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London – UK Thursday 27th October 2011
11th Scientific Symposium LVMH Recherche
London – UK Thursday 27th October 2011
The British Library
Dr. Barry Knight Head of Conservation Research
The British Library is the national library of the United Kingdom, a major research library holding over 150 million items from every country in the world, in many formats, print or digital: books, manuscripts, newspapers, journals, magazines, sound and music recordings, videos, maps, stamps, prints, drawings… For many years, the British Library has also developed a conservation research strategy and collaborative applied research programmes to maximize the future availability of collections. The British Library is a unique and fabulous place in the worldwide cultural and information network, an institution which supports research, guarantees access for future generations to the world’s knowledge, and enriches the cultural life of the nation.
Appearance and skin vitality are and will remain a subject of primary importance in daily life and for social well being. cellular and molecular biology. active ingredients. It is my great pleasure and honour to welcome you to the 2011 LVMH Recherche Symposium held at the British Library in London. The goal of these projects is to help women to achieve naturally radiant skin and to reestablish youthful facial characteristics. Today. an institution that supports research. Scientists are looking for new strategies able to regenerate the health and youth of the skin by producing a durable effect below the skin’s surface. Let me remind you that the aim of this LVMH Recherche symposium is to gather together leading scientists in order to discuss one of the major themes in the field of cosmetics and to generate transdisciplinary links. about one-third of women will be over 50. in the next 50 years. Rejuvenation is the central focus of thousands research projects in laboratories in the field of genetics. selected scientific presentations will cover a wide range of topics and will present the latest scientific discoveries in anti-aging and skin rejuvenation research. reprogramming strategies and formulation. which occupies a unique and inspiring place in the world’s cultural and information network.Welcome Frédéric Bonté Director of Scientific Communication Dear Colleagues. guarantees access to world knowledge to future generations and enriches the cultural life of nations. It is a great privilege to hold this symposium at the British Library. 5 . In many countries. the cosmetician’s role is to provide skin care and makeup products that allow a woman’s facial features to work in concert and reflect light with more harmony and equilibrium. If there is beauty to be found in every human face.
aim to identify biological targets and develop active Executive Vice-President R&D ingredients and formulas to help maintain the beauty LVMH Recherche and youth of the skin. To consumer panels worldwide. combined with eric perrier 6 . proteomics. and validating our results in clinical studies and Healthy skin is our main source of inspiration.that of phytochemists in our ethnobotanical network. skin biopsy. cell culture. international experts with whom we work. Our daily goal is to better understand the biological mechanisms that govern skin’s appearance. we seek to reach taibetter understand it. Research by our biologists. DNA chips. Center has developed a comprehensive set of investi. evolution and rhythm. skin respect of everyone’s skills. enriched by our own expertise as well as that of the advanced imaging and sensory maps. Our Philosophy: By combining our knowledge with information from “Research for emotion” the fields of sociology. among others. psychology and neurocosmetics. our Research and Development lored cosmetics solutions.Deeply rooted in a culture of sharing knowledge and gative tools in immunohistochemistry. our research philosophy is reconstruction.
Among antioxyLVMH Research is aimed at making advances in dants. Genetic sites involved Max santoul 8 . an era of rejuvenation. breakthrough in our formulations. Moreover. and we can by the discovery of aquaporins. complex molecules were isolated from specific understanding skin composition. cosmetics to describe new concepts. The area appears that our biological clock is part of a process of hydration.The regulation of proteasome (whose discovery also quences. for example. for which Peter Agre slow down its pendulum. repair and the enzymes of the skin nolic trimers (miyabenol) show remarkable biological – slowing or stimulating their production – as well as activities to fight skin ageing. Even better. such as dermaSome cells naturally live for many years and others toporosis. it is becoming earned a Nobel Prize in 2003. which was revolutionized of aging whose activation is not inevitable. but also in the areas vine shoots of rare french vines and some polypheof the protection. One could say that this is a drive towards the future that restores the conditions of a youthful past. it but no longer have quite the same meaning. Skin has a natural potential to conserve its beauty. Thus a new era that goes beyond anti-aging earned a Nobel Prize in 2004) represents another is emerging.processes that restructure the skin’s composition to Scientific adviser restore its lost momentum. has been important possible to prevent our biological clock from cutting to the formulation of our products for some years. while other terms have remained the same have an extraordinary power of renewal. Our research laboratory is currently working on many projects whose aim is to find active ingredients that would help in skin rejuvenation. Recently new terms have cropped up in the field of and probably contains the secrets of prolonged youth. time short and to compel it to reverse its conse.
Through this symposium we hope to share with you our enthusiasm for the latest advances in this exciting field. which has influenced the evolution of our species since the dawn of humanity. then they entered the era of anti-aging during the twentieth century. For millennia cosmetics were devoted to beautification. Current research has developed to the point where a youthful appearance is a right to which we can all aspire. of particular interest are sirtuins. and now they are moving towards the future. focusing on rejuvenation. waterproof garment that protects us from a hostile environment must stand the test of time. durable.This soft. It holds an exceptional power of longevity and perhaps. smooth.in aging may be targeted. and the protection of an organ as precious as the skin is becoming a duty. clothes our bodies in nudity. For example. we would say that it dates back to the earliest civilizations. 9 . stem cells reactivated. expandable. If we had to summarize the history of cosmetics. cellular enzymes in close contact with proteins that manage our genetic inheritance and affect cellular metabolism by regulating the expression of certain genes. secretly. with an emphasis on repair and protection (antioxydants are well-established examples). enzymatic processes optimized. a universal power of repair and renewal. This living envelope. with research on stem cells and agents capable of reversing the course of time.
