Elastin

Elastin is a protein encoded by the ELN gene in humans and many other animals. It is a key component of the elastic fibers that make up the extracellular matrix, and it provides the elasticity and recoil that return tissue to its original shape after it has been stretched or deformed by an external force. In skin, elastin forms the elastic fibers of the dermis and allows deformed skin to return to its original shape; it is a key element of skin elasticity, including that of facial skin.

Structure and function

Composition

An elastic fiber consists of a central core of elastin surrounded by a layer of microfibril proteins. Elastin makes up about 90% of the elastic fiber, and the microfibrils include fibrillin and fibulin. Elastic fibers account for about 4% of the dry weight of the dermis.

Elastin is rich in glycine, valine, alanine, and proline. The amino acid composition of human skin elastin has been reported as glycine 32%, alanine 23%, valine 12%, proline 11%, leucine 5%, lysine 1%, and others 16%. Elastin contains the unusual amino acids desmosine and isodesmosine; the chemical structure formed by repeated covalent cross-links between them gives elastic fibers their elasticity.

Distribution in tissues

Elastin is important in tissues that repeatedly stretch and relax, such as arteries and the aorta, the lungs, skin, ligaments and elastic cartilage, and the urinary bladder.

In skin, elastin is found in the dermis, where elastic fibers fall into three types according to thickness and location.

• Oxytalan fibers: Located in the uppermost part of the dermis and composed of bundles of microfibrils. They are arranged perpendicular to the dermal–epidermal junction, running toward the papillary dermis.
• Elaunin fibers: Located in the papillary dermis and arranged parallel to the dermal–epidermal junction. They contain abundant microfibrils but little elastin.
• Mature elastic fibers: Located in the reticular dermis. The fibers are thick and are arranged parallel to the skin surface together with collagen fibers.

Properties

Elasticity and recoil

Collagen is the basic material forming the structure of the dermis, and the main function of elastic fibers is to provide the elasticity that returns skin deformed by an applied force to its original shape. The elastic recoil of elastin is based on the flexibility of its molecular structure and on entropy. When an external force is applied, the molecular chains stretch and their arrangement changes; when the force is removed, the chains tend to return to a more disordered state and so come close to their original form.

Longevity

Elastin is a structural protein that persists in the body for a very long time, with a reported half-life of 70 years or more. Once it has been made in early life, it is hardly replaced under ordinary circumstances.

Changes with aging

A long lifespan does not mean that function is maintained unchanged for life. The decrease in skin thickness with aging is smaller than might be expected, and the loss of skin elasticity far exceeds the loss of thickness. Changes in elastic fibers contribute greatly to this functional loss. A study of Korean women reported that skin elasticity decreases rapidly from the 20s to the early 40s.

In non-exposed skin, where intrinsic aging predominates, the number and size of elastic fibers decrease. In exposed skin with severe photoaging, elastotic material accumulates in the upper dermis; it is fragmented and clumped and cannot perform normal elastic functions. Accumulation of elastic material therefore does not mean that skin elasticity improves. A three-dimensional imaging study likewise observed that, with increasing age, the number of elastic fibers in the dermis decreases, the remaining fibers become more fragmented, and connections between fibers weaken.

Biosynthesis

The biosynthesis of elastic fibers takes place in two steps. In the first step, microfibril proteins produced by fibroblasts are cross-linked in the extracellular space to form a temporary scaffold. In the next step, tropoelastin, the precursor of elastin, attaches to this scaffold; when enough tropoelastin has been deposited on the microfibril proteins, a mature elastic fiber is completed.

The gene that produces tropoelastin is ELN. Tropoelastin is a water-soluble precursor protein of about 50–70 kDa. After fibroblasts secrete it from the cell, it is converted into insoluble elastin through cross-linking. About 75% of tropoelastin residues are glycine, valine, alanine, and proline, and when intramolecular and intermolecular cross-links form between these and lysine residues, a rigid, hydrophobic, insoluble structure results. The elastin produced in this way is a strongly cross-linked, insoluble biopolymer that gives elastic fibers stiffness and durability.

This cross-linking is regulated by lysyl oxidase (LOX), and copper (Cu) is a cofactor required for the enzyme's activity. In Menkes disease, a genetic disorder of copper deficiency, mutation of the ATP7A gene, which encodes a copper-transport protein, impairs copper absorption in the intestine; the resulting copper shortage in the body is known to lower lysyl oxidase activity and thereby impair tropoelastin cross-linking and elastin production. In summary, the main building blocks of elastin are glycine, valine, alanine, and proline, and their cross-linking depends on lysyl oxidase and its cofactor copper.

