Maja Vugrinec, M.pharm., univ. mag. dermatopharmacy and cosmetology

Causes of skin aging

The skin is subject to two types of aging:

1. intrinsic aging is chronological aging caused by genetic inheritance and depends on the passage of time. It is characterized by skin atrophy, loss of elasticity and slowing down of metabolic activities. Signs of chronological aging are fine wrinkles, thin and transparent skin, loss of underlying fatty tissue and bone structure of the face, dryness of the skin, the inability of the sweat glands to sufficiently cool the skin, hair loss and the appearance of unwanted hair. Cell activity decreases, the skin becomes thinner. Subtle but constant skin changes result in progressive loss of its function. The main cause of aging is still considered to be the accumulation of damage. It has been proven that the speed of aging is genetically controlled, and by certain evolutionarily conserved biochemical processes.

2. extrinsic aging is caused by the influence of external factors. Among the numerous harmful environmental influences involved in this, the most significant is long-term and repeated exposure to UV rays, which causes photoaging. It is a cumulative process that primarily depends on the degree of exposure to sunlight and skin pigment. UV radiation causes complex processes on specific molecules, the response of which causes damage to the connective tissue of the skin. UV radiation accelerates and intensifies the changes caused by intrinsic aging. Photo­aging is manifested by the appearance of wrinkles, redness of the skin, dryness, loss of elasticity, appearance of telangiectasia, and pigmentary changes. Exposure to UV radiation increases the appearance of benign and malignant skin neoplasms on photo­exposed parts.

Oxidative stress is a biological phenomenon that creates free radicals which damage cell structures such as membranes and proteins in DNA. The body naturally produces free radicals, and cells naturally have a defense mechanism. However, with age, the imbalance between external stressors (oxidation) and the body's defense capabilities (antioxidants) grows. The number of potential causes of stress increases with age and life experiences (UV radiation, pollution, smoking, etc.), the body's defense mechanisms are overcome, and aging accelerates. That's why antioxidants play a key role in the fight against aging. They suppress free radicals or stop them (vitamins C and E), or strengthen the systems against free radicals in the skin (selenium, zinc, coenzyme Q10, and superoxide dismutase). They limit the harmful effect of oxidative stress on skin cells, which is responsible for skin aging. Other external factors that have a harmful effect on the skin are smoking, alcohol, improper diet, and lack of sleep.

Dermocosmetic products

Dermocosmetic products are complex formulations in which active substances with different mechanisms of action are incorporated into the appropriate base. Auxiliary substances that facilitate the permeation of active substances to the site of effect, ensure appropriate rheological and aesthetic properties and product stability. Anti­aging ingredients in dermocosmetic products should strengthen the barrier function of the skin, increase skin hydration, and reduce transepidermal water loss in the epidermis; enable antioxidant action to remove free radicals responsible for the loss of skin elasticity and firmness as well as the formation of wrinkles; stimulate the renewal of cells of the epidermal (surface) layer of the skin; stimulate the production of connective tissue in deeper layers to prevent the loss of elasticity and firmness of the skin and the formation of wrinkles. Their regular use should alleviate dryness and the feeling of tightness, and maintain the elasticity, shine, and tone of the skin. Active substances that have proven to be effective for this purpose are certainly collagen, elastin, coenzyme Q10, peptides, vitamin C, vitamin E, retinoids, bakuchiol, and resveratrol.

Humectants (substances that bind water) and moisturizers (substances that supply the skin with moisture) in preparations for local application increase the water content in the SC, by attracting and binding it, so such products are often more effective in suppressing dry skin than those without a humidifier. Water is important for maintaining skin elasticity. Therefore, natural moisturizing factors (NMFs) such as urea and hyaluronic acid are important for SC function, as they ensure moisture retention, maintain acidic pH and buffer SC capacity, ensure appropriate epidermal maturation and removal of redness, and reduce pathogenic bacterial colonization. When their concentration in the SC decreases, the water in the products alone cannot restore elasticity.

Numerous studies show that the local application of physiological lipids containing cholesterol, ceramides and fatty acids can improve the reduced epidermal protective barrier of the skin and the homeostasis of its permeability.

