About the skin ageing process. Know your enemy from the inside out!

Ageing is a process defined by science as “reduced functionality and reserve capacity in all organs, which increases the probability of illness with age”. As a result of this process, the ability to adapt to environmental stimuli of our organs, including our skin, is diminishing. The ageing of our skin is a consequence of the influence of our genes and environmental factors.

Aging is a physiological process that includes lowering the biological activity of our body’s cells, loss of ability to adapt and slowing down repair processes of the whole organism. The aging process of the skin manifests itself as dryness (resulting from the loss of ability to bind water and retain it in the epidermis), the skin loses elasticity, is dehydrated, and the epidermis becomes thinner and rough. The rate of multiplication of epidermal cells slows down, fibroblasts reduce their activity, which weakens collagen and elastin fibers, revealing wrinkles.

This applies primarily to the skin on the face, neck, décolletage and on the dorsal surface of the hands and forearms. Depending on their depth, there are superficial and deep wrinkles. Ageing skin may also be accompanied by pallor, independent of anemia. As a result of disturbances in the process of melanogenesis and changes in the skin vascular system, numerous discolorations and telangiectasias may occur. Old hemangiomas, lentigines and fibroma may become visible. In advanced skin aging disorders of keratosis, seborrhoeic warts, pre-cancerous lesions and basal or squamous cell carcinomas may appear.

Two processes affect the changes taking place in the skin at the same time: internal and external aging. The process of skin aging associated with innate genetic mechanisms is intrinsic aging, and the process of skin aging associated with the influence of the external environment – photo-aging (extrinsic aging).

Exogenous aging is conditioned by external factors such as cigarette smoke, UV radiation, environmental pollution, improper care or bad diet. All types of skin ageing overlap and share biological, biochemical and molecular mechanisms. They are strongly associated with the production of free radicals (ROS). Oxidative stress is the most harmful factor in skin aging.

There are several theories that try to explain the causes and sources of ageing. They can be divided into non-genetic, genetic and physiological theories. As far as non-genetic theories are concerned, they are based on the accumulation of harmful substances in the body. Degradation and lowering the activity of physiological systems is a physiological theory, and disorders at the DNA level – a genetic one. Among the theories, one can distinguish the theory of programmed cell death (immune, limited number of divisions, selfish gene, gene) and the theory of error accumulation (free radical, protein disorders, mitochondrial, membrane). Gene theory assumes that in the nuclei of nuclear cells, DNA contains genes responsible for the rate and nature of ageing. Old age does not only depend on extrinsic mutations, but also on the inhibition of DNA repair capabilities. Probably the key role in the aging process is played by endogenous nuclear DNA damage. Evidence of damage to DNA structures and the disruption of its repair ability as factors accelerating the aging process comes primarily from research into diseases such as Hutchinson-Gilforg’s disease (HGP), Werner’s syndrome and Cockayne’s syndrome. Currently, about 100 genes have been identified that may be responsible for skin aging. The telomere theory assumes that cellular aging determines the shortening of telomeres, i.e. the ends of eukaryotic chromosomes, which limits the number of cell divisions. The theory of a limited number of divisions – Hayflick’s theory – according to this theory, a cell can only divide a certain number of times and then die. With age, the telomerase activity decreases (the enzyme is responsible for maintaining a constant length of telomeresis). The theory of protein disorders recognizes that aging is accompanied by a decrease in protein synthesis, which impairs the proper functioning of cells. The membrane theory, on the other hand, assumes that with age the composition of the cell membrane changes and the lipid content increases. The membranes are more rigid and sticky. Transport through the membranes is difficult and toxic substances accumulate in the cells. Glycoprotein, the so-called “old age antigen”, which appears in the membrane composition with age, may be important. According to the mitochondrial theory, cell death can also be associated with disturbances in the mitochondria. With age, their number and activity decrease, which results in a decrease in adenosine triphosphate (ATP) production. As the number of non-repairable damage continues to increase, the number of ATP is further reduced and the regenerative capacity of cells is impaired. There is also a neuroendocrine theory, also known as cross-linking. With age, the number of additional cross-links in molecules with long half-life increases. This is caused by free radicals and lipid peroxidation products. Crosslinking concerns proteins and nucleic acids themselves. The result may be cellular transport disorders, inhibition or disturbances in DNA replication.

