ALIMENTATION ET VIEILLISSEMENT CUTANÉ : QUELS BILANS BIOLOGIQUES ?

1. ALIMENTATION ET VIEILLISSEMENT CUTANÉ : QUELS BILANS BIOLOGIQUES ? Dr. MOUTAPAM

2. L’Intensité de la Réaction Inflammatoire est Contrôlée par les Prostaglandines et les Leucotriènes et Dépend du Rapport AA/EPA Dr. MOUTAPAM

3. Photoprotective and anti-skin-agingeffects of eicosapentaenoicacid in human skin in vivo. Kim HH, Cho S, Lee S, Kim KH, Cho KH, Eun HC, Chung JH. J LipidRes. 2006 May;47(5):921-30. Skin agingcanbeattributed to photoaging (extrinsic) and chronological (intrinsic) aging. Photoaging and intrinsicaging are induced by damage to human skin attributable to repeatedexposure to ultraviolet (UV) irradiation and to the passage of time, respectively. In ourprevious report, eicosapentaenoicacid (EPA) wasfound to inhibit UV-induced matrix metalloproteinase-1 (MMP-1) expression in humandermalfibroblasts. Therefore, weinvestigated the effects of EPA on UV-induced skin damage and intrinsicaging by applying EPA topically to young and agedhuman skin, respectively. By immunohistochemicalanalysis and Western blotting, wefoundthattopical application of EPA reduced UV-inducedepidermalthickening and inhibitedcollagendecreaseinduced by UV light. It wasalsofoundthat EPA attenuated UV-induced MMP-1 and MMP-9 expression by inhibiting UV-induced c-Jun phosphorylation, whichiscloselyrelated to UV-inducedactivator protein-1 activation, and by inhibiting JNK and p38 activation. EPA alsoinhibited UV-induced cyclooxygenase-2 (COX-2) expression withoutaltering COX-1 expression. Moreover, itwasfoundthat EPA increasedcollagen and elasticfibers (tropoelastin and fibrillin-1) expression by increasingtransformingrowth factor-beta expression in agedhuman skin. Together, theseresultsdemonstratethattopical EPA has potential as an anti-skin-aging agent. Dr. MOUTAPAM

4. Omega-3 polyunsaturated fatty acids: photoprotective macronutrients. ExpDermatol. 2011 Jul;20(7):537-43. Dermatological Sciences, Inflammation Sciences Research Group, School of Translational Medicine, University of Manchester, Manchester Academic Health Science Centre, Salford Royal NHS Foundation Hospital, Manchester, UK. Ultraviolet radiation (UVR) in sunlight has deleterious effects on skin, while behavioural changes have resulted in people gaining more sun exposure. The clinical impact includes a year-on-year increase in skin cancer incidence, and topical sunscreens alone provide an inadequate measure to combat overexposure to UVR. Novel methods of photoprotection are being targeted as additional measures, with growing interest in the potential for systemic photoprotection through naturally sourced nutrients. Omega-3 polyunsaturated fatty acids (n-3 PUFA) are promising candidates, showing potential to protect the skin from UVR injury through a range of mechanisms. In this review, we discuss the biological actions of n-3 PUFA in the context of skin protection from acute and chronic UVR overexposure and describe how emerging new technologies such as nutrigenomics and lipidomics assist our understanding of the contribution of such nutrients to skin health. Dr. MOUTAPAM

5. Vitamine D Dr. MOUTAPAM

6. Association of facial skin aging and vitamin D levels in middle-aged white women. Chang AL, Fu T, Amir O, Tang JY. Cancer Causes Control. 2010 Dec;21(12):2315-6 To investigate the relationship between UV-induced skin photodamage and 25(OH) vitamin D levels, we performed a cross-sectional study in 45 female subjects aged >40. Menopausal status, smoking status, skin cancer history, oral supplement use, and season of blood draw were recorded and serum 25(OH)D measured. A single-blinded, dermatologist evaluated standardized digital facial images for overall photodamage, erythema/telangiectasias, hyperpigmentation, number of lentigines, and wrinkling. Adjusting for age and season of blood collection, women with lower photodamage scores were associated with a 5-fold increased odds of being vitamin D insufficient (OR 5.0, 95% CI: 1.1, 23). Low scores for specific photodamage parameters including erythema/telangiectasias, hyperpigmentation, and wrinkling were also significantly associated with vitamin D insufficiency. Our results suggest an association between skin aging and 25(OH)D levels. Dr. MOUTAPAM

