LVMHS Symposium on Skin Science

7/31/2019 LVMHS Symposium on Skin Science

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11th

Scientic SymposiumLVMH Recherche

Skin RejuvenationLondon UK

Thursday 27th October 2011


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11th

Scientic SymposiumLVMH Recherche

Skin RejuvenationLondon UK

Thursday 27th October 2011


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Dr. Barry KnightHead 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, newspa-

pers, journals, magazines, sound and music recordings,

videos, maps, stamps, prints, drawings

For many years, the British Librar y 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 worlds knowledge, and

enriches the cultural life of the nation.

The British Library


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Frdric BontDirector of Scientic Communication

Dear Colleagues,

It is my great pleasure and honour to welcome you

to the 2011 LVMH Recherche Symposium held at the

British Library in London.

In many countries, in the next 50 years, about one-third

of women will be over 50. Appearance and skin vitality

are and will remain a subject of primary importance in

daily life and for social well being. If there is beauty to

be found in every human face, the cosmeticians role is

to provide skin care and makeup products that allow a

womans facial features to work in concert and reect

light with more harmony and equilibrium. Scientistsare looking for new strategies able to regenerate the

health and youth of the skin by producing a durable

effect below the skins surface.

Today, selected scientic presentations will cover a wide

range of topics and will present the latest scientic

discoveries in anti-aging and skin rejuvenation research.

Rejuvenation is the central focus of thousands research

projects in laboratories in the eld of genetics, cellular

and molecular biology, active ingredients, reprogram-

ming strategies and formulation. The goal of these

projects is to help women to achieve naturally radiant

skin and to reestablish youthful facial characteristics.

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 eld

of cosmetics and to generate transdisciplinary links.

It is a great privilege to hold this symposium at the

British Library, which occupies a unique and inspiring

place in the worlds cultural and information network,

an institution that supports research, guaranteesaccess to world knowledge to future generations and

enriches the cultural life of nations.

Welcome

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Executive Vice-President R&D

LVMH Recherche

eric perrier

Our Philosophy:

Research for emotion

Healthy skin is our main source of inspiration. To

better understand it, our Research and Development

Center has developed a comprehensive set of investi-

gative tools in immunohistochemistry, cell culture, skin

reconstruction, skin biopsy, DNA chips, proteomics,

advanced imaging and sensory maps, among others.

Our daily goal is to better understand the biological

mechanisms that govern skins appearance, evolution

and rhythm. Research by our biologists, combined with

that of phytochemists in our ethnobotanical network,

aim to identify biological targets and develop active

ingredients and formulas to help maintain the beauty

and youth of the skin.By combining our knowledge with information from

the elds of sociology, psychology and neurocosme-

tics, and validating our results in clinical studies and

consumer panels worldwide, we seek to reach tai-

lored cosmetics solutions.

Deeply rooted in a culture of sharing knowledge and

respect of everyones skills, our research philosophy is

enriched by our own expertise as well as that of the

international experts with whom we work.


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Scientic adviser

Max santoul processes that restructure the skins composition torestore its lost momentum. One could say that this

is a drive towards the future that restores the condi-

tions of a youthful past.Recently new terms have cropped up in the eld of

cosmetics to describe new concepts, such as derma-

toporosis, while other terms have remained the same

but no longer have quite the same meaning. The area

of hydration, for example, which was revolutionized

by the discovery of aquaporins, for which Peter Agre

earned a Nobel Prize in 2003, has been important

to the formulation of our products for some years.

The regulation of proteasome (whose discovery also

earned a Nobel Prize in 2004) represents another

breakthrough in our formulations. Among antioxy-

dants, complex molecules were isolated from specic

vine shoots of rare french vines and some polyphe-

nolic trimers (miyabenol) show remarkable biological

activities to ght skin ageing.Our research laboratory is currently working on many

projects whose aim is to nd active ingredients that

would help in skin rejuvenation. Genetic sites involved

Skin has a natural potential to conserve its beauty,

and probably contains the secrets of prolonged youth.

Some cells naturally live for many years and others

have an extraordinary power of renewal. Moreover, it

appears that our biological clock is part of a process

of aging whose activation is not inevitable, and we can

slow down its pendulum. Even better, it is becoming

possible to prevent our biological clock from cutting

time short and to compel it to reverse its conse-

quences. Thus a new era that goes beyond anti-aging

is emerging, an era of rejuvenation.

LVMH Research is aimed at making advances in

understanding skin composition, but also in the areas

of the protection, repair and the enzymes of the skin

slowing or stimulating their production as well as


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the twentieth century, with an emphasis on repair

and protection (antioxydants are well-established

examples), and now they are moving towards the

future, focusing on rejuvenation, with research on

stem cells and agents capable of reversing the course

of time.

Through this symposium we hope to share with you

our enthusiasm for the latest advances in this exciting

eld.

in aging may be targeted, stem cells reactivated, enzy-

matic processes optimized. For example, of particular

interest are sirtuins, cellular enzymes in close contact

with proteins that manage our genetic inheritance and

affect cellular metabolism by regulating the expression

of certain genes. Current research has developed to

the point where a youthful appearance is a right to

which we can all aspire, and the protection of an organ

as precious as the skin is becoming a duty.

This living envelope, which has inuenced the evolution

of our species since the dawn of humanity, clothes ourbodies in nudity. This soft, smooth, durable, expandable,

waterproof garment that protects us from a hostile

environment must stand the test of time. It holds an

exceptional power of longevity and perhaps, secretly, a

universal power of repair and renewal.

If we had to summarize the history of cosmetics, we

would say that it dates back to the earliest civilizations.