Why does the skin age?
Skin ageing is a natural and unavoidable physiological process associated with a decrease in cell activity and a decrease in the regenerative and adaptive capacity of the body. Clinically, ageing skin manifests itself in wrinkles, flaccidity and dryness, atrophy of the epidermis and thickening of its stratum corneum, thinning of the dermis, pigmentation disorders, telangiectasias, formation of numerous sun keratosis and seborrhoeic warts. The most important seems to be the loss of normal skin structure with age, reduction of biological activity of skin cells and slowdown of regenerative processes, which causes loss of elasticity and elasticity (decrease in fibroblast activity, degradation of collagen and elastin fibers). The aging process on the face leads to various structural changes, such as flaccidity of eyelids, formation of mimic wrinkles, trapezoidal shape of the lower part of the face without the preserved oval of the face, intensification of nasolabial folds, line of puppets so called wrinkles of sadness or wrinkles around the mouth. In addition to flaccid skin, there is also a gradual loss of muscle tension, changes in the bone system of the skull and atrophy of subcutaneous tissue.

How does skin age with age?
The intensity of the skin ageing process is assessed on the Glogau scale. According to this classification we distinguish mild changes (28-35 years), medium-intensive changes (35-50 years), advanced changes (50-60 years) and very intensive changes (over 65 years). Mild lesions are characterized by lack of keratosis and presence of mimic wrinkles. Intermediate lesions are accompanied by yellow discolourations of the skin, which are in fact small lesions of solar keratosis. Static wrinkles, laughter lines and slight scarring appear. On the other hand, in advanced lesions there are distinct yellow spots of solar keratosis and telangiectasias. Wrinkles and furrows are visible all the time, as well as changes of scarring character. On the other hand, in very intensive changes, wrinkles, furrows and lines on the face deepen.

THE MOST IMPORTANT METHODS OF PREVENTING SKIN AGEING ARE..
healthy nutrition;
adequate irrigation;
physical activity;
body care;
avoiding stress;
taking care of sleep hygiene;
prevention and treatment of diseases;
hormone therapy;
the use of rejuvenating treatments and procedures.

Adequate diet
Scientific research shows that sugar, or precisely glucose, destroys collagen. Glucose molecules attach to collagen molecules and shorten their lifespan. This process is called glycation. The effect on the skin? Ageing – loss of skin firmness, sagging and wrinkles. The same reaction occurs when you consume carbohydrates with a high glycemic index, which convert into glucose during digestion. To maintain youthfulness, a diet rich in antioxidants, protein, low-glycemic index carbohydrates and healthy fats is the best. In the fight against glycaemia, we are supported by an appropriate diet and cosmetic care, especially peptides, especially the one called carnosine. It is one of the modern elixirs of youth. It has been proven that carnosine reverses the aging process – it prolongs the life of cells, extending the intervals between their divisions.

Ensuring an adequate level of collagen in the body
Collagen is a widely distributed extracellular animal protein, which is the main structural component of the dermis. Due to its biological properties, it is widely used in the cosmetics industry, pharmaceuticals and aesthetic medicine. The therapeutic potential of antiage, which is hidden in collagen, has been used in aesthetic medicine for almost 30 years in minimally invasive treatments with the use of tissue fillers. The collagen products used differ in the origin of protein, the type of its modification, indications and the duration of the effect. Recent research indicates that it is worth paying attention to collagen also in the aspect of dietary supplementation, which may have a beneficial effect on delaying the effects of chronological skin aging. Natural collagen has too large a molecule to be given from the outside and to penetrate deeper into the skin (e.g. in a serum or cream). But we can eat it. Gelatin is an inexpensive youth elixir available in every shop. It is actually powdered collagen.

Hyaluronic acid supplement
Hyaluronic acid also plays a significant role in the process of skin aging (or rather a decrease in its resources, which begins at the age of 25) and a disorder of the function of hyaluronidase – an enzyme that decomposes it (this causes the density of the gel structure, which forms hyaluronic acid with water, as a result of the accumulation of undissolved by the enzyme acid, as a result, it hinders the metabolism between cells and the environment, which in turn has a very adverse effect on the condition of the skin). In this context, we even talk about the hyaluronic mechanism of skin aging. The presence of hyaluronic acid in the skin in an optimal amount is so important, because almost half of it contained in the body occurs in the skin, largely affecting its proper physiology and appearance. Therefore, it is worthwhile to think about supplementing its deficiencies. Currently it is possible, because there are tablets with hyaluronic acid available in pharmacies.

