Sagging skin. What could be more a more pathognomonic sign of aging? What causes skin to sag, or not? How come I used to be able to stretch my skin and it would snap right back? And why can I no longer do that?
In a followup to our discussion of collagen in The Matrix:Collagen lets now turn out attention to elastin.
While it is true that all living things are made of cells, it is the extracellular matrix (ECM) that provides structure to tissues. In some cases the ECM accounts for more of the organism’s bulk than its cells. Collagen comprises the majority of fibrous tissue support within the ECM of mammals. This is especially true of the skin, but that is only part of the story, especially when it comes to skin changes seen with aging.
Soft, supple, resilient skin requires healthy elastin, despite it being considerably lesser a constituent of skin (by total volume) than collagen. While collagen has great tensile strength and provides robust mechanical and structural support, it is elastin that enables tissues to be stretched and pulled out of shape and then rebound back again. Without elastin, even young skin would hang and sag in places, simply to provide the slack necessary to enable changes in body angles, geometry and distance associated with movement and locomotion. Older people “hang and sag” for a different reason. Elastin and collagen both undergo considerable degeneration and reduction in mass over the decades.
Thinning, wrinkling, and laxity of skin is due to changes in collagen and elastin, and for both, the major culprit is repetitive and cumulative UV radiation. (Have you ever noticed that older sunbathers who have deep brown, year-round, all-over tans are the ones who also have deep, year-round, all-over wrinkles?) The UV radiation that induces melanocytes to reactively produce melanin also induces reactive oxygen species that damage proteins, lipids, and DNA (as well as damage DNA directly.) The damage to elastin occurs when the unique chemical structure that provides the ability to recoil is affected. A little background.
Composition of the ECM
The ECM of vertebrates (that includes humans) is composed of complex mixtures of:
- proteoglycans, and
- in the case of bone, mineral deposits.
Proteins are comprised primarily of amino acids, structured in a variety of geometric configurations but nearly all also containing short chains of carbohydrates, making them more precisely glycoproteins.
Collagen is glycosolated (contains carbohydrate) which provides hydroxyl groups where linkage with sulfur- sulfur bonds occurs to join collagen molecules together into their triple helix configuration. It is built up from single repeating elements that are long, narrow molecules.
Proteoglycans are also glycoproteins but consist of much more carbohydrate than protein; that is; they are huge clusters of carbohydrate chains often attached to a protein backbone.
Elastin is Unique
Elastin is comprised of protein molecules that contain no carbohydrate and hence have few chemical linkages among the molecules. This accounts for their inherent elasticity. Thus they have loosely connected coiled structures that can be stretched and then return to their original shape.
The side chains are not based on carbohydrate residues attached to protein molecules, but rather four lysine amino acids that link together giving the molecule the ability to stretch to 1.5 times its length. The linkages are called desmosine and isodesmosin. Elastin is produced by fibroblasts (important in the skin) and smooth muscle cells (hugely important in the walls of arteries.) This type of elastin is often referred to as amorphous elastin which is found within elastic fibers that indeed do have associated scaffolding structures.
The Formation of Elastic Fibers
The elastic fiber is formed from the elastic microfibril (consisting of numerous proteins such as microfibrillar-associated glycoproteins,fibrillin, fibullin, and the elastin receptor) and amorphous elastin.
The microfibril scaffolds and organizes the deposition of amorphous elastin. Amorphous elastin forms from monomers of solubletropoelastin which is insolubilized and crosslinked into amorphous elastin by lysyl oxidase. Lysyl oxidase reacts with specific lysineresidues and by oxidative deamination generates reactive aldehydes and allysine.
These reactive aldehydes and allysines can react with lysine and other allysine residues to crosslink and form desmosine, isodesmosine, and a number of other polyfunctional crosslinks that join surrounding elastin molecules to build an elastin matrix and elastic fiber. As discussed above, these unique crosslinks are responsible for elastin’s elasticity. So, there you have the synthesis of elastin. Now, for where it really counts.
Elastin is Important in Skin, but Not Compared to These Other Tissues
I don’t want to minimize the desirability of maintaining youthful looking skin, but when put into perspective, the importance of high quality, functional elastin in the skin is nothing compared to its importance in arteries, veins, lungs, and other tissues.
Elastin serves an important function in arteries as a medium for pressure wave propagation, and to help maintain downstream blood flow during diastole, the period while the heart is refilling prior to its next contraction. During the heart beat, systole, when blood is rapidly ejected into the aorta, it is the elastic nature of the aorta and other vessel walls than enable them to quickly expand and then continue to exert elastic recoil to maintain blood pressure.
