Aging skin typically shows changes such as a loss in tone and elasticity, hyperpigmentation, roughness and wrinkles caused by, among other factors, impaired hydration and barrier function. Wrinkling is associated with progressive atrophy of the dermis, as well as changes in architectural organization.1 Extracellular matrix dermis is mainly composed of proteins, proteoglycans and glycoproteins that produce a protective and supportive environment for cells and allow them to communicate with their surroundings. Collagen is the most abundant protein group in skin, accounting for 70–80% of skin’s dry weight,2 and the vast majority of it comprises types I and III. Fibrillar collagen in particular provides the tensile strength and recoil of skin.3
The most common amino acid sequence in a collagen molecule is Gly-X-Y, where X and Y may be any amino acid residue but often are proline and hydroxyproline (Hyp). This Gly-X-Y triplet facilitates the left-handed helix structure and, subsequently, the creation of the right-handed triple helical structure.4 Collagen synthesis involves many steps,5 as summarized in Figure 1. Each type of collagen is encoded by a specific gene and synthesized as the precursor preprocollagen. Post-translational modification follows, taking place in the lumen of the endoplasmic reticulum. This step involves the hydroxylation of specific prolines and the emergence of Hyp, and is catalyzed by prolyl-4-hydroxylase with ascorbate as a cofactor, and molecular oxygen, iron (II) and α-ketoglutarate, as cosubstrates.6
In collagen I, Hyp accounts for about 10% of all amino acids,7 and its presence is important for the proper arrangement and stability of collagen under physiological temperatures.6 Hydroxylations of prolines and lysines (step two in Figure 1) are also necessary for the rapid secretion of procollagen molecules into the cytoplasm—conversely, fewer hydroxylated molecules are prone to degradation. At this point in the collagen synthesis process, collagen molecules are readily soluble and transportable thanks to C- and N-propeptides. Newly synthesized procollagen chains associate into trimers via their C-propeptides, leading to nucleation and folding of triplehelical redion. Once procollagen is found in the extracellular matrix, the propeptides are removed by C- and N-proteases and the spontaneous self-assembly of collagen molecules into fibers is triggered.8
As stated, qualitative and quantitative changes in collagen in the dermis, and the extent of modification, occur with age.9 This phenomenon is even more pronounced in areas affected by photoaging.10 This reduced quantity and quality of collagen is not solely attributed to a drop in proliferative and synthetic activity in skin cells, or an increase in the activity of degradative enzymes.11 It also occurs due to a fall in the activity of enzymes catalyzing the post-translational modification of proline and lysine12—e.g., prolyl 4-hydroxylase.
