Antiaging Action of Retinol: From Molecular to Clinical (original) (raw)
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Proposed mechanisms of action for retinoid derivatives in the treatment of skin aging
Journal of Cosmetic Dermatology, 2005
Skin aging (intrinsic aging) and photoaging (extrinsic aging) involve a similar process that leads to the typical creased appearance of the skin, with the progressive loss of its physical and biologic properties. Photoaging is a premature skin aging caused by longterm exposure to the ultraviolet B radiations of the sun, and is more frequently associated to skin cancer than intrinsic aging. Retinoids are natural and synthetic vitamin A derivatives. They are lipophilic molecules and penetrate the epidermis easily. Their biologically active forms can modulate gene expression by binding to nuclear receptors and then to specific DNA sequences. Because of their ability to modulate genes involved in cellular differentiation and proliferation, they appear as good candidates to treat and prevent photoaging. Hyaluronate and collagen, two major constituents of the dermis, are progressively decreased and altered during aging. Various retinoids were shown to increase their synthesis and concentration in the skin and reduce their rate of degradation. Furthermore, retinoids share a common chemical structure containing several conjugated double bonds that enable them to trap free radicals and absorb UV radiations from the sun, thereby protecting cellular targets such as DNA, lipid membranes, or proteins by preventing direct photochemical damage or UV-induced oxidative stress. Therefore, retinoids may be beneficial in treating skin aging and photoaging because of their biologic, chemical, and physical properties, which act at several levels.
Journal of Investigative Dermatology, 1995
We investigated the clinical, histologic, and molecular responses of normal human skin to all-tl'atlsretinol (ROL) application, compared to those induced by topical all-traus-retinoic acid (RA), and measured ROL-derived metabolites. Up to 1.6% , ROL, 0.025% RA in vehicle (70% ethanol/30% propylene glycol), or vehicle alone were applied in a double-blind fashion to normal buttock skin and occluded for 4 d. ROL produced from none to only / trace erythema, which was clinically and statistically insignificant, whereas RA induced a significant 3. 7fold increase in erythema score compared to vehicle (n = 10, p < 0.01). However, ROL induced significant epidermal thickening (1.5-fold at 1.6°/.• ROL, p < 0.01), similar to RA (1.6-fold at 0.025% RA, p < 0.01), relative to the vehicle. ROL, co1npared with vehicle, also increased mRNA levels of cellular retinoic acid binding protein (CRABP-11) and cellular retinol binding protein (CRBP) genes as determined by Northern analysis (5-6-fold and 6-7-fold, respectively) and riboprobe in situ hybridization. CRABP-11 and CRBP protein levels were also higher following ROL than vehicle treatment, as measured by ligand binding A ll-lmlls-retlllo! _(ROL), b_ette~ ~mown as vitamin A:•• assumes a cntJCal ro le m VISIOn, spermatogenesis, and cellular growth and differe ntiation [1]. As the predominant retinoid in circulation, ROL is deEv-) ered to cells bound to re tinol binding protein. Within cells, it is converted to many different retinoids d e p endin g upon cell need and type. In human skin, besides ROL, retinyl esters
Applied Sciences
Physiological ageing due to the passing of time and prolonged exposure to harmful sun rays generate wrinkles and reduce skin elasticity. These visible and clinical signs can be prevented or reversed by known strategies, such as the daily use of cosmetic products with antioxidant combinations or retinoids. A new dermocosmetic formulation enriched with a complex of retinoids, called RETINOIDS SERUM, was investigated through in vitro assays using human skin cells. The experiments were carried out to assess the anti-ageing activity in normal human dermal fibroblasts (NHDF) and epidermal keratinocytes (HaCaT). After the preliminary MTT assay, the proliferation together with the synthesis of collagen and elastin fibers was performed on NHDF cells after 24 h treatment with the two non-cytotoxic concentrations. Using UVB-irradiated HaCaT cells, the measurement of matrix metalloproteinase-1 (MMP-1) levels was also investigated. In vitro studies show that the dermocosmetic product improves co...
Cellular retinoic acid binding protein-II expression and its potential role in skin aging
Aging, 2019
Skin aging is an intricate biological process consisting of intrinsic and extrinsic alterations of epidermal and dermal structures. Retinoids play an important role in epidermal cell growth and differentiation and are beneficial to counteract skin aging. Cellular retinoic acid binding protein-II (CRABP-II) selectively binds all transretinoic acid, the most active retinoid metabolite, contributing to regulate intracytoplasmic retinoid trafficking and keratinocyte differentiation. Immunohistochemistry revealed a reduced epidermal and dermal CRABP-II expression in aged human and mouse skin. To better clarify the role of CRABP-II, we investigated age-related skin changes in CRABP-II knockout mice. We documented an early reduction of keratinocyte layers, proliferation and differentiation rate, dermal and hypodermal thickness, pilosebaceous units and dermal vascularity in CRABP-II knockout compared with wild-type mice. Ultrastructural investigation documented reduced number and secretion of epidermal lamellar bodies in CRABP-II knockout compared with wild-type mice. Cultured CRABP-II knockout derived dermal fibroblasts proliferated less and showed reduced levels of TGF-β signal-related genes, Col1A1, Col1A2, and increased MMP2 transcripts compared with those from wildtype. Our data strongly support the hypothesis that a reduction of CRABP-II expression accelerates and promotes skin aging, and suggest CRABP-II as a novel target to improve the efficacy of retinoid-mediated antiaging therapies.
