Causes of skin aging

1
?????????

• ?????
• ???????

2
(No Transcript)
3
?????

• ????????????????????????
• ?????????,????????????????

4
Causes of skin aging
menopause
DRYNESS PRURITUS
WRINKLES
LOSS OF FIRMNESS
SPOTS
30 yr/o
40 yr/o
60 yr/o and over
50 yr/o
CAUSE N1
UVA rays
CAUSE N2
Genetic and hormonal aging
Environment Nutrition Lifestyle (smoking,
alcohol) Stress
AND AGGRAVIATING FACTORS
5
Why Does the Skin Age?
6
???????
?? ?? ???/???
? ? ????,?????
? ? ????,??????
? ? ????,????
? ? ???????,????
? ??? ????,???????
? ???? ????,???????
7
??????

• ???????????????????????????
• UVA (??320-400nm)
• UVB (??280-320 nm)
• UVC (??200-280 nm)

8
UVA

• ?????,????????????,???????????
• ?????????

9
UVB

• ?????????-??
• ????????,?????????????????

10
UVC

• ???????????
• ?????????????
• ?????? 1,???????????? 2??1900???,??????????????2
  530?????,??????????????60

11
????????
??
??
??
UVC
UVB
UVA
320
400
290
200
? ?
? ? ? ?
? ? ? ?
? ? ?
12
Treatment of Photoaging
13
???????

• ??????????????????
• ????????,???????,?????????????????

14
???????
?????
15
Commonly used ingredients in sunscreen
????? ??????
Inorganic Titanium oxide (????) UVAUVB
Inorganic Zinc oxide (???) UVAUVB
Organic PABA (Para-AminoBenzoic Acid) UVB
Organic Padimate O (octyl dimethylPABA) UVB
Organic Cinnamates UVB
Organic Anthranilates UVA UVB
Organic Benzophenones UVA
Organic Parsol 1789 UVA
Organic Mexoryl SX UVA
16
??SPF (Sun Protection Factor) ????

• ??UVB(??)?????
• SPF??????????/???????????
• ?10????,?SPF15 ??????15?150????????150??
• SPF15??????94?UVBSPF30 ?????97?UVB
• ??????????????????(2 ?/?2)

17
(No Transcript)
18
UVA????

• PA (UVA????) ????
• IPD ????????(?????????)
• PPD (?????????)
• PAPPD24
• PAPPD46
• PAPPD68
• ?????????????????????370nm????,PPDgt4 ? PA

19
UV Protection Factor (UPF)

• ????????UV???
• Good protection (UPF 15-24)
• 93.3 - 95.9 UV radiation Blocked
• Very good protection (UPF 25-39)
• 96.0 - 97.4 UV radiation Blocked
• Excellent protection (UPF 40-50)
• 97.5 or more UV radiation Blocked

20
????? (UVI, UV Index)

• ???????100J/m21 UVI
• ???????????,???????????
• 0-2 ???
• 3-4 ???
• 5-6 ???
• 7-9 ???
• 10-15 ???
• ??10??,??????10?20??,??????

21
(No Transcript)
22
???????
UVI 02 34 56 79 1015
?? ?? ? ?? ? ??
???? 30min? 20min? ??12min
??????? ????? ????? ??? ????? ??? ???? ????? ????? ??? ???? ????? ???? 10001600 ????? ????? ??? ???? ????? ???? 10001600 ?????
23
??????????

• Hypoallergic (????)
• Noncomedogenic (??????)
• Sweatproof (??)
• Water resistant
• ?????20??????????
• Very water resistant
• ?????80??????????

24
???????

• ????????????????,??????????????
• ??????????????

25
????

• ????????? ????????,
  ???????????
• ????
• ? ? ??????(Carnauba wax)?????(Candelilla wax)????
• ? ? ??????????? ---???????????????
• ?? ? ????????

26
?????????

• ???15?30???????,??????????
• ??????????????????,????????,????????????????????

27
???????

• ??????
• ?????????????60???,???????????(water-resistant)???
  ???
• ???????,????????????????
• ?????????,???300??,???????8-10?

