role of uv rays, intrinsic and extrinsic causes

1. AGING FACE: PATHOPHYSIOLOGY
By
Dr. D R Dhaked

2. Aging
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Begins day we are born and highly individualized
No single measure of how “old” a person is
Proceeds at different rates in different people
Gradual decline in organ functional reserves with
reduction in ability to maintain homeostasis under
stress

3. Facial Aging
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Begins with surface and subsurface
structural changes in multiple facial tissue
layers, including skin, fat, muscle and
bone.
Facial tissue layers age interdependently,
contributing to overall facial appearance.
Changes in one tissue layer have an
effect on the other layers.

4. Skin
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With age, skin undergoes several changes.
• More likely to wrinkle or sag
• Reduction in collagen
• Thinner
• Drier
• Less elastic

5. Fat
-A youthful look depends on having the right amount of facial
fat in right places. Redistribution, accumulation, and atrophy
of fat lead to facial volume loss.
• Some areas lose fat (forehead and cheeks).
• Other areas gain fat (mouth and jaw).
• Modification of the fat pads leads to contour deficiencies.

6. Bone
•There is a significant loss of facial bone with age.
•Aging of the craniofacial skeleton may be due to changes in relative
dynamics of bone expansion and bone resorption.
•Bone resorption leads to biometric volume loss.
•Without the structural support of bone, there are noticeable changes
in the other layers of overlying soft tissue and skin

7. Signs of Facial Aging
• Greater visibility of bony
landmarks, lines and
wrinkles
• Prominence of transverse
forehead lines
• Nasolabial folds become
more prominent
• Hollowing of the mid-face
(loose skin)
• Changes in area around the
mouth (vertical wrinkles, lip
thinning and flattening)
• Development of prejowl
depression

8. Aging
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INTRINSIC SKIN AGING (chronologic
aging) or normal aging
EXTRINSIC AGING

9. INTRINSIC SKIN AGING (chronologic aging)
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Inevitable natural aging process that occurs in all people
Occurs as part of a pre-programmed degeneration within
cells and extracellular matrix in all skin layers.
Although begin in 20’s, visible signs are not apparent for
many decades.
Intrinsic aging proceeds at highly variable rates between
different people
Primarily determined by unique genetic make-up and
underlying type of skin

10. Intrinsic Aging: Role of Telomeres

11. Telomeres
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Tandem repeats of short base sequences,
...TTAGGG... in mammals, at end of each
chromosome, that are required for
chromosome stability.
With continued cell division, telomeres are
shortened, resulting in loss of ability of
cells to divide.

12. Telomeres
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Telomerase activity is detected in vitro
and in vivo in normal human epidermis,
primarily in the proliferative basal layer
Not found in the dermal compartment of
skin or in cultured fibroblasts
Harle-Bachor, C, Boukamp, P: Telomerase activity in the
regenerative basal layer of the epidermis in human skin
and in immortal and carcinoma-derived skin
keratinocytes. Proc Natl Acad Sci USA 1996 93: 6476–
6481,

13. Cytoskeleton and Skin aging
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Aged skin has increased rigidity
Due to an increase in F actin filaments
Important in age related loss of elasticity
of the skin.

14. Endocrine System and Aging
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With aging, the levels of epidermal
precursor of vitamin D3 decrease.
Older individuals are more susceptible to
vitamin D3 deficiency in absence of
regular sun exposure.
May lead to osteoporosis, psoriasis and
skin cancer

15. Endocrine System and Aging
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Estrogen stimulates fibroblasts to make
collagen
Decreased levels of estrogen are
associated with loss of collagen and
increased wrinkling
HRT protects skin from aging
Baumann, L. “A dermatologist's opinion on hormone therapy
and skin aging,” Fertility and Sterility 2005 Aug;84(2):289290.

16. Age related changes in metabolic
functions
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Reduced oxidative phosphorylation by mitochondria
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Diminished synthesis of structural, enzymatic and
regulatory proteins
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Decreased capacity for uptake of nutrients
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Increased DNA damage and diminished repair of
chromosomal damage
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Accumulation of oxidative damage in proteins and
lipids (eg lipofuscin pigment)
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Accumulation of advanced glycosylation end
products

17. Morphological alterations
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Irregular and abnormally lobed nuclei
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Swollen, pleomorphic and vacuolated
mitochondria
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Decreased endoplasmic reticulum
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Distorted Golgi apparatus

18. INTRINSIC SKIN CHANGES
•
Epidermis
• Keratinocytes demonstrate slower turnover.
• Keratin sloughs more slowly with thickening of
keratin layer.
• Melanoctyes decrease in number and produce
less melanin.
• Uneven melanin pigment distribution.
• Flattening of the epidermis-dermis junction.
Prone to blistering.