7. Vitamine E Dr. MOUTAPAM

8. Vitamine E Dr. MOUTAPAM

9. Vitamine E • Antioxydant liposoluble • Absorbé dans l’intestin grêle • Première défense contre les effets des radicaux libres dans l’organisme • Protection des membranes cellulaires • Stocké dans le foie et les adipocytes. • Protège les composants cellulaires et leur membrane Shown to protect against LDL oxidation, raises HDL, lowers total cholesterol and improves blood preasure. Dr. MOUTAPAM

10. Vitamin E regulates mitochondrial hydrogen peroxide generation. Chow CK, Ibrahim W, Wei Z, Chan AC Free Radic Biol Med 1999 Sep;27(5-6):580-7 The mitochondrial electron transport system consumes more than 85% of all oxygen used by the cells, and up to 5% of the oxygen consumed by mitochondria is converted to superoxide, hydrogen peroxide, and other reactive oxygen species (ROS) under normal physiologic conditions. Disruption of mitochondrial ultrastructure is one of the earliest pathologic events during vitamin E depletion. The present studies were undertaken to test whether a direct link exists between vitamin E and the production of hydrogen peroxide in the mitochondria. In the first experiment, mice were fed a vitamin E-deficient or-sufficient diet for 15 weeks, after which the mitochondria from liver and skeletal muscle were isolated to determine the rates of hydrogen peroxide production. Deprivation of vitamin E resulted in an approximately 5-fold increase of mitochondrial hydrogen peroxide production in skeletal muscle and a 1-fold increase in liver when compared with the vitamin E-supplemented group. To determine whether vitamin E can dose-dependently influence the production of hydrogen peroxide, four groups of male and female rats were fed diets containing 0, 20, 200, or 2000 lU/kg vitamin E for 90 d. Results showed that dietary vitamin E dose-dependently attenuated hydrogen peroxide production in mitochondria isolated from liver and skeletal muscle of male and female rats. Female rats, however, were more profoundly affected by dietary vitamin E than male rats in the suppression of mitochondrial hydrogen peroxide production in both organs studied. hese results showed that vitamin E can directly regulate hydrogen peroxide production in mitochondria and suggest that the overproduction of mitochondrial ROS is the first event leading to the tissue damage observed in vitamin E-deficiency syndromes. Data further suggested that by regulating mitochondrial production of ROS, vitamin E modulates the expression and activation of signal transduction pathways and other redox-sensitive biologic modifiers, and thereby delays or prevents degenerative tissue changes. Le système de transport des électrons mitochondrial consomme plus de 85% de tout l’oxygène utilisé par les cellules; jusqu’à5% de l’oxygène consommé par les mitochondries est converti en superoxyde, peroxyde d’hydrogène et autres ROS, dans des conditions physiologiques normales. Un déficit en vitamine E résulte en une augmentation d’un facteur 5 de la production de peroxyde d’hydrogène dans le muscle squelettique et une augmentation d’un facteur 1 dans le foie en comparaison avec un groupe supplémenté en vitamine E. Dr. MOUTAPAM

11. UVB photoprotection with antioxidants: effects of oral therapy with d-alpha-tocopherol and ascorbic acid on the minimal erythema dose. Mireles-Rocha H, Galindo I, Huerta M, Trujillo-Hernandez B, Elizalde A, Cortes-Franco R. Acta Derm Venereol. 2002;82(1):21-4. Ultraviolet radiation absorption is responsible for the production of free radicals in damaged cells. This side effect may be neutralized using antioxidant substances. It has been reported that ascorbic acid and d-alpha-tocopherol scavenge reactive oxygen species. In a single-blind controlled clinical trial we studied 45 healthy volunteers divided into three groups. Group 1 received d-alpha-tocopherol 1,200 I.U. daily; Group 2 ascorbic acid 2 g daily and Group 3 ascorbic acid 2 g plus d-alpha-tocopherol 1,200 I.U. daily. Treatment was sustained for one week. Before and after treatment, the minimal erythema dose was determined in all participants. The results show that the median minimal erythema dose increased from 60 to 65 mJ/cm2 in Group 1 and from 50 to 70 mJ/cm2 in Group 3. No modifications were observed in Group 2. We conclude that d-alpha-tocopherol prescribed in combination with ascorbic acid produces the best photoprotective effect. We conclude that d-alpha-tocopherol prescribed in combination with ascorbic acid produces the best photoprotective effect. Dr. MOUTAPAM