28
????????

• ??????????,??????????,????
• ????
• ???????????????????
• ????UVA?UVB

29
?????????????,??????????????????????????
30
????????

• ?????????
• ??????,??????????
• ??????
• ?????,?????!
• ????????
• ??????????,??????
• ?????????
• ??????????
• ??????

31
(No Transcript)
32
(No Transcript)
33
?????-??

• ???????????????????
• ??????????,??????????,????,??????
• ?????????????????????????
• ????????????????????????????????????????????????,
  ????????

34
(No Transcript)
35
?????-??

• ??????, ????
• ???
• ????????
• ?????????
• ????????????
• ??
• ???
• ????

36
?????-????

• ????
• ????,?????
• ????

37
?????

• ????
• ????????????
• ??????
• ?????????
• ????
• ????
• ??????

38
?????

• ??????, pH 4.5-6.5?
• ???
• ???
• ?????????????
• ?????
• ??
• ????

39
???????????????? 90
40
????????????

• ??????????
• ????????????????????????
• ??????????????????????????????????????
• ????????????????????,????????????????????????????
  ,??????????,?????????,??????????????????????
• ??????????????????,?????????????

41
Pigmentation Pathway
Tyrosine(???)----gt DOPA(??) ---gt DOPA ---gt
Melanin Tyrosinase (?????)
42
Pigmentation Pathway

• Melanin???????????,???????Tyrosinase
• Melanin????Melanosome??Melanocyte,???????????
  (Keratinocyte)
• ????????-Melanocyte ?Keratinocyte??????,?????Epid
  ermal Melanin Unit (???????)
• ???????Melanocyte???,????Melanin????Melanosome
  ?????

43
(No Transcript)
44
Skin Lightening

• Sunprotection
• Depigmenting agents
• Laser

45
Depigmenting agents

• Work best when melanosis or melanocytosis is
  restricted to the epidermis
• can be divided into several groups
• Phenolic compounds
• Hydroquinone
• 4-Methoxyphenol
• 4-Hydroxyanisol
• Nonphenolic compounds
• Corticosteroids
• Tretinoin
• Azelaic acid
• N-acetylcysteine
• L-ascorbyl-2-phosphate
• Kojic acid
• Combination formulas
• Kligman's formula

46
Hydroquinones (????,??)

• ?????,????????,????????
• ?????????,???????,????????????
• ????????????????,?????5?,?????????????,??????????
  ????

47
Hydroquinone

• Improvement with HQ (monotherapy) is usually
  observed at 4-6 weeks
• Plateau at approximately 4 months

48
Arbutin???

• ?????????,??????,?????????????????,??,????????????
  ?

????????
49
Retinoids

• ????????,????????????????
• ???A????????????????
• ???A??A??A??A??A??????????,?????????A?

50
Combination formulas

• Kligman formula (????? ) in a hydrophilic
  ointment base
• 5 HQ
• 0.1 retinoic acid
• 0.1 dexamethasone
• Tri-Luma (???) in a cream formulation
• 0.01 fluocinolone
• 4 HQ
• 0.05 tretinoin

51
(No Transcript)
52
(No Transcript)
53
(No Transcript)
54
Kojic Acid (??)

• ???????????,??????????
• ????,?????????????,??????,???,????????????????????
  ????
• a competitive and reversible inhibitor of animal
  and plant polyphenol oxidases, xanthine oxidase,
  and D- and some L-amino acid oxidases.
• ???????????????(???)
• Food Chem Toxicol. 2004 Jan42(1)93-105.

