What Is Skin Made Of!
You are here: Skin Biology >What Is the Skin Made of?
The skin is the largest organ in the body, comprising about 15% of the body weight. The total skin surface of an adult ranges from 12 to 20 square feet. In terms of chemical composition, the skin is about 70% water, 25% protein and 2% lipids. The remainder includes trace minerals, nucleic acids, glycosoaminoglycans, proteoglycans and numerous other chemicals.
The skin consists of three main layers: epidermis, dermis and subcaneous tissue.
The epidermisThe epidermis is the topmost layer of the skin. It is the first barrier between you and the outside world. The epidermis consists of
three types of cells keratinocytes, melanocytes and Langerhans cells. Keratinocytes, the cells that make the protien keratin, are the predominant type of cells in the epidermis. The total thinkness
of the epidermis is usually about 0.5 - 1 mm. At the lowermost portion of the epidermis are immature, rapidly dividing keratinocytes. As they mature, keratinocytes lose water, flatten out and move
upward. Eventually, at the end of their life cylce, they reach the uppermost layer of the epidermis called stratum corneum. Stratum corneum consists mainly of dead keratinocytes, hardened proteins
(keratins) and lipids, forming a protective crust. Dead cells from stratum corneum continuously slough off and are replaced by new ones coming from below. The skin completely renews itself every 3 -
5 weeks. Most mild peels work by partly removing the stratum corneum and thus speeding up skin renewal.
Another significant group of cell in the epidermis are melanocytes, the cells producing melanin, the pigment responsible for skin tone and color. Finally, Langerhans cells are essentially a forepost of the immune system in the epidermis. They prevent unwanted foreingn substances from penetrating the skin.
The condition of epdermis determines how "fresh" your skin looks and also how well your skin absorbs and holds moisture. Wrinkles, however, are formed in lower layers.
The dermisThe dermis is the middle layer of the skin located between the epidermis and subcutaneous tissue. It is the thickest of the skin layers and comprises a tight, sturdy mesh of collagen and elastrin fibers. Both collagen and elastin are critically important skin proteins: collagen is responsible for the structural support and elastin for the resilience of the skin. The key type of cells in the dermis is fibroblasts, which synthesize collagen, elastin and other structural molecules. The proper function of fibroblasts is highly important for overall skin health.
The dermis also contains capillaries (tiny blood vessels) and lymph nodes (depots of immune cells). The former are important for oxygenating and nourishing the skin, and the latter -- for protecting it from invading microorganisms.
Finally, the dermis contains sebacious glands, sweat glands, hair follicles as well as a relatively small number of nerve and muscle sells. Sebacious glands, located around hair follicles, are of particular importance for skin health as they produce sebum, an oily protective substance that lubricates and waterproofs the skin and hair. When sebacious gland produce too little sebum, as is common in older people, the skin becomes excessively dry and more prone to wrinkling. Conversely, overproduction or improper composition of sebum, as is common in adolescents, often leads to acne.
The dermis is the layer responsible for the skin's structural integrity, elasticity and resilience. Wrinkles arise and develop in the dermis. Therefore, #an anti-wrinkle treatement has a chance to succeed only if it can reach as deep as the dermis. Typical collagen and elastin creams, for example, never reach the dermis because collagen and elastin molecules are too large to penetrate the epidermis. Hence, contrary to what some manufacturers of such creams might imply, these creams have little effect on skin wrinkles.
Subcutaneous tissueSubcutanous tissue is the innermost layer of the skin located under the dermis and consisting mainly of fat. The predominant type of cells in the subcutaneous tissue is adipocytes or fat cells. Subcutaneous fat acts as a shock absorber and heat insulator, protecting underlying tissues from cold and mechanical trauma. Interestingly, most mammals lack subcutaneous tissue because their fur serves as a shock absorber and heat insulator. Sweat glands and minute muscles attached to hair follicles originate in subcutaneous tissue.
