Dermagenesis Continued

There is increasing evidence that reactive oxygen species play a pivotal role in the process of ageing. The skin, as the outermost barrier of the body, is exposed to various exogenous sources of oxidative stress, in particular UV-irradiation. These are believed to be responsible for the extrinsic type of skin ageing, termed photo-ageing. It therefore seems reasonable to try to increase levels of protective low molecular weight antioxidants through a diet rich in fruits and vegetables or by direct topical application. Indeed, various in vitro and animal studies have proved that low molecular weight antioxidants, especially vitamins C and E, ascorbate and tocopherol, as well as lipoic acid, exert protective effects against oxidative stress. However, controlled long-term studies on the efficacy of low molecular weight antioxidants in the prevention or treatment of skin ageing in humans are still lacking.

PMID: 11696061 [PubMed - indexed for MEDLINE

Topical vitamins.

Burgess C.

The Center for Dermatology and Dermatologic Surgery, Washington, DC, USA. cheryl.burgess@ctr4dermatology.com This e-mail address is being protected from spambots. You need JavaScript enabled to view it

Vitamins are a natural constituent of human skin and are part of a system of antioxidants that protect the skin from oxidative stress. There has been an increased interest in the use of natural antioxidants such as vitamins to help restore dermal antioxidant activity. Vitamins A, C, E, and B3 have been shown to have potent antioxidant and anti-inflammatory properties, but to achieve optimal effectiveness, products must be delivered in appropriate formulations. Products containing alpha-tocopherol (vitamin E), L-ascorbic acid (vitamin C), retinol (vitamin A), and niacinamide (vitamin B3), are effective for the treatment of photoaging. These compounds have also shown effectiveness in the treatment of inflammatory dermatoses, acne, and pigmentation disorders and wound healing. There is emerging evidence that combinations of vitamins have additive effects that provide enhanced efficacy compared with individual compounds.

PMID: 18681152 [PubMed - indexed for MEDLINE]
Improvement of naturally aged skin with vitamin A (retinol).

Kafi R, Kwak HS, Schumacher WE, Cho S, Hanft VN, Hamilton TA, King AL, Neal JD, Varani J, Fisher GJ, Voorhees JJ, Kang S.

Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

OBJECTIVE: To evaluate the effectiveness of topical retinol (vitamin A) in improving the clinical signs of naturally aged skin. DESIGN: Randomized, double-blind, vehicle-controlled, left and right arm comparison study. SETTING: Academic referral center. PATIENTS: The study population comprised 36 elderly subjects (mean age, 87 years), residing in 2 senior citizen facilities. INTERVENTION: Topical 0.4% retinol lotion or its vehicle was applied at each visit by study personnel to either the right or the left arm, up to 3 times a week for 24 weeks. MAIN OUTCOME MEASURES: Clinical assessment using a semiquantitative scale (0, none; 9, most severe) and biochemical measurements from skin biopsy specimens obtained from treated areas. RESULTS: After 24 weeks, an intent-to-treat analysis using the last-observation-carried-forward method revealed that there were significant differences between retinol-treated and vehicle-treated skin for changes in fine wrinkling scores (-1.64 [95% CI, -2.06 to -1.22] vs -0.08 [95% CI, -0.17 to 0.01]; P<.001). As measured in a subgroup, retinol treatment significantly increased glycosaminoglycan expression (P = .02 [n = 6]) and procollagen I immunostaining (P = .049 [n = 4]) compared with vehicle. CONCLUSIONS: Topical retinol improves fine wrinkles associated with natural aging. Significant induction of glycosaminoglycan, which is known to retain substantial water, and increased collagen production are most likely responsible for wrinkle effacement. With greater skin matrix synthesis, retinol-treated aged skin is more likely to withstand skin injury and ulcer formation along with improved appearance.

PMID: 17515510 [PubMed - indexed for MEDLINE]

Proposed mechanisms of action for retinoid derivatives in the treatment of skin aging.

Sorg O, Kuenzli S, Kaya G, Saurat JH.

Department of Dermatology, University Hospital, Geneva, Switzerland.

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 long-term 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.

PMID: 17168870 [PubMed - in process]



Protective effects of topical antioxidants in humans.

Dreher F, Maibach H.

Department of Dermatology, University of California, San Francisco, Calif., USA.

Human studies have convincingly demonstrated pronounced photoprotective effects of 'natural' and synthetic antioxidants when applied topically before UVR exposure. Particularly with respect to UVB-induced skin damage such as erythema formation, the photoprotective effects of antioxidants are significant when applied in distinct mixtures in appropriate vehicles. Topical application of such combinations may result in a sustained antioxidant capacity of the skin, possibly due to antioxidant synergisms. And, since UVA-induced skin alterations are believed to be largely determined by oxidative processes [26], topical administration of antioxidants might be particularly promising [27, 28]. In fact, topical application of antioxidants or antioxidant mixtures resulted in a remarkable increase in the minimal dose to induce immediate pigment darkening after UVA exposure [18, 23] and diminished the severity of UVA-induced photodermatoses [22] in humans. In conclusion, regular application of skin care products containing antioxidants may be of the utmost benefit in efficiently preparing our skin against exogenous oxidative stressors occurring during daily life. Furthermore, sunscreening agents may also benefit from combination with antioxidants resulting in increased safety and efficacy of such photoprotective products [11, 29].