55
Azelaic acid (????)

• ??????,?????????
• ????????(Azalea)????????,?????????????
• ????(Pityrosporum ovale)??????????????????????
• ??tyrosinase??
• ??????100,????????65

56
Paper Mulberry (??)

• 5-(3-2,4-dihydroxyphenylpropyl)-3,4-bis
  (3-methyl-2-butenyl)-1,2-benzenediol
• From paper mulberry root bark
• Tyrosinase inhibitor
• Scavenge free radicals
• The concentration causing 50 inhibition of the
  activity of tyrosinase
• 0.396 paper mulberry
• 5.5 for HQ
• 10.0 for kojic acid
• 1 paper mulberry extract
• No irritation or sensitization

57
Thioctic Acid (a-Lipoic Acid, a-??? )

• Disulfide derivative of octanoic acid
• ROS scavenger and redox regulator
• Inhibits tyrosinase activity probably by
  chelating the copper ions

58
Unsaturated Fatty Acids

• Oleic acid (C181), linoleic acid (C182), and
  a-linolenic acid (C183) suppress pigmentation in
  vitro
• Linoleic acid accelerates the degradation of
  tyrosinase, inhibiting melanogenesis

59
Glabridin ???? (Licorice extract,????)

• The active agents liquiritin and isoliquertin
• Liquiritin induces skin lightening by dispersing
  melanin
• Inhibited tyrosinase activity of melanocytes
  without cytotoxicity
• Inhibition of superoxide anion production and
  cyclooxygenase activity
• UV-Binduced pigmentation and erythema were
  Inhibited by topical application of 0.5
  glabridin
• 0.4 licorice extract 0.05 betamethasone
  0.05 retinoic acid

60
Aleosin ???

• From the aloe vera plant
• Inhibit tyrosinase by competitive inhibition at
  the dihydroxyphenylalanine oxidation site
• Limited ability to penetrate the skin because of
  its hydrophilic nature

61
???C ???

• ??????????lysin?proline??????,??procollagen??coll
  agen
• ?????????????
• ?????(photoprotection)??UVA?UVB??????
• ????????????
• ???????????

62
?????,???C ???????
??????
????
???? ???
???
c
??????? ?????
?????????
??????
63
???C

• ?????????C?70-75??,?????C??????????????????,??????
  ??????????
• ????
• ?????

64
???C????????
?? ???
???C??(??) -
?????
Vit C?
Vit C????
Vit C??liposome
65
Soybean trypsin inhibitor

• 3 weeks of raw soy milk application
• Inhibits the activation of protease activated
  receptor-2 pathway (PAR-2) reversible
• a pathway necessary for keratinocyte phagocytosis
  of melanosomes and melanosome transfer

66
N-acetyl glucosamine

• Inhibits the glycosylation of tyrosinase
• 2 N-acetyl glucosamine applied twice daily for 8
  weeks in a cosmeceutical moisturizer showed
  modest pigment lightening
• NAG 2 niacinamide 4 formulation

67
Tranexamic acid (???)

• ?????????3
• ??tyrosinase activity

68
Chamomile ET (?????)

• ?????????0.5
• ?????(endothelin)
• ???

69
Ellagic Acid (???)

• ?????????0.5
• ??????
• ???????????,??????????

70
????
???
????
???
??
??
???
??
71
???????

• ????(OH)?????????
• ?-hyroxy acid (AHA)
• ??? (glycolic acid)
• ?? (lactic acid)
• ??? (tartaric acid)
• ?-hydroxy acid (BHA)
• ??? (salicylic acid)
• ?,?-hydroxy acid (ABHA)
• ??? (malic acid)
• ??? (citric acid)

72
a-Hydroxy acids

• Act as chelators (calcium ions), reduce epidermal
  calcium ions
• cause a loss of calcium ions from the cadherins
  of the desmosomes and adherens junctions?Disruptio
  n of cell adhesion and desquamation
• Promote cell growth and retard cell
  differentiation
• Increease type I collagen mRNA and hyaluronic
  acid content in human skin

73
Alpha-hydroxy acids (?? ??????)

• ????????,?????????,???????
• AHA????????????????????????
• ??????????,???????????,?????????
• ?????????????????,????????????,????????,??????????
  ???????????????????????????

74
???????????

• ?????????
• lt3 ?????????,??????????????
• 3-10???????????????????????????????
• gt10 ?????,??????????????????????????????????
• ?????????lt15
• ????20-70
• ??????

75
?????????

• ???????????
• ?????????????
• ?????
• ????????
• ?????
• ?????
• ????