The loss of subcutaneous tissue, often occuring with age, leads to facial sag and accentuates wrinkles. A common procedure performed by dermatologists to counteract this process is to inject fat (collected elsewhere in the body) under the wrinkles on the face.
You are here: Skin Biology >Important Skin Molecules
Health, resilience and youthful appearance of the skin depends, among other things, on several key classes of biological molecules, just like the quality of a house depends on the quality of bricks, beams and concrete. The most important skin molecules are collagen, elastin, glycosoaminoglycans and proteoglycans.
Collagen is a protein forming the structural grid that holds other skin structures. It plays a role somewhat similar to that of steel rods in a reinforced concrete block. It gives the skin its strength and durability. As any other protein, collagen is composed of amino acids. However, it is unusually rich in a few specific amino acids, proline, hydroxyproline, lysine and glycine. Some experts believe that foods or supplements rich in these amino acids may benefit the skin by stimulating collagen production. There is a number of other ways to stimulate collagen production, including topical vitamin C and copper peptides. Increasing collagen production is important because age-related decline in the collagen synthesis is partly responsible for the signs of skin aging such as thinning, wrinkles and sagging.
Elastin is also a protein. It is more stretchable than collagen and helps maintain skin resilience and elasticity. Elastin contains two special amino acids, desmosine and isodesmonsine. When both elastin and collagen and abundant and undamaged, the skin easily regains its shape after being stretched or folded. Just as collagen, elastin deteriorates with age, leading to wrinkles and facial sag.
Glycosoaminoglycans (GAGs) and proteoglycans are special biological polymers whose key role is to hold moisture in the skin. In essense, they are extremely effective natural moisturizers - far more effective that common cosmetic moisturizers. Hydrated GAGs and proteoglycans help the skin stay plump and fresh and provide mechanical support for skin cells. GAGs are composed of special units (mainly water-holding sugars) such as glucosamine hydrochloride, N-acetyl glucosamine, and glucosamine sulfate. These units combine to form various types of GAGs, such as hyaluronic acid, keratin sulfate, heparin, heparin sulfate, dermatin sulfate, and chondroitin sulfate. Proteoglycans are larger than GAGs and are formed when certain types of GAGs are attached to a protein backbone. Since GAGs and proteoglycans are composed largely of water-holding sugars, supplementing one's diet with these sugars may enhance the skins production of GAGs and proteoglycans. In particular, N-acetyl-D-glucosamine, D-glucosamine hydrochloride, and D-glucosamine sulfate are often used as supplemets to increase skin moisture.
You are here: Skin Biology >Sebum, Sweat, Skin pH and Acid Mantle
Sebum is an oily secretion produced by sebacious glands, tiny ducts adjacent to hair follicles. Sebum is secreted into the follicle, from which it spreads over the hair and skin. The main role of sebum is to waterproof the skin and hair. Both excess and lack of sebum are undesirable. Excess sebum is associated with oily skin and acne. It is particularly common in adolescents as the increased levels of sex hormones stimulate sebum production. Lack of sebum, which is common in middle and older age, leads to skin dryness and accelerates wrinkle formation.
Sweat is a salty, watery solution produced by sweat glands, numerous microscopic channels opening onto the skin surface. As sebum and sweat mix up on the skin surface, they form a protective layer often referred to as the acid mantle . Acid mantle has a particular level of acidity characterized by pH from about 4 to 5.5. A pH of 7 is considered neutral, above 7 is alkaline, and below is acidic. The pH of acid in the human stomach, for example, is usually from 1 to 2, which is highly acidic. The skin, on the other hand, is mildly acidic. In addition to helping protect skin from "the elements" (such as wind or pollutants), acid mantle also inhibits the growth of harmful bacteria and fungi. If acid mantle is disrupted or loses its acidity, the skin becomes more prone to damage and infection. The loss of acid mantle is one of the side-effects of washing the skin with soaps or detergents of moderate or high strength.
