lvmhs symposium on skin science
TRANSCRIPT
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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,
LVMH Recherche, Saint Jean de Braye, France
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,
LVMH Recherche, Saint Jean de Braye, France
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
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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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