For millennia cosmetics were devoted to beautica-

tion, then they entered the era of anti-aging during


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WelcomeEric Perrier, Frdric Bont,

LVMH Recherche, Saint Jean de Braye, France

Introduction

Dr. Barry Knight, Head of Conservation Research, British Library, London, UK

Prospects for truly comprehensive repair of aged skin

Dr. Aubrey de Grey, Chief Science Ofcer,

SENS Foundation, Mountain View, USA

A dermatologists view on skin rejuvenation

Dr. Leslie Baumann, Chief Executive Ofcer, Baumann Cosmetic & Research

Institute, Miami, FL, USA

Stem cells and skin rejuvenation

Pr. Carlo Pincelli, Professor of Dermatology,

School of Biosciences and Biotechnologies,University of Modena and Reggio Emilia, Italy

Translational reverse-aging research: latest advances

Melanie Swan, MBA, Futurist and Applied Genomics Exper t,

MS Futures Group, DIYgenomics, Palo Alto, USA

Skin-cell rejuvenation

Dr. Carine Nizard, Bio-Science Innovation Manager,


Signalling pathways and rejuvenation: risks and opportunities

Oleg Kvitko, Ph.D., Leading scientist, Institute of Genetics and

Cytology, National Academy of Sciences, Minsk, Belarus

Controlled wound healing for skin rejuvenation:

recent progress and future challenges

Dr. Laure Ritti, Research Investigator,Department of Dermatology Photoaging and Aging Research Program,

Ann Arbor, University of Michigan, USA

Program


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Chief Science Ofcer, SENS

Foundation, Mountain View, USA

aubrey de grey ventions to repair and/or obviate that damage. He hasdeveloped a possibly comprehensive plan for such

repair, termed Strategies for Engineered Negligible

Senescence (SENS), which breaks aging down intoseven major classes of damage and identies detailed

approaches to addressing each one. A key aspect of

SENS is that it can potentially extend healthy lifespan

without limit, even though these repair processes will

probably never be perfect, as the repair only needs to

approach perfection rapidly enough to keep the ove-

rall level of damage below pathogenic levels. Dr. de

Grey has termed this required rate of improvement

of repair therapies longevity escape velocity. Dr. de

Grey is a Fellow of both the Gerontological Society

of America and the American Aging Association, and

sits on the editorial and scientic advisory boards of

numerous journals and organisations.

Dr. Aubrey de Grey is a biomedical gerontologist

based in Cambridge, UK, and is the Chief Science

Ofcer of SENS Foundation, a California-based cha-

rity dedicated to combating the aging process. He

is also Editor-in-Chief of Rejuvenation Research, the

worlds highest-impact peer-reviewed journal focused

on intervention in aging. He received his BA and Ph.D.

from the University of Cambridge in 1985 and 2000

respectively. His original eld was computer science,

and he did research in the private sector for six years

in the area of software verication before switching

to biogerontology in the mid-1990s. His research

interests encompass the characterisation of all the

accumulating and eventually pathogenic molecular

and cellular side-effects of metabolism (damage) thatconstitute mammalian aging and the design of inter-


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Prospects for trulycomprehensive repair of aged skin

are broadly similar. In all cases they can be classied

into just seven major categories. Furthermore, for

each such category, it seems likely that all examples

within a category will in due course be amenable torepair by broadly the same type of intervention.

Two of these seven categories concern extracellu-

lar material: accumulation of miscellaneous detritus

that has escaped the attention of all mechanisms for

degradation or excretion, and biophysical dysfunc-

tion caused by chemical or physical alterations to the

extracellular matrix. In the skin, the latter is of parti-

cular interest in relation to the basal lamina separating

the dermis and the epidermis, and also the interstitial

extracellular matrix permeating the dermis. These

lattices of structural proteins (mostly collagen and

elastin) are recycled only slowly, with half-lives of the

same order of magnitude as the human lifespan, so

they have ample opportunity to accumulate damage.

One major type of such damage is random crosslin-

king, predominantly caused by sequences of reactions

between circulating monosaccharides and lysine or

arginine residues of ECM proteins. These reactions,

collectively referred to as glycation, sometimes

result in covalent linkages (especially one particular

structure termed glucosepane) between juxtaposed

proteins, progressively diminishing the elasticity of theECM as a whole, with macroscopic consequences

in terms of skin vitality. Similar chemistry also results

Though aging of the skin is not in itself a l ife-threatening

process, the immense demand for skin care products

demonstrates how important skin aging is in dimi-

nishing self-esteem and quality of life. In spite of conti-nued progress in improving the efcacy of skin rejuve-

nation methods, existing techniques remain far from

fully effective. 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 skin

is a rather complex tissue, incorporating two verydifferent layers of cells (the dermis and the epider-

mis), each of which possesses multiple cell types and

which are separated by an extracellular lamina that

also undergoes age-related degradation. Accordingly, it

is very likely that a panel of simultaneous interventions

will be required, each addressing a subset of the many

types of dysfunction that aged skin exhibits. Secondly,

the skin is in intimate contact with the rest of the body,

especially via the circulation, and is therefore adversely

affected by the aging of all other tissues. It is difcult

to quantify the impact of this as a driver of skin aging,

but there are reasons to suspect that it is substantial.