Total elastin ranges from 58 to 75% of the weight of the dry defatted artery. When arterial walls are stressed 35%, a minimum of 48% of the arterial load is carried by elastin, and a minimum of 43% of the change in stiffness of arterial tissue with aging is due to the change in elastin stiffness.
Elastin is also a recognized target for injury in COPD, chronic obstructive pulmonary disease. In COPD the ability of the small air-sacs to return to their deflated state is diminished, so airflow into and out of the structures, where blood takes on oxygen and gives off carbon dioxide, is hindered.
In emphysema, some of the little air-sacs are ruptured which reduces the blood/air interface for gas exchange. Elastin is a tissue component particularly susceptible to injury through toxins found in tobacco smoke and is also dramatically impacted in certain genetic conditions, such as alpha 1 anti-trypsin deficiency. In these cases, injury to elastin is not an inconvenience noticeable in the mirror; it is a threat to life.
What Else Can Go Wrong with Elastin?
Cutis laxa is a group of rare connective tissue disorders in which the skin becomes inelastic and hangs loosely in folds. In most cases, cutis laxa is inherited and can be autosomal dominant or recessive, or sex linked. Mutations in the elastic fibers of dermis have been identified in these conditions. Acquired forms have also been described.
Marfan’s syndrome is another genetic condition in which there are abnormalities in elastin. Individuals with Marfan’s syndrome are tall with lanky builds and longer than normal limbs. Defective tissue leads to subluxation of the lens of the eye but more importantly, can lead to fatal deterioration of blood vessel walls, the most notable aneurysms of the thoracic aorta which can rupture spontaneously.
Although born long before the development of the genetic testing that could confirm his diagnosis, you may recognize the most famous person that many medical experts agree most likely was afflicted with this condition.
Repair and Protection of Elastin in the Skin
Like topical collagen, topical elastin offers no reparative function to dermal tissue. The molecules are too large to be absorbed and simply layer on the surface. Likewise, elastin supplements will undergo digestion and result in absorption of constituent amino acids and small peptide. In fact, elastin powder has been applied to open wounds on rats without any perceived benefit in healing.
In a tissue culture study, retinoic acid (a.k.a. tretinoin) was shown to increase elastin synthesis in chick embryonic vascular smooth muscle cells up to 2.8-fold. There is some ground to believe that topical retinoids may also stimulate elastin synthesis in the human skin.
Skin rejuvenation is not just about producing more of the key components of the skin matrix, such as collagen and elastin. It is also about protecting the one you have from excessive degradation. Such degradation is caused primarily by the enzymes matrix metalloproteinases (MMP). There are many types of MMP and some are involved in breaking down elastin: MMP-2, MMP-9, MMP-12, and possibly others. Inhibiting these MMP may increase the skin content of elastin by reducing the rate of its degradation.
Controlled tissue injury procedures
Some skin rejuvenation procedures (e.g. lasers or medium-to-deep peels or deep dermarolling) work by inducing controlled tissue injury followed by skin remodeling, which leads to increased production of new skin matrix and skin remodeling. The predominant protein produced during healing is collagen but the synthesis of elastin increases as well.
As the primary signal molecules for many cellular functions, it should come as no surprise that cytokines are also involved with elastin synthesis and breakdown. When cells (e.g. keratinocytes, skin cells) are damaged, or have died, inflammatory cytokines are released that then communicate with fibroblasts. The inflammatory cytokines then cell up immune cells to begin the process of wound healing through the formation of granulation tissue. Proteases are released, breaking down collagen and elastin fibers. In healthy young humans, this process is rapid, and is replaced rather quickly when mesenchymal stem cells are called up from distant and nearby depots, e.g. bone marrow. They they turn off the inflammatory (destructive) process and coordinate the next phase of healing, heralded by rebuilding. They are responsible for turning off MMP’s.
In older humans the process is far less efficient, due to fewer mesenchymal stem cells, and the inflammation lasts longer. Older persons cannot mount the healing cytokine response of an infant. With aging, this takes it toll. Elastin rebuilding is greatly reduced, and the elastic quality of the elastin is lessened. The net result of all this is wrinkling and sagging of skin.