Avoiding stress and oxidative stress
Oxidative stress is one of the fundamental causes of ageing of our skin. It is defined as an imbalance between the effects of reactive oxygen species called ROS and our natural ability to remove or repair damage caused by ROS activity. It is often said that reactive oxygen species have only a negative effect on our body, but many studies suggest that reactive oxygen species also play a positive role in our body. In fact, not the ROS itself, but oxidative stress, i.e. the moment when ROS activity is too high or our body’s natural ability to defend itself against them is reduced, is unfavourable. For example, a significant increase in reactive oxygen species activity on our skin can be caused by the sun’s UVA and UVB radiation. Even with moderate ROS activity on the skin, our ability to combat their negative effects can be significantly reduced also as a result of chronic disease. Oxidative stress causes unfavourable ageing processes of the skin and the whole body. A breakthrough theory regarding ROS was the study by Denham Harman, published as early as 1956, which concluded that ROS are the primary cause of somatic ailments in old age and that aging is the result of random harmful effects of ROS on our tissue. His theory is one of the most recognized aging theories. Since then, many studies have confirmed that oxidative stress is the main cause of aging, which unfortunately we are unable to fully control. Currently, many studies are being conducted, which consist in finding the appropriate gene mutation in yeast, mouse and insects, thanks to which it would be possible to reduce oxidative stress. Numerous gene mutations have been found that reduce the impact of oxidative stress on the body. However, there are still no spectacular discoveries that could revolutionize medicine. Despite in-depth genetic research, the scientific community is divided regarding the possible use of genetic mutations in humans.

Use of cosmetics and supplements containing anti-aging ingredients 
The first group of anti-aging substances are compounds protecting the skin against free radicals, the so-called antioxidants. They have the ability to connect with ROS and prevent them from reacting with cellular structures. Antioxidants can be taken orally or locally. These are: vitamins A, C, E, plant antioxidants and retinoids. Vitamin C stimulates collagen production, counteracts harmful effects of UV radiation on the skin and is a cofactor of enzymatic reactions associated with the production of connective tissue. In addition, it supports the immune system by acting anti-inflammatory, inhibits the production of pro-inflammatory cytokines. It also supports the cycle of vitamin E metabolism. Tocopherols, in turn, protect against free radicals lipids of cell membranes. They have an anti-inflammatory effect and increase the binding of moisture in the skin. Plant antioxidants are mainly flavonoids, carotenoids and polyphenols. They inhibit the action of atomic oxygen and active oxygen radicals, such as peroxide anions, hydroxyl radicals, peroxy-lipid radicals and hydroperoxides. In turn, retinoids are responsible for capturing and stabilizing reactive oxygen species, protecting cell membranes. Retinoic acid also stimulates fibroblasts, making the skin more hydrated, thicker and more elastic. Retinoids stimulate the creation of new vessels in the skin and inhibit the metalloprotease of extracellular matrix protect against UV radiation. Another group of anti-aging substances are substances imitating the action of TIMPs metalloprotease inhibitors. These are plant extracts, such as extract from lychee fruit skin, blackberry or pumpkin leaves and peptides: Tripeptyd-2 (inhibiting elastase and MMP-1), Myristoyl Tetrapeptide-20 and Acetyl Hexapeptide-20. By inhibiting MMP, these substances protect collagen and elastin fibers, promote proper organization of fibers, increase collagen I synthesis and stimulate the expression of molecules forming the extracellular matrix. Growth factors are important among anti-aging substances. They mediate many physiological and pathological processes, stimulate cell division, differentiation and growth. Currently, two types of growth factors are used in cosmetology – produced by bacterial systems and extracted from platelet rich plasma. Epidermal growth factor (EGF), transforming growth factor (TGF) and platelet growth factor (PDGF) are used. Phytohormones, i.e. organic compounds that regulate the growth and development of plants, have become very important components of anti-aging preparations. This group includes substances with a spatial structure or similar effects to estrogen hormones. The representatives are derivatives of sterols, isoflavones and lignans. The presence of plant equivalents of estradiol, occurring in amounts exceeding 50 mg/kg, was found, among others, in alfalfa (Medicago sativa L.), red clover (Trifolium incarnatum L.), lupine (Lupinus polyphyllus L.), liquorice (Glicyrhiza glabra L.). Hormonal extracts also include the Cimcifuga racemosa root, an old Indian beauty centre. They play the role of free radical scavengers, inhibit cell mutations and have an anti-cancer effect. Thanks to these properties, used externally in cosmetics, they prevent oxidation and damage to cell membranes. They also limit the activity of enzymes, including collagenase decomposing the support fibres of the dermis. Just like human hormones, they stimulate cell division and affect various physiological processes in the skin. Thanks to their action, skin tension and elasticity are improved and small wrinkles become less visible.