You are here: Skin Biology >Skin collagen: More than meets the eye.Everybody knows that collagen is important for the skin. Indeed, it is the principal structural protein holding the skin together. The quantity and quality of your skin's collagen has a major role in your appearance. Therefore, it may be tempting to think that simply getting more collagen into the skin should lead to dramatic rejuvenating effects. While there is a grain of truth to that, things are more complicated than they look as far as collagen is concerned.
Chemistry of collagenCollagen is not like most proteins, which are essentially compact molecular clumps -- it is basically a fiber or, when fully
mature, a mesh of fibers. Not surprisingly, collagen's composition is also unusual. It is particularly rich in four amino acids: lysine, proline, hydroxylysine and hydroxyproline. The most common
patterns in the amino acid sequence of collagen are lysine-hydroxylysine-proline and lysine-hydroxylysine-hydroxyproline.
The types of collagenCollagen is found in the majority of organs, not just the skin. It occurs in different forms known as types. Hence, it is not enough to have the right amount of collagen in the right place - it has to be the collagen of the right type.
Type I Collagen - The most abundant collagen in the body. Found in tendons, bones, skin and other tissues. Particularly abundant in the scar tissue.Types II, IX, X, XI - CartilageType III - Common in fast growing tissue, particularly at the early stages (Phase 1) of wound repair. Much of it is replaced later by the type stronger and tougher type I collagen.Type IV - Basal lamina (filtration membrane of capillaries)Type V, VI - Generally found alongside type IType VII - Epithelia (lining of GI tract, urinary tract, etc.)Type VIII - Lining of blood vesselsType XII - Found alongside and interacts with types I and IIIThe most abundant types of collagen in the skin are I and III; their fibrils form the mesh largely responsible for the skin's mechanical properties. Other types of collagen in the skin are V, VI, and XII. They are found in much smaller amounts and appear to have a supportive role, whose details remain unclear.
Types of collagen and the aging process.Overall, the amount of collagen in the skin tends to decline with age. However, different types of collagen behave differently. In particular, a child's skin has a lot of collagen III, the type is common in fast growing tissues. The abundance of the type III collagen is partly responsible for the softness of the young skin. As the body growth slows down, the skin content of type III collagen declines, while that of type I increases. In fact, type I collagen continues to build up until about the age of 35, when the skin reaches the peak of its mechanical strength. After that, type I begins to decline as well. The dynamic of age-related changes in other collagen types remains unclear. However, we do know that by the age of 60, all types of collagen are significantly below their youthful levels.
Understanding collagen types is important for a number of reasons. First, different agents capable of stimulating collagen synthesis may affect different collagen types differently. That's one reason why some collagen boosters are more appropriate for the skin than others. Second, if you know the optimal skin collagen composition and could measure your own, you may have a better chance of selecting skin care that will work for you. Unfortunately, skin collagen composition analysis is still confined to advanced research facilities and the effect of most skin care treatments (with some notable exceptions, such as vitamin C) on specific collagen types remains unknown. But much research is going in that direction and its results may enter consumer market relatively soon.
Quantity vs qualityHaving a lot of collagen in your skin is not enough. Even having the right mix of the collagen types is not enough. It is also important that collagen be undamaged and properly deposited. Collagen freshly deposited by young, healthy fibroblasts has a coherent and orderly structure. When collagen is damaged by UV rays, free radicals, impaired glucose metabolism, smoking or other factors, its structure becomes distorted, leading to poor skin texture, wrinkles and other imperfections. In this scenario, a common approach is to clear up the damaged collagen (e.g. via a peels, laser, activation of proteases or other means) and then stimulate the production of a more regular new collagen. Many skin care procedures and products address one or both steps of this approach.
Synthesis vs degradationMost components of the skin, including collagen, undergo continuous turnover. New collagen is continually produced and recycled throughout life. At a younger age the synthesis of collagen predominates, whereas after about age of 40, the degradation of collagen picks up speed. Therefore, to keep your skin's collagen in balance, after certain age you may benefit from steps to boost collagen synthesis and reduce its degradation.
