The New Strategy To Reverse Aging

Newstrategytoreverse

signsofaging

SWSCC Educational Seminar & Suppliers Day

August 23, 2012 - Las Colinas

Who is Unipex? 2

questforeternallifeimmortality

alchemistshuntedinvainfortherejuvenatingPhilosophersstone

SkinAging

Chronologicalaging

Photoaging

External/Internalfactors:pollution,foods,alcohol,tobacco,emotions

Genetic

Antiagingcream

Plasticsurgery

Makeupandphotoshop

Strategiestoreverseskinaging SkinAging

Physiologicalchangeswithage

Hyper orhypopigmentationSeborrheic keratoses

Dry,scalyskinIncreaseinskinfragility(barrierfunction)

Increaseinroughness,wrinklesLaxity

EasybruisingDecreaseimmunefunction

AGING

MatureskinYoungskin

Stratumcorneum CompactFlaky

Dermis

Epidermis

Hypodermis

SC

DEJ

EpidermisThickness =properskinbarrier

Keratinocytes,Mc: proliferation,maturationProteoglycanssynthesis

Thick Thin

++++++

DermislevelECMcomponent(collagens,elastin..)

MMPsactivitiesImmunefunctions

Low+++

+++

FlatDermal Epidermal junctionDermis/epidermiscohesion

Wavy+++

HypodermislevelSubcutaneousfat+++

Skinchangeswithage

AGING

Ourstrategytoreverseskinaging



Low

Stratumcorneum CompactFlakyEpidermis

Thickness =properskinbarrierKeratinocytes,Mc,proliferation,maturation

Proteoglycanssynthesis

Thick Thin

++++++


Wavy

Dermis

Epidermis

Hypodermis

SC

DEJ

HypodermislevelSubcutaneousfat

+++

+++

+++

+++ +++ Progerin+/- Progerin

AGING

Structuralagingduetosenescencemarker:progerin

Lamin A/CFrom Cao et al. 2011

Thisprocessofaginggallopstoaboutseventimesthenormalrate

Progerin asanewmarkerofaging Progerin isanalteredformoftheLamin Aprotein(nuclearintermediatefilamentprotein) Accumulationofprogerin innucleus OriginallyassociatedwiththeHutchinsonGilfordSyndrome(=Progeria)

Progerin andaccelerationofaging Accumulation ofprogerin inducesvariousdefectsinnuclearstructureandfunctions Alterationscellcycleprogressioncausedbyprogerin knowntoacceleratehumanaging

1

Progerin is expressed in healthy cells (fibroblasts and terminally differentiated keratinocytes mainly) andaccumulated with age (3% per year)

The same molecular mechanisms responsible for premature aging in progeria act at low level in healthy cells

Cell nuclei from old individuals acquire defects similar to those of progeria patient cells

Progerin inhealthycells

Progerin hasbeenlinkedtophysiologicalageingaspresenceofprogerin isconcomitantwithalterationsofthedermalcompartment suchasdisorganizedconnectivetissue

From Scaffidi et al. 2008

1

9yearsold 96yearsold Progeria

TT2 abiomimeticstructuralpeptideFocus on biomimetic peptide derived from structural proteins and enzymes implicated in the maintenance ofdermal structure and connective tissue organizationTT2 (INCI: F3Acetyl Tripeptide2) : 3 amino acid peptide derived biomimetic of Elafin, an enzyme inhibitor

1

Protocol Maturehumandermisfibroblastswereincubatedfor96hourswithTT2peptide TheprogerinwasquantifiedusinganELISAmethodology.Resultsaregiveninpgofprogerinpergofproteins

TT2peptide decreasessignificantlytheproductionofprogerin,attestingitsefficacyonthesenescenceprocess

