What is Collagen

Collagen, a group of naturally occurring proteins and the main component of connective tissue, is the most abundant protein making up 25% to 35% of the whole-body protein content. Collagen fibers (fine fibers about 1 nm in diameter) are mostly found in fibrous tissues (skin, tendon, ligament) and are also abundant in cornea, cartilage, bone, blood vessels, the gut, and intervertebral disc. The fibroblast is the most common cell which synthesize collagen. Collagen fiber is a triple helix consisting of two identical α1 chains and an α2 chain with  slightly different chemical composition. Collagen has an atypical amino acid composition with most common motifs of “Glycine-Proline-X and Glycine-X-Hydroxyproline” (X is any amino acid other than glycine, proline or hydroxyproline).

The synthesis of collagen occurs inside and then outside of the fibroblast. Procollagen is synthesized inside the cell and then packaged into a secretory vesicle to be secreted into the extracellular matrix. Once outside the cell, Collagen peptidases (a membrane bound enzyme) remove the “loose ends” of the procollagen molecule, forming tropocollagen. This step is absent for synthesizing collagen type III. Procollagen is the precursor of collagen which is converted to collagen through a hydroxylation reaction where the proline at certain points in the polypeptide chains is converted to hydroxyproline, making hydroxyproline the most abundant amino acid in collagen. This hydroxylation reaction secures the chains in the triple helix of collagen. Next, the lysine is converted to hydroxylysine and extracellular enzyme lysyl oxidase convert lysines and hydroxylysines to aldehyde groups in the final step, which will then cross linking tropocollagen/procollagen molecules, forming a polymer of tropocollogen/procollagen known as a collagen fibril. The triple helix tropocollagen or collagen is the subunit of larger collagen fibrils.

So far, 28 types of collagen have been identified and described. The five most common types are:

• Collagen I: The most abundant type, distributed in skin, tendon, vascular ligature, organs, bone, scar tissue
• Collagen II: cartilage (main component of cartilage)
• Collagen III: reticulate (main component of reticular fibers), commonly found alongside type I. Also Found in quickly-growing tissue, such as that found in wounds in the early stages of repair or in child’s skin, and is often replaced later on by the stronger and tougher Type I collagen.
• Collagen IV: forms bases of cell basement membrane
• Collagen V: cell surfaces, hair and placenta

Types of Collagen In Skin Layers

Collagen plays a pivotal role in maintaining skin’s architecture and accounts for as much as 70% of the weight of the skin. The collagen produced in the skin accounts for approximately 80 to 90% of the body’s total collagen. The formation of new collagen fibres is therefore essential for healthy, firm skin. The skin contains multiple types of collagen. Type I and type III collagen are present in the highest levels in the skin, forming 80% and 15% of the total collagen present respectively. Their fibrils form the mesh largely responsible for the skin’s mechanical properties. Collagen type III is a fibrillar collagen that is found in extensible connective tissues such as skin, lung, and the vascular system, frequently in association with type I collagen. Reticular fibers, or reticulin (the fine meshwork of crosslinked reticular fibers) a histological term used to describe a type of fiber in connective tissue of the skin composed of type III collagen.

Type IV collagen is the main component of the lamina densa. Lamina densa is a 50nm thick layer and a component of the basement membrane zone between the epidermis and dermis of the skin. Lamina densa is synthesized by the basal cells of the epidermis, and composed of type IV collagen, anchoring fibrils made of type VII collagen, and dermal microfibrils. Type VII collagen is a major constituent of the anchoring fibrils beneath the lamina densa, at the epidermal-dermal interface. Type V collagen is found pericellularly. Other types of collagen in the skin are V, VI, and XII. They are found in much smaller amounts and appear to have a supportive role, whose details remain unclear. Collagen type distribution and fiber organization of connective tissue is not exactly same in different layers of skin. Reproducible evidence was obtained for a somewhat higher ratio of type III/type I collagen synthesis in the papillary dermis and the subcutaneous fat compared to the reticular layer. Constant amounts of collagen I (alpha 1 trimers) and type V collagen were found in all layers.

Changes In Collagen Types And Quantities In Aged Skin – The Type I/Type III ratio

The content and ratio of type I and III collagen in skin differ with age and injury. Overall, the amount of collagen in the skin tends to decline with age. However, different types of collagen alters with age differently. A child’s skin is made up of fast-growing tissues, and has an abundance of type III collagen partly responsible for the softness of the young skin. Its role has been correlated with tissue extensibility. As the body growth slows down, the skin content of type III collagen declines, while that of type I increases. It has been generally believed that type III collagen decreases significantly with age 20. Type I collagen productivity increases significantly as type III declines when body growth approaches its peak. Type I naturally regenerates itself until the skin reaches the peak of its mechanical strength around age 35. After that, type I collagen begins to decline as well. All types of collagen are significantly decreased in aged skin (>60). The dynamic of age-related changes in other collagen types remains unclear.

Collagen contributes to skin aging via three dynamic processes –

1. decreased new collagen synthesis by fibroblast,
2. decreased quality of collagen fiber mesh due to the collagen damage via cross-linking by glycation, and other external factors such as UV radiation and free radicals,
3. increased degradation of collagen fiber due to the increased level of matrix metalloproteinase (MMPs) enzymes, which are known to degrade and recycle collagen.

During aging, fibroblasts in the skin do not produce so much collagen. Both cellular fibroblast aging and defective mechanical stimulation in the aged skin tissue contribute to reduced collagen synthesis. Fibroblasts in severely aged or photodamaged skin have less interaction with intact collagen and as a result experience a reduction in mechanical tension. Decreased collagen synthesis is (presumed to be) the result. A reduction in mechanical stimulation in chronologically aged skin was inferred from a greater percentage of the cell surface attached to collagen fibers and more extensive cell spreading in young skin compared with old skin. Reduced collagen synthesis in chronologically aged skin was caused by two different underlying mechanisms: cellular fibroblast aging and a lower level of mechanical stimulation. Reduced fibroblast interaction with intact collagen was found to be the mechanism for decreased collagen synthesis in photodamaged skin too. Dermal cells in healthy skin are attached to collagen fibrils over a large part of the cell border, have a flattened/spread (two-dimensional) appearance and have abundant actin in their cytoplasm. In contrast, cells in photodamaged skin are often in contact with fragmented collagen or amorphous debris rather than intact collagen, have a collapsed/elongated shape, and have a lower amount of actin. Collagen synthesis is reduced in severely photodamaged skin relative to collagen synthesis in corresponding sun-protected skin.

Most components of the skin, including collagen, undergo continuous turnover. New collagen is continually produced and recycled throughout life. whereas after about age of 40, the degradation of collagen inceases. Same as collagen synthesis, collagen degradation is an ongoing, natural process. Collagen degradation tends to speed out of control and contribute to weakening and wrinkling of the skin. A number of external factors (UV rays, smoking, chlorinated water, free radicals, inflammation, irritation and others) accelerate this process even further with detected increased level of MMP activity: matrix metalloproteinases (MMP-s).

Different anti-wrinkle ingredients capable of stimulating collagen synthesis may affect different collagen types differently. That’s one reason why some collagen boosters are more appropriate for the skin than others. Vitamin C has an important role in collagen synthesis whose capacity to stimulate both type I and III collagen has been shown in a number of studies. Vitamin C can induce hydroxylation reactions in forming the collagen fibers. At the same time, topical MMP inhibitors may be used alone or in conjunction with stimulating the synthesis to reduce collagen degradation.