The flexibility of skin, and other elastic tissue such as blood vessel walls, depends upon the structural arrangement of elastin in the extracellular matrix. Elastin is largely laid down during the developmental period of life, and not much repaired thereafter. Disruption of this structure is progressive over time, and is a major contribution to the changing physical properties and appearance of aging skin. The effects on blood vessels and other internal tissues are more important: loss of elasticity in blood vessels cascades to cause a great deal of downstream damage and dysfunction via its effects on blood pressure, on development of atherosclerosis, on supply of nutrients to tissues, and so forth.
Repair of elastin is a challenging problem. One cannot just add elastin to a tissue and hope for improvement, as the precise structure, amount, and interactions with other components of the extracellular matrix are all important. The only realistic approach is to guide cells into performing the same work of elastic depositition that occurred in early life. This is not a solved problem, as it is quite possible to trigger behavior that leads to unhelpful or even harmful elastin deposition, in which the structure and amounts are incorrect. Regulatory networks must be clearly identified and then manipulated in the right ways.
Some therapies tested over the past few decades do manage to create some improvement in measures of tissue elasticity, with good evidence for this improvement to involve elastin deposition. The use of minoxidil, for example, was originally introduced as a way to treat age-related hypertension. The side-effects at the necessary doses are significant and health-threatening, however, such as cardiac edema. A great deal of work remains to produce a viable elastic deposition approach that could be widely used.
Elastin is the main component of elastic fibers, which provide stretch, recoil, and elasticity to the skin. Normal levels of elastic fiber production, organization, and integration with other cutaneous extracellular matrix proteins, proteoglycans, and glycosaminoglycans are integral to maintaining healthy skin structure, function, and youthful appearance. Although elastin has very low turnover, its production decreases after individuals reach maturity and it is susceptible to damage from many factors. With advancing age and exposure to environmental insults, elastic fibers degrade. This degradation contributes to the loss of the skin's structural integrity; combined with subcutaneous fat loss, this results in looser, sagging skin, causing undesirable changes in appearance.
The most dramatic changes occur in chronically sun-exposed skin, which displays sharply altered amounts and arrangements of cutaneous elastic fibers, decreased fine elastic fibers in the superficial dermis connecting to the epidermis, and replacement of the normal collagen-rich superficial dermis with abnormal clumps of solar elastosis material. Disruption of elastic fiber networks also leads to undesirable characteristics in wound healing, and the worsening structure and appearance of scars and stretch marks. Identifying ways to replenish elastin and elastic fibers should improve the skin's appearance, texture, resiliency, and wound-healing capabilities. However, few therapies are capable of repairing elastic fibers or substantially reorganizing the elastin/microfibril network.
Current intrinsic treatment modalities, which stimulate or modulate endogenous elastin, typically involve cosmetics and topical skincare products. However, given the complexity of tropoelastin production, assembly, and crosslinking, there is limited evidence that topical skincare products can reach the dermal layers of the skin or sufficiently stimulate elastin production.
Successful extrinsic treatment modalities to replenish elastin may require delivery of structurally intact tropoelastin or elastin; most experimental strategies have utilized elastin fragments that are inappropriate for in vivo elastin assembly. Proposed therapies for the connective tissue disorder cutis laxa provide other potential targets for restoring elastin. For example, although no specific treatments for cutis laxa exist, it has been suggested that the disordered elastic fiber assembly in this disease might be corrected by supplementing certain carrier molecules that have a role in the secretory pathways for elastolytic enzymes involved in elastin production. Other potential therapeutic strategies for increasing elastin production include stimulation of elastin gene expression. However, because tropoelastin expression and elastin production are substantially reduced in adult tissues, even large increases in their expression are unlikely to be physiologically relevant.
Considering tropoelastin is the main component of elastin, a more viable approach to repairing elastic fiber networks may be to use recombinant human tropoelastin-based treatments. The recombinant human tropoelastin may act as a substrate for skin fibroblasts to promote collagen production and glycosaminoglycan deposition, contributing to tissue repair and improved hydration in skin. A recent study showed that surgical delivery of exogenous tropoelastin via a collagen-based dermal substitute leads to the development of an extensive elastic fiber network in the deep dermis. Recombinant human tropoelastin has demonstrated early promise for wound repair, scar prevention and treatment, cosmetic applications, and aesthetics; it can be used by skin cells as a substrate to produce new elastic fibers. The applied use of tropoelastin for these indications is therefore a promising area of study.