Skin aging is a part of a natural human “aging mosaic” which becomes evident and follows different trajectories in different organs, tissues and cells with time. While the aging signs of internal organs are masked from the ambient “eyes,” the skin provides first obvious marks of the passing time.
Skin aging is a complex biological process influenced by combination of endogenous or intrinsic (genetics, cellular metabolism, hormone and metabolic processes) and exogenous or extrinsic (chronic light exposure, pollution, ionizing radiation, chemicals, toxins) factors.1 These factors lead together to cumulative structural and physiological alterations and progressive changes in each skin layer as well as changes in skin appearance, especially, on the sun-exposed skin areas.2-12 In contrast to thin and atrophic, finely wrinkled and dry intrinsically aged skin, premature photoaged skin typically shows a thickened epidermis, mottled discoloration, deep wrinkles, laxity, dullness and roughness.13-18 Gradual loss of skin elasticity leads to the phenomenon of sagging.19 Slowing of the epidermal turnover rate and cell cycle lengthening coincides with a slower wound healing and less effective desquamation in older adults. This fact is important when esthetic procedures are scheduled.20 On the other side, many of these features are targets to product application or procedures to accelerate the cell cycle, in the belief that a faster turnover rate will yield improvement in skin appearance and will speed wound healing.21 A marked loss of fibrillin-positive structures22 as well as a reduced content of collagen type VII (Col-7), may contribute to wrinkles by weakening the bond between dermis and epidermis of extrinsically age skin.23 Sun-exposed aged skin is characterized by the solar elastosis. The sparse distribution and decrease in collagen content in photoaged skin can be due to increased collagen degradation by various matrix metalloproteinases, serine, and other proteases irrespective of the same collagen production.24-28 In older skin, collagen looks irregular and disorganized, the ratio of Col-3, to Col-1 has been shown to increase, due, significantly, to a loss of Col-1.29 The overall collagen content per unit area of the skin surface is known to decline approximately 1%/year.30 Glycosaminoglycans (GAGs) are among the primary dermal skin matrix constituents assisting in binding water. In photo-aged skin, GAGs may be associated with abnormal elastotic material and thus be unable to function effectively.31 The total hyaluronic acid (HA) level in the dermis of skin that age intrinsically remains stable; however, epidermal HA diminishes markedly.32
Three primary structural components of the dermis, collagen, elastin and GAGs have been the subjects of the majority of anti-aging research and efforts for aesthetic-anti-aging strategies pertaining to the skin, from ”anti-wrinkle creams” to various filling agents.21
Presentation of aging of the entire face is associated with the gravity impact, muscles action, loss of volume, diminishing and redistribution of superficial and deep fat, loss of bony skeleton support what all together lead to the face sagging, changes in shape and contour. Regardless of the fact that aging is a biological inevitable process and not a pathological condition it is correlated with various skin and body pathologies, including degenerative disorders, benign and malignant neoplasms.
The ‘successful aging’ paradigm, focuses on health and active participation in life, counters traditional conceptualizations of aging as a time of disease and is increasingly equated with minimizing age signs on the skin, face and body.33-35 From this perspective, preventative aesthetic dermatology might supplement the request for healthy aging, treat or prevent certain cutaneous disorders, notably skin cancer, and delay skin aging combining local and systemic methods of therapy, instrumental devices and invasive procedures.36,37The mainspring of any skin anti-aging therapy is to achieve a healthy, smooth, blemish-free, translucent and resilient skin.38 In clinical practice, “to look better” doesn’t mean to “look younger.” That is why it is so important to understand patients’ wishes and to orientate them to the treatment modality that will give the most satisfying results whereas knowing all available treatment techniques.39 The age, previous procedures or surgery, general health status, type of the skin, style of life and many other factors should be taken into consideration before choosing the strategy for the individual case. The desired therapeutic anti-aging effect of the skin is continuous, step-by step process, which combines various methods of the skin bio-revitalization and rejuvenation, augmentation, restoration of each skin layer individually and in the light of many other factors—from a style of the life to the immune, genetic, emotional and health status in general. This review will emphasize the most important topical and systemic therapeutic agents and trends in the use of invasive procedures.
Topical Pharmacological Agents with Anti-Aging Properties
There are two main groups of agents that can be used as anti-aging cream components, the antioxidants and the cell regulators. The antioxidants, such as vitamins, polyphenols and flavonoids, reduce collagen degradation by reducing the concentration of FR in the tissues. The cell regulators, such as retinols, peptides and growth factors (GF), have direct effects on collagen metabolism and influence collagen production.
Vitamins C, B3, and E are the most important antioxidants because of their ability to penetrate the skin through their small molecular weight.52 The water-soluble, heat-labile local L-ascorbic acid (vitamin C) in concentrations between 5 and 15% was proven to have a skin anti-aging effect by inducing the production of Col-1, and Col-3, as well as enzymes important for the production of collagen, and inhibitors of matrixmetalloproteinase (MMP) 1 (collagenase 1).43,53 Clinical studies have proven that the antioxidative protection is higher with the combination of vitamins C and E than with the vitamin C or E alone.54,55Niacinamide (vitamin B3) regulates cell metabolism and regeneration, and it is used in 5% concentration as an anti-aging agent.56 In some studies, improvement of skin elasticity, erythema and pigmentations after 3 mo of topical treatment has been observed.52,54 Vitamin E (α-tocopherol) used as a component of skin products has anti-inflammatory and antiproliferative effects in concentrations between 2 and 20%. It acts by smoothing the skin and increasing the ability of the stratum corneum to maintain its humidity, to accelerate the epithelialization, and contribute to photoprotection of the skin. The effects are not as strong as with vitamins C and B3.57
An in vivo study has proven that the topical application of green tea polyphenols before UV exposure leads to an increase of the minimal erythema dose, decreases the number of Langerhans cells and reduces DNA damage in the skin.58 Other botanicals that act as antioxidants are for example the isoflavones from soya.
Cell regulators, such as vitamin A derivatives, polypetides and botanicals, act directly on the collagen metabolism and stimulate the production of collagen and elastic fibers.
Vitamin A (retinol) and its derivates (retinaldehyde and tretinoin) are also a group of agents with antioxidant effects. They can induce the biosynthesis of collagen and reduce the expression of MMP 1 (collagenase 1). Retinol is, at the moment, the substance that is most often used as an anti-aging compound and, compared with tretinoin, causes less skin irritation.59,60 It has been shown that retinol has positive effects not only on extrinsic but also on intrinsic skin aging and has a strong positive effect on collagen metabolism.60,61Tretinoin, a nonaromatic retinoid of the first generation, is approved for application as an anti-aging treatment in a concentration of 0.05% in the United States. It has been shown to be able to reduce the signs of UV-induced early skin aging, such as wrinkles, loss of skin elasticity and pigmentation.
Polypeptides or oligopeptides are composed of amino acids and can imitate a peptide sequence of molecules such as collagen or elastin. Through topical application, polypeptides have the ability to stimulate collagen synthesis and activate dermal metabolism.62
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