Luckily, the specic types of molecular and cellular

damage accumulating in all tissues, the skin included,


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in adducts attached to individual amino acids: these

probably do not alter the ECMs biomechanical pro-

perties, but they may be immunogenic, especially in the

increasingly autoimmunity-prone aged environment. In

addition, simple rupture of the peptide backbone of

ECM proteins will go unrepaired until the protein is

subjected to wholesale degradation and replacement,

which as noted above is a rare process. This may be

a less signicant type of ECM damage than in other

tissues, such as the walls of the major arteries, but it

cannot safely be ignored. Accordingly, there is a strongcase for exploring methods to stimulate faster turno-

ver of the skin ECM, thereby to replace it with pristine

ECM lacking these modications. Unfortunately, there

is evidence that crosslinking renders ECM somewhat

resistant to degradation by proteases naturally secre-

ted by broblasts an obstacle that must be over-

come if the loss of elasticity just mentioned can be

fully reversed. However, after many years of pessimism,

there is now new hope for the development of phar-

maceuticals capable of cleaving the most abundant

glycation-induced crosslinks.

Similarly, at the intracellular level there are changes

during aging which may contribute substantially to the

skins biophysical properties and thus compromise its

perceived youth. The most important may be the ac-

cumulation in quiescent dermal broblasts, typically in

the lysosome, of a variety of molecular detritus that is

created as byproducts of normal metabolism but is not

then degraded or excreted. Pigmented material in par-

ticular, whether intracellular or extracellular, constitutes

an important aspect of aging. A promising approach

to repairing this type of damage is to introduce intocells enzymes (or the genes encoding them), found

elsewhere in the biosphere (especially in bacteria), that

can degrade such compounds.

It is also necessary to consider aging at the cellular

level, i.e. changes in cell number as opposed to cell

structure. Thinning of the skin, especially the dermis,

contributes greatly to skin aging, and is largely a conse-

quence of depletion of broblast density. In the epi-

dermis, stem cell number may also decline. Cell loss

is the natural target for stem cell therapies of various

means, and especially in relation to the epidermis we

are already seeing encouraging progress, not least as

a result of the relevance to burns therapy.In sum, 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 uto-

pian goal. With sufcient resources and determina-

tion, it can be achieved within the foreseeable future.


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Dr. Leslie Baumann, Chief Executive Ofcer,

Baumann Cosmetic & Research Institute,

Miami, FL, USA

leslie bauMann Her New York Times bestselling book The Skin TypeSolution is in 5 countries and describes her skin

typing system that is based on her years of research

on skin care. She authors a skin care blog on Yahoo!

Health that is read by millions of people. Dr. Leslie

Baumann does not have her own skin care line. Her

clinical approach for skin care and cosmetic medicine

combines science with practical solutions.

Dr. Leslie Baumann is a dermatologist, researcher, pro-

fessor and well-known author. In 1997, she chaired the

rst Division of Cosmetic Dermatology in the USA

at the University of Miami. Her textbook Cosmetic

Dermatology (McGraw Hill 2002, 2010) was the rst

textbook on the subject and is currently the bestselling

cosmetic dermatology textbook worldwide.She performed the research trials in the USA that

led to FDA approval of Botox, Dysport, Sculptra,

Juvederm, and many other products and procedures.

She has performed clinical research trials for over 50

cosmetic and pharmaceutical companies.


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A Dermatologists Viewon Skin Rejuvenation

unsuccessful in treating the loss of collagen, elastin

and hyaluronic acid with the exception of retinoids.

The science of topical retinoids and the use of dermal

llers and botulinum toxin to treat aged skin will bediscussed.

Facial volume loss is a major cause of skin aging. Stem

cells, fat and dermal llers are being used to correct

facial volume defects. The state of the art of stem cells

will be discussed.

The second step in planning a facial rejuvenation plan

is determining the patients Baumann Skin Type using

a questionnaire known as the Baumann Skin Type

Indicator (BSTI). There are 16 individual Baumann

Skin Types based on the combinations of the following

parameters:

1. Oily vs dry

2. Sensitive vs resistant

3. Pigmented vs nonpigmented

4. Wrinkled vs non-wrinkled (tight)Combining these 4 parameters gives 16 possible

combinations. This lecture will briey describe the 16

skin types and will focus on the science behind what

causes the various skin conditions.

A future research aim is to identify the genetic nger-

print of various skin types.

Skin Rejuvenation requires a multifaceted approach.

The most successful outcomes occur when the pa-

tient is properly educated and motivated, and a proper

skin care regimen is combined with in-ofce pro-cedures. The current trend is to develop at home pro-

cedures that mimic in-ofce procedures. This lecture

will discuss the thought process that dermatologists go

through when selecting skin care products and cosme-

tic procedures for facial rejuvenation.

The rst step in planning a facial rejuvenation plan is

evaluating these 4 facial characteristics to decide what

cosmetic procedures are best suited for the patient.

1. Evenness of skin color

2. Skin surface texture

3. Presence of wrinkles

4. Facial volume.

A youthful face has evenness of color. Visible blood

vessels and accumulation of melanin contribute to

unevenness of color. Lasers, light devices, skin peels andskin care products are combined to treat uneven skin

tone. The theory of photothermolysis and use of light

to treat skin discoloration will be discussed.

Skin surface texture is determined by the condition of

the stratum corneum. Methods used to smooth the

stratum corneum include facial scrubs, facial brushes,

microdermabrasion and chemical peels.

Wrinkles are caused by the loss of collagen, elastin

and hyaluronic acid. Topical products have been largely


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Professor of Dermatology, School

of Biosciences and Biotechnologies,

University of Modena andReggio Emilia, Modena, Italy

carlo pincelli As epidermal expert, he has brought particularcontributions in areas such as stem cells, mole-

cular and cell biology and apoptosis, exploring

deeply the pathogenic mechanisms implicated in skin

pathologies.