Anti-aging ingredients in dermocosmetic products

Ceramides are a specific group of lipids in the stratum corneum of the skin. They are the most important structural element of the natural protective barrier of the epidermis. Numerous studies show that their local application (phospholipids and sphingolipids, obtained from vegetable oils) in a very short time restores the damaged hydrolipidic barrier of the stratum corneum of the epidermis, thereby reducing the possibility of large transepidermal water loss. Ceramides used in cosmetic preparations are produced by a patented fermentation process and have the same structure as ceramides that are naturally present in the skin.

Collagen is a type of protein contained in the natural composition of the skin, i.e. in the dermis. Its role is to connect the skin with the structures beneath it. It gives the skin firmness, elasticity, and tone. The human body has the ability to constantly synthesize collagen, which is necessary for the growth and replacement of worn­out tissues and for the healing and restoration of injured tissues. When the amount of collagen is sufficient, the skin is more resistant to the effects of external factors. However, due to the aging process, its renewal capacity gradually decreases over time. In youth, the loss of collagen is quickly replaced, but with age it becomes more pronounced. It negatively affects the appearance and function of the entire body, and leads to various degenerative changes, the formation of wrinkles, and fine lines. In order for it to penetrate the skin locally, the molecule must be extremely small, which is very difficult to achieve in preparations that are applied locally. However, the popularity of these products lies in the fact that collagen leaves a film on the skin that fills in irregularities on the surface. When the product dries, the protein film tightens, causing a subtle tightening of skin wrinkles.

Elastin enables the formation of elastic connective tissue, which allows the skin to stretch and return to its original state. Along with collagen, it gives the skin firmness and elasticity that is lost with aging.

Peptides are short chains of amino acids that act as cellular messengers. There are three categories present in antiaging cosmetic products: carrier peptides (eg pal­KTTKS or matrixyl), neurotransmitters (eg AcEEMQRR or argyrelin), and enzyme modulators (eg soy and rice proteins). Matrixyl is very potent because it provides positive effects even in the lowest doses. In a double­blind, placebo­controlled study, it caused an improvement in the appearance of wrinkled skin. Peptides strengthen collagen and elastin, stimulate their further formation in the skin and stabilize the connection between the dermis and the epidermis so that the skin remains firmer.

Coenzyme Q10 is a liposoluble antioxidant naturally present in the body. Neutralizes free radicals that damage the cellular structure and protective function of the skin. There is in vitro evidence that it can suppress fibroblast-induced production of UVA-induced collagenases, thereby reducing collagen breakdown. It has also been shown to be effective against UVA damage caused by oxidative stress in human keratinocytes.

Vitamin C (ascorbic acid) participates in the synthesis of collagen and elastin, and in the binding of keratin fibers. As an antioxidant, it reduces skin damage from pollution, the sun, and other free radicals. It inhibits the enzyme tyrosinase, thereby reducing hyperpigmentation. In order to optimize percutaneous absorption and achieve vitamin C activity, it is very important to produce an adequate formulation for its effective topical delivery. Namely, it is a very unstable molecule that loses its antioxidant capacity under the action of UV rays or in the air and becomes inactive. Some studies have shown that the esterification of the hydroxyl group solves the problem of instability within the formulation. New formulations for stabilizing vitamin C, such as microcapsules, liposomes and microemulsions, are being intensively researched, although many of them are already on the market.

Vitamin E (tocopherol) is an antioxidant and moisturizer, soluble in lipids. It prevents the oxidation of unsaturated fatty acids (membrane lipids) and neutralizes free radicals that accelerate the aging process. In addition to being used in dermocosmetic products for skin care and regeneration, it often has a role as an antioxidant and preservative. When applied topically, numerous studies have recorded its effect in protection against UVB radiation, and acute reduction of erythema in sunburns, tanning and photoaging has also been recognized. Out of a total of 32 vitamin E isomers, only d­α-tocopherol is topically effective.

Retinoids are derivatives of vitamin A and the socalled gold standard among dermocosmetic products against skin aging. Their positive effects are visible in the area of the epidermis where they normalize the keratinocyte cell cycle, reduce keratinocyte atypia and normalize the distribution of melanosomes. They are also visible in the layers of collagen and elastic dermis, where they lead to an increase in collagen biosynthesis and an increase in the amount of elastin. It was recently discovered that they can also induce the deposition of fibrillin-rich microfibrils near the epidermal junction, which would re­establish the lost physical connection between the superficial layers of the skin and the mature elastic fibers in the deeper dermis. Most of the retinoids listed below, including vitamin A, have an antioxidant effect, the ability to whiten dark spots, and reduce the appearance of wrinkles on the face. However, retinoids can also be strong irritants, extremely unstable in the presence of oxygen and light, and their use as antioxidants in sun protection preparations is controversial because they do not provide any UV protection. Oral retinoids have been proven to be teratogenic, so they are not recommended for pregnant women and women planning to become pregnant, even as topical ones.