76
Beta-Hydroxy Acids (BHA) (??, salicylic acid)

• BHA????????????????????
• ???????????????????????????????
• ?????????????????????0.2-1.5??,???????????

77
??(Phytic acid, Inositol hexaphosphate, IP6)

• ???????????????
• ????????????,??????????????? (phytic acid had
  anti-neoplastic properties in breast, colon,
  liver, leukemia, prostate, sarcomas, and skin
  cancer Complement Ther Med. 2002
  Dec10(4)229-34. )
• Topical application of IP6 inhibited skin tumor
  development significantly in a dose-dependent
  manner (Nutr Cancer. 20034666-72 )
• ???????????????????????

78
???????????
79
Retinoids

• ????????,????????????????
• ???A????????????????
• ???A??A??A??A??A??????????,?????????A?

80
Retinoids

• 0.05 tretinoin and isotretinion improve fine
  and coarse wrinkling and lighten actinic
  lentigins and mottled hyperpigmentation (36-weeks
  period)
• Compaction of the stratum corneum
• Epidermal hyperplasia
• Correction of atypia
• Dispersion of melanin granules
• Increased dermal collagen synthesis
• Angiogenesis

81
Retinoid dermatitisoccur within first month of
treatment

• Erythema
• Scaling
• Pruritus
• Burning
• Stining
• Dryness

82
Kinerase ???

• Kinerase??????N6-furfuryladenine (Kinetin, ???)
• 0.1 N6-furfuryladenine?????
• ??????A?(Retinoids)??,???????
• ?????,?????????,???Rosacea??????????
• ????????
• ???????????,?????

Biochem Biophys Res Commun. 15201(2)665-72,
1994.
83
Antioxidants

• Limited efficiency of sunscreens
• No one product provides excellent protection over
  the whole UVA range (320-400 nm)
• Most people apply sunscreen 0.5 mg/cm2
• UV-induced DNA damage and immunosuppression are
  still present at suberythemal levels of
  irradiation
• Components of sunscreens and their photoproducts
  free radicals

84
???C ???

• ??????????lysin?proline??????,??procollagen??coll
  agen
• ?????????????
• ?????(photoprotection)??UVA?UVB??????
• ????????????
• ???????????

85
???C

• ?????????C?70-75??,?????C??????????????????,??????
  ??????????
• ????
• ?????

86
Vitamin E (Tocopherols)

• 90 of tissue Vit Ea- tocopherol
• Topical a- tocopherol
• Prevent UV-induced free radical formation
• Protect endogenous epidermal antioxidants
• Prevent lipid peroxidation
• Prevent UV-induced systemic immunisuppresion

87
??? E

• ????,???????,??????
• ???E?????????????,?????????????????,??????????????
  ?
• ???E??????,??????,????????????????????????
• ??????????????????????

88

• Cosmetics contain tocopheryl acetate or other
  tocopheryl esters
• No direct antioxidant properties
• Not tocopherol precursors owing to the lack of
  adequate esterase in the skin

89
Antioxidants Oral supplements

• Combination of l-proline, l-lysine, manganese,
  copper, zinc, quercetin, grape seed extract,
  N-acetyl d-glucosamine, and glucosamine sulfate
  was shown to improve wrinkles by 34
• Combination of vitamin E, vitamin C, carotenoid,
  selenium, and proanthocyanidin led to a
  significant decrease in induction of MMP after UV
  exposure

90
???Q10 (CoQ10)

• ??Q10 (Coenzyme Q10)???????????????,??????????,???
  ??????(mitochondria)?,?????K??????
• ?????Q10?????,??????????,????Q10??????,??????????,
  ????????????Q10??????????Q10??????????
• ??????????????
• ?????????,???????????????????,?????????????,CoQ10
  ???2?3???,??????

Biofactors. 19999(2-4)371-8.
91
a-Lipoic acid (a-???)

• An antioxidant and anti-inflammatory agent that
  has been previously shown to reduce the
  production of transcription factors such as NF-?B
  and indirectly affect the gene expression of
  inflammatory cytokines

92
a-Lipoic acid (a-???)