Leslie Baumann. FL. LVMH Recherche. Saint Jean de Braye. USA Skin-cell rejuvenation Dr. Saint Jean de Braye. London. Palo Alto. MS Futures Group. Chief Executive Officer. Department of Dermatology Photoaging and Aging Research Program. France Introduction Dr. Bio-Science Innovation Manager. University of Michigan. Ph. Leading scientist.. USA 11 . USA A dermatologist’s view on skin rejuvenation Dr. LVMH Recherche.D.Program Welcome Eric Perrier. Minsk. Carine Nizard. Mountain View. France Signalling pathways and rejuvenation: risks and opportunities Oleg Kvitko. Laure Rittié. Barry Knight. Carlo Pincelli. Chief Science Officer. Head of Conservation Research. MBA. SENS Foundation. Institute of Genetics and Cytology. National Academy of Sciences. Research Investigator. Professor of Dermatology. UK Prospects for truly comprehensive repair of aged skin Dr. Futurist and Applied Genomics Expert. Baumann Cosmetic & Research Institute. British Library. Belarus Controlled wound healing for skin rejuvenation: recent progress and future challenges Dr. Ann Arbor. Frédéric Bonté. USA Stem cells and skin rejuvenation Pr. Italy Translational reverse-aging research: latest advances Melanie Swan. University of Modena and Reggio Emilia. DIYgenomics. Aubrey de Grey. School of Biosciences and Biotechnologies. Miami.
Mountain View. accumulating and eventually pathogenic molecular and cellular side-effects of metabolism (“damage”) that constitute mammalian aging and the design of inter- aubrey de grey 12 . a California-based cha. the probably never be perfect. A key aspect of Officer of SENS Foundation. de and he did research in the private sector for six years Grey is a Fellow of both the Gerontological Society in the area of software verification before switching of America and the American Aging Association. He without limit. Aubrey de Grey is a biomedical gerontologist seven major classes of damage and identifies detailed based in Cambridge. termed Strategies for Engineered Negligible Foundation. even though these repair processes will is also Editor-in-Chief of Rejuvenation Research. of repair therapies “longevity escape velocity”. He has Chief Science Officer.ventions to repair and/or obviate that damage. He received his BA and Ph. and to biogerontology in the mid-1990s.SENS is that it can potentially extend healthy lifespan rity dedicated to combating the aging process. de from the University of Cambridge in 1985 and 2000 Grey has termed this required rate of improvement respectively. as the repair only needs to world’s highest-impact peer-reviewed journal focused approach perfection rapidly enough to keep the oveon intervention in aging. His original field was computer science. SENS developed a possibly comprehensive plan for such repair. rall level of damage below pathogenic levels. UK.D. His research sits on the editorial and scientific advisory boards of interests encompass the characterisation of all the numerous journals and organisations. and is the Chief Science approaches to addressing each one. Dr. USA Senescence (SENS). Dr. which breaks aging down into Dr.
each of which possesses multiple cell types and which are separated by an extracellular lamina that also undergoes age-related degradation. In all cases they can be classified into just seven major categories. incorporating two very different layers of cells (the dermis and the epidermis).Prospects for truly comprehensive repair of aged skin Though aging of the skin is not in itself a life-threatening process. are broadly similar. These reactions. Similar chemistry also results 13 . In spite of continued progress in improving the efficacy of skin rejuvenation methods. predominantly caused by sequences of reactions between circulating monosaccharides and lysine or arginine residues of ECM proteins. with half-lives of the same order of magnitude as the human lifespan. the skin is a rather complex tissue. Luckily. the specific types of molecular and cellular “damage” accumulating in all tissues. it seems likely that all examples within a category will in due course be amenable to repair by broadly the same type of intervention. One major type of such damage is random crosslinking. and biophysical dysfunction caused by chemical or physical alterations to the extracellular matrix. Where will future major breakthroughs in addressing skin aging come from? There are two distinct classes of obstacle to achieving truly comprehensive skin rejuvenation. Firstly. the immense demand for skin care products demonstrates how important skin aging is in diminishing self-esteem and quality of life. progressively diminishing the elasticity of the ECM as a whole. the skin is in intimate contact with the rest of the body. with macroscopic consequences in terms of skin vitality. each addressing a subset of the many types of dysfunction that aged skin exhibits. sometimes result in covalent linkages (especially one particular structure termed glucosepane) between juxtaposed proteins. These lattices of structural proteins (mostly collagen and elastin) are recycled only slowly. In the skin. it is very likely that a panel of simultaneous interventions will be required. so they have ample opportunity to accumulate damage. the skin included. and is therefore adversely affected by the aging of all other tissues. and also the interstitial extracellular matrix permeating the dermis. Secondly. Accordingly. especially via the circulation. but there are reasons to suspect that it is substantial. collectively referred to as glycation. Furthermore. Two of these seven categories concern extracellular material: accumulation of miscellaneous detritus that has escaped the attention of all mechanisms for degradation or excretion. existing techniques remain far from fully effective. It is difficult to quantify the impact of this as a driver of skin aging. the latter is of particular interest in relation to the basal lamina separating the dermis and the epidermis. for each such category.