Retinoic acid or tretinoin, a non-aromatic firstgeneration retinoid, is considered one of the most powerful components for removing signs of skin aging such as wrinkles and age spots. However, due to a number of unwanted effects such as irritation and burning of the skin, it must be used with caution, and newer systems for the delivery of the active substance should reduce side effects.

Retinol or vitamin A is the biologically active form of that vitamin, which in vivo studies have shown to have only moderate biological activity when applied topically compared to topical retinaldehyde and retinoic acid. On the other hand, two randomized controlled studies reported a significant improvement in fine lines during 12 and 24 weeks of application. Currently, retinol is the most commonly used component in antiaging cosmetic products and is better tolerated by the skin than trans­retinoic acid.

Retinaldehyde, an intermediate form during the conversion of retinol to retinoic acid, also works against signs of aging. Studies have shown that it causes significant correction of softer and deeper wrinkles.

Retinol esters, such as retinol propionate, retinyl propionate, and retinyl palmitate, are less commonly used retinoids, but there is evidence of their effectiveness. In double­blind, placebo­controlled facial testing, retinol and retinyl propionate were highly effective in reducing wrinkles and hyperpigmentation. Retinyl palmitate has also been clinically tested, which, although it has a lower potential for causing irritation, has a lower effectiveness even in very high concentrations of 2%. However, in almost all studies, retinol esters have been shown to be more tolerable than retinol.

Bakuchiol is a natural antioxidant found in the seeds and leaves of the plant Psoralea corylifolia , commonly known as babchi, which grows in India, China and parts of Africa. It is a natural alternative to retinol, without any negative effects. It has been clinically shown to reduce hyperpigmentation and wrinkles as effectively as retinol, with better tolerance. It works directly in the skin cells, where it affects the production of several types of collagen useful for health, but also the youthful appearance of the skin, while not affecting the glands, which means that it does not lead to irritation or dryness. One of the most important advantages over retinol is that it does not make the skin more sensitive to UV rays.

Resveratrol is a natural polyphenol and a strong antioxidant. It is found in many foods, among which the most famous are black grapes, blueberries, cranberries, wine, cocoa, and dark chocolate. Plants produce it in response to injury, ozone exposure, UV radiation, and fungal or bacterial infections. It serves them for faster healing of damaged parts, cuts, and cracks. The vine produces resveratrol to protect itself from mold and regenerate itself; enabling it to live up to 100 years. Clinical studies have confirmed that it can also protect human skin from UV radiation. It also stimulates the production of collagen and elastin, and stops glycation, which is responsible for deep wrinkles.

Hyaluronic acid (HA) is a glycosaminoglycan, an integral part of the connective tissue of the dermis. It fills the space between collagen and elastic fibers, it is broken down and rebuilt during life. Its role is multiple ­ it participates in the transport of nutrients, and hydration of the skin, but also as a defense against mechanical and chemical damage. A high concentration of HA is found in soft connective tissues, in the fluid surrounding the eyes, and in some cartilages, it is present in all living organisms. Even more than 50% of the total HA in the body is present in the skin.

It has been shown to be very effective in re-epithelialization processes and in controlling the proliferation and migration of keratinocytes from the epidermal basal layer. It is a strong humectant. In young skin, collagen fibers bind to glycosaminoglycans, forming proteoglycans that form a gelatinous mass, and like a sponge, it can bind large amounts of water and release it in the same way. Thanks to this ability, young skin is taut and shiny, without wrinkles. However, with age, collagen fibers ripple, and the ability to bind water decreases more and more, the skin dries out, loses volume and wrinkles appear. Therefore, HA is one of the most common components of dermal fillers. In dermocosmetic products, molecules are found in different sizes, which is important to know, because the skin will absorb them differently. High-molecular (long­chain) HA consists of a long chain of molecules and therefore has a large molecular weight. It does not penetrate the skin, it creates a protective film on the surface of the epidermis where it improves hydration. Medium­molecular (medium­chain) HA works in a similar way to high­molecular­weight HA. Low­molecular (short­chain) HA consists of a short chain of molecules and therefore has a low molecular weight. It penetrates deep into the skin and helps to store moisture in the connective tissue of the skin, and stimulates its own production of hyaluronic acid. This makes the skin more supple and firmer, but also visibly reduces wrinkles.

