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

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

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