22%inhibitionprogerin

production

TT2peptide

EffectofTT2peptide ondermalstructureandconnectivetissueorganization

MMPs

Elastase,collagenase

Dermis contraction

Syndecan

Progerin

MMP1,MMP3&MMP9inhibition

1

Progelinecontrol Progelinecontrol

T0 After24h

+27%collagen contraction

TT2peptide TT2peptide

EffectofTT2peptide ondermalstructureandconnectivetissueorganization

MMPs


Dermis contraction

Syndecan

Progerin

1

Control +collagenase +collagenase +Progeline

Collagenfibers

43%inhibitioncollagenase

TT2peptide

100%inhibitionelastase

Elastinfibers

Control +Elastase +Elastase +ProgelineTT2peptide

13

EffectofTT2ondermalstructureandconnectivetissueorganization

MMPs


Dermis contraction

Syndecan

Progerin

Bymodulangsenescenceprocess(progerin),

TT2peptide inducesseveralbiological

responsesatthedermis&epidermislevels

1

ClinicalStudiesFirmness,Laxity

1

Clinicalevaluationofantisaggingeffectonjawlines

TT2peptide decreasessignificantlythevolumeofthejawlinesafter28and56days

Protocol

10healthyvolunteers :5464yearsoldwithagedskin Formulation:2%TT2peptide emulsion creamorplacebo Application:splitface andsplitneck 2X/dayfor56days Measurementofthevolumeofthejawlines ofthefacebyinvivo

fringeprojectionprofilometry

80%ofvolunteers had animprovement

1

TT2peptide2%

Clinicalevaluationoffirmness&elasticityCutometryProtocol

13healthyvolunteers(54 66yearsold)withsaggyskin(lossoffirmness,slackeningskin) Formulation:2%TT2peptideemulsioncreamorplacebo Application:splitface andsplitneck 2X/dayfor28days Measurementsareperformedonbothcheeks(diameterprobe=2mm)bycutometry

1

Improvement upto: 93%ofcutaneous elasticity 82%ofcutaneous firmness 42%ofcutaneous viscoelasticity

TT2peptide increasessignificantlyfirmness,elasticityandviscoelasticityafter28days

TT2peptide2%

D0

Slight improvement

Majorbuildingeffect overtime!

Clinicalevaluationoffirmness&elasticity 1

TT2peptide

Summary TT2peptideeffect 1

SyndecanDermis contractionElastase,collagenasesProgerine

LaxityFirmness,Elasticity

Reverseeffect ofTT2peptide

Ourstrategytoreverseskinaging



Low

Stratumcorneum CompactFlakyEpidermis

Thickness =properskinbarrierKeratinocytes,Mc,proliferation,maturation

Proteoglycanssynthesis

Thick Thin

++++++


Wavy

Dermis

Epidermis

Hypodermis

SC

DEJ

HypodermislevelSubcutaneousfat

+++

+++

+++

+++

1 2

Youngskin

Fullfatcompartments

Matureskin

Deflatedfatcompartments

Nasolabialwrinkles

Structural agingduetolipoatrophy 2

Hormesis concept 2

Concept launched by Givenchy with Vaxin (2010) :This vaccinelike serum is formulated with a unique complex capable ofgenerating microstimuli, which encourage the skin's cells to produce theirown agedefying protein HSP70

The word hormesis comes from the greek root hormeticos, which meansstimulation and the first mention of the term hormesis in the open scientificliterature was published in 1943

- ++

++

Hormesis : homeostatic and adaptative beneficial response of cells to microstressexposure in order to correct a physiological imbalance

Activationofadipocyteanabolism

Adipogenesisactivation

(adipocytedifferenciation)

LipolysisInhibition

(freefattyacidrelease)

Lipogenesisactivation

(triglyceridesynthesis)

Adiposetissuegrowth

HIF1

+

Lipohormesis Newproprietarypatentedconcept 2

Lipohormesis = hormesis applied to adipose tissue

Various stresses in the adipose tissue are able to stimulate its expansion through theactivation of Hypoxia Inducible Factor (HIF1), a transcription factor

ReverseagingWrinklereduction

Plumperskin

Youngskin

Matureskin

L.O. Alipofillinglikealternative 2 LO(INCI:Ornithine(and)Phospholipids(and)Glycolipids):Lornithine,anaminoacid

obtainedbybiotechnologyfromvegetablestarch,encapsulatedinaIonosome

Ionosome: new generation of delivery system (proprietary patented). Polysaccharidecoated encapsulation: polysaccharides (stearoyl inulin) inserted in the

phospholipid membrane = protective coating

Ionosome benefits: Resistantdeliverysystem Highpenetrationcapacitytotargetadipocytes Higherefficacy

Lipophilicside

Hydrophilicside

C18

C18

C18

C18

L-ornithine

LO

LOreproduceslipohormesis phenomenonandmimics lipofilling result byincreasingfatty tissuevolumewith aglobalaction