He is co-founder and Chief Executive Of-cer of the

academic spinoff Pincell S.r.l.Pr. Pincelli is also co-in-

ventor of two international patents and author of

over hundred-fty articles in peer-reviewed jour-

nals. In 2006-2007, he has been President of

the European Society for Dermatological Research

(ESDR). He is currently member of the Board ofTrustees of the European Skin Research Foundation

(ESRF).

Carlo Pincelli received his training in Dermatology at

the University of Modena and Reggio Emilia in Italy

and at St. Johns Hospital for Diseases of the Skin in

London. 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 ofDermatology Boston University in 1994 as a visiting

scientist.

He became Professor of Clinical Dermatology in

1990. Five years later he was appointed as Director of

Research of the Laboratory of Cutaneous Biology at

the University of Modena and Reggio Emilia.


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Stem cells and skin rejuvenation

throughout life, it was tacitly understood that the

epidermal stem cell remained functional as long as

the organism l ived and that this cell population met

the continual demand for new cells. Studies in mouseskin conrmed that epidermal stem cells remain func-

tional and appear to resist to cellular ageing. Recent

works, 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. TA cells appear to be

more affected than stem keratinocytes by ageing also

in human epidermis.

KSCs reside in a special microenvironment, the niche,

that allows them to maintain their unique features

and stemness. KSC are located within the basal

layer of epidermis and rest upon the basal mem-

brane that is rich in extracellular matrix and growth

factors. As basal keratinocytes exit the niche, they

move into suprabasal layers, and different microenvi-romental stimuli inuence their destiny. Under normal

conditions, basal keratinocytes leave the basal niche

to undergo terminal differrentiation. This critical pro-

cess is regulated by an increasing number of signals.

The niche concept in itself implies that KSCs, in order

to maintain longevity and to ensure continue tissue

renewal, need to be protected from apoptosis, and all

the factors implicated have to be taken into conside-

ration during skin ageing. Some integrin family mem-

bers are downregulated during skin ageing. Moreover,

Ageing is an inevitable process, with both intrinsic and

extrinsic determinants, which involves all tissues and

organs of the body and has particular repercussions and

evidence in the skin. Intrinsic ageing of the skin occursas a natural consequence of physiological changes over

time at variable rates. Extrinsic factors are, to varying

degrees, controllable and include exposure to sunlight,

pollution or nicotine, repetitive muscle movements

like squinting of frowning, and miscellaneous lifestyle

components such as diet, sleeping position and overall

health. Skin aging involves increased susceptibility to

injury and infection, reduced wound healing, loss of

dermal elasticity, poor epidermal barrier maintenance,

wrinkling, hair loss, and increased cancer risk.

Since birth, skin homeostasis and integrity is guaranteed

by the presence of Keratinocyte Stem Cells (KSC) and

by the correct balance between proliferation, differen-

tiation and apoptosis. KSCs self-renew and generate

the different lineages that form the mature tissue.As we grow old, epidermis becomes more fragile and

susceptible to trauma, with an increasing rate of impai-

red wound healing. The decline of tissue regenerative

potential is a hallmark of ageing and may be due to

related changes in tissue-specic stem cells. Anyway,

given that epidermal functionality must be maintained


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survivin, an Inhibitor of Apoptosis Protein (IAPs) family

member, implicated in cell cycle regulation and sup-

pression of apoptosis, is strongly expressed in KSCs

and protect these cells from apoptosis induced by

UVB radiations. Among other factors, Notch ligands

expressed in basal keratinocytes bind to Notch

receptors in suprabasal cells, thus promoting the

commitment of basal keratinocytes to differentiation.

Notch proteins and their signaling pathways seem to

be modulated dur ing skin ageing. Finally, neurotrophins

and their receptors play an important role in mantainigepidermal homeostasis.

Furthermore, dermis plays a critical role in sustaining the

stem cell population. The crosstalk between the epider-

mal and dermal compartment is necessary to maintain

epidermal homeostasis. For instance, factors produced

in the dermal compartment can act on stem cells.

The chronological aging and photoaging of skin is

accompanied by an extensive ECM remodelling in the

dermis, with a decrease in collagen production and

a reduction of skin tone and elasticity, brosis and

increased risk to develop aggressive and invasive skin

cancers.

Therefore, we can conclude that KSCs behaviour is

surely age-dependent and strictly related to individual

characteristics. However, KSC descendent cells and all

the factors involved in KSC niche have to be taken

into account in human skin during ageing, in order to

plan cosmetical and medical interventions in physio-

logical and pathological conditions.


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Futurist and Applied Genomics Expert,

MS Futures Group, DIYgenomics, Palo Alto, USA

Melanie swan Economics from Georgetown University, and recentcoursework in bioscience, nanotechnology, physics,

computer science, and philosophy.

She is a faculty member at Singularity University and

an Afliate Scholar at the Institute for Ethics and

Emerging Technologies. Ms. Swan serves as an advisor

to research foundations, government agencies, corpo-

rations, and startups and is active in the community

promoting science and technology, and opportunities

for women.

