Dr Judey Pretorius looks at how the structures within the epidermis, dermis and subcutaneous layer of the skin are affected by the ageing process.
A host of physiological changes take place throughout the body during the ageing process. But on no part of the body is it more outwardly obvious than the skin, which is what we will be looking at in this article.
The epidermis is the outermost layer of the skin and comprises a particular cell type known as keratinocytes, which form the skin’s external protective barrier. The epidermis also comprises the pigment producing cells, i.e. melanocytes, as well as Langerhans cells that assist with skin antigen characteristics.
The average epidermal thickness is 0.1 mm, which is about the thickness of a sheet of paper. The epidermis acts as a protective shield for the body and totally renews itself approximately every 28 days.
Aged skin is prone to dryness and itching, cutaneous infections, autoimmune diseases, vascular complications, and increased risk of malignancy. As we age, pH can increase from between 4.8 to 5.8 to a higher pH range of 6.2 to 7.2. A higher skin pH will undoubtedly have an effect on ionic exchange, which may disrupt the homeostatic regulation within the skin. Fluctuating pH on the skin may have a direct impact on the skin microbiome.
The dermis is located between the hypodermis and the epidermis. It is comprised of a wide array of extracellular matrix proteins, produced with dermal skin cells known as fibroblasts.
The dermis hosts the skin’s vascular supply, and is a fibrous network of tissue that provides structure and resilience to the skin. While dermal thickness varies, it is on average about 2 mm thick.
As we age, the major components of the dermis are compromised and stop working together as a network. This mesh-like network is composed of structural proteins (collagen and elastin), blood and lymph vessels, and specialised cells called mast cells and fibroblasts.
These are surrounded by a gel-like substance called the ground substance, composed mostly of glycosaminoglycans. The ground substance plays a critical role in the hydration and moisture levels within the skin.
Both collagen and elastin proteins are produced in specialised cells called fibroblasts, located mostly in the upper edge of the dermis bordering the epidermis.
The blood vessels in the dermis help with the thermoregulation of the body by constricting or dilating to conserve or release heat. They also aid in immune functioning and provide oxygen and nutrients to the lower layers of the epidermis. These blood vessels do not extend into the epidermis.
Nourishment that diffuses into the epidermis only reaches the very bottom layers. The cells in the upper layers of the epidermis are dead because they do not receive oxygen and nutrients.
The junction between the dermis and epidermis is a wave-like border that provides an increased surface area for the exchange of oxygen and nutrients between the two sections. Along this junction are projections called dermal papillae. As you age, dermal papillae tend to flatten, decreasing the flow of oxygen and nutrients to the epidermis.
Subcutaneous tissue hypodermis
The hypodermis is the deepest section of the skin and refers to the fat tissue underneath the dermis that insulates the body from cold temperatures and provides shock absorption. Fat cells of the hypodermis also store nutrients and energy. As we age, the hypodermis begins to deteriorate, contributing to the thinning of ageing skin.
Dermal physiology associated with the ageing process
1. Chronological ageing versus premature ageing
It has been reported that there are two types of ageing, the first of which is known as ageing caused by genes we inherit, which can be denoted as chronological or intrinsic ageing. Another type of ageing is also defined as extrinsic ageing or premature ageing, which is caused due to the exposure of extremities and environmental factors such as sun exposure and pollution.
2. The photoaged skin
Photoageing is a cumulative process and depends on the exposure of the skin to the sun and accounts for approximately 80% to 90% of visible skin damage. Individuals such as albinos and individuals with low counts of melanocytes are more at risk against UV damage. UVA and UVB rays play an important role in the degradation of skin. UVB rays only penetrate into the epidermis of the skin and produce the erythema associated with sunburn. UVA penetrates into the dermis and is associated with more chronic skin damage.
3. Sun exposure and skin ageing
The skin ages with sun exposure. The number of melanocytes decreases significantly on skin exposed to UV rays. Photoageing affects the sun-exposed areas and is characterised fine lines and visible wrinkles on the skin, while roughness, dryness and a loss of tensile strength and pigmentary changes become more visible on its outer layer. The development of benign and malignant neoplasms also becomes more prominent on the skin during photoageing, with UVB rays, in particular, being fully absorbed in the epidermis.
Ageing and photoageing can be readily distinguished, and essential molecular features such as signal transduction pathways that promote matrix-metalloproteinase expression are noted. UV radiation increases oxidative stress and photoaged skin shows more vascular damage than chronologically aged skin.