thereby to replace it with pristine ECM lacking these modifications. not least as a result of the relevance to burns therapy. This may be a less significant type of ECM damage than in other tissues. With sufficient resources and determination. i. However. A promising approach to repairing this type of damage is to introduce into cells enzymes (or the genes encoding them). but they may be immunogenic. In addition. but it cannot safely be ignored. Pigmented material in particular. changes in cell number as opposed to cell structure. typically in the lysosome. and is largely a consequence of depletion of fibroblast density. it can be achieved within the foreseeable future. In the epidermis. after many years of pessimism.e. especially in the increasingly autoimmunity-prone aged environment. contributes greatly to skin aging. 14 . stem cell number may also decline. especially the dermis.The most important may be the accumulation in quiescent dermal fibroblasts. and especially in relation to the epidermis we are already seeing encouraging progress. there is evidence that crosslinking renders ECM somewhat resistant to degradation by proteases naturally secreted by fibroblasts – an obstacle that must be overcome if the loss of elasticity just mentioned can be fully reversed. at the intracellular level there are changes during aging which may contribute substantially to the skin’s biophysical properties and thus compromise its perceived “youth”. Cell loss is the natural target for stem cell therapies of various means. Unfortunately. a sophisticated multi-component assault will probably be necessary if we are to achieve complete rejuvenation of aged skin – but this is no longer a utopian goal. Similarly. whether intracellular or extracellular. which as noted above is a rare process. constitutes an important aspect of aging. that can degrade such compounds. In sum. there is a strong case for exploring methods to stimulate faster turnover of the skin ECM. of a variety of molecular detritus that is created as byproducts of normal metabolism but is not then degraded or excreted. Thinning of the skin.in adducts attached to individual amino acids: these probably do not alter the ECM’s biomechanical properties. simple rupture of the peptide backbone of ECM proteins will go unrepaired until the protein is subjected to wholesale degradation and replacement. found elsewhere in the biosphere (especially in bacteria). Accordingly. such as the walls of the major arteries. It is also necessary to consider aging at the cellular level. there is now new hope for the development of pharmaceuticals capable of cleaving the most abundant glycation-induced crosslinks.
USA Dr. She has performed clinical research trials for over 50 cosmetic and pharmaceutical companies. professor and well-known author. Sculptra. FL. In 1997. Juvederm. Miami. She authors a skin care blog on Yahoo! Health that is read by millions of people. Leslie Baumann. 16 . Her New York Times bestselling book “The Skin Type Solution” is in 5 countries and describes her skin typing system that is based on her years of research on skin care. Dr. she chaired the first Division of Cosmetic Dermatology in the USA at the University of Miami.leslie bauMann Dr. researcher. Leslie Baumann is a dermatologist. Dysport. She performed the research trials in the USA that led to FDA approval of Botox. Chief Executive Officer. Her clinical approach for skin care and cosmetic medicine combines science with practical solutions. 2010) was the first textbook on the subject and is currently the bestselling cosmetic dermatology textbook worldwide. Her textbook “Cosmetic Dermatology” (McGraw Hill 2002. and many other products and procedures. Leslie Baumann does not have her own skin care line. Baumann Cosmetic & Research Institute.
elastin and hyaluronic acid with the exception of retinoids. 17 . Evenness of skin color 2.Topical products have been largely unsuccessful in treating the loss of collagen. and a proper skin care regimen is combined with in-office procedures. Facial volume. microdermabrasion and chemical peels. Skin surface texture is determined by the condition of the stratum corneum. Methods used to smooth the stratum corneum include facial scrubs. Sensitive vs resistant 3. A youthful face has evenness of color. fat and dermal fillers are being used to correct facial volume defects. Wrinkled vs non-wrinkled (tight) Combining these 4 parameters gives 16 possible combinations. facial brushes. The theory of photothermolysis and use of light to treat skin discoloration will be discussed. Lasers. Skin surface texture 3. The most successful outcomes occur when the patient is properly educated and motivated. Pigmented vs nonpigmented 4. Visible blood vessels and accumulation of melanin contribute to unevenness of color. There are 16 individual Baumann Skin Types based on the combinations of the following parameters: 1. This lecture will discuss the thought process that dermatologists go through when selecting skin care products and cosmetic procedures for facial rejuvenation. light devices.A Dermatologist’s View on Skin Rejuvenation Skin Rejuvenation requires a multifaceted approach. The state of the art of stem cells will be discussed. skin peels and skin care products are combined to treat uneven skin tone. Stem cells. The science of topical retinoids and the use of dermal fillers and botulinum toxin to treat aged skin will be discussed. Oily vs dry 2. Facial volume loss is a major cause of skin aging. The second step in planning a facial rejuvenation plan is determining the patient’s Baumann Skin Type using a questionnaire known as the Baumann Skin Type Indicator (BSTI). 1. This lecture will briefly describe the 16 skin types and will focus on the science behind what causes the various skin conditions.The current trend is to develop at home procedures that mimic in-office procedures. Presence of wrinkles 4. Wrinkles are caused by the loss of collagen. The first step in planning a facial rejuvenation plan is evaluating these 4 facial characteristics to decide what cosmetic procedures are best suited for the patient. elastin and hyaluronic acid. A future research aim is to identify the genetic fingerprint of various skin types.