Considering that collagen type I and III seem to predominate in the skin, the agents and treatments shown to stimulate the synthesis of these types are particularly promising. One good example of such an agent is topical Vitamin C, whose capacity to stimulate both type I and III collagen has been shown in a number of studies. (We discuss the use of vitamin C and other collagen boosters in the Anti-aging Treatments section and Skin Rejuvenation Infopack.)
Just like the synthesis, collagen degradation is an ongoing, natural process. You may ask: why would the skin want to destroy its key structural proteins? Isn't it like cutting the legs of your own chair? Well, not quite. There are situations when removing collagen makes sense, e.g. when collagen it excessively damaged or when there is an infection and a passageway needs to be cleared for the immune cells. But as we age, collagen degradation tends to spin out of control and contribute to weakening and wrinkling of the skin. On top of that, a number of external factors increase it even further: UV rays, smoking, chlorinated water, free radicals, inflammation, irritation and others. Minimizing all of the above is always a good idea but may not be enough to keep collagen degradation under control. A more advanced approach is to inhibit the enzymes called matrix metalloproteinases (MMP-s). These enzymes (particularly the one called collagenase) chopping up collagen into small pieces which then get recycled.
Considering that older skin does not respond to collagen synthesis boosters particularly well, inhibiting the degradation of collagen by MMP-s -- used alone or in conjunction with stimulating the synthesis -- may prove to be a better approach. Much research is currently being done to find effective topical MMP inhibitors. Unfortunately, despite claims by some manufacturers, none of the topical agents currently on the market has been proven to directly inhibit MMP-s. However, such agents are likely to appear in the near future. In the meantime, it is useful to know that some common skin care ingredients appear to inhibit MMP-s indirectly, e.g. by inhibiting certain pathways of inflammation or suppressing the synthesis of MMP-s. Such agents include lipoic acid, retinoids and others.
Elastin: A neglected essential of skin youthWhen asked what protein is the most important for maintaining youthful skin (i.e. firm, bouncy, sag-free, unwrinkled skin), the majority of people and many experts would say collagen. (Well, ok, the majority might say "No idea!" or "what's a protein?" but you know what I mean...). Indeed, collagen is important for the skin - it is the principal structural protein holding the skin together. Yet, there is another skin protein that is at least as important: elastin. Elastin is a protein found in any elastic connective tissue. It is responsible for the ability of tissues to resume original shape after being stretched.
Chemistry of elastinElastin is a protein primarily composed of the amino acids glycine, valine, alanine, and proline. Just as collagen, it is
produced by the connective tissue cells called fibroblasts. More accurately, fibroblasts secrete tropoelastin, the soluble immature form of elastin. Tropoelastin molecules are then cross-linked in a
reaction catalyzed by the enzyme lysyl oxidase, forming a durable, resilient web of elastin fibers that behaves akin to latex.
Elastin and agingOne simple test for skin aging is to check how long it takes for the skin to snap back after being pinch-pulled away. (You can try it on the back of your hand.) Young skin snaps back almost immediately. The old one takes up to several seconds. The reason for such difference is quantity and quality of elastin in the skin.
The amount of elastin in the skin usually peeks in adolescence or early adulthood and declines thereafter. Fibroblasts in older skin have a much reduced capacity to produce new elastin. This deficiency does not appear to be a result of the loss of fibroblasts or mutations in elastin-encoding genes. More likely, age-related changes in the skin's biochemical environment shut down elastin production. Therefore, at least in theory, elastin production can be restored to its youthful levels with proper biochemical signals.
Can you boost elastin in your skin?Boosting elastin in the skin is a somewhat neglected topic in skin care. In part, this is a result of excessive focus of cosmetic industry and dermatologic research on collagen - arguably at the expense of elastin. The skin's collagen content and composition can be increased/improved by a number of topical formulas (e.g. ascorbic acid, copper peptides, etc.) as well as procedures (lasers, resurfacing and so forth). Unfortunately, much less is known about boosting the skin's elastin. Yet it is just as important for successful skin rejuvenation. Below I list a few approaches that show at least some promise to restore and/or preserve elastin levels in aging skin. However, as of the time of this writing, none is reliably proven to do so.
