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Aging skin: Physiological changes. By Doaa Hegab Ass. Lecturer of Dermatology & Venereology Tanta University.
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Aging skin: Physiological changes By Doaa Hegab Ass. Lecturer of Dermatology & Venereology Tanta University
The process of skin aging involves many functional and structural changes that evolve over time, and are influenced by environmental insults, particularly ultraviolet light and individual practices as smoking. Skin aging can be divided into: -Chronological or intrinsic aging. -Premature or extrinsic aging.
The most conspicuous process is certainly the progressive loss of skin tissue. Skin loss amounts on the average to about 7% per decade with large individual variations. This loss of skin tissue, which underlies most of the easily noticed morphological modifications of the skin, can be attributed to several factors such as loss of cells and loss of extracellular matrix (ECM). • Cell loss concerns both the epidermal and dermal layers. • Loss of ECM is evident when histological skin sections from young and old individuals are compared. Loss of ECM is the result of: - Cell loss - Decreased biosynthetic capacity of remaining cells - Progressive increase of matrix degrading enzymes.
Loss of cells Loss of cells is attributed to two distinct processes: 1-Slow-down of cell division because of telomere loss. 2- Exit of cells from the mitotic pool mediated by some antioncogenes through a ‘‘switch mechanism’’ enabling cells to quit the mitotic pool entering the senescent phenotype.
Increased degradation of skin-ECM The most conspicuous factor in aging of connective tissues, was the progressive upregulation of elastase-type endopeptidase activity, causing increased degradation of ECM.
Progerin accumulates gradually in skin during aging. Progerin is a dominant negative form of lamin A, a nuclear membrane protein which is produced in cells of young individuals affected by the progeria and who die young (12–15 years) with cardiovascular symptoms.
Postsynthetic mechanisms of skin aging • The Maillard reaction • Proteolytic production of toxic peptides • Loss and uncoupling of receptors (Robert L, et al. 2008)
The Maillard reaction Glycation by reducing sugars and related molecules is important for the aging of connective tissues. A great number of studies were published on the production of advanced glycation end-products (AGE-products) and on their role in tissue aging. AGE-products are derived not only from local production in tissues by glycation and glycoxydation but are also absorbed with dietary sources • AGE-products could directly kill fibroblasts. • AGE-products strongly increased cell death. • AGE-products increase elastase-type endopeptidase expression.
Proteolytic production of toxic peptides Fibronectin (FN) production is increasing with age. The two chains of FN are easily degraded by proteolyticenzymes, which are shown to be upregulated during aging. Several of the peptides released by proteases were shown to exhibit harmful effects: potentiation of malignant transformation, pro-inflammatory activity, proteolytic activity absent in the parent-molecule. Similar processes were shown to be produced by degradation products of other ECM macromolecules such as elastin peptides.
Loss and uncoupling of receptors • aging is accompanied by the progressive loss of a number of receptors. The loss of important receptors as those mediating several hormone actions and the activity of the autonomous nervous system can be considered as important factors in the age-dependent loss of tissue and cell homeostatic regulations. • With aging, uncoupling of the receptor recognising elastin peptide sequences occurs. • The overall result of receptor uncoupling was therefore the loss of all physiologically useful effects of the elastin receptor with the maintenance of only the harmful effects such as upregulation of elastase-production and of free radical release. • As elastin peptides are present in the blood and body fluids, the elastin receptor is constantly exposed to its agonists producing the above-mentioned harmful effects.
Skin problems related to chronological aging
The clinical changes associated with aging affect all skin functions. Categories of clinical aging changes include: • Decreased strength • Impaired skin barrier • Altered immunity • Skin appendages and vascular changes • Decrease in skin protective functions.
The general anatomical changes of the skin associated with aging result in • Atrophy • Laxity • Wrinkling • Sagging • Dryness • Neoplasms • Skin pallor • Pigment and blemish development Chronological aging changes affect both epidermis and dermis.