An important group are the so-called biomimetic peptides – synthetic chemical compounds imitating natural peptides. Currently, more than 300 biomimetic peptides are used in aesthetic medicine. They are produced on the basis of bacterial systems. Since two or threepeptides permeate through the epidermis, larger peptides require methods supporting their introduction into the skin, e.g. needle mesotherapy or their closure in liposomes. Plant stem cells are increasingly used in cosmetology. They stimulate our own stem cells and other cells, including fibroblasts for multiplication. An example of such plant extracts is an extract from the callus cultures of Damascus rose. It has a beneficial effect on the alleviation of inflammation of the skin. It has an anti-aging effect, reduces wrinkles and brightens the skin. Also, resveratrol contained in grapes is of great importance in anti-aging medicine. It is many times stronger antioxidant than vitamin C or E.

Avoiding tobacco, nicotine and cigarette smoke
Smoking causes adverse changes in the skin, causing or intensifying the course of many skin diseases, including cancer. In addition, tobacco smoke significantly accelerates the natural aging process of the skin. It has been observed that the skin of addicted smokers at the age of 40 looks like the skin of never-smoking 70 year-olds. The effect of tobacco smoke damage on the skin is irreversible, but further deterioration can be avoided by stopping smoking. Lifestyle can have a major impact on acceleration, but also, although rarely, on the natural ageing process of the skin. Cigarette smoking is definitely one of the factors that significantly increase the rate of appearance of changes characteristic of ageing skin. The only way to reduce the adverse changes and delay the aging processes caused by smoking is nicotine abstinence.

Hormonal supplementation in the period of shortages and menopause
In particular, the changes typical of ageing skin intensify in women during the menopause. As a result of hormonal disorders, there is a lack of stimulation of estrogen receptors manifested by, among others, weakening of fibroblast activity. The synthesis of glycosaminoglycans, especially hyaluronic acid and collagen, is inhibited. The synthesis, differentiation and regeneration of keratinocytes is also decreased. There is a significant decrease in skin hydration and firmness.

Active protection against UV radiation
The effects of UV radiation on the skin depend on the amount of energy absorbed and the degree of penetration. The body protects itself against radiation penetration by thickening the stratum corneum, pigmentation, urocaic acid secretion from sweat (endogenous compound, which is a factor of suppressor effect, is formed in the stratum corneum under the influence of UV) and activation of enzymatic repair of DNA damage). UVB radiation (280-320 nm) is the most harmful component of sunlight. Approximately 5% of the UVB radiation reaches the surface of the Earth. It has high energy and causes erythema. It is responsible for sunburn as well as pigmentation. UVB emissions should be avoided from 10 a.m. to 3 p.m. and also in summer, because the intensity of this radiation is the strongest. Frequent exposure of the body to this radiation contributes to the formation of cataracts, weakened immune system and cancer. UVB radiation leads to an immediate reaction, associated with the formation of free radicals, which contribute to the denaturation of cell membranes. The Earth receives 95% of the UVA radiation (320-400 nm). This radiation is divided into UVA-1 (340-400 nm) and UVA-2 (320-340 nm). UVA-2 has a similar effect to UVB on the skin, but is more carcinogenic. UVA-1 penetrates deeper into the skin, but is less harmful. UVA emissions initiate the tanning process. Unlike UVB, it does not cause erythema and sunburn. However, UVA penetrates into the reticular and papillary layers of the dermis, causing more damage than UVB radiation. UVA radiation is responsible for the ageing of the skin. It contributes to photo-allergic reactions. There is a delayed reaction to nucleic acids and proteins. Bridging between protein molecules occurs, which leads to the formation of collagen crosslinking and changes in the configuration of elastin molecules, leading to the so-called solar elastose. This causes photo-aging. This term describes many adverse changes in the appearance, function and structure of the skin caused by excessive and prolonged exposure to ultraviolet radiation and artificial UV radiation, e.g. in a solarium. UVA and UVB radiation are responsible for photoaging. 50% of UVA rays reach the papillary and reticular layers of the dermis, where they affect fibroblasts, dendritic cells, inflammatory infiltration cells, including T lymphocytes, granulocytes and mast cells and vascular endothelial cells. Approximately 9-14% of UVB radiation reaches the living epidermis layer. The main symptoms of extrinsic aging include: hypertrophic changes, skin dryness and roughness, pre-cancerous changes (solar keratosis), deep wrinkles, telangiectasias, pigmentation disorders (discolorations, discolorations, lentigines), decreased elasticity, skin flaccidity, sebaceous glands hypertrophy (formation of large blackheads, skin becomes yellow-brown and rough). Clinical changes mentioned above largely depend on the length and frequency of exposure to the sun, as well as the occurrence of sunburn and, most importantly, depends on the skin phototype (most often in categories I and II). The most common histological change is elastin, i.e. accumulation of atrophic elastin-like material in the papillary layer of the dermis. This may be manifested by deep furrows, nodules, papules. This phenomenon does not occur in protected skin, even in older people. The epidermal lesions are primarily an increase in its thickness accompanied by a cytological atypes. In the basal layer there is an uneven distribution of melanocytes, which may result in discoloration and discoloration. There is a decrease in Langerhans cells, which are responsible for the efficient functioning of the immune system. An increased number of cells such as fibroblasts, macrophages and mast cells can be observed in the photoaging skin. Natural and biological ageing caused by various factors leads to many irreversible changes. Protection against UV radiation is therefore very important and contact with radiation should be limited. You can try to reduce the effects of photoageing by using retinoids topically, which can cause receding changes, and local and general antioxidants, as well as various forms of exfoliation of the epidermis.