PMID: 11225195 [PubMed - indexed for MEDLINE]
The antioxidant network of the stratum corneum.

Thiele JJ, Schroeter C, Hsieh SN, Podda M, Packer L.

Department of Dermatology and Allergology, Friedrich Schiller University, Jena, Germany. thiele@derma.uni-jena.de This e-mail address is being protected from spambots. You need JavaScript enabled to view it

Many studies have demonstrated beneficial health effects of topical antioxidant application; however, the underlying mechanisms are not well understood. To better understand the protective mechanism of oxogenous anti-oxidants, it is important to clarify the physiological distribution, activity and regulation of antioxidants. Also, the generation of ROS by the resident and transient microbial flora and their interaction with cutaneous antioxidants appears to be of relevance for the redox properties of skin. Our studies have demonstrated that alpha-tocopherol is, relative to the respective levels in the epidermis, the major antioxidant in the human SC, that alpha-tocopherol depletion is a very early and sensitive biomarker of environmentally induced oxidation and that a physiological mechanism exists to transport alpha-tocopherol to the skin surface via sebaceous gland secretion. Furthermore, there is conclusive evidence that the introduction of carbonyl groups into human SC keratins is inducible by oxidants and that the levels of protein oxidation increase towards outer SC layers. The demonstration of specific redox gradients within the human SC may contribute to a better understanding of the complex biochemical processes of keratinization and desquamation. Taken together, the presented data suggest that, under conditions of environmentally challenged skin or during prooxidative dermatological treatment, topical and/or systemic application of antioxidants could support physiological mechanisms to maintain or restore a healthy skin barrier. Growing experimental evidence should lead to the development of more powerful pharmaceutical and cosmetic strategies involving antioxidant formulations to prevent UV-induced carcinogenesis and photoaging as well as to modulate desquamatory skin disorders.

PMID: 11225199 [PubMed - indexed for MEDLINE

Age-dependent increase of collagenase expression can be reduced by alpha-tocopherol via protein kinase C inhibition.

Ricciarelli R, Maroni P, Ozer N, Zingg JM, Azzi A.

Institut für Biochemie und Molekularbiologie, Universität Bern, Switzerland.

Total protein kinase C (PKC) activity in human skin fibroblasts increases during in vivo aging as a function of the donor's age. During in vitro aging protein kinase C activity is also increased, as a function of cell passage number. Using PKC isoform specific antibodies, we demonstrate that the increase in total PKC activity is mainly due to the PKC a isoform. PKC alpha protein expression increased up to 8 fold during in vivo aging. Collagenase (MMP-1) gene transcription and protein expression also increased with age, concomitant with the increase in protein kinase C alpha. Furthermore, alpha-tocopherol, which inhibits protein kinase C activity, is able to diminish collagenase gene transcription without altering the level of its natural inhibitor, tissue inhibitor of metalloproteinase, TIMP-1. We propose that an aging program leads to increased protein kinase C alpha expression and activity. This event would induce collagenase overexpression followed by increased collagen degradation. Our in vitro experiments with skin fibroblasts suggest that alpha-tocopherol may protect against skin aging by decreasing the level of collagenase expression, which is induced by environmental insults and by aging.

PMID: 10515576 [PubMed - indexed for MEDLINE]

Effectiveness of antioxidants (vitamin C and E) with and without sunscreens as topical photoprotectants.

Darr D, Dunston S, Faust H, Pinnell S.

North Carolina Biotechnology Center, Raleigh, N.C., USA.

Considerable interest has been recently generated concerning the use of natural compounds, anti-oxidants in particular, in photoprotection. Two of the best known anti-oxidants are vitamins C and E, both of which have been shown to be somewhat effective in different models of photodamage. Very little has been reported, however, on the effectiveness of a combination of the two (known to be biologically the more relevant situation); nor have there been detailed studies on the ability of these antioxidants to augment commercial sunscreen protection against UV damage. We report that (in swine skin) vitamin C is capable of additive protection against acute UVB damage (sunburn cell formation) when combined with a UVB sunscreen. A combination of both vitamins E and C provided very good protection from a UVB insult, the bulk of the protection attributable to vitamin E. However, vitamin C is significantly better than vitamin E at protecting against a UVA-mediated phototoxic insult in this animal model, while the combination is only slightly more effective than vitamin C alone. When vitamin C or a combination of vitamin C and E is formulated with a commercial UVA sunscreen (oxybenzone), an apparently greater than additive protection is noted against the phototoxic damage. These results confirm the utility of anti-oxidants as photoprotectants but suggest the importance of combining the compounds with known sunscreens to maximize photoprotection.