Theories of ageing
Theories of ageing are particularly addressed by focusing on how and why the skin ages. Some of the theories include the following:
- Cellular mitochondria reduction and cellular energy depletion.
- Crosslinking glycation hypothesis of ageing – this is based on the observation that with age, skin proteins, DNA and other structural molecules develop inappropriate attachments or cross-links to one another. These links or bonds decrease the mobility and elasticity of the skin.
- Evolutionary senescence theory of ageing – focused on the failure of natural selection to affect late life traits.
- Genome maintenance hypothesis of ageing – the theory of evaluating DNA decline and repair, the formation of polymorphisms and mutagens within the skin.
- Neuroendocrine hypothesis of ageing – the evaluation of complex connections between the brain and nervous systems and our endocrine glands, which produce hormones. As we age, this system becomes less functional.
- Oxidative damage and free radical hypothesis of ageing.
- Rate of living theory of ageing – components such as where we live geographically, what we consume, our genetic material and overall lifestyle have direct impacts on our rate of ageing.
- Replicative senescence hypothesis of ageing – the protection of our genetic material, which shortens over time during cellular diffusion. This decreases cellular stability and makes the DNA more prone to mutagenic formation.
Collagen, elastin and hyaluronic acid degradation
A major feature of aged skin is the fragmentation of the dermal collagen matrix. A reduction of fibrillar (types I and III) collagen is a characteristic feature of chronologically aged skin and is enhanced in photodamage. If a decrease in collagen synthetic capacity occurs as a function of fibroblast (cellular) ageing, this leads to a loss of mechanical tension, which has a direct impact on the density and pore size of the skin.
Changes in elastin fibres are so characteristic in photoaged skin that the condition known as elastosis is considered a hallmark of photoaged skin. This is characterised by an accumulation of amorphous elastin protein and a breakdown in the typical structural layout, which results in decreased skin elasticity and tensile strength. This phenomenon accounts for why more mature skin takes longer to assume its original position when extended or pulled.
Skin ageing is associated with the loss of skin moisture and the key molecule involved in skin moisture is hyaluronic acid (HA), which has unique water-retention capacity.
Loss of skin adhesion
The respective layers and cells all form part of the skin’s connective tissue. In order for optimal cellular proliferation migration and differentiation to take place, cell-to-cell communication is very important, allowing for ion channelling and protein migration to take place. During the skin ageing process, adhesion between the respective skin cells is less prominent, and protein migration and ion channelling are hindered. This inherently also disrupts the acid mantle characteristics of the skin and deteriorates the overall lipid component, which is crucial for gene signalling between cells and the transportation of extra- and intracellular proteins.
The architectural integrity of skin is altered during ageing and the skin becomes more dry, thin and flattened. The fibroblasts are responsible for collagen production, and a decrease in fibroblast cellular differentiation leads to a decrease in collagen production, which inherently reduces the elasticity and density of the skin. This is also typically associated with a rough skin texture and enlarged pores.
Cutaneous blood vessels embedded in the skin play a role in the pathogenesis of photoageing. Photoaged skin shows respective vascular damage that is absent in intrinsically aged skin. Vascularisation patterns are dilated and distorted within the skin typically when exposed to acute and chronic UVB irradiation.
Sebaceous gland activity
Sebaceous glands are usually connected to hair follicles and secrete sebum to help lubricate the follicle as it grows. Sebum also contributes to the lipids and fatty acids within the moisture barrier, while oil production within the sebaceous gland is regulated by androgen levels (hormones such as testosterone).
The human sebaceous gland undergoes both extrinsic and intrinsic ageing. The latter is associated with morphological changes and a shift in sebaceous gland activity. The high androgen-dependent sebum secretion in neonates falls during childhood, starts to rise again during puberty and reaches its peak in young adults. While the number of sebaceous glands remains the same during life, sebum levels tend to decrease after menopause in females, whereas no major changes appear until the eighth decade of life in men.
Keratin is a tough, fibrous protein found in fingernails, hair and skin. The body may produce extra keratin as a result of inflammation, as a protective response to pressure, or as a result of a genetic condition. During the process of ageing, hyperkeratosis can occur in the form of plantar warts or callous, due to a change in skin pH or inflammatory stimuli such as UV irradiation. In order to prevent hyperkeratosis, the acid mantle integrity needs to be maintained, as the acidity of the skin helps maintain the hardness of keratin proteins, keeping them tightly bound together.
The atrophy of facial muscles causes premature ageing. During the process of ageing, muscle fibres also start to shrink and deplete, which has an impact on the integrity of the skin’s connective tissue. This has an effect on the firmness and flexibility of the skin, which becomes looser while gravitational forces on the connective tissue increase.
