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  • Premature skin aging

    induced by air pollution:

    New in vitro insights

    approaching realistic

    conditions

    Imke Meyer, Symrise AG

    Anti-ageing Skin Care Conference

    London, 07. June 2016

  • PM, the new UV?

    The anti-air pollution proof

    Conclusion

    How do PM affect skins youth?

    4

    3

    2

    2

    1

    Taking anti-pollution protection to a new level

  • PM, the new UV?

  • US 23%

    Mexico 43%

    Brazil 37%

    Pakistan 37%

    Spain 34%

    UK 21%

    Russia 56%

    China 51%

    India 40%

    South Korea 39%

    Japan 21%

    Atmospheric pollution gets global awareness Perceived as a primary cause of skin and hair problems

    2013+2014

    Lack of sleep 1 Pollution & dirt,

    chemicals in the air (car exhaust/ factories)

    2

    Stress/ conflict 3

    Sunrays 4

    My age 5

    Source: Cosmetic Ingredients Consumer Study, 11 countries, n = 2000-2500 per country; Q23_A. In your opinion what are the main causes of your skin, scalp and hair problems? 4

  • People understand Air Pollution does not stop at the surface

    5 Source: Cosmetic Ingredients Consumer Study, 11 countries, n = 2000-2500 per country; Q23_A. In your opinion what are the main causes of your skin, scalp and hair problems? (Applies in %).

    More than 80% of consumers across the globe think

    that the skin absorbs the pollution that is in the air.

    Consumers in Brazil, Mexico, Pakistan and India are most

    sensitive to dust and dirt, followed by Russia and China.

    With greater urge to act in China, Pakistan, India, Mexico

    and Brazil.

  • Atmospheric pollutants ? Emergence of new indexes

    UV / Visible / IR O3 NO2 SO2

    PM 2.5

    & 10

    6

  • SO2 UV /

    Visible / IR O3 NO2

    Atmospheric pollutants ? Emergence of new indexes

    PM 2.5

    & 10

    7

    Among those,

    PM have been pointed out

  • VEHICULAR EXHAUST /

    TRAFFIC

    COAL BURNING POWER

    PLANTS & INDUSTRIAL

    COMBUSTION

    CIGARETTE

    SMOKE

    DOMESTIC HEATING

    KITCHEN EMISSION

    PM come from many different sources

    8

  • Pigment spots

    on forehead:

    +16% by traffic

    related particles

    PM accelerate extrinsic skin aging major epidemiological study 2010 / Prof. Dr. Jean Krutmann

    Vierkoetter et al., J Invest Dermatol (2010) 130, 27192726

    Pigment spot

    on forehead & cheeks:

    + 22% & +20% increased by soot,

    respectively

    Pigment spots

    on cheeks:

    +8% increased by PM10

    (particulate matter)

    9

  • PM surveillance Major population in cities is exposed to exceeding AQG levels

    WHOs Ambient Air Pollution database Update 2014 10

    12% of the assessed population are exposed to PM10 or PM2.5 complying with AQG levels.

    27% for the interim target 3 (IT3, 30 g/m3 for PM10 and 15 g/m3 for PM2.5), 49% for IT2 (50 g/m3 for PM10 and 25 g/m3 for PM2.5), and 62% for IT1 (70 g/m3 for PM10 and 35 g/m3 for PM2.5).

    only

  • Consumers increasing demand

    - to check the actual pollution levels,

    - to check the forcast of air quality,

    - and finally to protect skin by cosmetic products against these harmful

    factors.

    PM surveillance How do consumers adapt?

    http://aqicn.org/forecast/beijing/ 11

  • How do PM affect skins youth ?

  • Classification of particles

    according to diameter:

    PM10: < 10 m

    PM2.5: < 2.5 m

    Ultrafine particles: < 100 nm

    Countries / cities are encouraged

    by WHO to measure and monitor

    PM10 and PM2.5

    WHO Air quality guidelines for particulate matter,

    ozone, nitrogen dioxide and sulfur dioxide

    Global update 2005

    Their size is 25 times smaller than human hair

    13

    Keratinocyte 20m

    PM10

  • However small, PM do not really penetrate the skin

    14

    But they use

    the hair follicle

    as a passage

    to deeper layers.

    E P I D E R M I S

    D E R M I S

  • What is effected by PM?

    15

    In the skin inter alia reactive oxygen

    species (ROS) are induced.

    Also the biosynthesis of cytokines like

    interleukin (IL-) 1, 6 and 8 is enhanced.