Urea is a humectant and moisturizer. It maintains the desired level of moisture in the skin, softens it, and improves its elasticity. In this way, it prevents premature aging and the appearance of wrinkles, because they occur on dry skin with insufficient care. It is a common ingredient in creams for skin hydration, not only for cosmetic use but also for the treatment of dermatoses in which extremely dry, flaky skin occurs. In particular, its deficiency in the stratum corneum is associated with atopy, psoriasis, and xerosis in older people. It has a beneficial effect on the healing of wounds and skin damage. Concentrations of up to 2­5% are used in preparations for regular care and a mild keratolytic effect, and 5-15% for a more intense keratolytic effect. One placebo-controlled study showed that preparation with 5% urea was responsible for improving the barrier function of the skin. After repeated applications of this preparation, the transepidermal water loss in the SC decreased and the skin irritation induced by sodium lauryl sulfate (SLS) decreased.

Omega fatty acids are part of the hydrolipidic film and epidermis. Essential omega-3 and omega-6 fatty acids play an important role in the formation of lipids in the skin and have a positive effect on the prevention of aging, regeneration, and hydration of the skin. Their deficiency can lead to dry and irritated skin and various unwanted dermatological conditions. There is scientific evidence that shows that topical application of a combination of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid (e.g. from fish oil) and gamma-linolenic acid (GLA) (which is abundant in evening primrose oil, for example) can improve skin elasticity. Thanks to their anti-inflammatory effect, they can be of great benefit in inflammatory skin conditions such as psoriasis, acne, and atopic dermatitis. Their beneficial effects have also been proven in the reduction of signs of photoaging cau­ sed by excessive exposure to UV radiation, and will also alleviate various hyperpigmentation and dark spots on the skin.

Panthenol is an alcohol analog of pantothenic acid (vitamin B5) and as such a provitamin of vitamin B5. In the body, it is quickly oxidized into pantothenate (pantothenic acid). Panthenol occurs in the form of two enantiomers, D and L. Only D­panthenol (dexpanthenol) is biologically active, but both forms have hydrating properties. For dermocosmetic use, panthenol comes either in the D form or as a racemate (DL­panthenol). Dexpanthenol is a very viscous transparent liquid. It has emollient and humectant properties. It has an anti-inflammatory effect, removes itching and promotes epithelization of the skin. Glycerol is the simplest alcohol with three hydroxyl groups. It is easily absorbed into the skin and due to its ability to bind water, it maintains the hydration of the skin.

The pH5 citrate buffer restores the skin's natural pH level, so the skin's enzyme activities can return to normal, which enables hydration and strengthening resistance to irritants.

Natural vegetable oils

In modern times, more and more dermocosmetic products contain natural plant oils in their composition and less and less vaseline, paraffin and mineral oils. Paraffin and petrolatum are petroleum derivatives, and synthetic hydrocarbons are not related to skin lipids. In addition, their molecules are too large to penetrate the skin, so such products are not absorbed, but remain on the surface and interfere with the skin's natural functions such as absorption and elimination. Skincare with vegetable oils is a far more natural way to maintain youthful, hydrated, clean, and healthy skin because they are rich in essential fatty acids, vitamins, and minerals. When we talk about vegetable oils in cosmetics, the best quality oils are those obtained by cold pressing, because they contain all the naturally present ingredients. They are often similar to the composition of the skin, and as such are best preserved. Therefore, the skin recognizes and incorporates them into its cells, which is not the case with synthetic ingredients.

Dermocosmetic products contain different preservatives such as parabens. Nowadays, there are effective and at the same time harmless preservatives of natural origin, as well as eco­preservatives accepted by Ecocert, allowed for use in ecologically and organically certified cosmetics. There are two types of preservatives: anti­oxidants that prevent the oxidation of unsaturated fatty acids in vegetable oils (vitamin E, rosemary leaf extract...) and at the same time care for the skin, and microbiological preservatives that prevent the development of bacteria and mold (e.g. dehydroacetic acid and benzyl alcohol).