carlo pincelli Professor of Dermatology. Five years later he was appointed as Director of Research of the Laboratory of Cutaneous Biology at the University of Modena and Reggio Emilia. He became Professor of Clinical Dermatology in 1990. 18 . In 2006-2007. He is currently member of the Board of Trustees of the European Skin Research Foundation (ESRF). University of Modena and Reggio Emilia. Modena. Italy Carlo Pincelli received his training in Dermatology at the University of Modena and Reggio Emilia in Italy and at St. John’s Hospital for Diseases of the Skin in London. he has been President of the European Society for Dermatological Research (ESDR). He spent two years as a visiting research fellow at the University of California San Francisco in 1986-1988 and 9 months at the Department of Dermatology Boston University in 1994 as a visiting scientist. As epidermal expert. exploring deeply the pathogenic mechanisms implicated in skin pathologies. he has brought particular contributions in areas such as stem cells.l. School of Biosciences and Biotechnologies. Pincelli is also co-inventor of two international patents and author of over hundred-fifty articles in peer-reviewed journals. He is co-founder and Chief Executive Of-ficer of the academic spinoff Pincell S.r. molecular and cell biology and apoptosis.Pr.
basal keratinocytes leave the basal niche to undergo terminal differrentiation. need to be protected from apoptosis.Stem cells and skin rejuvenation Ageing is an inevitable process. Skin aging involves increased susceptibility to injury and infection. and increased cancer risk. 19 . Studies in mouse skin confirmed that epidermal stem cells remain functional and appear to resist to cellular ageing. KSCs reside in a special microenvironment. which involves all tissues and organs of the body and has particular repercussions and evidence in the skin. the niche. loss of dermal elasticity. controllable and include exposure to sunlight. it was tacitly understood that the epidermal stem cell remained functional as long as the organism lived and that this cell population met the continual demand for new cells. Some integrin family members are downregulated during skin ageing. reduced wound healing. Recent works. hair loss. differentiation and apoptosis. pollution or nicotine. Intrinsic ageing of the skin occurs as a natural consequence of physiological changes over time at variable rates. TA cells appear to be more affected than stem keratinocytes by ageing also in human epidermis. skin homeostasis and integrity is guaranteed by the presence of Keratinocyte Stem Cells (KSC) and by the correct balance between proliferation. epidermis becomes more fragile and susceptible to trauma. The niche concept in itself implies that KSCs. This critical process is regulated by an increasing number of signals. Since birth. KSCs self-renew and generate the different lineages that form the mature tissue. and all the factors implicated have to be taken into consideration during skin ageing. demonstrate that it is the Transit amplifying (TA)-cells population whose functionality changes as skin ages and that this change mantains the integrity of the epidermis in old mice. Moreover. The decline of tissue regenerative potential is a hallmark of ageing and may be due to related changes in tissue-specific stem cells. with an increasing rate of impaired wound healing. and different microenviromental stimuli influence their destiny. to varying degrees. Anyway. with both intrinsic and extrinsic determinants. given that epidermal functionality must be maintained throughout life. Extrinsic factors are. As basal keratinocytes exit the niche. sleeping position and overall health. repetitive muscle movements like squinting of frowning. that allows them to maintain their unique features and “stemness”. As we grow old. Under normal conditions. in order to maintain longevity and to ensure continue tissue renewal. KSC are located within the basal layer of epidermis and rest upon the basal membrane that is rich in extracellular matrix and growth factors. poor epidermal barrier maintenance. they move into suprabasal layers. wrinkling. and miscellaneous lifestyle components such as diet.
dermis plays a critical role in sustaining the stem cell population. However. For instance. with a decrease in collagen production and a reduction of skin tone and elasticity. Notch ligands expressed in basal keratinocytes bind to Notch receptors in suprabasal cells. 20 . in order to plan cosmetical and medical interventions in physiological and pathological conditions.survivin. neurotrophins and their receptors play an important role in mantainig epidermal homeostasis. is strongly expressed in KSCs and protect these cells from apoptosis induced by UVB radiations. implicated in cell cycle regulation and suppression of apoptosis. Furthermore. KSC descendent cells and all the factors involved in KSC niche have to be taken into account in human skin during ageing. we can conclude that KSCs behaviour is surely age-dependent and strictly related to individual characteristics. The chronological aging and photoaging of skin is accompanied by an extensive ECM remodelling in the dermis. an Inhibitor of Apoptosis Protein (IAPs) family member. fibrosis and increased risk to develop aggressive and invasive skin cancers. Notch proteins and their signaling pathways seem to be modulated during skin ageing. thus promoting the commitment of basal keratinocytes to differentiation. factors produced in the dermal compartment can act on stem cells.The crosstalk between the epidermal and dermal compartment is necessary to maintain epidermal homeostasis. Among other factors. Finally. Therefore.
