Transcript Ageing Skin

Ageing

Skin

Dr Bill Revell

AGEING

Process of progressive generalised impairment of function

Resulting in an increasing age- specific death rate

Tom Kirkwood

Ageing

Results from accumulation of un-repaired damage of somatic cells and tissues

Progressive failure of maintenance mechanisms to respond to environmental attrition

Free radical damage may offer a unifying theory for cellular senescence, underlying human ageing and age related diseases

Deteriorating Tissue Function

Associated with change in cell functioning

+/- Change in cell turnover when old or defective cells are not replaced

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

Ageing skin; a preamble……….

Huge efforts to hide and disguise

Gerontological discussion has little to do with morbidity or mortality; very few patients die of old skin, or succumb to skin failure

Importance is primarily psychological

Emotional impact of skin ageing should not be underestimated

Ageing skin

Wrinkled

Most pronounced on sun exposed parts

Age or liver spots

Loss of hair

Sagging facial muscles

Increased fragility

Skin contains less collagen and elastin; abnormal

changes to collagen and elastin

Thinner; less elastin; less collagen

Abnormal elastin and collagen

Wrinkling; most pronounced on sun exposed skin

Collagen Cross Links

Eg 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

A

dvanced

G

lycosylation

E

nd Products

Post-translational modification of collagen by sugar (AGE products)

Non-enzymatic attachment of glucose to proteins

Formation of irreversible cross links

Structural age changes in skin

dermis

Age related changes – “normal” ageing

Epidermis

Epidermis thinner

Increased “scaling off”

Declining rate of cell division

Decrease in dermal papillae

Decrease in “interdigitation”

epidermis held less tightly

Looser feel of ageing skin

By age 80yr keratinocyte turnover in epidermis slows to 50%

Age related changes – “normal” ageing

Dermis

Reduction in fibroblast numbers

Less matrix turnover

Dermis thins more than epidermis (transparency)

Collagenous fibres become larger and coarser

Fat, water, matrix content diminishes

Elastic fibres less resilient

Formation of cross links; some calcification

Skin less able to “smooth out”

Wrinkles

Loss of smooth padding provided by fat cells of the hypodermis

Age related changes – “normal” ageing

Dermis

Reduction in sweat glands and sebaceous glands

Gradual atrophy

Sweat less; drier and scaly skin

Reduced ability to regulate body temperature

Heat exhaustion more likely

Generalised reduction of blood flow to skin

Skin surface cooler; slow growth of hair and nails

Nails yellowish, ridged, thicker with Ca 2+ deposits

Decrease in hair follicles, loss of body hair

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cf (males) eyebrow, nostril, ear hair becomes coarse and grow more rapidly Reduced hair pigment – grey/white is default colour

Age related changes – “normal” ageing

Hypodermis

Layer of loose connective tissue, containing fat

Subcutaneous tissue; not part of skin (technically)

…. but changes affect skin….

Generalised loss of fat; most obvious in face and limbs

Major cause of wrinkles

“old age is when, upon getting out of the bath, you notice the full length mirror is steamed up – and you are glad of it” (Modern Maturity)

Age related changes – “normal” ageing

Hypodermis

Loss of subcutaneous fat also loss of padding

Combine with reduction of blood supply to skin

Bed sores in areas of constant pressure over bony prominences

Loss of fat

Diminished insulation; allows heat to escape

Need to keep rooms warmer than young people can tolerate

“Age” or “liver spots”

Intrinsic – resulting from the ageing process

Resulting from UV damage: photo-ageing

dermatoheliosis

Free radical damage

Lipofuscin deposition in cells, often in secretary cells of sweat glands

End product of lipid peroxidation

Senile FRECKLES involving melanocytes 

pigmented area (melanin) surrounded by normal-appearing skin.

melanocytes are present; may be increased in number

may evolve slowly over years, or may be eruptive and appear suddenly

Pigmentation may be homogeneous or variegated, with a colour ranging from brown to black. cf solar LENTIGO

Age related dysfunctions

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Senile angiomas

75% >70yr

Elevated clusters of dilated capillaries Seborrheic keratosis

Benign epidermal tumours

Greasy wart-like crust often forms on surface of tumours Senile pruritis (itching)

Loss of oil secreting sebaceous gland

Dry, less pliant skin; cracks

Deep fissures that exude tissue fluid

Herpes Zoster (shingles)

Viral disease Peak incidence 50-70yrs Varicella (chicken pox) when young Remains dormant in nervous system When reactivated, attacks sensory nerve fibres and skin supplied by nerves Itching, red papules, fluid filled vesicles, dries down and forms crust, scales off, leaving pigmented area 1 – 2 weeks, pain for months

Skin Cancers

cancers of all types increase with age

Melanoma – most serious

Associated with sun UV light

Develops in pigment cells (melanocytes) of a pre existing epidermal mole

Non-melanoma skin cancers >50%

pink, red or white 

Basal cell carcinoma

Most common

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Develops from cells in basal layer of epidermis Most common in regions with strong sunlight

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Most prevalent in light skinned races Head and neck usually Rarely metastasise Variously reddish patches; small open sores; bumps Growths can invade underlying tissue

Non-melanoma skin cancers

Squamous cell carcinoma

Less common

Associated with excessive sun exposure

More common in elderly, esp. older men

Appears as a wart

Often in form of hard nodule, with small reddened areas showing through surface

May be ulcerous