• One of the most visible roles of lipoic acid is
  as a cofactor in aerobic metabolism, specifically
  the pyruvate dehydrogenase complex.
• Since the early 1990s lipoic acid has been used
  as a dietary supplement, typically at doses in
  the range of 100200 mg/day.
• Treatment with 5 a-lipoic acid has led to
  significant improvements in clinical and
  objective measurements of photoaging, including
  laser profilometry

Br J Dermatol 149 841849, 2003
93
Estrogens

• Oral estrogen use was associated with a
  statistically significant decrease in the risk
  for dry skin and wrinkling
• Topical estrogen therapy can also lead to
  significant increases in collagen, firmness, and
  elasticity, as well as wrinkle depth measured by
  optical profilometry

Int J Dermatol 35669-74, 1996.
94
Growth factors and cytokines

• Topical application of a combination of growth
  factors and cytokines has been evaluated in a
  pilot study for its effect on photoaged skin
• A majority of patients showed clinical
  improvement in at least one facial area and a
  significant change in objective measurements by
  optical profilometry
• New collagen formation was observed in biopsy
  specimens

95
FROP-3

• Fucose-rich oligo- and polysaccharide
• Stimulation of fibroblast proliferation
• Downregulation of skin matrix degrading enzymes
  as matrix metalloproteinases MMP-2 and MMP-9
• Free radical scavenging
• Increase of skin elastin biosynthesis
• Improvement of collagen fibrillogenesis
• Increases glycosamino-glycan biosynthesis in
  fibroblast cultures

Skin Research and Technology 2005 11 4752
96
FROP-3

• In a pilot study examining skin-surface
  microrelief, the pattern of fine wrinkling found
  in skin of any age, a cream containing FROP-3
  showed a 10- to 15-year decrease in apparent age
  after 4 weeks of treatment

97
Emerging Therapies
98
Antioxidants

• Oral soy isoflavones (?????)
• can enhance the activity of endogenous
  antioxidant enzymes and protect against
  UV-induced aging
• ??????????????????????,???0.20.4????????????????
  ?,?????????????12?,??????????????23
  Daidzin(D)?64 Genistin(G)?13 Glycitin?????Daidze
  in(De)?Genistein(Ge)?Glycitein

99
Antioxidants

• Topical genistein (?????) and N-acetyl cysteines
  (NAC, N-???-L-???? )
• prevent c-Jun and collagenase up-regulation after
  UV exposure in human skin in vivo
• an inhibitor of tyrosine kinase activity and may
  inhibit signal transduction induced by UV light

100
Antioxidants

• Gluconolactone (???????)
• a polyhydroxy acid
• capable of chelating metals and may also function
  by scavenging free radicals, thereby protecting
  skin from some of the damaging effects of UV
  radiation
• a preventive treatment for solar elastosis

101
Antioxidants

• Green tea polyphenols (GTPs)
• potent antioxidants
• Oral administration of GTPs markedly inhibited
  UV-induced expression of MMP in mouse skin.
• Even in the absence of UV light,
  ()-epigallocatechin-3-gallate, a component of
  green tea, was shown to inhibit the expression of
  various MMPs

102
Silmarin

• Silymarin????????????(Milk Thistle)????????,??????
  ???
• 1968?,??????????????? silibinin,
  silidianin?silicristin
• ????????????,??????,???????????(???????)??????????
  ?????????,????????????
• ??????????,??????????????,????????E
• ????????
• ????????

103
Grape seed

• Grape seed proanthycyanidin extract (GSPE) are a
  group of biologically active polyphenolic
  bioflavonoids
• Strong antioxidants (Clin Cancer Res 62921-30,
  2000)
• GSPE containing 5000 ppm resveratrol Potently
  upregulates oxidant and tumor necrosis
  factor-alpha inducible VEGF expression in human
  keratinocytes (Free Radic Biol Med 3138-42, 2001)

104
Grape seed

• Topical application of GSPE accelerated wound
  contraction and closure, represents a feasible
  and productive approach to support dermal wound
  healing (Free Radic Biol Med 331089-96 2003)

105
Ginkgo biloba

• ?????????????,?????????
• ???????(Gingoflavonglycoside)???????( Super Oxide
  dismutase,??SOD)??