Swan serves as an advisor to research foundations. Ms. 22 . She is a faculty member at Singularity University and an Affiliate Scholar at the Institute for Ethics and Emerging Technologies. nanotechnology. and opportunities for women. The goal of DIYgenomics is to realize personalized medicine by establishing baseline measures of wellness and custom interventions while conditions are pre-clinical. corporations. Her educational background includes an MBA in Finance and Accounting from the Wharton School of the University of Pennsylvania. Ms. and recent coursework in bioscience. and startups and is active in the community promoting science and technology. a BA in French and Economics from Georgetown University. DIYgenomics. government agencies. The organization is engaged in the design and operation of research studies investigating genotype-phenotype linkage and personalized intervention. Swan has a quantitative risk assessment background and became interested in the predictive risk modeling and practical applications of personal genomics in 2008. and philosophy. computer science. USA Melanie Swan is a Research Fellow at DIYgenomics. Palo Alto.Melanie swan Futurist and Applied Genomics Expert. MS Futures Group. physics. a non-profit research organization she founded in March 2010.
development of freckles and solar lentigines. the DIYgenomics aging study investigates whether TERT (telomerase reverse transcriptase) mutations may lead to a phenotypic predisposition for shorter-thanaverage telomeres which may be improved through telomerase activation therapy that may also improve skin fitness. RNA expression. Personalized genomics is an emerging field that incorporates the genetic sequencing profiles of individuals into health-related decisions. The generalized hypothesis and methodology of personalized genomic medicine developed by DIYgenomics is that one or more genetic polymorphisms may give rise to out-of-bounds phenotypic biomarkers which may be ameliorated through personalized intervention. Genomic studies are not as well established in antiaging skin research as in general disease risk and drug response research. and drug response.Translational reverse-aging research: latest advances This talk provides a review of some of the most important advances in translational anti-aging skin research. skin lesions. using information about an individual to select or optimize preventive or therapeutic care by cohort or individual. dryness. disease risk. particularly with regard to personalized genomics. genomic associations have been found in melanoma and cutaneous basal cell carcinoma. Over 100. In skin cancers. in the U. personalized genomics has been linked to acne. psoriasis. 23 . For example. Personalized medicine contemplates an extensive range of health and wellness outcomes ranging from cure to improvement to normalization to prevention to enhancement. Some current applications of personalized genomics include the assessment of ancestry. premature aging. irritation.. As of July 2011. sun damage. structural variation. and microbiome integration. Cockayne syndrome. and Kindler syndrome. Personalized genotyping is carried out through medical professionals and consumer-directed services. The broader role for personalized genomics is as a component of personalized medicine. xeroderma pigmentosa. The field investigates genetic point mutations. the Food and Drug Administration has validated genomic biomarkers for approximately 75 drugs.000 individuals worldwide have subscribed to personal genome services since they became available in late 2007.S. Genomic disease profiling In disease profiling for skin conditions. However drug response is more definitive and accepted. carrier status. The validity and utility of disease risk assessment has been criticized as there is variance between services in disease risk interpretation. but are nevertheless surfacing interesting links between genomic polymorphisms and phenotypic conditions. eczema (atopic dermatitis). erythema. epigenomics.
photoaging. ECM degradation. In skin anti-aging. Wrinkle formation: possibly caused by sun damage. alopecia areata. cancer response. and retinyl N-formyl aspartamate. 24 . Related to skin. loss of subcutaneous fat. and telomere shortening Wrinkle formation is a central concern of translational anti-aging skin research. regenerative medicine. ECM degradation may be facilitated by telomere shortening which triggers a wound healing phenotype that produces collagen and elastin which degrades the ECM and leads to wrinkle formation. Fibrosis is another factor: fibrin (insoluble proteins) in cells becomes infused with deposits over time and turn into fibrosis (thickened connective tissue) which becomes loosened from ECM proteins and triggers wrinkle formation. and skin substitutes Important research is being carried out in stem cells and regenerative medicine. The loss of subcutaneous fat is another important factor in the aging of skin which may contribute to wrinkle formation. personalized genomics may be used to determine an individual’s general profile for different kinds of healthiness. general aging response.Genomic links also exist for hair conditions such as hair loss. and UV-induced damage) is a critical factor. and thickness and curliness of hair. a newly synthesized photostable retinol derivative. aluminum powder. Retin-A is one of the most widely used skin creams for acne and wrinkles but causes an allergic reaction in a significant percent of individuals. Genomic associations have been found in the skin care product areas of antioxidant treatment. UV-radiation may trigger DNA damage which causes skin to fold and wrinkle. 3-D skin printing. Vitamin A. Potential substitutes include retinyl retinoate (a novel hybrid retinoid) to increase the stability of retinol which may have an antiwrinkle effect. anti-aging DHEA treatment. Stem cells. Sun damage (also known as photodamage. Genomic product response profiling A potential opportunity in personalized genomics is the development of skin care products customized to individuals per genetic profiles. male pattern baldness. the topical application of CoQ10 (to reduce reactive oxygen species (ROS) production and DNA damage triggered by UV-radiation). In addition. A variety of solutions to impede or reverse wrinkle formation have been suggested in recent research including DNA repair enzymes. Products could be recommended based on predicted response (efficacy and side effects). premature hair graying. losartan-treated mice developed less fibrosis than controls. a predictive indicator of which conditions may arise over time. UV-radiation may also trigger the activation of heparanase (an extracellular matrix (ECM) degradation molecule) that increases growth factor interaction between epidermis and dermis and causes wrinkles. There may be multiple causes of wrinkle formation. and in conjunction with microbiome research. for example in one study. and other factors leading to dermis and epidermis wellness. a prominent area for potential near-term health advance. immune system response. and willow bark-derived salicin (activating heat shock proteins (HSPs) which protect cells from stress-induced damage). Solutions might include protease inhibitor drugs. and disease risk and wellness profiling. and ACE inhibitors. for personalized mosquito repellent. Genomic wellness profiling In wellness profiling. RNA editing capability. areas of genomic wellness profiling include DNA damage repair response.
