Glycosaminoglycans
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Glycosaminoglycans (GAGs) are long, unbranched polysaccharides composed of repeating disaccharide units. They constitute an important component of the skin's extracellular matrix, a three-dimensional network surrounding cells and supporting fibers. Glycosaminoglycans include, among others, hyaluronic acid, dermatan sulfate, chondroitin sulfate, heparan sulfate, and keratan sulfate. These molecules bind water, co-form proteoglycans, regulate collagen organization, and participate in intercellular communication. Their importance is therefore not limited to passive skin “hydration”. GAGs also influence cell proliferation, migration, and differentiation, the course of inflammation, wound healing, and the availability of growth factors. Aging disrupts the quantity, distribution, and structure of these compounds.
Glycosaminoglycans - what are they?
Chemically, glycosaminoglycans consist of repeated disaccharides, usually containing an amino sugar, for example N-acetylglucosamine or N-acetylgalactosamine, and a uronic acid. The presence of carboxyl and sulfate groups gives many GAGs a strong negative charge. As a result, they attract ions and water molecules, forming a hydrated gel that fills the spaces between cells.
The skin primarily contains:
- hyaluronic acid, also known as hyaluronan, a non-sulfated GAG that is not covalently linked to a core protein;
- dermatan sulfate, present, among others, in decorin and biglycan;
- chondroitin sulfate, primarily associated with versican;
- heparan sulfate, found in perlecan, syndecans, and glypicans;
- keratan sulfate, the amount of which in the skin is lower than in cartilage or the cornea;
- heparin, found mainly in mast cell granules.
With the exception of hyaluronic acid, GAGs are most commonly attached to a core protein, forming proteoglycans. Therefore, these terms should not be equated: a glycosaminoglycan is a sugar chain, whereas a proteoglycan consists of a protein and one or more GAG chains.
Glycosaminoglycans - where are they found in the skin?
Glycosaminoglycans are found in the epidermis, basement membrane, dermis, vessel walls, hair follicles, and around glands. However, their content is significantly higher in the dermis than in the epidermis.
Skin structure | Key GAGs and proteoglycans | Biological significance |
Epidermis | hyaluronic acid, syndecans | keratinocyte differentiation and migration, maintenance of the aqueous environment |
Dermal-epidermal junction | heparan sulfate, perlecan | stabilization of the basement membrane, regulation of signaling between the epidermis and dermis |
Dermis | hyaluronic acid, dermatan and chondroitin sulfate, decorin, biglycan, versican | hydration, collagen organization, mechanical properties of the matrix |
Surroundings of elastic fibers | versican with chondroitin sulfate | participation in the organization of the elastic network |
Vessels and cell surface | heparan sulfate, syndecans, glypicans | cell adhesion, angiogenesis, and signaling |
Hair follicles and glands | hyaluronic acid and proteoglycans | creation of cellular niches and regulation of tissue renewal |
Hyaluronic acid is present in both the epidermis and the dermis. In the epidermis, it is mainly located in the spaces between keratinocytes. In the dermis, it surrounds fibroblasts as well as collagen and elastic fibers. Decorin binds to collagen fibers, whereas perlecan is an essential component of the basement membrane.
Glycosaminoglycans - what are they responsible for?
The function of glycosaminoglycans depends on their type, molecular weight, degree of sulfation, and location. Their most important functions include:
- maintaining matrix hydration and volume by binding water and electrolytes;
- providing resistance to pressure, as the hydrated GAG gel resists tissue compression;
- organizing collagen fibers, particularly through decorin and biglycan;
- contributing to the elastic properties of the skin through the associations of proteoglycans with the elastin network;
- regulating cell proliferation, migration, and differentiation;
- binding growth factors, chemokines, and cytokines, thereby controlling their availability to receptors;
- participating in wound healing, angiogenesis, and matrix remodeling;
- modulating the inflammatory and immune response;
- maintaining the integrity of the dermal-epidermal junction.
The significance of hyaluronic acid also depends on its chain length. High-molecular-weight hyaluronan forms a stable, highly hydrated matrix and usually exhibits homeostatic activity. In contrast, shorter fragments formed during tissue damage can act as danger signals and influence inflammation, cell migration, and angiogenesis. Therefore, the biological activity of GAGs cannot be assessed solely on the basis of their total amount.
Glycosaminoglycans and hyaluronic acid
Hyaluronic acid is the best-known glycosaminoglycan of the skin, but it represents only one of several classes of GAGs. It is formed at the cell membrane by hyaluronan synthase enzymes: HAS1, HAS2, and HAS3. Its degradation is controlled by, among other factors, hyaluronidases and oxidative processes.