A particular pattern of cytokines, isolated in a laboratory from mesenchymal stem cells in culture, identical to those your own body produced in abundance when younger, can be applied therapeutically to augment repair and renewal of elastin. They can be used alone, as a key active ingredient in an anti-aging serum, or as an adjunct to controlled tissue injury procedures, to signal the matrix to generate new elastin.
How do you explain when only one side of your fine is sagging (more like minor labial lines forming) I’m 24 year old male with acne prone skin, and I had pretty bad acne growing up and it has subsided but left me with a lot of scars. Could acne be the cause for this? I also hit the gym rigrously 5-6x a week lifting very heavy, not sure maybe if over training can lead to signs of aging in the skin. I’ve been using RETINA ceram 0.1% at night for about 6 months now and Topical vitamin C 20% in the mornings every 2-3 days. Could I see improvement from such combination. i would like to be able to send you a photo to demonstrate what I mean. What is your take on this?
I’ve been intrigued with the bombardment on the issue of collagen lately, that the issue of elastin was placed on the back burner. A refreshing article on elastin; especially combining the significant noting of the overall vitality of elastin within the entire body. In fact, It was quite humbling to read: “…In these cases, injury to the elastiin is NOT AN INCONVIENCE NOTICEABLE IN THE MIRROR, it is a threat to life.” Puts things in perspective, doesn’t it?
BTW, I always thought that President Lincoln’s facial appearance was just a result of the chronic stress he was under. Thanks for shedding light on that tidbit of info..
One of the interesting observations I made during medical school, was that for every tissue or cell type in the body, if something could go wrong, it most likely did. This might mean only a handful of individuals are affected, as is the case in rare genetic disorders, or it might be a general problem that affects most people at one time or another, if they live long enough. The human body is incredibly complex – from the simple gross structure and morphology of organs, to the more intricate structure of cells and tissues, to the amazingly complex world of innumerable biochemical processes, the scale of which is molecular with hundreds if not thousands of participant molecules. This is the realm in which cytokines play such an important role; where specialized receptor molecules are “triggered” to then start a cascade of sequential downstream events. Truly amazing that it all works so well most of the time….
Mike,thank you for your interesting question. As you may know, it’s quite normal for one side of the face or body to be dissimilar from the other – it’s all a matter of degree. Check out the website below to see some graphic illustrations of how bizarre some famous people look when both sides of their face are identical.
As background, there are a number of possible reasons for accentuated differences. Congenital disorders such as facial hemi-trophy or hypertrophy of superfacial tissue on one side; muscle and bone injury or disease; Inflammatory with abscess, cellulitis, cysts and resultant scarring; neurologic such as Bell’s palsy with laxity or atrophy of facial muscles; even teeth clenching or chewing one side of the mouth can results in one side looking different.
In your question, you mentioned acne which could be a factor, and the fact that you work out several times a week, which if it includes pronounced repetitive facial grimacing might also lead to changes in skin over time, and they need not be identical. I think it is wise to continue using facial treatments as they can mitigate damage.
A recent report on a professional truck driver who was exposed to sun UV through the driver’s window graphically demonstrates how much more one side of the face can suffer damage if protective measures are not taken. Hope this helps.
Thanks for the response. Just one last question, what is your opinion onmicro needling or collagen induced therapy as they call it? I spoke to Dr. Des from South Africa who is the pioneer of micro needling and he recommends I use 3.00 MM needles to stimulate the production of collagen for the purpose of acne scarring problematic skin. Do you know of any studies that can validate such claims? it seems like a cost effective treatment compared to Laser and with possibly less side effects. I’m thinking about using RETINA and needling to maximize the effects.
Mike, thank you for your question. It is timely for several reasons. For readers who may not be aware of this technique, dermarolling is a process where rollers with many small needles are used in vertical, horizontal, and oblique repetative passes on the skin to create many small holes through the stratum corneum. Depending on the length of the needle, they puncture into deeper dermal layers and do have proven efficacy in improving the appearance of scarring, most commonly post-acne scarring. Needles come in a variety of lenths (0.5 to 3.0 mm is a typical range). Obviously, longer needles penetrate deeper into the dermis and create more “damage”, the response to which is fibroblast proliferation and increased matrix production. The shorter dermarolling needles are helpful in inproving drug delivery to the skin since the stratum corneum is an effective barrier, especially for water-borne compounds.