Its application in disease risk assessment. hair follicles. and product response customization may only grow over time and lead to many useful innovations in translational antiaging skin research. drug response determination. and skin substitutes that integrate organic and inorganic material.the interrelation between stem cell generation. and other purposes is a key application. Personalized genomics is an important emerging field of science being applied to human biology and medicine. wound healing. wellness profiling. and microRNA expression is being investigated. Producing skin for grafts. 3-D printing of skin with bioscaffolds. 25 . wound healing. A number of techniques are being explored including regenerating skin from an individual’s own stem cells.
phoApplied Toxicology in 1990 at the French University toageing. LVMH Recherche. Paris 7. Three years later she joined the melanogenesis.Louis Vuitton) cosmetic brands. oxidative stress and Paris Diderot. Research Centre LVMH Recherche as a researcher She has supervised several PhD students and postin the field of skin cells and in 2002 she became a doctoral fellows. She participated to articles in peer-reviewed journals and she is co-auresearch projects dedicated to innovation for skin care.Since 2008 she has been a Research Manager speciaBio-Science Innovation Manager. Nizard obtained her PhD in Fundamental and specific areas of interest: protein maintenance. she developed new models of human skin cell cultures and discovered the pharmacological activity of many new active ingredients. carine nizard 26 . She has published more than 20 Bio-Science Innovation Manager. Saint Jean de Braye. France She has conducted over 20 research projects in her Dr. thor of 13 patents. lized in anti-ageing and longevity research for LVMH (Moët Hennessy . heat shock proteins.
However. Both systems have been documented to exhibit an age-related decline. rather than attack free radicals directly. populations are ageing and over the last 100 years the average life expectancy of people has approximately doubled. notably for the proteasome in human epidermal cells and dermal fibroblasts. For the skin. Importantly. sophisticated complementary strategies emerged based on activation of chaperone proteins that protect structures of cellular proteins. a loss in Msr activity would be likely to diminish the antioxidant response. and DNA-all of which have been extensively reviewed. Therefore antiageing skin care emerged that contained natural freeradical scavengers or technologies focusing upstream with active ingredients which.Skin-cell rejuvenation In industrialized countries. and others based on the activation of detoxifying proteins such as proteasome which helps to recycle damaged proteins. The idea that ageing is an active continuation of a genetically programmed development of organisms has been partially discredited. free radicals generated by ultraviolet radiation and internal metabolism are considered to be the most important deleterious ageing agents on cellular proteins. This process is dependent on an increased occurrence of oxidative damage to proteins and also on a decreased elimination of oxidatively modified protein. UV-irradiation of skin cells is known to induce oxidative stress and to promote protein oxidative damage leading to the formation of carbonyl groups as well as the formation of protein adducts with lipid peroxidation products. glycans. hence 27 . lipids. Recently. Ageing is now admitted to be a loss of equilibrium between the capability of an organism to maintain its repair potential and the frequency and intensity of the damage to which it is exposed. a multifactorial phenomenon in which improvement in nutrition and medicine and easier working conditions have played an important role. Elimination of oxidized proteins is mainly achieved through degradation by the proteasomal system while certain oxidative protein modifications such as oxidation of methionine residues can be reversed within proteins by the methionine sulfoxide reductases (Msrs) system which represents one of the few repair mechanisms for oxidized proteins. the most exposed organ to environmental injuries. the fate of such important protein maintenance systems like the proteasome and the Msrs upon UV irradiation has only been recently addressed in skin relevant cellular models. reinforced the natural cellular proteins that detoxify these free radicals. Accumulation of oxidized proteins is a hallmark of cellular ageing and is believed to be one of the main contributors to the aged phenotype.
LVMH Recherche has performed these 3 skin-cell rejuvenation strategies based on experimental work (in LVMH laboratories or within academic collaborations) with innovative ingredients to develop cosmetic products for LVMH brands. an activity that is both stressful and damaging due to the production of free radicals. acids. Irreversible growth arrest at the G1/S phase of the cell cycle is namely due to the overexpression of cyclin-dependent kinase inhibitors such as p21waf1 and p16ink4a. 28 . protecting or stimulating such enzymes responsible for the repair of specific forms of oxidative modification would also be expected to help fight against the accumulation of non functional and potentially harmful oxidized proteins. These approaches enable us to have interesting in-vitro skin-cell rejuvenation experimental data and in vivo quantifiable benefits for skin following their cosmetic use. The paradigm for hormesis is exercise. However. which represents one of the major deleterious effects associated with intrinsic skin ageing and photo-ageing. It makes use of the body’s intrinsic capacity for self-maintenance and repair. Therefore for the proteasome.favouring the accumulation of oxidized proteins. Another interesting concept known as hormesis has recently attracted attention in the field of anti-ageing research. Recently new active ingredients of natural origin have been proposed to fight the skin cells entry in senescence. short telomeres and changes in the expression level of many genes. Human diploid fibroblasts (HDFs) in replicative senescence are characterized by a typically enlarged cell shape. apoptosis etc. senescence-associated b-galactosidase activity. the hormetic effect of this strenuous activity has a wide range of health-promoting effects. which carry signals. leading to hypophosphorylation of the retinoblastoma protein. activate the processes of proliferation (dividing). All cells in the organism produce specific molecules . Through the secretion of various regulatory molecules senescent cells can influence other cells triggering their ageing processes.is known as hormesis. The theory behind the approach . and unfavourably influence keratinocytes recovery from oxidative stress encountered during UV irradiation. Limited mitotic life span is observed in many eukaryotic cell types and is interpreted as a manifestation of cellular ageing. differentiation. stress hormones and tissue damage.that low doses of toxic or harmful substances have a protective effect .cytokines. as an inducer of repair and maintenance processes. including slowing down ageing. by exposing cells and organisms to brief periods of stress.