Melanie Swan is a Research Fellow at DIYgenomics, a

non-prot research organization she founded in March

2010. The goal of DIYgenomics is to realize persona-

lized medicine by establishing baseline measures of

wellness and custom interventions while conditions are

pre-clinical. The organization is engaged in the design

and operation of research studies investigating geno-

type-phenotype linkage and personalized intervention.Ms. Swan has a quantitative risk assessment background

and became interested in the predictive risk modeling

and practical applications of personal genomics in

2008. Her educational background includes an MBA

in Finance and Accounting from the Wharton School

of the University of Pennsylvania, a BA in French and


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Translational reverse-agingresearch: latest advances

Personalized medicine contemplates an extensive

range of health and wellness outcomes ranging from

cure to improvement to normalization to prevention

to enhancement. The generalized hypothesis andmethodology of personalized genomic medicine

developed by DIYgenomics is that one or more ge-

netic polymorphisms may give rise to out-of-bounds

phenotypic biomarkers which may be ameliorated

through personalized intervention. For example, the

DIYgenomics aging study investigates whether TERT

(telomerase reverse transcriptase) mutations may

lead to a phenotypic predisposition for shorter-than-

average telomeres which may be improved through

telomerase activation therapy that may also improve

skin tness.

Genomic studies are not as well established in anti-

aging skin research as in general disease risk and drug

response research, but are nevertheless surfacing

interesting links between genomic polymorphismsand phenotypic conditions.

Genomic disease proling

In disease proling for skin conditions, personalized

genomics has been linked to acne, eczema (atopic

dermatitis), irritation, erythema, dryness, psoriasis,

skin lesions, sun damage, premature aging, xeroderma

pigmentosa, development of freckles and solar lenti-

gines, Cockayne syndrome, and Kindler syndrome. In

skin cancers, genomic associations have been found

in melanoma and cutaneous basal cell carcinoma.

This talk provides a review of some of the most impor-

tant advances in translational anti-aging skin research,

particularly with regard to personalized genomics.

Personalized genomics is an emerging eld that incor-porates the genetic sequencing proles of individuals

into health-related decisions. The eld investigates ge-

netic point mutations, structural variation, epigenomics,

RNA expression, and microbiome integration. Some

current applications of personalized genomics include

the assessment of ancestr y, carrier status, disease r isk,

and drug response. Personalized genotyping is carried

out through medical professionals and consumer-di-

rected services. Over 100,000 individuals worldwide

have subscribed to personal genome services since

they became available in late 2007. The validity and

utility of disease risk assessment has been criticized

as there is variance between services in disease risk

interpretation. However drug response is more de-

nitive and accepted. As of July 2011, in the U.S., theFood and Drug Administration has validated genomic

biomarkers for approximately 75 drugs.

The broader role for personalized genomics is as a

component of personalized medicine, using informa-

tion about an individual to select or optimize pre-

ventive or therapeutic care by cohort or individual.


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Genomic links also exist for hair conditions such as hair

loss, male pattern baldness, alopecia areata, premature

hair graying, and thickness and curliness of hair.

Genomic wellness proling

In wellness proling, personalized genomics may be

used to determine an individuals general prole for

different kinds of healthiness, a predictive indicator

of which conditions may arise over time. Related

to skin, areas of genomic wellness proling include

DNA damage repair response, RNA editing capability,

immune system response, cancer response, generalaging response, and other factors leading to dermis

and epidermis wellness.

Genomic product response proling

A potential opportunity in personalized genomics is

the development of skin care products customized

to individuals per genetic proles. Products could be

recommended based on predicted response (efcacy

and side effects), and disease risk and wellness pro-

ling. Genomic associations have been found in the skin

care product areas of antioxidant treatment, anti-aging

DHEA treatment, aluminum powder, and in conjunc-

tion with microbiome research, for personalized mos-

quito repellent.

Wrinkle formation: possibly caused by sun damage,

ECM degradation, loss of subcutaneous fat, and telo-

mere shortening

Wrinkle formation is a central concern of translational

anti-aging skin research. There may be multiple causes

of wrinkle formation. Sun damage (also known as pho-

todamage, photoaging, and UV-induced damage) is a

critical factor. UV-radiation may trigger DNA damage

which causes skin to fold and wrinkle. 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. The loss of subcu-

taneous fat is another important factor in the aging

of skin which may contribute to wrinkle formation.

Fibrosis is another factor: brin (insoluble proteins)

in cells becomes infused with deposits over time and

turn into brosis (thickened connective tissue) which

becomes loosened from ECM proteins and triggers

wrinkle formation. Solutions might include protease

inhibitor drugs, and ACE inhibitors, for example in one

study, losartan-treated mice developed less brosisthan controls. In addition, 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.

A variety of solutions to impede or reverse wrinkle

formation have been suggested in recent research

including DNA repair enzymes, the topical applica-

tion of CoQ10 (to reduce reactive oxygen species

(ROS) production and DNA damage triggered by

UV-radiation), Vitamin A, and willow bark-derived

salicin (activating heat shock proteins (HSPs) which

protect cells from stress-induced damage). Retin-A is

one of the most widely used skin creams for acne and

wrinkles but causes an allergic reaction in a signicantpercent of individuals. Potential substitutes include

retinyl retinoate (a novel hybrid retinoid) to increase

the stability of retinol which may have an antiwrin-

kle effect, and retinyl N-formyl aspartamate, a newly

synthesized photostable retinol derivative.

Stem cells, regenerative medicine, 3-D skin printing,

and skin substitutes

Important research is being carried out in stem cells

and regenerative medicine, a prominent area for

potential near-term health advance. In skin anti-aging,


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the interrelation between stem cell generation, hair

follicles, wound healing, and microRNA expression is

being investigated. Producing skin for grafts, wound

healing, and other purposes is a key application. A

number of techniques are being explored including

regenerating skin from an individuals own stem cells,

3-D printing of skin with bioscaffolds, and skin subs-

titutes that integrate organic and inorganic mater ial.

Personalized genomics is an important emerging eld

of science being applied to human biology and medi-

cine. Its application in disease risk assessment, wellnessproling, drug response determination, and product

response customization may only grow over time and

lead to many useful innovations in translational anti-

aging skin research.