106

• Ginger extracts
• Metallothionein (????? )
• Evening Primrose (???)
• CoffeeBerry

107
Iron chelators

• MMP activation is dependent on iron, the iron
  chelator kojic acid was investigated to determine
  its potential preventive effects on photoaging
• Kojic acid is produced by the fungus Aspergillus
  oryzae and is found in Japanese soy-based
  products

108
Anti-inflammatory agents

• The protective effects of topical hydrocortisone,
  naproxen, and ibuprofen were examined in the
  hairless mouse.
• Celecoxib has been shown to reduce inflammation
  caused by short- and long-term UV exposure.

109
Minerals ?(Selenium)

• ????????????E????????????????????
• ??????,??????????????,???????????????????
  25mcg,??????????? 200mcg,??????????63????53???46
  ??
• ???????????????????????????????????????????

110
???? (La Roche-Posay )

• ?????????????????????????????????? BRGM
  ??,????????? ? ? ????????
• ? 60 ug/L
• ???? 30mg/L
• ???? 396mg/L
• ? 140mg/L
• ????  

111
(No Transcript)
112
???

• ???1200?????
• ???????????????????????,??????,?????,???????,???
  ?
• ???? ?? ,??????? ,???? ,????
• ???? ??????????????????????????? ??? ??????
  ??????????? ?????????? ,??????

113
(No Transcript)
114
Clinical study
ORIGINAL MEASURES
a

• CLINICAL MORPHING
• Video-morphing made on
• not retouched IN VIVO photos.

• DERMAL PROTEINS DOSAGE
• Molecular marking on biopsies

b
T0 T1,5m T3m T4,5m
T6m
Collagens Type I, III, IV, VII
GAG
PG
Elastin
MMP 1 et 9
N.B.based on biopsies from the clinical pivot
study on Active c.the molecular marking focused
on only 2 types of derma proteinscollagens 1
and III. Samples were only taken at T6
months.Results were compared to Active C T6
months against placebo.For Redermic the biopsies
were taken at T0 and at T6 months, which enabled
comparison of T6mths v.s. the control and also
v.s.T0.
115
?????(Idebenone)

• Idebenone is a synthetic analog of coenzyme Q10.
  This lower molecular weight molecule is presumed
  to penetrate skin more efficiently than its
  parent compound.

116
?????(Idebenone)
117
Tertiary therapies

• Chemical peels
• Resurfacing techniques
• Laser systems

118
????
???
????
???
??
??
???
??
119
Phenol Peeling
120
(No Transcript)
121
(No Transcript)
122
(No Transcript)
123
Radiofrequency technology

• Produce an electric current that generates heat
  through resistance in the dermis and subcutaneous
  tissue
• Reflect collagen contraction followed by
  secondary collagen synthesis and remodeling
• Adverse events erythema, soreness, and
  second-degree burning

124
Botulinum toxins

• Exotoxin produced by Clostridium botulinum that
  prevents local neuromuscular transmission
• The toxin facilitates cleavage of synaptosomal
  associated membrane protein (SNAP)-25, which is
  required for exocytosis of acetylcholine, thereby
  inhibiting muscle contraction

125
Botulinum Toxin A Injection
126
(No Transcript)
127
Soft tissue augmentation, Filler

• Autologous lipoaugmentation
• Bovine collagen
• An acellular dermal graft derived from human
  cadavers
• Hyaluronic acid (HA) derivatives
• A mixture of microspheres of polymethyl-methacryla
  te (20) and bovine collagen (80)

128
(No Transcript)
129
???????

• ?????????,?????????????????????
• ??????????????,?????????????
• ?????????????,?????????,??????????
• ???????????????,?????????????????????????,??????
  ?
• ???????????????????,???????????????,?????????????
  ???,????????
• ????????????????????????????,???????????

130
???????
???????!!