The overall thickness of the skin decreases. The epidermis becomes thinner with aging, primarily due to retraction of the rete pegsanddecline in the thickness of the stratum spinosum. The vertical height of the keratinocytes decreases, corneocyte surface area enlarges, keratinocyteadherencedecreases, and epidermal turnover rate generally slows. • The usual 28-day turnover time for skin increases approximately 30% to 50% by age of 80.
Flattening of the dermo-epidermal junction. • The basal cells also normally display numerous villous cytoplasmic projections into the dermis at the dermal-epidermal junction, but this corrugated appearance disappears after the sixth decade.
The mitotic activity in the basal layer is reduced and the transit time from the basal layer to the stratum corneum is increased. The orderly maturation of the skin proceeds in a slower and incomplete or disjointed fashion. • the senescent keratinocytes become resistant to apoptosis and may survive long enough to accumulate DNA and protein damage leading to increased incidence of cancerous changes.
The intercellular lipid structure is normal but focally decreased. • The total lipid component is decreased but has the normal distribution of cholesterol, ceramides, and free fatty acids. Cholesterol synthesis is profoundly reduced.
The ability of the stratum corneum to regenerate after barrier disturbance is slowed, likely influenced by a decrease is cytokine response in the senescent epidermal cells. • The amino acid content of the corneocytes is reduced with a decrease of the natural moisturizing factors, water-binding, and strength and flexibility of the corneocytes.
Melanocytes, Langerhans cells, and Merkel cells in the epidermis drop out. • By age 80, the Langerhans cellsdecrease in number as much as 50%. This is exaggerated in sun-exposed areas. These dendritic cells are the most important part of the innate immune system. Changes of aging Langerhans (dendritic) cells include fewer dendrite projections infiltrating the skin, reduced antigen trapping capacity, and atrophic morphology.
Melanocyte dropout is less in sun-exposed areas but these cells are functionally impaired and irregularly spaced, producing an irregular pigmentation on sun exposure. • The dropout of melanocyte number and function leads to graying of hair. • The melanocytes decrease about 8% to 20% percent each decade after age of 30.
Changes in the cutaneous nerves lead to an impaired early warning function of pain with an increase in pain threshold. • Resolution of post-injury hyperalgesia is slower. • Dropout of nerve function stunts the ability to thermoregulate through vasodilation and sweating.
The pH of the skin is constant until about age 70; then it increases, especially in the lower limbs. • Vitamin D synthesis -an endocrine function of the skin- declines with age along with the general trend of reduced sun exposure, leading to a lack of vit.D production. The inadequate supply of active vitamin D also has an adverse effect on the differentiation and development of the skin.
Dermal changes are significant in the cellular and cell matrix components. The dermis thins. Senescent fibroblast changes include an increase in matrix metalloproteinase expression and a decrease in its inhibitors. The number of fibroblasts and their functional capacity decreases.
New collagen production decreases and the matrix of the dermis declines. The dermis loses turgor, due to reduction of glycosaminoglycans, especially hyaluronic acid and dermatan sulfate. • Collagen fiber disorganization and random orientation, thickening, and collagen fragmentation lead to overall dermal disorganization. • Elastic fibers undergo irreversible structural and compositional changes that progress with age, leading to a substitution of the fibers with amorphous elastin with poor functional activity.
Histological features of sun-protected skin from young and old individuals. Thick collagen bundles are present throughout the upper dermis of sun-protected young skin. Inset:Some fibroblasts can be seen oriented in the plane of the fiber bundles. In the old skin sample, the bundles have been replaced with thin, disorganized fibers. There is more open space in the dermis. Interstitial cells are round or oblong, and some are surrounded by open space.
The number of capillary loops projecting from the subpapillary plexus decreases with age. The subpapillary plexus appears more tortuous, elongated, disorganized, and dilated. • Cutaneous blood flow through the capillaries decreases with the decline in rete pegs. Skin capillary blood flow in response to heat is decreased partly due to a decline in sensory nerve function. The endothelial-dependent response to vasodilator chemicals is reduced.