Dermarolling is uncomfortable, particularly when longer needles are used, so topical anesthetics are usually applied to reduce discomfort. While minimally damaging in reality, it can look worse than it is as deeper penetration results in bleeding from the skin which may alarm some people. Dermarolling has been described as similar to ablative laser in its effectiveness but without the same degree of damage that laser produces, and especially without the risks of post-procedure hyperpigmentation that laser can sometimes produce is susceptible people. Anyone with a blood coagulation disorder, tendency to form keloid scars, or darker skin should stay away from dermarolling.
Interestingly, we recently received notice from a dermarolling afficionado that use of our AnteAGE products resulted in a much shorter healing time – instead of 5 or 6 days to return to normal, her skin healed in only 2.5 days which is consistent with anecdotal accounts of rapid skin healing with AnteAGE from people who had suffered burns, cuts, and abrasions, including some of the subjects of our clinical trial. Inflammation and pain were reduced and healing augmented because of the stem cytokines and other actives (including retinol) – just as we would predict. Drjohn and I are planning to explore the benefits of stem cytokines to not only dermarolling, but laser and dermabrasion as well. We already have one subject who experienced noticable benefit after microdermabrasion.
If you are treating acne scarring, best results will occur with needles 2.5 to 3.0 mm. Good luck.
A brief reveiw can be found at: http://cbmcbmymen.com/Collagen%20Dermaroller.pdf
Fascinating stuff! So, I wonder if by increasing the amount of certain nutrients we consume elastin production can be increased? While complete nutrition is no doubt important in preventing or slowing the degradation of the skin matrix some people believe that supplement the diet with specific nutrients can increase the body’s ability to produce elastin and collagen (eg: vitamin C, lecithin, hyaluronic acid etc). Do you have any opinions on how supplementation of the diet might help or hurt the skin?
I see you addressed supplements in the “collagen” edition of this Skin Matrix series! Of course collagen supplements do nothing to increase the body’s production of collagen. Are there any nutrients that could potentially be increased that would help?
Certain nutrients and co-factors (e.g. vitamin C in the synthesis of collagen) are absolutely necessary to produce collagen and elastin, BFT is unaware, however, of any circumstance where, assuming there is a generally adequate and well-balanced dietary intake, a deficit would exist to impact their synthesis. We have already discussed that the digestive and absorption process would preclude collagen or elastin from being delivered to tissues in their molecular form. For this reason, dietary supplements are useless. Likewise, topical application is folly as the molecules can not penetrate to where they are needed, nor are capable of being incorporated into the dermal matrix directly.
Where do we find the stem cytokines? Thanks
You can find them in AnteAge products (http://anteage.com) that we have created in our laboratories, and others based on human stem cell derived cytokines and growth factors.
What are your thoughts on using a dermaroller and the anteage products combined with red light therapy? My issues are with acne scarring, fine lines and oily skin. Thanks.
I think its a solid combo. Dr Lance (Setterfield) is our light+microneedling expert so we will check with him as well.
Hi, I’ve read that white tea has been shown to strongly inhibit the MMP’s that break down elastin. The tricky thing is knowing how much white tea has to be consumed for this effect, and what type of white tea (green tea was shown to be effective too, but far less so). If you search for it, there’s a study published with its abstract available online, but I couldn’t find the whole article to get more info on the methods and how much or what type of white tea was used. But perhaps consuming 6 bags worth of white tea per day in the form of iced tea, as I do, can do a lot to protecting the elastin throughout our bodies. I wish I knew more specifics.
With regard to your product using stem cytokines (AnteAGE), I’m wondering how those can penetrate the skin’s surface and have a true effect without being surgically or hypodermically injected.
There are several supporting articles attesting to the fact that topical bio-signals (growth factors and cytokines) indeed penetrate adequately into the skin to achieve physiologic effect. This has been documented using radioactive and fluorescein tagged molecules. Use of nonoliposomes is helpful (a technology we use in our products). Because of autocrine amplification (the synthesis within cells of many, many identical bio-signals to that which has activated cell surface membrane receptors) cells can “talk” to deeper layers of cells and propagate the “message”. Finally, there is no such thing as a perfectly intact stratum corneum, especially with advancing age. The epidermis get thinner with age and photodamage. There are tiny imperceptible injuries to the skin from the physical trauma of life that creates pathways for molecules to enter. Throw in any skin condition that has an inflammatory component and penetration will be more likely. Finally, there are pores, hair follicles, and glandular structures (sweat and sebum) that traverse from the surface to deeper dermal structures. With more than 500 articles attesting to skin benefits from topically applied bio-signals published over nearly two decades and the question of penetration is well settled.