Facial expressions’ control
We contribute to the formation of wrinkles by smiling, wrinkling our foreheads or squinting our eyes. As a result, lines appear between the eyebrows (lion’s wrinkle) or wrinkles in the corners of the eyes (crow’s feet). However, certain muscle reflexes can be worked out in such a way as to eliminate their negative impact on the appearance of the face.

Using modern scientific achievements in the field of:
cosmetology;
aesthetic medicine;
plastic surgery;
effective cosmetics containing appropriate substances: e.g. vitamin A, retinol and its derivatives – are converted into vitamin A acid in the body, which stimulates cell regeneration. UVA and UVB protective filters – protection against photo-ageing (light-induced skin ageing). Hydroxy acids (especially glycolic acid because of its smallest molecule) – support renewal and regeneration mechanisms. Antioxidants (antioxidants) – support protective and regenerative mechanisms. These include vitamin C, which, as shown by research, protects the skin, prevents its photoaging and stimulates the production of collagen. However, in order for vitamin C to work, its concentration in preparations must be at least 10%. Substances improving the structure and function of the epidermis Hormonal-like substances such as soya slows down the formation of wrinkles Hyaluronic acid is a substance that strongly binds water in the connective tissue. It fills the spaces between collagen fibres and maintains skin elasticity. The substances protecting the skin: the skin condition, its smoothness, elasticity and tension are primarily responsible for three substances: hyaluronic acid and its salts – very important components of the intracellular binding substance. Mucopolysaccharides – protein components, one of the basic components of the skin. They have a protective, supportive and smoothing effect, maintain proper skin tension. Chondroitin sulphate – a substance conditioning skin hydration, binding water. Apart from the skin, it also occurs in cartilage.

The multitude of skin ageing theory and multidirectional changes accompanying this process make it so difficult to develop one fully effective and safe method to inhibit this process. Scientists from all over the world are conducting research, constantly developing new substances with anti-aging properties, some of them more or less effective.

The literature:
1. Czogała J., Goniewicz M., Czubek A. i wsp.: The influence of smoking on appearance, aging and pathological changes of skin and mucous membranes. Przegl. Lek. 2008, 65, 732. 
2. Ewa Gliwa, Anna Goździalska, Jerzy Jaśkiewicz Division of UV rays
3. Dermatology for cosmetologists, Wydawnictwo Naukowe Uniwersytetu Medycznego im. Karola Marcinkowskiego, Poznań 2008. 
4. Dylewska-Grzelakowska J., Applied cosmetics, Wydawnictwa Szkolne i Pedagogiczne, Warszawa 1999. 
5. estetologia.pl Collagen - structure and application
6. Photo by Cristian Newman on Unsplash
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