2EffectofLOontheactivationofHIF1andadipocyteanabolismProtocol Human preadipocytes were isolated from biopsiesandcultivated fordifferentiation. 0.02%LO was added onadipocytesculture Genic expressionwas evaluated through cDNA methodology

ResultsAdipofill

HIF1

genes involvedinadipogenesis

genes involved inlipolysis

genes involvedinlipogenesis

Adipocytedifferenciation

Freefatty acidrelease

Triglyceridesynthesis

LOinhibitslipolysisanddecreasesthereleaseoffattyacidsfromadipocytesbyincreasinglipidstorage

Protocol

Lipidstorageenhancement lipolysis 2

Increase insize

Increase inlipid content

Humanadipocyteobtainedfromapieceofsurgicalresectionwereincubatedwith0.05%and0.2%LO Free fatty acids (NEFA) were quantified in the media using a spectrophotometric method and the adipocyte

size was evaluated through the measurement of their average diameter after staining with red oil (specific forlipids)

LO

LO

ClinicalStudiesNasogenian fold

2

Protocol 20healthyvolunteers(40 60yearsold)withnasogenian folds. Formulation:2%LOemulsioncreamorplacebo Application:splitfaceandsplitneck2X/dayfor56days Measurementofdepth androughness byprofilometry andevaluationofsmoothness byadermatologist

Reductionofnasogenian fold 2

85% of volunteers hadan improvement

LOstronglyreducestheappearanceofnasogenian foldafteronlyonemonth

Reduction upto: 27.5%ofroughnesss 37.6%ofwrinkle depth

LO2% LO2%

Reductionofnasogenian fold 2

D0

D60

LOstronglyreducestheappearanceofnasogenian fold

Summary LOeffect 2

HIF1AdipogenesisLipogenesisLipolysisAdiposetissue

Nasogenian fold

Reverseeffect ofLO

TT2peptide

21LO

+

Bymodulangsenescenceprocess(progerin),

TT2peptide targetsDERMIS restructurationfora

remodellingeffectandwrinklesreduction

Byinducinglipohormesis(HIF1),LO targetsHYPODERMIS restructurationfora

lipofilling effectandnasogenian foldreduction

21

4LaSpiritCream

forasynergisticefficacy

LaSpiritCream

TT2peptide:Improves firmness &reduces wrinkles andsagging

LO: Reversesagerelated lipoatrophy toplump theskin

UNIQUE, SOPHISTICATED AND BIO-EFFICIENT ACTIVE INGREDIENTSAND DELIVERY SYSTEMS

DELICIOUS TEXTURES THATDELIVER EXQUISIT SKIN FEEL

Hydrogenated Lecithin (and)C1216Alcohols (and)Palmitic acid:Brings the

phospholipids touch (coolness,softness)&comfort

SodiumAcrylatesCopolymer (and)Lecithin:Brings alighttexturetothe

emulsion

SKINBENEFITS AFTER1WEEK

AFTER4WEEKS

Theproductispleasant toapply 100% 100%

Thetextureissmooth 96% 97%

Theskinfeelssofter 92% 97% 87% IRISDATABASE*

Theskinfeelssuppler 86% 91% 89%

Theskinseemshydrated 85% 87% 84%

Theskinismoreluminous 71% 73% 73%

Theskinlooksmoreuniform 67% 79% 77%

Thesignsoffatigue arelessvisible 69% 75%

Theskintexture looksimproved 67% 75%

Theskinfeelsfirmer 63% 73%

Theskinhaveahealthyglow 56% 72%

Theskinlooksvisiblysmooth out 51% 70%

LaSpiritCreamTested by62women (45to70)twice aday for28day

Compared toIris

historical result on

antiaging consumer

tests2567tests

Conclusion

Focusonstructuralaging

YoungSkin MatureSkin

Reverseeffect ofTT2peptide&LO

Cutaneous aging characterized by a loss of elasticity, appearance of wrinkles

Structural aging due to a lipoatrophy (loss of adipose tissue)

Cellularagingwithaprogressivedysfunctionofthecellmetabolism(progerin)

JeanneCalment (1875 1997)

ThankYou!

Livingtotheageof122years=44724days

The New Strategy To Reverse Aging

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