    E P I D E R M I S

    D E R M I S

    PM

    ROS

    ROS

    cyto-

    kines

    ROS

    cyto-

    kines

    cyto-

    kines

    HM

  • Skin cells are receptive to PAHs Via the Aryl hydrocarbon Receptor (AhR)

    16

    AhR

    AhR

    AhR

    The PAH-AhR toxic complex

    can pass into the nucleus

    PAHs bind to AhRs

    Inside keratinocytes

    Aryl Hydrocarbon (AhR) receptors PAH

  • The chain reaction alter the cells functions

    17

    OXIDATIVE STRESS

    COLLAGEN ALTERATION

    DARK SPOTS

    INFLAMMATION

    AhR

    AhR

    AhR

    Inside the nucleus, it stimulates the expression

    of CYP1A1, MMP-1, POMC and IL6 PAH

  • The Solution:

    A molecule designed by Symrise

    with the ideal architecture

    Arylhydrocarbon Receptors (AhR)

    preferably bind to :

    Flat molecules made up of benzene rings

    consisting mainly of hydrogen and carbon atoms

    (aryl hydrocarbon)

    The strategy :

    Reversibly block the AhR from interacting with aryl

    hydrocarbons

    The idea to neutralize the AhR

    18

    by an AhR antagonist

  • BDDI, an AhR antagonist

    Benzylidene Dimethoxydimethylindanone

    19

    BDDI temporarily

    binds to the AhR

    The AhR is no longer available

    to connect to PAHs

    PAHs are kept outside the nucleus

    Adverse reactions are limited

    PAH

    BDDI

  • The anti-pollution proof

  • An original model, designed by Symrise Evaluate product efficacy against actual PM

    21

    Identify suitable surrogate samples for the study of authentic street particles. 1

    National Institute of Standards and Technology, Gaithersburg, MD, USA

    SRM 1650b

    Bulk diesel particulate material collected from the heat exchangers of a dilution tube facility, following 200 engine hours of particulate accumulation. Representative of heavy-duty diesel engine particulate emissions (DEP).

    Mean Particle Diameter: 0.18 m

    SRM 2975

    The material was collected from a filtering system designed specifically for diesel-powered forklifts.

    Mean Particle Diameter: 19.4 0.3 m

    Both are associated with polycyclic aromatic hydrocarbons (PAHs) and nitro-substituted polycyclic aromatic hydrocarbons (nitro-PAHs).

    2

    Comparison of authentic street particulate matter collected at a traffic intensive road in Copenhagen, Denmark, on 5 weekdays in September 2000 to SRM2975 & SRM1650b 3

    Danielsen et al, Particle and Fibre Toxicology 2008, 5:6

  • NHEKs were stimulated with 1.5 g/cm2 particulate matter for 6h or 24h.

    In the presence or absence of different actives. Test-compounds have been applied 2h or 24h prior to

    particulate matter.

    qRT-PCR is performed to determine gene expression (upregulation of gene expression)

    Protocol:

    In-vitro test protocol

    22

    Cells of different donors were used; inter alia Keratinocytes from adult female Caucasian donor

    (53 years) Keratinocytes from adult female Asian donor

    (67 years)

    NHEKs were cultured in starved conditions for 24h prior to stimulation.

    NHEKs: Normal Human Epidermal Keratinocytes

    Gene expression

  • 4 indicators Gene expression

    23

    PHASE I METABOLISM

    Cyp1A1 (cytochrome P450, family 1,

    subfamily A, polypeptide 1)

    is upregulated by AhR

    (aryl hydrocarbon receptor)

    agonists like polycyclic

    aromatic hydrocabons

    (PAHs).

    WRINKLE FORMATION

    MMP-1 (matrix metallo proteinase-

    1) is an enzyme involved

    in degradation of collagen

    UNEVEN SKIN TONE

    POMC (proopiomelanocortin,

    precursor of -MSH and

    ACTH) released by

    keratinocytes, triggering

    the melanin biosynthesis

    in melanocytes

    INFLAMMAGING

    Cytocines like IL-6

    (interleukin-6) are involved

    in different premature

    aging mechanisms of the

    skin initiated by

    inflammatory processes.

  • PROTECT FROM

    THE APPEARANCE OF

    WRINKLES

    Characteristics:

    Synthetic material

    Recommended use level: 0.1 - 0.5%

    Light yellow to yellow powder

    Easy to formulate (soluble in oils at the recommended use level)

    Characteristics of BDDI

    24

    INCI: Benzylidene Dimethoxydimethylindanone

    Activity profile:

    AhR an tagon is t

    Protection against UVB induced premature aging via the

    AhR antagonism

    Regulatory: can be used worldwide except China DEFENDER

    SKIN CELL

    O

    O

    O

  • Both DEPs stimulate CYP1A1 gene expression significantly with SRM1650 as a stronger stimulant. BDDI prevents this increase significantly. Comparable results for Asian and Caucasian keratinocytes. All further experiments done with Caucasian keratinocytes.

    Phase 1 Metabolism

    25

    *p

  • untreated 0% 0.000077%

    Prevention of melanin stimulation

    26

    + *

    SRM1650b stimulated

    +

    0.00031%