Advances in Dermatology and Allergology, 2019
Vitamin A is the first vitamin approved by the Food and Drug Administration as an anti-wrinkle agent that changes appearance of the skin surface and has anti-aging effects. Vitamin A is in a group of fat-soluble substances and belongs to the category of retinoids. Apart from retinol, that group includes structurally related substances with the biological properties of retinol. Since the biological activity of the substances differs, for the purpose of standardization, it is given in retinol equivalents. Vitamin A and its derivatives are among the most effective substances slowing the aging process. Retinoids regulate the cell apoptosis, differentiation and proliferation. Anti-wrinkle properties of retinoids promote keratinocytes proliferation, strengthen the protective function of the epidermis, restrain transepidermal water loss, protect collagen against degradation and inhibit metalloproteinases activity. Retinoid activity is related to high affinity for nuclear receptors: RAR-retinoid acid receptors and RXR-retinoid X receptors.
2015
Skin aging is a slow multifactorial process influenced by both internal as well as external factors. Ultra-violet radiations (UV), diet, smoking and personal habits are the most common environmental factors that affect skin aging. Fat contents and fibrous proteins as collagen and elastin are core internal structural components. The direct influence of UV on elastin integrity and health is central on aging of skin especially by time. The deposition of abnormal elastic material is a major marker in a photo-aged skin. Searching for compounds that may protect against cutaneous photodamage is exceedingly valued. Retinoids and alpha hydroxy acids have been endorsed by some researchers as possible candidates for protecting and or repairing the effect of UV damaged skin. For consolidating a better system of antiand protective effects of such anti-aging agents, we evaluated the combinatory effects of various dosages of lactic acid and retinol on the dermal fibroblast’s elastin levels exposed...
Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety
Clinical Interventions in Aging, 2006
Aging of skin is an intricate biological process consisting of two types. While intrinsic or chronological aging is an inevitable process, photoaging involves the premature aging of skin occurring due to cumulative exposure to ultraviolet radiation. Chronological and photoaging both have clinically differentiable manifestations. Various natural and synthetic retinoids have been explored for the treatment of aging and many of them have shown histological and clinical improvement, but most of the studies have been carried out in patients presenting with photoaged skin. Amongst the retinoids, tretinoin possibly is the most potent and certainly the most widely investigated retinoid for photoaging therapy. Although retinoids show promise in the treatment of skin aging, irritant reactions such as burning, scaling or dermatitis associated with retinoid therapy limit their acceptance by patients. This problem is more prominent with tretinoin and tazarotene whereas other retinoids mainly represented by retinaldehyde and retinol are considerably less irritating. In order to minimize these side effects, various novel drug delivery systems have been developed. In particular, nanoparticles have shown a good potential in improving the stability, tolerability and effi cacy of retinoids like tretinoin and retinol. However, more elaborate clinical studies are required to confi rm their advantage in the delivery of topical retinoids.
Influence of retinoids on skin fibroblasts metabolism in vitro
Acta poloniae pharmaceutica
The most dangerous environmental factor for our skin condition is ultraviolet light radiation. Chronic exposition to ultraviolet light can induce epidermal atrophy, keratosis, depigmentation and dysplasia. In the dermis, UV light causes dramatic up-regulation of extracellular matrix-degrading enzymes. Matrix metalloproteinases (MMPs) are engaged in collagen, elastin and other extracellular matrix components degradation. In addition, to increase level of destructive enzymes, UV light has been shown to decrease collagen production. As a consequence of UV impact on skin, it shows signs of aging including loss of tone and elasticity, increased skin fragility, blood vessels weakness and wrinkles. The most dangerous effect of UV on skin is an increased risk of melanoma and other skin cancers. Retinoids are well known antiaging agents. For many years this vitamin has been used for the prevention and treatment of photoaging. Retinoids abolish cellular atypia, increase compacting of the stra...
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2020
Topical retinol application effectively reduces the effects of photoaging and improves skin condition, e.g. influences the process of keratinization of the epidermis, which improves stratum corneum structure and reduces transepidermal water loss. However, cosmetics use lower concentrations of retinol, which has been associated with emerging hypersensitivity reactions as well as redness and irritation of the skin. The question arises whether the vehicle used in the cosmetic may be important in stimulating the inflammatory reaction in the skin and if the concentration of retinol used could significantly affects the growth of epidermal cells. The aim of this study was to evaluate the effects of different concentrations of liquid crystal retinol (0.15%, 0.3% and 0.5%) on the clinical and histological characteristics of a reconstructed epidermis skin model. It also compares the effectiveness of 0.3% retinol formula in liquid crystal to that in lipid. The study used reconstructed human ep...
British Journal of Dermatology, 2010
Skin, being exposed directly to the environment, represents a unique model for demonstrating the synergistic effects of intrinsic and extrinsic factors on the ageing process. Ultraviolet radiation (UVR) is the major factor among exogenous stressors responsible for premature skin ageing. The problem of skin ageing has captured public attention and has an important social impact. Different therapeutic approaches have been developed to treat cutaneous ageing and to diminish or prevent the negative effects of UVR. Topical retinoids represent an important and powerful class of molecules in the dermatologist's hands for the treatment of photodamaged skin. Since their introduction more than 20 years ago, topical retinoids have shown beneficial efficacy and good safety profiles in the management of photodamaged skin, and as therapeutic anti-ageing agents. This review provides a brief retrospective of the development of topical retinoids in the treatment of photodamaged skin, elucidates their mechanism of action, delineates their use and addresses clinical, pharmaceutical and regulatory issues in connection with their intended use.