The eccrine and apocrine sweat glands reduce in number and show cellular degeneration and the response to thermal stimulation and acetylcholine is reduced. • The number of sebaceous glands remains the same but sebum production decreases and the sebaceous glands become hypertrophic. • The pericytes (contractile cells of the capillaries that support, stabilize, and help regulate capillary blood flow) progressively reduce with age. These changes reduce the contact of the dermis with the epidermis, capillary perfusion, communication between the layers, and nourishment.
Dermal regeneration and repair are impaired due to matrix, cellular, and vascular aging changes. The connections between the dermis and epidermis weaken due to the flattening of the rete pegs and the basal cell layer connections to the dermis at the dermal-epidermal junction. • The supportive role of the dermis to the epidermis as far as nourishment, structural, vascular support, and repair when injured is impaired.
Innate and acquired immune function are less effective. Recognition of and response to possible pathogens is blunted and the skin is not able to defend itself effectively. • Cell signaling is also blunted and the secondary inflammatory response to injury, harmful chemicals, and pathogens is not as efficient. • The tendency for dermatitis may be enhanced due to exposure of the body to allergens from disruption of the skin barrier. • Irritation from chemicals or other potential irritants is also more likely.
Hair aging comprises: -Weathering of the hair shaft (with progressive degeneration of the hair fiber from the tip to the root) and -Aging of the hair follicle, which manifests as: *Decrease melanocyte function (hair graying) and *Decreased hair production in senescent and androgenetic alopecia.
Hair weathering • Aging hair is frequently associated with problems of hair thinning, dryness and hair damage (trichoptilosis and trichorrhexis nodosa). • Dry hair lacks sufficient moisture and shine and is difficult to style. • The cuticle of hair becomes heavily weathered and porous with age and the cortex becomes exposed and can’t retain humidity.
Hair graying • Hair color change is probably one of the most obvious signs of aging. With aging, the hair follicle produces less melanin. • Graying often begins in the 30s, although this varies widely. Graying usually begins at the temples and extends to the top of the scalp. Hair becomes progressively lighter, eventually turning white. • By the time they are in their 40s, about 40% of all people have some gray scalp hair. Body and facial hair also turn gray, but usually later than scalp hair. The hair in the armpit, chest, and pubic area may gray less or not at all. • Graying is genetically determined. Gray hair tends to occur earlier in Caucasians and later in Asian races. Nutritional supplements, vitamins, and other products will not stop or decrease the rate of graying.
With aging, the follicle produces less melanin. Aged hair follicles are no longer sufficiently prepared for new hair growth.
Senescent alopecia • Senile involutional or senescent alopecia has been defined as non androgen dependent hair thinning found in those over 60 years of age. • It involves a progressive decrease in the number of anagen follicles and hair diameter. It frequently occurs with AGA complicating it. • Senescent alopecia did not appear to follow a perfectly regular course. Periods of stability, or even partial remission, alternated with periods of more marked evolution, reflecting perhaps the influence of individual factors such as general health , life style and risk factors for accelerated aging.
The nails change with aging, growing more slowly, and becoming dull and brittle. • The color may change from translucent to yellowed and opaque. • Nails, especially toenails, may become hard and thick and ingrown toenails may be more common. The tips of the fingernails may fragment. Sometimes, lengthwise (longitudinal) ridges will develop in the fingernails and toenails. This can be a normal aging change. However, some nail changes can be caused by infections, nutritional problems, trauma, and other problems.
The message • Realizing the increased risk of skin problems associated with aging and its different stressors and conditions can trigger the onset of therapy. • The cumulative effects of aging are accelerated by photoaging, medication side effects, organ failure in other systems, and comorbidities such as diabetes mellitus, nutritional deficiency, and general vascular changes.