PMID: 8869680 [PubMed - indexed for MEDLINE]

The role of vitamin E in normal and damaged skin.

Nachbar F, Korting HC.

Dermatologische Klinik und Poliklinik, Ludwig-Maximilians-Universität, München, Germany.

The generation of free oxygen radicals is believed to play an important pathogenic role in the development of various disorders. More than other tissues, the skin is exposed to numerous environmental chemical and physical agents such as ultraviolet light causing oxidative stress. In the skin this results in several short- and long-term adverse effects such as erythema, edema, skin thickening, wrinkling, and an increased incidence of skin cancer or precursor lesions. However, accelerated cutaneous aging under the influence of ultraviolet light, usually termed photoaging, is only one of the harmful effects of continual oxygen radical production in the skin. Others include cutaneous inflammation, autoimmunological processes, keratinization disturbances, and vasculitis. Vitamin E is the major naturally occurring lipid-soluble non-enzymatic antioxidant protecting skin from the adverse effects of oxidative stress including photoaging. Its chemistry and its physiological function as a major antioxidative and anti-inflammatory agent, in particular with respect to its photoprotective, antiphotoaging properties, are described by summarizing animal studies, in vivo tests on human skin and biochemical in vitro investigations. The possible therapeutic use in different cutaneous disorders, and pharmacological and toxicological aspects are discussed. Many studies document that vitamin E occupies a central position as a highly efficient antioxidant, thereby providing possibilities to decrease the frequency and severity of pathological events in the skin. For this purpose increased efforts in developing appropriate systemic and local pharmacological preparations of vitamin E are required.

PMID: 7633944 [PubMed - indexed for MEDLINE]

Evidence for the photoprotective effects of vitamin E.

Fryer MJ.

Department of Biology, University of Essex, Colchester, UK.

The antioxidant vitamin E (alpha-tocopherol) may protect both animal and plant cell membranes from light-induced damage. The various biochemical and biophysical modes of protection are considered. An examination is made of the evidence that vitamin E plays an important prophylactic role against a number of serious light-induced diseases and conditions of the eye (cataractogenesis and retinal photodeterioration) and skin (erythrocyte photohemolysis, photoerythema, photoaging and photocarcinogenesis) that are mediated by photooxidative damage to cell membranes.

PMID: 8415922 [PubMed - indexed for MEDLINE]

The effect of reactive oxygen species on the biosynthesis of collagen and glycosaminoglycans in cultured human dermal fibroblasts.

Tanaka H, Okada T, Konishi H, Tsuji T.

Biochemical Research Institute, Nippon Menard Cosmetic Co. Ltd., Gifu, Japan.

The purpose of this study was to evaluate the possibility that the biological changes observed in connective tissue matrix components of photoaging skin may be induced by an alteration of biosynthesis in fibroblasts damaged by reactive oxygen species (ROS). We investigated the effect of ROS induced by xanthine and the xanthine oxidase system on the biosynthesis of connective tissue matrix components, collagen and glucosaminoglycans (GAGs) in cultured human dermal fibroblasts. ROS decreased collagen production and increased GAGs synthesis. Interestingly, these changes were consistent with the biological alterations of connective tissue matrix components observed in photoaging skin. Moreover, catalase and alpha-tocopherol completely prevented the ROS-induced alterations of collagen and GAGs biosynthesis, whereas superoxide dismutase had no effect on the ROS-induced changes. These results suggest that ROS may be one of the factors which cause the biological changes of connective tissue matrix components observed in photoaging skin.

PMID: 8215584 [PubMed - indexed for MEDLINE]

Free radicals and aging of the skin.

Emerit I.

Free Radical Research Group, University of Paris VI, France.

Cutaneous aging is the result of genetically determined or intrinsic aging superimposed by degenerative changes due to actinic irradiation, also called photoaging. The manifestations of cutaneous aging, as it relates to the perception of age, is caused by ultraviolet light, in particular in those parts of the body exposed daily to solar radiation. Free radical generation in the skin by UV light and from other sources, such as cellular infiltrations or the xanthine oxidase reaction, may be detected by direct and indirect methods. The decrease in antioxidant enzymes and small molecular weight antioxidants such as glutathione, vitamin E and ubiquinone upon exposure to UV light is an indication that the pro-antioxidant balance can be overwhelmed by acute or chronic photo-oxidative stress. Antioxidant supplementation is therefore a means for prevention or at least retardation of premature cutaneous aging.

PMID: 1450595 [PubMed - indexed for MEDLINE]
More References to be added soon.