His experimental and theoretical work has been published in over 140 publications. In 1980. Kvitko graduated from the biological faculty of the Belarus State University (Minsk) in 1974 and went to the Institute of Genetics and Cytology of the National Academy of Sciences of Belarus (IGC NANB). In these studies he. 30 . his research increasingly concentrated on cellular ageing. Kvitko is a member of the Belarussian Society of Geneticists and Breeders. with his research team.This resulted in the two new theoretical concepts: participation theory of ageing and developmental theory of rejuvenation. Minsk. used the informative experimental method based on continuous computer videorecording of microscopic images (computerized videomicroscopy) of living cell cultures revealing unknown processes during aging. Oleg Kvitko performs an analysis of data and theories in biology of ageing. Belarus Oleg V. aiming to explain the causes of ageing and mark ways to elaboration of effective means of slowing ageing and rejuvenation at the levels of a cell and an organism. he did a PhD in biology (specialization in genetics) within IGC NANB. a head of Minsk branch of the Gerontological Society of the Russian Academy of Sciences and an associate editor of the journal “Theoretical biology and medical modelling”. Institute of Genetics and Cytology. cancer transformation and stem cells. National Academy of Sciences. In the last 20 years. KVitKo Leading scientist.oleg V.
One may object to that because telomere shortening. that is the violation of normal physiologically optimal differentiated state of cells. not epigenetic process. may be classified rather as a genetic. Both mechanisms participate in chromatin remodeling and. disturbances of intercellular communications and deviations from normal cell density. For searching the means of retardation or reversal of aging the possibility of selective epigenetic reprogramming leading to rejuvenation is of special interest. In contrast to the short-termed metabolic alterations of gene expression epigenetic changes causing ageing are relatively stable and lead to disdifferentiation (the term proposed by Richard Cutler).Signalling pathways and rejuvenation: risks and opportunities Finding new effective rejuvenation means can be greatly helped by knowledge of the mechanisms of biological ageing and opposite processes of restoration (repair) of age-related damage. In its turn. phosphorylation and others). thereby. unlike DNA methylation and histone modifications. anomalous proportions of different cell types. In addition to these two processes telomere shortening may be mentioned among the important epigenetic mechanisms of ageing that are perspective targets for rejuvenation. Under this rejuvenating process restoration of telomeric repeats at the ends of chromosomes and physiologically optimal (for a particular cell type) pattern of differential gene activity (determined by DNA cytosine methylation and modifications of chromosomal histone proteins) should take place but dedifferentiation (that happens during somatic cell nuclear transfer into oocyte cytoplasm and construction of induced pluripotent stem cells) should not occur. Two molecular mechanisms of epigenetic changes triggering ageing gained a special attention. However. because it results in changes of a primary nucleotide sequence. 31 . similarly to conventional epigenetic processes (and in contract to genetic mutations). According to the developmental theory of rejuvenation proposed by the author the natural mechanisms of epigenetic rejuvenation exist but do not always work effeciently enough to withstand the age-related accumulation of epigenetic damage. regulate gene expression at a global level. telomere shortening is reversible due to a special enzyme telomerase or other (alternative) mechanisms of telomere elongation. Significant experimental evidence supports the opinion that epigenetic changes underlying unfavourable deviations of gene expression are the major mechanism of ageing. In addition. disbalance of gene expression leads to the damage in tissues due to accumulation of dysfunctional cells. telomere shortening happens regularly (in every mitotic division of many cell types). These are DNA methylation and modifications of chromatin histones (acetylation.
thereby. FGF. It is known that Wnt (one of morphogens) can activate the Myc protooncogene which incodes a transcription factor that activates the production of telomerase and regulates expression of 15% of all genes through recruiting histone acetyltransferases that modify chromosomal histones. In addition to systemic methods of rejuvenation. In particular. simultaneously with performing their “canonical” morphogenetic functions. In frames of the developmental theory of rejuvenation a new meditation technique has been proposed – developmental meditation (Kvitko. As a rule. That is why species with extended growth periods have long lifespans. Possible involvement of protooncogenes in rejuvenation signalling should be taken into consideration in cell culture experiments aiming at finding effective and safe regimes of topical application of rejuvenation ingredients. TGF-beta and others). rejuvenates cells. optimal regimes of using rejuvenation means may be based on 32 . The natural process of rejuvenation is driven by the same extracellular morphogenetic molecules (morphogenes) that regulate embryogenesis. Since human species has a genetically restricted growth.During embryogenesis and postnatal growth the special signalling mechanism reverses epigenetic mistakes and. skin provides unique possibilities for the elaboration and practical application of topical rejuvenation means. There are several families of morphogenes (Wnt. stimulate telomerase and trigger restoration of physiologically optimal gene expression by regulation of enzymes that modify DNA (methylation) and chromosomal histone proteins. which stimulate or repress gene expression. some fishes or mollusks grow throughout their life with little or no senescence.and growth-coupled rejuvenating epigenetic repair insures the delay of functional decline to the point of an organism’s ability to produce progeny. In this context it seems reasonable to consider some additional aspects of a possible mechanism of rejuvenation signalling. and only an excessive size. At the systemic level stimulation of epigenetic rejuvenation in different parts of the body may be achieved by neuroendocrine regulation. This idea is supported by the recent research on influence of some forms of meditation on telomere shortening and telomerase activity in immune cells (Jacobs et al. In particular. After the end of development and growth fluctuations of morphogens in tissues decrease (“flatten”) and become insufficient for initiating the cascades of events resulting in rejuvenation of the whole body. topical influences may give invaluable rejuvenation effects. Because of the regulatory pleiotropy (when one molecule takes part in different signalling pathways) morphogenes. extracellular morphogenetic signals may stimulate rejuvenation pathways through protooncogenes. morphogenes bind to specific cell membrane receptors activating signalling pathways inside cells.. Notch. These species have an indeterminate growth (for example. Hedgehog. 2011).. for counteracting aging and extending human life intensive (embryo-like) production of morphogenes should be reestablished in many or all tissues of an adult organism. 2009).This rejuvenation mechanism also prevents aging in organisms with “negligible senescence”. For example. Thus. This development. not “ordinary” ageing is a major reason of their death). rejuvenation-promoting modifications of neuroendocrine processes can be reached by special psychological practices. 1935) may be explained by the prolongation of postnatal growth and extension of the work of a growth-coupled rejuvenation process. It appears also that the well known life-extending effect of caloric restriction in rodents (McCay et al.
