The skin, as the largest organ of the body, protects all other organs from the external environment. The skin is a complex organ with multiple structures and cell types and is divided into three layers: epidermis, dermis and subcutaneous tissue. The epidermis is mainly composed of keratinocytes, pigment-producing melanocytes, and antigen-presenting Langerhans cells. The basement membrane separates the epidermis from the dermis, which predominantly contains extracellular proteins produced by underlying fibroblasts. The vascular supply of the skin is located in the dermis. Subcutaneous tissue consists of fat cells that underlie a network of connective tissue. Type I collagen is the most abundant protein in the connective tissue of the skin. Other proteins of the extracellular matrix, which are part of the connective tissue of the skin, are collagens (3, 5 and 7), elastin, proteoglycans, fibronectin, etc. Newly synthesized type I procollagen is secreted into the dermal extracellular space where it undergoes enzymatic processing to arrange it into a triple helix configuration. In addition to protecting the environment from radiation, skin functions include heat regulation, immune response, biochemical synthesis, sensory detection, regulation of water and electrolyte absorption/loss. The main role is played by the stratum corneum formed by non-viable keratinocytes. Keratin is aligned in cross-linked disulfide macrofibers together with filaggrin, the major protein component of the keratolytic granule. The cells develop a horny coat that is the result of the crosstalk between involucrin and keratohyalin. Lamellar lipids accumulate in the intercellular spaces and are strongly hydrophobic. The combination of cornified hydrophilic cells with hydrophobic intercellular material forms a barrier for external hydrophilic and hydrophobic substances. With age, the natural process of skin rejuvenation slows down drastically and the skin becomes thinner, drier and less elastic.
What are the underlying processes of aging?
There are two main processes of skin aging, intrinsic and extrinsic. Intrinsic aging, known as intrinsic aging, is governed by genetic background and is considered inevitable as time passes. This means that this type of aging is not subject to manipulation by changes in our behavior.
On the other hand, extrinsic aging is the result of factors originating from the outside and introduced into the body, such as smoking, excessive alcohol consumption, improper diet and chronic exposure. These factors, which are often voluntary, can cause premature aging of the skin. Chronic sun exposure, for example, is considered one of the biggest sources of skin damage, with 80% of skin aging believed to be from this source.
This means that, as intrinsic aging is not under control, external factors that accelerate aging that we can partially control by changing our lifestyle and habits.
What is the role of topical treatments in combating aging?
Under ideal conditions, the skin has a series of enzymatic and non-enzymatic oxidants that are used to protect against damage caused by free radicals. Enzymatic antioxidants include glutathione peroxidase, superoxide dismutase, glucose-6-phosphate dehydrogenase, and catalase; non-enzymatic antioxidants include vitamin C, glutathione, vitamin E, coenzyme K10 (ubiquinone-10), and alpha lipoic acid. Exposure to UV light has been shown to naturally deplete antioxidants that occur as well as chronological aging. Without adequate antioxidant protection, free radicals generated go unchecked, resulting in skin aging.
Application of topical antioxidants has been shown to provide additional protection against sun damage, preventing skin aging and ultimately improving the appearance of the skin. However, cosmetic chemists have long faced challenges in formulating topical antioxidants. The biggest problem is the instability of antioxidants, which makes them difficult to incorporate into stable formulations. Also, it is difficult to achieve that the active component penetrates the epidermis and lasts in the skin long enough to achieve the desired effect. Only when these challenges are successfully overcome, local antioxidants can be effective in their function.
How do antioxidants help in anti-aging skincare?
Topical antioxidants have been used to treat photoaged and chronologically aged skin. Currently available cosmetic formulas include vitamin, enzyme and botanical antioxidants. The reason for their use stems from the increased production of free radicals that occurs when the skin is exposed to ultraviolet (UV) light and as part of the natural aging process. Free radicals are known to promote the oxidation of nucleic acids, proteins and lipids, and can damage intracellular structures including DNA. Free radicals also regulate transcription factors such as activator protein 1 (AP-1) and nuclear transcription factor-kappa B (NF-κB). AP-1 is responsible for the production of metalloproteinases that break down existing collagen, contributing to skin wrinkling. NF-κB regulates the transcription of proinflammatory mediators such as interleukin-1 (IL-1), IL-6, IL-8, and tumor necrosis factor-α. Acting through receptors on the cell surface, these pro-inflammatory mediators are further activated by AP-1 and NF-κB, leading to more damage. It is a collection of these events that are responsible for skin aging.
What are the importance of retinoids in skincare?
The importance of retinol (vitamin A) was discovered during the First World War, and later research showed that its deficiency leads to xerosis and follicular hyperkeratosis. The Retinoid Drug Project was initiated in 1968 to synthesize compounds similar to vitamin A by chemically manipulating its molecule to improve clinical efficacy and safety. The use of these substances in therapy dates back about 3000 years in ancient Egypt, where the liver was used to treat endemic night blindness. The modern history of retinoids, however, began in 1909 when an essential factor in embryonic viability was discovered in a fatty extract of the yolk, called vitamin A. Retinoids were finally introduced to the treatment of dermatological diseases, including photoaging, more than two decades ago.
How does the suppression of harmful effects contribute to the skin?
To avoid the side effects of retinoids, it is recommended to reduce the frequency of their application or switch to less irritating retinoid formulations. Addition of 3% indomethacin or 1% hydrocortisone to the retinoid formulation or contemporary treatment with low- to moderate-potency topical corticosteroids is also suggested to relieve symptoms of retinoid reactions.
In the event that patients cannot tolerate even the smallest concentration of retinoids, then it is advised to discontinue their use. Some studies show that the modern use of natural agents or extracts, such as β-sitosterol, Magnoliae flos, β-glycyrrhetinic acid, scleroglucan, ginkgo extract, raspberry extract, schizandra extract, cola extract, Enna complex or red wine oil extract. can help counteract the irritating effects of retinoids.
Other approaches include the use of new synthetic retinoids that show good efficacy in managing aging skin without causing irritation. System modulation for retinoid delivery may be one way to counteract side effects, which should be an area of interest for further research in optimizing topical retinoid therapy.
What is the conclusion regarding topical approaches for aging skin?
Skin aging is considered a dynamic and multifactorial process, best understood in two basic types: intrinsic or natural aging and extrinsic aging. Intrinsic aging is mainly defined by genetic factors and its effects are inevitable, being a function of heredity and the result of the passage of time. In contrast, extrinsic aging results from external factors, such as sun exposure, and can be avoided.
Sun exposure, which is the primary source of extrinsic aging, is often associated with photoaging. This term is used to describe skin aging that is caused by the sun and is one of the basic parts of extrinsic aging. Because wrinkles and pigmentation in the shoulder are associated with photo-aging, many doctors use these symptoms as a way to encourage an individual’s greater concern about the appearance of the skin. In addition, the clinical appearance of photoaging includes rough, dry skin, spots and wrinkles that can be indicators not only of aging, but also of possible skin problems such as skin cancer.
Physicians play an important role in educating patients about the importance of sun protection and the use of antioxidants and retinoids to reduce skin damage and promote a healthier appearance. Using sun creams, regular application of antioxidants and retinoids, as well as general concern for protecting the skin from the negative effects of the sun, can be an effective way to fight photo-aging and protect the skin from aging and other damage.
