Papers published over the past two decades describing how changes in elastin are associated with skin photoaging are both puzzling and varying. Some point toward the activation of proteolytic enzymes that cleave elastin in a randomized manner, leading to decreasing structural integrity and inelasticity; others point to an accumulation of the secreted soluble precursor protein tropoelastin, in a condition termed solar elastosis. Though there is consensus on the importance of elastin in skin health and appearance, no systematic method has elucidated how the clinical manifestations of elastin in the dermal layer are correlated to its structure-function attributes.
In this paper, the authors review key findings in the published research and highlight measurable gaps, which potentially could marry these two divergent analyses for a complete picture. This prospective knowledge may contribute to understanding changes in elastin structure and, hence, function and implications for aged skin, elasticity and disease, with potential for future skin care targets. Elastin plays an important biological role in skin’s structural and mechanical integrity, thus the development of unbiased targeted and quantitative studies to investigate the production and integrity of elastin, its soluble precursor tropoelastin and its variants (such as through structural and functional proteomics) is warranted.
Elastin Isoforms and Skin Metabolism
Elastin is a cross-linked network of monomeric polypeptides rich in insoluble amino acids, including glycine and proline. This network depends on hydrated milieus, which form unstructured hydrophobic regions bound by cross-links between lysine residues.1 In the dermal skin layer, elastin forms, together with collagen, the extracellular matrix (ECM), which is the skin’s physical and mechanical foundation. Similar networks are present in other connective tissues (notably in the lungs and arteries), allowing tissues to return to their original rest-state shape after extending or tightening. The ECM, therefore, plays a key role in skin’s structural integrity and biomechanics, permitting for persistent flexibility and repeated stretch and relaxation cycles. Elastin integrity is greatly reduced with aging, injury and sun exposure. Presumably, this can be associated with persistent catabolism by proteolytic enzymes, which break down its three-dimensional structure; consequently, skin gradually loses elasticity.
The elastin precursor tropoelastin is soluble, and exists in multiple transcript variants to encode for different isoforms. Due to the many possible isoforms, the same elastin gene translates to diversity within the elastin proteome, generating a family of structurally related proteins that vary in their mechanics, orientation, responsiveness to stimuli and, hence, their functionality. In fact, the elastin gene, when translated to mRNA, can be expressed in a variety of patterns that differ in their arrangement, interaction with ligands, stability to proteolytic degradation and functionality at the protein level. Stated another way, functions in the body are not carried out only by nucleus entities (i.e., DNA or mRNA) but by proteins. Nucleic acids are just codes. In fact, 50% of the nucleus material is protein, which controls functionality at the nucleus level. Therefore, measurements of levels of elastin and/or tropoelastin gene expression at the mRNA level can provide only partial information about biological activities