19. 
Dermis
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Fibroblasts – Decreased number and less
collagen production.
Collagen – Decreased quantity. Abnormal,
weakened structure.
Elastin – Thickened fibers with less elasticity.
Matrix – Decreased quantity.
Blood vessels – dilated, thinned and
weakened walls, prone to rupture.

20. 
Subcutaneous Layer
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Fat loss and thinning.
Weakening of the retaining ligaments.
Fewer blood vessels.
Sweat glands - decreased.
Sebaceous glands – Fewer with less sebum
production.
Hair shafts – fewer and thinner with less
pigment.

21. EXTRINSIC AGING –
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Outside factors that accelerate intrinsic
aging.
Photoaging
Smoking
Malnutrition
Hormonal Disorders
Chronic Disease States
Repetitive facial expressions
Gravity

22. Photoaging
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Caused by harmful effects of sunlight
Ultraviolet light is the prinicipal cause of photoaging
UVB penetrates only into epidermis and is
responsible for redness and blistering associated
with sunburns.
UVA penetrates more deeply into dermis, related to
photoaging

23. 
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Photoaged skin shows
deep coarse wrinkling,
excessive dryness,
severe brown spots
dry leathery texture when
compared to intrinsically
aged skin

24. PHOTOAGING
3 types of reactions to UV exposure:
 Free Radicals, essentially due to UVA
 Direct cell death, essentially due to UVB
 MMP Enzymes
24

25. FREE RADICALS
Free radicals or ROS (reactive oxygen
species) can lead to breakage of
important molecules:
 DNA (mutations, renewal failure, cell
death)
 collagen, elastin, GAG (skin firmness)
 lipids (membrane or structural)
25

26. UV DAMAGE AND
OXIDATIVE STRESS
DNA effects
Matrix effects
DNA fragmentation
MMP : TIMP ratio
UV
damage
Membrane effects:
ROS
Lipids peroxidation
Hydroperoxides
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Enzymatic systems
SOD
Glutathion peroxidase
Heme oxidase

27. DNA DAMAGE
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UVA acts through oxidative stress forming
“reactive oxygen species” (ROS) that will
damage the DNA and lead to cancer
UVB impact on DNA in the cell creating
damages which may lead to cancer: nonmelanoma skin cancer (NMSC)

28. Advanced Glycosylation End Products
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Post-translational modification of collagen
by sugar (AGE products)
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Non-enzymatic attachment of glucose to
proteins
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Formation of irreversible cross links

29. UVB DAMAGE
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Following structural changes in DNA,
there is an altered expression of
oncogenes and tumor suppression genes,
such as p53
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NMSC show a high incidence of mutation
in p53 gene
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30. p 53 GENE
Plays an important role in:
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blocking the cell cycle after exposure to DNAdamaging agents e.g. UV, in order to allow for
repair before duplication
or killing the cell to avoid multiplication of
damaged cells (formation of sunburn cells)

31. p 53 GENE
The induction of detectable levels of p53 in
human epidermis after UV exposure is
relevant to skin carcinogenesis
31

32. Collagen & Photodamage
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Major structural component of ECM
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70% of the dry weight of skin
Collagen degradation is believed to play a
role in formation of wrinkles

33. Collagen Cross Links
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Intermolecular cross links between lysine
residues in adjacent collagen helices
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Non-reducible cross links increase with age
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Arise as a side effect of free radical damage

34. MMP ENZYMES
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Collagenases (1 to 4) are specific to
various collagen,
Gelatinases (A & B) are non specific
Stromelysins (1-3) specific of fibronectin,
laminin, collagen IV,
Elastase: elastin

39. Smoking
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Acts primarily via vasoconstriction of blood
vessels going to and through skin layers.
Decreased blood flow results in
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decreased nutrients,
decreased oxygen supply
increased inflammatory byproducts (free radical
oxidation byproducts).
Net effect
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decreased collagen production and turnover,
poor quality collagen and elastin,
decreased quantity of matrix components and
less gland secretions.

40. Gravity.
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Constantly pulls on bodies.
In 50s, when skin’s elasticity declines
dramatically, effects of gravity become
evident.
Causes tip of nose to droop, ears to
elongate, eyelids to fall, jowls to form, and
upper lip to disappear while lower lip
becomes more pronounced.

41. THANK YOU