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Bio-Science Innovation Manager,


carine nizard Since 2008 she has been a Research Manager specia-lized in anti-ageing and longevity research for LVMH

(Mot Hennessy - Louis Vuitton) cosmetic brands.

She has conducted over 20 research projects in her

specic areas of interest: protein maintenance, pho-

toageing, heat shock proteins, oxidative stress and

melanogenesis.

She has supervised several PhD students and post-

doctoral fellows. She has published more than 20

articles in peer-reviewed journals and she is co-au-

thor of 13 patents.

Dr. Nizard obtained her PhD in Fundamental and

Applied Toxicology in 1990 at the French University

Paris Diderot, Paris 7. Three years later she joined the

Research Centre LVMH Recherche as a researcher

in the eld of skin cells and in 2002 she became a

Bio-Science Innovation Manager. She participated to

research projects dedicated to innovation for skin care,

she developed new models of human skin cell culturesand discovered the pharmacological activity of many

new active ingredients.


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Skin-cell rejuvenation

cellular proteins, and others based on the activation

of detoxifying proteins such as proteasome which

helps to recycle damaged proteins.

Accumulation of oxidized proteins is a hallmark ofcellular ageing and is believed to be one of the main

contributors to the aged phenotype. This process is

dependent on an increased occurrence of oxidative

damage to proteins and also on a decreased elimi-

nation of oxidatively modied protein. Elimination

of oxidized proteins is mainly achieved through

degradation by the proteasomal system while certain

oxidative protein modications 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. Both systems have been docu-

mented to exhibit an age-related decline, notably for

the proteasome in human epidermal cells and dermal

broblasts. UV-irradiation of skin cells is known toinduce oxidative stress and to promote protein oxi-

dative damage leading to the formation of carbonyl

groups as well as the formation of protein adducts

with lipid peroxidation products. However, 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. Importantly, a loss in Msr activity would be

likely to diminish the antioxidant response, hence

In industrialized countries, populations are ageing and

over the last 100 years the average life expectancy

of people has approximately doubled, a multifactorial

phenomenon in which improvement in nutrition andmedicine and easier working conditions have played an

important role. The idea that ageing is an active conti-

nuation of a genetically programmed development of

organisms has been partially discredited. Ageing is now

admitted to be a loss of equilibrium between the capa-

bility of an organism to maintain its repair potential and

the frequency and intensity of the damage to which it is

exposed. For the skin, the most exposed organ to envi-

ronmental injuries, free radicals generated by ultravio-

let radiation and internal metabolism are considered

to be the most important deleterious ageing agents

on cellular proteins, lipids, glycans, and DNA-all of

which have been extensively reviewed. Therefore anti-

ageing skin care emerged that contained natural free-

radical scavengers or technologies focusing upstreamwith active ingredients which, rather than attack free

radicals directly, reinforced the natural cellular proteins

that detoxify these free radicals. Recently, sophisticated

complementary strategies emerged based on activa-

tion of chaperone proteins that protect structures of


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favouring the accumulation of oxidized proteins, and

unfavourably inuence keratinocytes recovery from

oxidative stress encountered during UV irradiation.

Therefore for the proteasome, protecting or stimu-

lating such enzymes responsible for the repair of

specic forms of oxidative modication would also be

expected to help ght against the accumulation of non

functional and potentially harmful oxidized proteins,

which represents one of the major deleterious effects

associated with intrinsic skin ageing and photo-ageing.

Another interesting concept known as hormesis hasrecently attracted attention in the eld of anti-ageing

research. The theory behind the approach - that low

doses of toxic or harmful substances have a protective

effect - is known as hormesis. It makes use of the bodys

intrinsic capacity for self-maintenance and repair, by

exposing cells and organisms to brief periods of stress.

The paradigm for hormesis is exercise, an activity that

is both stressful and damaging due to the production

of free radicals, acids, stress hormones and tissue

damage. However, as an inducer of repair and mainte-

nance processes, the hormetic effect of this strenuous

activity has a wide range of health-promoting effects,

including slowing down ageing.

Limited mitotic life span is observed in many eukaryotic

cell types and is interpreted as a manifestation of cellu-lar ageing. 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 p21waf-

1 and p16ink4a, leading to hypophosphorylation of

the retinoblastoma protein. Human diploid broblasts

(HDFs) in replicative senescence are characterized by

a typically enlarged cell shape, senescence-associated

b-galactosidase activity, short telomeres and changes

in the expression level of many genes. All cells in the

organism produce specic molecules - cytokines, which

carry signals, activate the processes of proliferation

(dividing), differentiation, apoptosis etc. Through the

secretion of various regulatory molecules senescent

cells can inuence other cells triggering their ageing

processes. Recently new active ingredients of natural

origin have been proposed to ght the skin cells entry

in senescence.

LVMH Recherche has performed these 3 skin-cell

rejuvenation strategies based on experimental work

(in LVMH laboratories or within academic collabora-tions) with innovative ingredients to develop cosmetic

products for LVMH brands. These approaches enable

us to have interesting in-vitro skin-cell rejuvenation

experimental data and in vivo quantiable benets

for skin following their cosmetic use.


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Leading scientist, Institute of Genetics

and Cytology, National Academy

of Sciences, Minsk, Belarus

oleg V. KVitKo Oleg Kvitko performs an analysis of data and theo-ries in biology of ageing, 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. This resulted in the two new

theoretical concepts: par ticipation theory of ageing

and developmental theory of rejuvenation.