12. VitamineA Dr. MOUTAPAM

13. Le Beta Carotene est un précurseur hydrosoluble de la vitamine A, et est un antioxydant en soi, alors que la vitamine A n’a pas d’activité antioxydante. On en trouve dans: Maïs, courge et carottes, jaune d’oeuf, fruits et légumes pigmentés (couleur jaune). VitamineA et B - carotene (précurseur) Dr. MOUTAPAM

14. VITAMINE A: ROLES Dr. MOUTAPAM

15. 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. Arch Dermatol. 2007 May;143(5):606-12. 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. Dr. MOUTAPAM

16. 8-hydroxy-2'-deoxyguanosine Dr. MOUTAPAM

17. Urinary 8-hydroxy-2'-deoxyguanosine excretion as a biomarker for estimating DNA oxidation in patients undergoingexternalradiotherapy and/or brachytherapy. Yamazaki H, InoueT, Koizumi M, Tanaka E, Yoshioka Y, Nakamura H, InoueT. OncolRep. 2005 May;13(5):847-51. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) isconsidered to be a biomarker of cellular oxidative stress and to beassociatedwithcarcinogenesis. To estimate the oxidative stress caused by radiotherapy, weused the enzyme-linkedimmunosorbentassay (ELISA) to monitor urinary 8-OHdG levels in 72 patients undergoingradiotherapy. Subjectsconsisted of 23 breast cancer patients undergoing post-operativeexternalradiotherapy for breastconservingtherapy, 12 tongue and seven prostate cancer patients undergoinginterstitialradiotherapy, 19 esophageal cancer patients undergoingexternalradiotherapy and chemotherapy, and 11 cervical cancer patients undergoingexternalradiotherapy and brachytherapywith or withoutchemotherapy. Beforeradiotherapy, cervical cancer patients showed a higherurinary 8-OHdG level (16.0+/-8.8 ng/mg) thanbreast cancer patients (5.3+/-5.5 ng/mg, p=0.001). In the otherthree groups, urinary 8-OHdG levelswere in the medium range (prostate cancer patients: 6.6+/-6.3 ng/mg; esophageal cancer patients: 8.8+/-11.1 ng/mg; tongue cancer patients: 10.2+/-6.7 ng/mg). Radiotherapydid not cause changes in the excretionlevel of urinary 8-OHdG in patients withbreast, esophageal and tongue cancer. However, radiotherapyreduced 8-OHdG excretionlevels in patients with cervical cancer, whereasinterstitialradiotherapytransientlyincreasedtheselevels in patients with prostate cancer. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) isconsidered to be a biomarker of cellular oxidative stress and to beassociatedwithcarcinogenesis. Dr. MOUTAPAM

