Collagen pathway of skin aging

1. Collagen pathway of skin aging
Collagen polypeptide chains have an increased number of cross-links in old age. During aging, the accumulation of the number of covalent crosslinks in human collagen transforms the protein into an insoluble form. As a result, it accumulates in tissues to the detriment of cells, causing disruption in the functioning of organs and the whole organism. With aging, the amount of soluble collagen in the skin decreases, while the amount of insoluble collagen increases. A study of the tail skin extract of rats aged from 1.5 to 24 months was carried out. As a result, it was found that the number of single collagen α-chains decreased rapidly with age, the number of collagen α-chain trimers increased, and the number of collagen dimers remained constant in all age groups. At the same time, the amount of insoluble collagen increased (see Fig. 1)

2. Equilibrium process of synthesis and destruction of collagen
Collagen with elastin and reticulin is a support-structural protein located in the dermis. Collagen is the main component of the dermis (up to 70%) and is the main structural component of connective tissue. This protein, specific in amino acid composition and structure, does not dissolve in water under normal conditions (it only swells). Proteolytic enzymes (pepsin, trypsin, papain) break down only soluble fragments of collagen filaments. Collagenase is an enzyme that is capable of modifying a collagen filament (fibril) into a soluble state due to partial hydrolysis (see Fig. 2).
Thus, the aging process of the body is accompanied by the accumulation of insoluble forms of collagen that do not react with collagenase. That is, a certain amount of collagen is removed from the equilibrium process of synthesis and destruction of collagen filaments, and the lifetime (τ) of these molecules increases to infinity. As a result, the number of cross-links in the molecules of collagen that is not reactive with respect to collagenase continues to increase, the collagen matrix of the skin becomes more rigid and, as a result, the elasticity of the skin decreases and the appearance (fixation) of wrinkles. Hard collagen accumulates in the skin and inevitably contributes to its aging. Unchanged collagen fragments continue to participate in the cyclic equilibrium process, synthesizing new unmodified ("young") collagen structures. The total amount of collagen per unit volume of the skin is constant throughout life. Given this, the need for the use and effectiveness of cosmetic preparations with collagen is highly questionable. Let's say we are using a collagen cream composition. It is natural to believe that the molecules of such collagen have practically no intra- and intermolecular cross-links and therefore are quite elastic. The obvious result of applying such a cream to the skin will be a momentary increase in elasticity. However, the effect will disappear immediately after the cream removal procedure (taking into account the skin's permeability limit). High-molecular collagen structures cannot penetrate deep into the skin and will remain on the skin surface. A completely different situation arises when using collagen structures with molecular weights below 100 kDa. Such structures have the ability to cross the transepidermal barrier. On the one hand, they more effectively increase the elasticity of the skin, affecting not only its surface, but also affecting deeper layers. On the other hand, collagen fragments are able to distract the enzyme from interacting with the skin's own collagen matrix and, as a result, the rate of the main reaction decreases - a state known in biochemistry sets in - competitive inhibition of the main process. Such inhibition increases the lifetime of its own collagen structures and, accordingly, the likelihood of the formation of intra- and intermolecular cross-links. All this inevitably leads to the acceleration of skin aging. Thus, the use of preparations with collagen (M.m. less than 100 kDa) can have negative consequences and accelerate the aging process of the skin.

3. Collagenase enzyme as an ingredient in cosmetic preparations
If the intrinsic (endogenous) collagenase in the skin matrix begins to "pass" collagen crosslinks with age, then an additional amount of the enzyme must be introduced into the skin. In this case, it is necessary to fulfill the following conditions:
- the molecular weight of the enzyme should provide real access to the internal structures of the skin;
- injected collagenase should have a lower specificity of action compared to endogenous collagenase of human skin or interact with a wider range of substrates;
- interaction with cellular systems should be sufficiently gentle.
Such a drug prevents or inhibits the mechanism of skin aging associated with the accumulation of crosslinks in collagen. The molecular weight of the enzyme allows you to reach the area of ​​localization of collagen filaments (papillary dermis).
Collagenase cosmetics act on collagen threads together with endogenous collagenase and accelerate the rate of their degradation. The preparation will help to reduce the lifetime of collagen crosslinks and, accordingly, reduce the likelihood of accumulation of crosslinks (wrinkles).