His experimental and theoretical work has been pu-

blished in over 140 publications. Kvitko is a member of

the Belarussian Society of Geneticists and Breeders, a

head of Minsk branch of the Gerontological Society

of the Russian Academy of Sciences and an associateeditor of the journal Theoretical biology and medical

modelling.

Oleg V. 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 1980, he did a PhD in biology (speciali-

zation in genetics) within IGC NANB. In the last 20

years, his research increasingly concentrated on cellularageing, cancer transformation and stem cells. In these

studies he, with his research team, used the informative

experimental method based on continuous computer

videorecording of microscopic images (computerized

videomicroscopy) of living cell cultures revealing

unknown processes during aging.


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Signalling pathways and rejuvenation:risks and opportunities

netic mechanisms of ageing that are perspective tar-

gets for rejuvenation. One may object to that because

telomere shortening, unlike DNA methylation and

histone modications, may be classied rather as agenetic, not epigenetic process, because it results in

changes of a pr imary nucleotide sequence. However,

similarly to conventional epigenetic processes (and

in contract to genetic mutations), telomere shorte-

ning happens regularly (in every mitotic division of

many cell types). In addition, telomere shortening is

reversible due to a special enzyme telomerase or

other (alternative) mechanisms of telomere elon-

gation. For searching the means of retardation or

reversal of aging the possibility of selective epigenetic

reprogramming leading to rejuvenation is of special

interest. Under this rejuvenating process restoration

of telomeric repeats at the ends of chromosomes and

physiologically optimal (for a particular cell type) pat-

tern of differential gene activity (determined by DNAcytosine methylation and modications of chromoso-

mal histone proteins) should take place but dediffe-

rentiation (that happens during somatic cell nuclear

transfer into oocyte cytoplasm and construction of

induced pluripotent stem cells) should not occur.

According to the developmental theory of rejuve-

nation proposed by the author the natural mecha-

nisms of epigenetic rejuvenation exist but do not

always work effeciently enough to withstand the

age-related accumulation of epigenetic damage.

Finding new effective rejuvenation means can be

greatly helped by knowledge of the mechanisms of

biological ageing and opposite processes of restora-

tion (repair) of age-related damage. Signicant experi-

mental evidence supports the opinion that epigenetic

changes underlying unfavourable deviations of gene

expression are the major mechanism of ageing. 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), that is the viola-

tion of normal physiologically optimal differentiated

state of cells. In its turn, disbalance of gene expres-

sion leads to the damage in tissues due to accumu-

lation of dysfunctional cells, anomalous proportions

of different cell types, disturbances of intercellular

communications and deviations from normal cell den-

sity. Two molecular mechanisms of epigenetic changes

triggering ageing gained a special attention. These areDNA methylation and modications of chromatin

histones (acetylation, phosphorylation and others).

Both mechanisms participate in chromatin remodeling

and, thereby, regulate gene expression at a global level.

In addition to these two processes telomere shorte-

ning may be mentioned among the important epige-


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During embryogenesis and postnatal growth the spe-

cial signalling mechanism reverses epigenetic mistakes

and, thereby, rejuvenates cells. This development- and

growth-coupled rejuvenating epigenetic repair insures

the delay of functional decline to the point of an orga-

nisms ability to produce progeny. That is why species

with extended growth periods have long li fespans. This

rejuvenation mechanism also prevents aging in orga-

nisms with negligible senescence. These species have

an indeterminate growth (for example, some shes or

mollusks grow throughout their life with little or nosenescence, and only an excessive size, not ordinary

ageing is a major reason of their death). It appears also

that the well known life-extending effect of caloric res-

triction in rodents (McCay et al., 1935) may be explai-

ned by the prolongation of postnatal growth and ex-

tension of the work of a growth-coupled rejuvenation

process. The natural process of rejuvenation is driven

by the same extracellular morphogenetic molecules

(morphogenes) that regulate embryogenesis. As a rule,

morphogenes bind to specic cell membrane recep-

tors activating signalling pathways inside cells, which

stimulate or repress gene expression. There are seve-

ral families of morphogenes (Wnt, Notch, Hedgehog,

FGF, TGF-beta and others). Because of the regulator y

pleiotropy (when one molecule takes part in differentsignalling pathways) morphogenes, simultaneously with

performing their canonical morphogenetic functions,

stimulate telomerase and trigger restoration of phy-

siologically optimal gene expression by regulation of

enzymes that modify DNA (methylation) and chromo-

somal histone proteins. After the end of development

and growth uctuations of morphogens in tissues

decrease (atten) and become insufcient for initia-

ting the cascades of events resulting in rejuvenation of

the whole body. Since human species has a genetically

restricted growth, for counteracting aging and exten-

ding human life intensive (embryo-like) production

of morphogenes should be reestablished in many or

all tissues of an adult organism. At the systemic level

stimulation of epigenetic rejuvenation in different

parts of the body may be achieved by neuroendo-

crine regulation. In particular, rejuvenation-promoting

modications of neuroendocrine processes can be

reached by special psychological practices. This idea

is supported by the recent research on inuence ofsome forms of meditation on telomere shortening

and telomerase activity in immune cells (Jacobs et

al., 2011). In frames of the developmental theory of

rejuvenation a new meditation technique has been

proposed developmental meditation (Kvitko, 2009).

In addition to systemic methods of rejuvenation, topi-

cal inuences may give invaluable rejuvenation effects.