18. 8-hydroxy-2' -deoxyguanosine (8-OHdG): A criticalbiomarker of oxidative stress and carcinogenesis. Valavanidis A, Vlachogianni T, Fiotakis C. J Environ SciHealth C Environ CarcinogEcotoxicolRev. 2009 Apr;27(2):120-39. There is extensive experimentalevidencethatoxidative damage permanentlyoccurs to lipids of cellular membranes, proteins, and DNA. In nuclear and mitochondrial DNA, 8-hydroxy-2' -deoxyguanosine (8-OHdG) or 8-oxo-7,8-dihydro-2' -deoxyguanosine (8-oxodG) is one of the predominantforms of free radical-inducedoxidativelesions, and has therefore been widelyused as a biomarker for oxidative stress and carcinogenesis. Studiesshowedthaturinary 8-OHdG is a good biomarker for riskassessment of various cancers and degenerativediseases. The mostwidelyusedmethod of quantitative analysisis high-performance liquidchromatography (HPLC) withelectrochemicaldetection (EC), gaschromatography-mass spectrometry (GC-MS), and HPLC tandem mass spectrometry. In order to resolve the methodologicalproblemsencountered in measuringquantitatively 8-OHdG, the European Standards Committee for Oxidative DNA Damage was set up in 1997 to resolve the artifactualoxidationproblemsduring the procedures of isolation and purification of oxidative DNA products. The biomarker 8-OHdG or 8-oxodG has been a pivotal marker for measuring the effect of endogenousoxidative damage to DNA and as a factor of initiation and promotion of carcinogenesis. The biomarker has been used to estimate the DNA damage in humansafterexposure to cancer-causing agents, such as tobaccosmoke, asbestosfibers, heavymetals, and polycyclicaromatichydrocarbons. In recentyears, 8-OHdG has been usedwidely in manystudies not only as a biomarker for the measurement of endogenousoxidative DNA damage but also as a risk factor for manydiseasesincluding cancer. In recent years, 8-OHdG has been used widely in many studies not only as a biomarker for the measurement of endogenous oxidative DNA damage but also as a risk factor for many diseases including cancer. Dr. MOUTAPAM

19. UBIQUINONE ou COENZYME Q10 Dr. MOUTAPAM

20. CoQ10 Dr. MOUTAPAM

21. Mechanisms of inhibitory effects of CoQ10 on UVB-induced wrinkle formation in vitro and in vivo. Inui M, Ooe M, Fujii K, Matsunaka H, Yoshida M, Ichihashi M. Biofactors. 2008;32(1-4):237-43. Photodamaged skin exhibits wrinkles, pigmented spots, dryness and tumors. Solar UV radiation induces cyclobutane pyrimidine dimers (CPD) and further produces base oxidation by reactive oxygen species (ROS). ROS are thought to be a major factor to initiate the up-regulation of matrix metalloproteinases (MMPs) in keratinocytes and fibroblasts via activation of receptor proteins on the cell membrane of keratinocytes and fibroblasts, and to degrade fiber components in dermis, leading to wrinkle formation. Coenzyme Q10 (CoQ10) was reported to reduce ROS production and DNA damage triggered by UVA irradiation in human keratinocytes in vitro. Further, CoQ10 was shown to reduce UVA-induced MMPs in cultured human dermal fibroblasts. We speculated that UVB radiation-induced cytokine production in keratinocytes may be inhibited by CoQ10, resulting in the reduction of MMPs in fibroblasts leading to wrinkle reduction. Our in vitro studies showed that UVB-induced IL-6 production of normal human keratinocyte (NHKC) decreased in the presence of CoQ10. Furthermore, MMP-1 production of fibroblasts cultured with the medium containing CoQ10 collected from UVB-irradiated NHKC significantly decreased during 24 h culture. In the clinical trial study, we found that the use of 1% CoQ10 cream for five months reduced wrinkle score grade observed by a dermatologist. Taken together, our results indicate that CoQ10 may inhibit the production of IL-6 which stimulate fibroblasts in dermis by paracrine manner to up-regulate MMPs production, and contribute to protecting dermal fiber components from degradation, leading to rejuvenation of wrinkled skin. Dr. MOUTAPAM

22. Evaluation des défenses Anti-Oxydantes Vitamine A ß-carotens Vitamin E SuperoxydeDismutase Zinc Cupper Glutathion Peroxydase Selenium Coenzyme-Q10 Dr. MOUTAPAM

23. Selenium Antioxidant supplements improve parameters related to skin structure in humans. Heinrich U, Tronnier H, Stahl W, Béjot M, Maurette JM. Pharmacol Physiol. 2006;19(4):224-31. In the present study we investigated the influence of two different antioxidant supplements composed of carotenoids, vitamin E and selenium on parameters related to skin health and skin aging. Thirty-nine volunteers with healthy, normal skin of skin type 2 were divided into 3 groups (n = 13) and supplemented for a period of 12 weeks. Group 1 received a mixture of lycopene (3 mg/day), lutein (3 mg/day), beta-carotene (4.8 mg/day), alpha-tocopherol (10 mg/day) and selenium (75 microg/day). Group 2 was supplemented with a mixture of lycopene (6 mg/day), beta-carotene (4.8 mg/day), alpha-tocopherol (10 mg/day) and selenium (75 microg/day). Group 3 was the placebo control. Upon supplementation serum levels of selected carotenoids increased in both verum groups. Skin density and thickness were determined by ultrasound measurements. A significant increase for both parameters was determined in the verum groups. Roughness, scaling, smoothness and wrinkling of the skin were determined by Surface Evaluation of Living Skin (Visioscan). Roughness and scaling were improved by the supplementation with antioxidant micronutrients. In the placebo group no changes were found for any of the parameters. Dr. MOUTAPAM

