AGING FACE: PATHOPHYSIOLOGY

By

Dr. D R Dhaked

Aging

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

Facial Aging

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.

Skin

With age, skin undergoes several changes.

• More likely to wrinkle or sag

• Reduction in collagen

• Thinner

• Drier

• Less elastic

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.

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

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, lipthinning and flattening)• Development of prejowl depression

Aging

INTRINSIC SKIN AGING  (chronologic aging) or normal aging

EXTRINSIC AGING

INTRINSIC SKIN AGING  (chronologic aging)

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

Intrinsic Aging: Role of Telomeres

Telomeres

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.

Telomeres

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,

Cytoskeleton and Skin aging

Aged skin has increased rigidity Due to an increase in F actin filaments Important in age related loss of elasticity of

the skin.

Endocrine System and Aging

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

Endocrine System and Aging

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):289-290.

Age related changes in metabolic

functions

Reduced oxidative phosphorylation by mitochondria

Diminished synthesis of structural, enzymatic and

regulatory proteins

Decreased capacity for uptake of nutrients

Increased DNA damage and diminished repair of

chromosomal damage

Accumulation of oxidative damage in proteins and

lipids (eg lipofuscin pigment)

Accumulation of advanced glycosylation end

products

Morphological alterations

Irregular and abnormally lobed nuclei

Swollen, pleomorphic and vacuolated

mitochondria

Decreased endoplasmic reticulum

Distorted Golgi apparatus

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.

Dermis 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.

Subcutaneous Layer 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.

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

Photoaging 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

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

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)

26

UV DAMAGE AND OXIDATIVE STRESS

DNA effects DNA fragmentation

Matrix effects MMP : TIMP ratio

Membrane effects: ROS Lipids peroxidation Hydroperoxides

Enzymatic systems SOD Glutathion peroxidase Heme oxidase

UV damage

27

DNA DAMAGE

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: non-melanoma skin cancer (NMSC)

Advanced Glycosylation End Products

Post-translational modification of collagen

by sugar (AGE products)

Non-enzymatic attachment of glucose to

proteins

Formation of irreversible cross links

29

UVB DAMAGE

Following structural changes in DNA, there is an altered expression of oncogenes and tumor suppression genes, such as p53

NMSC show a high incidence of mutation in p53 gene

30

p 53 GENE

Plays an important role in: blocking the cell cycle after exposure to DNA-

damaging 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

32

Collagen & Photodamage

Major structural component of ECM 70% of the dry weight of skin

Collagen degradation is believed to play a role in formation of wrinkles

Collagen Cross Links

Intermolecular cross links between lysine

residues in adjacent collagen helices

Non-reducible cross links increase with age

Arise as a side effect of free radical damage

34

MMP ENZYMES

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

#######

Smoking Acts primarily via vasoconstriction of blood vessels going to and

through skin layers.  Decreased blood flow results in

decreased nutrients, decreased oxygen supply increased inflammatory byproducts (free radical oxidation byproducts). 

Net effect decreased collagen production and turnover, poor quality collagen and elastin, decreased quantity of matrix components and less gland secretions. 

Gravity. 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. 

THANK YOU