For example, skin provides unique possibilities for the

elaboration and practical application of topical reju-

venation means. In this context it seems reasonable

to consider some additional aspects of a possible

mechanism of rejuvenation signalling. It is known that

Wnt (one of morphogens) can activate the Myc pro-

tooncogene which incodes a transcription factor that

activates the production of telomerase and regulatesexpression of 15% of all genes through recruiting

histone acetyltransferases that modify chromosomal

histones. Thus, extracellular morphogenetic signals

may stimulate rejuvenation pathways through pro-

tooncogenes. Possible involvement of protoonco-

genes in rejuvenation signalling should be taken into

consideration in cell culture experiments aiming at

nding effective and safe regimes of topical applica-

tion of rejuvenation ingredients. In particular, optimal

regimes of using rejuvenation means may be based on


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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. Learned from nature safe and effec-

tive means of rejuvenation that works in developing

and growing organism may exploit nonlinear, pulsed

regimes of rejuvenation signalling. Improved methods

of long-term (from days to months) uninterrupted

computer videomicroscopy of living cell cultures pro-

vide unique experimental tools for elaboration of neweffective formulas for topical rejuvenation.


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Research Investigator, Department

of Dermatology Photoaging and

Aging Research Program, Universityof Michigan, Ann Arbor, USA

laure ritti the molecular and cellular basis for impaired woundhealing in aged human skin and the effects of aging on

follicular stem cell functions in human skin. Her cur-

rent research focuses on elucidating the mechanisms

of altered skin re-epithelialization in aging.

Dr. Ritti received an American Skin Association

Research Scholar Award in 2007, and a National

Institute of Health Research Scientist Development

Award four years later. She wrote four book chapters

and published dozens of articles in peer-reviewed

scientic journals. She also teaches the Basic Science

Journal Club to Dermatology Residents at theUniversity of Michigan.

Dr. Ritti received her Master of Science in Cell

Biology in 1996 and her PhD in Biochemistry and

Molecular Biology in 2001 from the Universit de

Reims Champagne-Ardenne in France. She comple-

ted postdoctoral trainings at the Universit de Reims

Champagne in the Department of Biochemistry andMolecular Biology, and in the United States, in the

Department of Dermatology at the University of

Michigan during four years.

She has been recruited as Research Investigator to

join the Dermatology Department Faculty at the

University of Michigan in 2006. She studied specically


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Controlled Wound Healing for

Skin Rejuvenation: Recent progressand Future Challenges

Cutaneous wound healing is a regulated process

that involves an initial clear ing of the wound through

an inammatory phase, followed by tissue restora-

tion including intense deposition of type I collagenand other extracellular matrix proteins. In the past

decades, various laser-based devices have been

developed to generate a controlled wound healing

reaction that ideally triggers minimal inammation

and maximal collagen production in photoaged skin.

Providing a detailed analysis of the molecular and cel-

lular alterations induced by several of these lasers, we

will show that controlled wound healing is an effective

strategy for skin rejuvenation, and will provide a ratio-

nal for future optimization of treatment strategies and

protocols.

Photoaging denes the premature aging of the skin

that primarily results from chronic exposure to ultra-

violet (UV) irradiation from the sun. Photoaged skin is

characterized by the presence of damaged extracel-

lular matrix components, including type I collagen, the

major structural protein in the dermis. Damage to type

I collagen is initiated by UV irradiation-induced metal-

loproteinase activity that degrades collagen bers into

fragments. UV irradiation concomitantly inhibits procol-

lagen production by dermal broblasts, thus preventing

the dermis to efciently repair itself. With repeated

exposure to UV light overtime, collagen fragmenta-

tion accumulates in the skin. The resulting decreased

mechanical tension in the dermis is responsible for a

self-sustained negative feedback decreasing collagen

production in the skin. Thus, damaged collagen cannot

be replaced. To reverse this vicious cycle, skin rejuve-

nation strategies must be aimed at stimulating collagen

production in photodamaged skin.


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Founded in 1980, LVMH Recherche is a

Groupement dIntrt Economique (GIE),

whose members are Parfums Christian Dior,

Guerlain, Parfums Givenchy and Fresh. LVMH

Recherche has about 260 researchers, loca-

ted in Saint Jean de Braye, Paris, Tokyo and

Shanghai. Its mission? To design and develop

perfume, fragrance derivatives, skincare pro-

ducts and makeup for several brands of the

LVMH Group (Mot Hennessy - LouisVuitton).

Our research spans everything from know-

ledge of skin and cosmetics users to the

creation of formulations suitable for strong

perceived efcacy and for an international

use. Throughout the process, innovation is

expressed through the ingredients, formula-

tions and processes that we develop, 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 yearMore than 200 patents

More than 50 scientic papers per year

Research teams in St Jean de Braye, Paris,

Tokyo and Shanghai

LVMH Recherche

Perfumes & Cosmetics

36


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Layout and design: www.pariri.com

Printer: Chirat Impression

This document has been produced following

sustainable standards

Initiated 6 years ago, LVMH Recherches commitment to quality has recently

been recognised and proven successful. On January 3, 2011, cosmetic productResearch and Development for LVMH cosmetic and fragrance brands has been

certied with an ISO 9001:2008.

This document is printed on 100% PEFC (Programme for the Endorsement of

Forest Certication Scheme) paper, ensuring clearly identied paper pulp

prepared from sustainable forests management in terms of the environment,

economy and social conditions.

Chirat Impression adheres to stringent ImprimVert standards ensuring reducedpollution, particularly in waste treatment.

Locationand contactsLVMH Recherche

Research Centre

185, Avenue de Verdun,

45800 Saint Jean de Braye, France

Scientic Communication Department

Frdric Bont | Anglique Thomas

Phone : (33) 02 38 60 33 88 | 32 61

E-mail : [email protected]

www.lvmhrecherche-symposium.com

Contacts:

Website:


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Documents

LVMHS Symposium on Skin Science