24. Caroténoïdes Dr. MOUTAPAM

25. STATUT EN CAROTENOÏDES Dr. MOUTAPAM

26. Carotenoids and FlavonoidsContribute to Nutritional Protection against Skin Damage from Sunlight. Stahl W, Sies H. Mol Biotechnol. 2007 Sep;37(1):26-30. The concept of photoprotection by dietarymeansisgainingmomentum. Plant constituentssuch as carotenoids and flavonoids are involved in protection againstexcess light in plants and contribute to the prevention of UV damage in humans. As micronutrients, they are ingestedwith the diet and are distributedinto light-exposed tissues, such as skin or the eyewheretheyprovidesystemicphotoprotection. beta-Carotene and lycopeneprevent UV-inducederythema formation. Likewise, dietaryflavanolsexhibitphotoprotection. After about 10-12 weeks of dietary intervention, a decrease in the sensitivitytoward UV-inducederythemawasobserved in volunteers. Dietarymicronutrientsmaycontribute to life-long protection againstharmful UV radiation. Dr. MOUTAPAM

27. Immediate effects of UV radiation on the skin: modification by an antioxidant complex containing carotenoids. Cesarini JP, Michel L, Maurette JM, Adhoute H, Bejot M. FondationOphtalmologique A de Rothschild, Paris, France. PhotodermatolPhotoimmunolPhotomed. 2003 Aug;19(4):182-9. BACKGROUND/AIMS: The ultraviolet (UV) portion of sunlight is involved in the induction and development of skin cancers against which a limited photoprotection may be provided by reduced time of exposure, clothing, and sunscreen applications. The concept of an effective, safe, systemic photoprotection will circumvent many of the shortcomings. The UV-induced oxidative stress is a cause of DNA damage and a few publications have shown, in humans, minimal benefits, if any, of the oral intake of antioxidant complex, contrasting with the large literature showing beneficial effects in vitro or in animal models. METHODS: We investigated, in 25 healthy individuals, the capacity of an antioxidant complex (AOC) - vitamins (lycopene, beta-carotene, alpha-tocopherol), selenium - to reduce UV-induced damages. The AOC was administered orally, daily during 7 weeks. Before and after irradiations, before and after the intake of the product, six parameters were studied: skin color by chromametry, minimal erythemal dose and, on skin biopsies, sunburn cells (SBCs), p53 detected by immunohistochemistry, pigmentation index, and levels of lipoperoxides (thiobarbituric acid reaction). RESULTS: After the oral intake of AOC, we observed an elevation of the actinic erythema threshold (+20%, P=0.01) and a general reduction of the UV-induced erythemas, a reduction of the UV-induced p53 expression (P<0.05) and of SBCs (P<0.01), and a parallel reduction of the lipoperoxide levels (P<0.01). The pigmentation was increased (P<0.01). CONCLUSION: After the oral intake of an antioxidant complex, many parameters of the epidermal defense against UV-induced damages are significantly improved. The oral intake of AOC could provide a safe, daylong and efficient complement to photo-protective measures provided by topical and physical agents and may contribute to reduce the DNA damages leading to skin aging and skin cancers CONCLUSION: After the oral intake of an antioxidant complex, many parameters of the epidermal defense against UV-induced damages are significantly improved. The oral intake of AOC could provide a safe, daylong and efficient complement to photo-protective measures provided by topical and physical agents and may contribute to reduce the DNA damages leading to skin aging and skin cancers Dr. MOUTAPAM

28. DermaScreen Dr. MOUTAPAM