The most common structural component within the dermis is the protein collagen. It forms a mesh-like framework that gives the skin strength and flexibility. Glycosaminoglycans – moisture-binding molecules – enable collagen fibres to retain water and provide moisture to the epidermis.
Skin discolouration during ageing is observed in 10% to 20% of people over 30 years of age, as melanocytes decrease within the skin. Sun-exposed skin has approximately twice as many pigment cells as unexposed skin and chronic exposure to sunlight may stimulate the epidermal melanocyte system rather than accelerating chronological ageing.
Changes in healing capacity
Cellular ageing will have a dramatic effect on wound healing, as the optimal integrity of growth factors, angiogenesis and collagen fibres deteriorates over time. A lack of the aforementioned results in:
- Reduced skin elasticity: During ageing, skin loses elasticity due to the degradation of the elastic tissue and collagen fibres in the outer dermal layer. These elements provide strength and flexibility, but also help tissue recover and restore to its original state. Since the tissue is less elastic and supple, restoration of the skin to its natural shape and colour is more prolonged. This means older people have a higher risk of scarring from a wound.
- Age-related diseases: Certain diseases and medical conditions are more common in the elderly. Cardiovascular disease, diabetes and others – particularly those that affect blood flow – can be detrimental to the recovery process. When blood cannot properly reach the affected area, the area becomes malnourished and oxygen deprived, thereby stalling the wound healing phases.
Effects of ageing on bone density and structure
Skin collagen content and bone mass density share comparable regressive changes during ageing. Bone mass decreases as time elapses, particularly during menopause. Bone mineral density decreases markedly during ageing and this decrease has a direct impact on the reduction of skin thickness and texture. This is because the skin’s connective tissue and platform is compromised and decreased alongside the bone strength, which, over time, increases the fragility of the skin.
Extrinsic and intrinsic influences on ageing
Skin ageing is driven by several intrinsic (e.g. genetics, metabolism) and extrinsic (e.g. pollution, smoking) factors. Both intrinsic and extrinsic factors lead to cumulative alterations in the holistic skin structure, function and appearance. The intrinsic or chronological component of ageing is thought to be regulated by the genetic code and is generally associated with a defective DNA repair mechanism.
The extrinsic component of ageing is a degenerative process produced by ample and amplified exposure to environmental toxins such as solar or UV rays, nicotine from cigarette smoke, or high nitrogen oxide counts due to atmospheric pollution.
Human skin is also affected by ambient conditions such as temperature and humidity. If the temperature is raised within the skin, then the rate of water loss by means of evaporation is increased; in contrast to this, low temperatures harden and densify the skin, reducing water evaporation and affecting the physiological characteristics of skin proteins and lipids. Additionally, certain topical medication may have a direct impact on disproportionate cellular diffusion and proliferation, and abnormal desquamation.
The effects of smoking alter the structure of the skin
Smoking is associated with skin elastosis and damages the skin by diminishing the capillary blood flow, which inherently deprives the cutaneous tissue of oxygen and essential nutrients. It has been shown that smokers have fewer collagen and elastin fibres in the dermis, which has a reduced effect on the elasticity and tensile strength of the skin. The skin appears rougher in texture and wrinkles are more prominently observed.
The effects of atmospheric pollution and the prevalence of skin deficiencies and cancers have risen exponentially over the last three decades. The depletion of the stratospheric ozone layer and increased environmental pollution – such as the emission of hydrofluorocarbons and the combustion of fossil fuels – have aggravated serious genetic damage.
Additionally, environmental exposure to xenobiotics and pesticides also sees these to some extent absorbed into the skin. This has been shown to have significant systemic effects related to the release of immunologically active molecules from the skin.
Physiology of tissue degeneration and regeneration
The physiological characteristics of the respective layers of the skin and the regeneration of new skin cells slowly deteriorate over decades. Cell-to-cell signalling is compromised due to depleted protein synthesis and the reduction of cellular energy. Cellular division and viability decrease, which inherently has an effect on protein and tissue regeneration (such as collagen and elastin). The degeneration of protein inherently reduces moisture retention, which leads to an acute reduction of metabolic activity and cellular dehydration.
A2 Disclaimer: This article is published for information purposes only, and should therefore not be taken as an endorsement – nor should it be regarded as a replacement for sound medical advice.
This article was written by Dr Judey Pretorius and edited by the A2 team EXCLUSIVELY for the A2 Aesthetic & Anti-Ageing Magazine June 2018 Edition (Issue 26).
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