the concept of transient (reversible) immortalization. This proposition is supported by the experimental evidence on transient immortalization of mammalian cells. Irreversible immortalization is dangerous and inappropriate. pulsed regimes of rejuvenation signalling. Learned from nature safe and effective means of rejuvenation that works in developing and growing organism may exploit nonlinear. Improved methods of long-term (from days to months) uninterrupted computer videomicroscopy of living cell cultures provide unique experimental tools for elaboration of new effective formulas for topical rejuvenation. 33 .
She has been recruited as Research Investigator to join the Dermatology Department Faculty at the University of Michigan in 2006. She wrote four book chapters and published dozens of articles in peer-reviewed scientific journals. Dr. and a National Institute of Health Research Scientist Development Award four years later. She completed postdoctoral trainings at the Université de Reims Champagne in the Department of Biochemistry and Molecular Biology. She also teaches the Basic Science Journal Club to Dermatology Residents at the University of Michigan. USA Dr. in the Department of Dermatology at the University of Michigan during four years. University of Michigan. 34 . Ann Arbor. Rittié received an American Skin Association Research Scholar Award in 2007. Rittié received her Master of Science in Cell Biology in 1996 and her PhD in Biochemistry and Molecular Biology in 2001 from the Université de Reims Champagne-Ardenne in France. and in the United States. She studied specifically the molecular and cellular basis for impaired wound healing in aged human skin and the effects of aging on follicular stem cell functions in human skin.laure rittié Research Investigator. Her current research focuses on elucidating the mechanisms of altered skin re-epithelialization in aging. Department of Dermatology Photoaging and Aging Research Program.
With repeated exposure to UV light overtime. including type I collagen. the major structural protein in the dermis. Damage to type I collagen is initiated by UV irradiation-induced metalloproteinase activity that degrades collagen fibers into fragments. UV irradiation concomitantly inhibits procollagen production by dermal fibroblasts. we will show that controlled wound healing is an effective strategy for skin rejuvenation. and will provide a rational for future optimization of treatment strategies and protocols. The resulting decreased mechanical tension in the dermis is responsible for a self-sustained negative feedback decreasing collagen production in the skin. thus preventing the dermis to efficiently repair itself. Thus. skin rejuvenation strategies must be aimed at stimulating collagen production in photodamaged skin. followed by tissue restoration including intense deposition of type I collagen and other extracellular matrix proteins. various laser-based devices have been developed to generate a controlled wound healing reaction that ideally triggers minimal inflammation and maximal collagen production in photoaged skin. Photoaged skin is characterized by the presence of damaged extracellular matrix components. In the past decades. damaged collagen cannot be replaced.Controlled Wound Healing for Skin Rejuvenation: Recent progress and Future Challenges “Photoaging” defines the premature aging of the skin that primarily results from chronic exposure to ultraviolet (UV) irradiation from the sun. Cutaneous wound healing is a regulated process that involves an initial clearing of the wound through an inflammatory phase. collagen fragmentation accumulates in the skin. 35 . To reverse this vicious cycle. Providing a detailed analysis of the molecular and cellular alterations induced by several of these lasers.
Parfums Givenchy and Fresh. Throughout the process. fragrance derivatives. located in Saint Jean de Braye. Tokyo and Shanghai. LVMH Recherche has about 260 researchers. Paris. formulations and processes that we develop. Its mission? To design and develop perfume. Guerlain. Paris.LouisVuitton). innovation is expressed through the ingredients. Our research spans everything from knowledge of skin and cosmetics users to the creation of formulations suitable for strong perceived efficacy and for an international use. Tokyo and Shanghai 36 . skincare products and makeup for several brands of the LVMH Group (Moët Hennessy . all united in a single objective: the creation of new beauty solutions inducing emotion of use to our customers. LVMH Recherche by the numbers: 260 employees More than 1200 products developed per year More than 200 patents More than 50 scientific papers per year Research teams in St Jean de Braye. whose members are Parfums Christian Dior.LVMH Recherche Perfumes & Cosmetics Founded in 1980. LVMH Recherche is a Groupement d’Intérêt Economique (GIE).
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