The timing of elastin production is clearly limited. In humans, expression of the ELN gene begins before birth, an elastic fiber network forms in the fetal papillary dermis in late pregnancy, and activity is very high until about age 5. It then remains at a constant level for several decades and declines sharply once aging begins in earnest. Elastin synthesis is rare in adult fibroblasts, and damaged elastic fibers are not always properly repaired. A situation in which new elastic fiber synthesis increases in adults is skin injury, for example severe photoaging, but the elastic fibers that increase in this case are elastotic material that does not perform normal elastic functions.

Research

Elastin research falls broadly into two approaches: forming elastic fibers using exogenous precursors, and inducing the skin's own elastin biosynthesis. In a study using recombinant human tropoelastin, the possibility of forming new elastic fibers was confirmed, but improvement in the appearance or pliability of scars was not significantly demonstrated.

In vitro study

Chung et al. (2021) treated human dermal fibroblasts (Hs27) with amino acid mixtures consisting of glycine, L-proline, L-alanine, L-valine, L-leucine, and L-lysine hydrochloride, together with copper sulfate pentahydrate at various concentrations, and compared gene and protein expression. The copper concentrations were 0 (EL1), 3.3 (EL4), 1.67 (EL11), and 0.33 (EL12) µg/mL for the respective formulations.

• The amino acid mixture without copper had no effect on ELN and COL1A2 gene expression.
• EL4 and EL11, which contain copper, increased the expression of both genes in a dose-dependent manner, while EL12 did not increase gene expression.
• At the protein level, EL4 and EL11 significantly increased collagen I and elastin expression. EL12 did not increase elastin gene expression but did significantly increase elastin protein expression.
• Copper alone (3.3 µg/mL) also increased gene and protein expression, but the increase in protein was larger with EL4, which also contained amino acids.
• Significant cytotoxicity appeared at copper concentrations above 3.3 µg/mL.

The authors interpreted these results as showing that copper induces gene expression and that combining it with amino acids has a synergistic effect that further increases protein synthesis. A follow-up paper summarized this result as more than a two-fold increase in collagen and more than a three-fold increase in elastin.

Small human trial

Kim et al. (2022) conducted an open-label, single-center trial of a skin booster containing amino acids, copper, and hyaluronic acid (Elastic Lab). From 21 October to 17 December 2020, at the Global Medical Research Center, the face of each of five healthy adults aged 25–60 was treated four times at one-week intervals, and results were compared with baseline one week after the last treatment. There was no control group, and the Wilcoxon signed-rank test was used for statistical analysis.

Before and after treatment (mean of five subjects)

Measure	Before	After	Rate of change	p-value
Eye wrinkle depth (mm)	0.067 ± 0.038	0.061 ± 0.033	−8.955%	0.042
Skin moisture (%)	48.9 ± 4.126	55.893 ± 3.371	14.301%	0.043
Inner skin elasticity (Ur/Ue)	0.35 ± 0.029	0.432 ± 0.06	23.429%	0.042
Skin thickness (µm)	1652.8 ± 302.06	1773.8 ± 293.58	7.321%	0.043
Skin density (µm)	53.88 ± 2.72	60.62 ± 4.201	12.509%	0.042

All five subjects improved on every measure, and no adverse reactions were reported. The paper states that statistical significance is relatively low because of the small number of subjects.

Clinical experience in dermatology

Noh (2021), in a special advertisement feature in The Clinical Journal of the Association of Korean Dermatologists, described a pilot clinical experience of applying Elastic Lab with a microneedle roller and sonophoresis. Eleven Korean adult women (aged 31–72, mean 42.5) were treated 10 times at one-week intervals; 10 of the 11 were satisfied, and 9 showed moderate or greater cosmetic improvement. The melanin index decreased by 8.9% on the cheek, 6.3% under the eyes, and 5.8% on the forehead; the infraorbital wrinkle index decreased by an average of 15.5%, and the number of enlarged pores on the cheek by an average of 21.3%. Mild erythema (average 1.4 days) and temporary dryness (average 2.5 days) occurred after treatment, but no one reported side effects. The article presents no control group or statistical tests and reports no quantitative measurement of skin elasticity itself.

Limitations

Increased elastin expression in in vitro studies is a separate matter from whether it leads to functional elastic fiber formation in human skin, and the trial by Kim et al. (2022) did not directly measure the actual deposition of new elastin fibers. The human studies involved 5 and 11 subjects and both lacked control groups, and the authors themselves stated that large-scale clinical trials and measurement of elastin and collagen content in tissue are needed. Three authors of Kim et al. (2022) and one author of Chung et al. (2021) are affiliated with Elastic Lab, and Noh (2021) was published in a special advertisement feature. Independent controlled clinical trials are therefore needed to confirm whether promoting elastin biosynthesis leads to long-term improvement in skin elasticity.

---