The most commonly used vegetable oils in anti-aging dermocosmetic products

Wild rose fruit oil is golden­red to red in color due to the presence of carotenoids from the fruit. It contains essential fatty acids, vitamins and minerals, and smaller amounts of vitamin A acid derivatives, which are excellent for skin regeneration. It is extremely valuable in regenerative skincare and is very effective

in the treatment of burns, wrinkles, scars, eczema, hyperpigmented, and prematurely aged skin. It has natural antioxidant properties and a mild astringent effect. It is an ideal choice for formulations intended for mature and photodamaged skin, when it is necessary to restore and even out pigmentation. It has proven to be very effective in inflammatory skin diseases (psoriasis, seborrheic and atopic dermatitis).

Argan oil is rich in oleic and linoleic acid, carotenoids, and vitamin E. It is suitable for treating dry, mature, and wrinkle­prone skin. Argan oil soothes and regenerates.

Wheat germ oil is rich in vitamins A, E, D and essential fatty acids. Due to the high content of vitamin E, it has a strong antioxidant effect, promotes the regeneration of skin cells, and at the same time promotes the maintenance of an optimal hydrolipidic barrier, thus preventing drying of the skin. It stimulates circulation while simultaneously softening the skin. It is excellent for the care of dry and damaged skin. Apricot seed oil is rich in vitamins and minerals. It is good for the care of dry, sensitive, and prematurely aged skin and for inflammatory skin processes. It softens, nourishes, and regenerates the skin. It is a very light oil, but at the same time extremely emollient, with a high content of oleic and linoleic acids.

Almond oil is rich in essential fatty acids and vitamins A, B1, B2, B6, and E, and is used as an emollient to soften sensitive skin and scalp. It is also suitable for children and pregnant women. It is traditionally used for various types of eczema, psoriasis, and dry and inflamed, itchy elephant skin, and it has been used for years in the prevention and treatment of stretch marks. It has a light texture that is easily absorbed by the skin.

Shea butter is a vegetable fat rich in stearic, oleic and linoleic acids. It contains a high proportion of unsaponifiable residue (up to 8%) and is made up of provitamin A, vitamin E, sterols, triterpene alcohols, and cinnamic acid esters (provide UVB protection). It protects the skin from external influences and drying, restores moisture and softness. It is suitable for the care of all skin types, especially dry and mature skin. It is used to treat sunburns, diaper rash, dermatitis, seborrhea, scars, wrinkles, and stretch marks. It is perfect for atopic skin care (neurodermatitis), especially in small children.

Coconut oil stands out for its high content of saturated fatty acids, and it also contains phytosterols, which are responsible for its anti-inflammatory and regenerative effects. It perfectly moisturizes and softens the skin. It is ideal for dry and sensitive skin.

Food supplements in the form of liquids or tablets also contain anti­aging ingredients such as collagen, elastin, ceramide, hyaluronic acid, coenzyme Q10, and vitamins and minerals. They act on the skin in a similar way but from the inside.

Conclusion

Visible changes on the skin are the result of the aging of all parts of the skin. In the epidermis, there is a reduced synthesis of lipids, which breaks the skin barrier. This leads to transepidermal water loss (TEWL) resulting in dehydration and dry skin. This phenomenon can be even more pronounced on the skin of the face. Namely, in addition to the fact that the skin of the face is the most exposed to factors such as UV rays, pollutants, and chemicals, the epidermis can also be very thin, only 0.02 mm (compared to the average thickness of 0.1 mm in other areas). Most dermocosmetic products intended for the care of aging skin try to improve the epidermal protective barrier by replenishing lipids, especially ceramides. Aging also leads to a reduced value of NMF concentration in the SC. Therefore, humectants and humectants in topical preparations may also improve epidermal barrier function. In the dermis, aging leads to the fragmentation of collagen and elastin fibers, while in the hypodermis, the deterioration of fat cells occurs.

Aging cannot be stopped, but with the regular use of dermatocosmetic preparations containing antiaging ingredients, aging processes in the skin can be delayed and alleviated. Protection from the sun and other damages, a healthy diet, and regular exercise can also contribute to this. When choosing dermocosmetic preparations, attention should be paid to the fact that they contain ingredients of natural origin and active substances that have clinically proven effects in slowing down aging.

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