Hyaluronan molecules form extensive aggregates with proteoglycans and impart viscoelastic properties to the matrix. They also support appropriate conditions for fibroblasts and keratinocytes. The biological activity of HA is mediated through surface receptors, primarily CD44, as well as RHAMM.
A distinction should be made between:
- endogenous skin hyaluronan, continuously synthesized and degraded;
- topically applied hyaluronic acid, whose action depends, among other things, on molecular weight and formulation;
- non-cross-linked HA administered intradermally, used mainly in procedures to improve skin hydration and quality;
- stabilized or cross-linked HA, used for prolonged tissue persistence, bioremodeling, or volume restoration.
A cosmetic product containing hyaluronan can reduce water loss and improve hydration of the stratum corneum, but it is not the biological equivalent of intradermal product administration.
Why does the amount of glycosaminoglycans decrease with age?
The term “decrease in glycosaminoglycans” is a simplification. In chronological aging, a decrease in the content of functional hyaluronic acid and certain proteoglycans is often observed, but in skin chronically damaged by UV radiation, an abnormal accumulation of specific GAGs may occur, especially versican-associated chondroitin sulfate. This material is distributed differently than in a young, normal matrix and does not restore its properties.
The most important mechanisms of age-related changes include:
- fibroblast senescence, which is the loss of their normal proliferative and synthetic capacity;
- decreased expression of hyaluronan synthases, especially HAS1 and HAS2;
- impaired signaling via CD44 and RHAMM;
- collagen fragmentation, which limits the proper mechanical tension of fibroblasts;
- oxidative stress, causing non-enzymatic cleavage of hyaluronan chains;
- chronic UV exposure, exacerbating inflammation and matrix remodeling;
- changes in the activity of hyaluronidases and other degradation enzymes;
- glycation of matrix components, hindering their proper interactions;
- postmenopausal estrogen decline, affecting fibroblast activity, matrix synthesis, and skin hydration.
The consequences are a reduced water-binding capacity, disruption of collagen organization, loss of viscoelasticity, skin thinning, and slower regeneration. However, clinical changes do not result from a deficiency of a single compound, but from the disorganization of the entire extracellular matrix.
How to protect the skin's glycosaminoglycans?
The best-documented measure to limit extrinsic matrix aging is daily photoprotection. It should include a product with broad-spectrum UVA and UVB protection, an adequate amount of the product, and its reapplication during prolonged exposure. Avoiding tanning beds and tobacco smoking is also important.
In topical care, the following find application:
- humectants, including hyaluronate and glycerin, which improve stratum corneum hydration;
- emollients and epidermal barrier-restoring ingredients;
- retinoids, which can affect matrix remodeling and increase cutaneous GAG content;
- antioxidants, treated as a complement to, rather than a replacement for, photoprotection.
There is no basis to interpret every sign of skin dryness or laxity as an isolated “glycosaminoglycan deficiency”. Oral and cosmetic ingredients do not reach the skin directly in an unaltered form, and their effects depend on metabolism, formulation, and route of administration.
Treatments related to glycosaminoglycans available at Ambasada Urody
The procedures do not halt physiological aging nor do they restore all classes of GAGs to an equal degree. However, they can replenish hyaluronic acid, improve matrix hydration, or indirectly stimulate its remodeling. Treatments available at Ambasada Urody related to this area include:
- hyaluronic acid mesotherapy, including non-cross-linked and partially stabilized preparations, used to improve skin hydration and quality;
- Xela Rederm redermalization, combining non-cross-linked hyaluronic acid with sodium succinate;
- Profhilo, utilizing stabilized complexes of high- and low-molecular-weight hyaluronic acid for tissue bioremodeling;
- Sunekos and Jalupro, containing hyaluronic acid and amino acids used in biorevitalization procedures;
- Karisma, combining recombinant type I collagen with non-cross-linked hyaluronic acid;
- Lenisna, a hybrid preparation containing poly-L-lactic acid and hyaluronic acid;
- cross-linked hyaluronic acid-based fillers, used to correct wrinkles, volume loss, and facial contours;
- Neauvia Organic Stimulate, combining hyaluronic acid with calcium hydroxyapatite microspheres;
- polynucleotides, Juvelook, poly-L-lactic acid, calcium hydroxyapatite, platelet-rich plasma and platelet-rich fibrin, which are not GAGs, but can indirectly support fibroblasts and matrix remodeling.
The choice of procedure requires an assessment of the skin condition, indications, and contraindications by a qualified specialist. Fillers and biostimulators differ in composition, injection depth, mechanism of action, and the profile of potential complications.