In a tissue culture study, retinoic acid (a.k.a. tretinoin, Retin A, Renova) was shown to increase elastin synthesis in chick embryonic vascular smooth muscle cells up to 2.8-fold. Interestingly, retinol (a form of vitamin A often touted in skin care as a better tolerated substitute for retinoic acid) had no effect on elastin synthesis in that study. There is some ground to believe that topical retinoids may also stimulate elastin synthesis in the human skin. But any definitive research to that effect is lacking. (See also our articles on tretinoin and other retinoids.)
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. (See our article on MMP inhibitors.)
Controlled tissue injury procedures
Some skin rejuvenation procedures (e.g. lasers or medium-to-deep peels) 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. However, whether such procedures lead to the sustained improvement in the density and quality of elastin in the skin remains unclear. (See our section on noninvasive procedures.)
As we discussed earlier, fibroblasts synthesize the immature soluble form of elastin (tropoelastin), which then permeates the dermis and fuses into an elastic web. What if tropoelastin were applied to the skin in a cream? Would that help? At least one skin care company, DermaPlus, Inc. (not affiliated with SmartSkinCare.com in any way), sells topical tropoelastin in a cream called DermaLastyl. The company claims that their products increase skin content of elastin, thereby reducing wrinkles and firming skin. Unfortunately, their research data have not been published in any peer-reviewed research journals. Furthermore, large molecules like tropoelastin generally do not penetrate into the dermis easily enough to produce clinically significant effects. Some skin penetration (all the way into the dermis) is occasionally possible even for large molecules, including certain proteins. However, the claims that topical tropoelastin restores youthful levels of dermal elastin will require solid, independent scientific evidence before they can be taken seriously.
Ethocyn (ethoxyhexyl-bicyclooctanone) is a small molecule tht easily penetrates into the dermis. It is claimed to specifically increase the synthesis of elastin to the levels seen in early adulthood. At present, the evidence backing such claims appears sparse. (See our acricle on Ethocyn.)
Hyaluronic acid: Skin matrix health is not just about proteins
The skin matrix is what would remain if you took the dermis (the fibrous middle layer of the skin) and removed all cells from it. The skin matrix is responsible for structural integrity, mechanical resilience, stability and many other properties of the skin. The degradation of the skin matrix plays an important role in the development of wrinkles and other signs of skin aging. The best known components of the skin matrix are structural proteins (notably collagen and elastin), which are vital to skin health and youthfulness. However, just like steal beams and rebar are necessary but insufficient for building a skyscraper, structural proteins are necessary but insufficient for a healthy skin matrix. In addition to the framework of structural proteins, the skin matrix also needs appropriate fillers, which provide mechanical cushioning, hold moisture, enhance barrier function, and so forth. The principal skin matrix fillers are glycans, a class of glucose-based polymers that includes glycosoaminoglycans and proteoglycans. As far as skin rejuvenation is concerned, the most important glycan may be hyaluronic acid (a.k.a. hyaluronan, hyaluronate or HA).
Chemistry of hyaluronic acidHyaluronic acid is a polymer whose unit consits of D-Glucuronic acid and N-Acetyl Glucosamine. Hyaluronic acid chains
can be up to 25,000 units long or even longer; their molecular weight ranging from about 5,000 to 20,000,000 Da.
Hyaluronic acid is synthesized by the enzymes called hyaluronan synthases. Humans have at least three types of hyaluronic acid synthases: HAS1, HAS2, and HAS3. HAS1 and HAS2 synthases produce high molecular weight HA whereas HAS3 produces low molecular weight HA. Hyaluronic acid is degraded by the enzymes called hyaluronidases, of which there also appear to be several types.
Hyaluronic acid and skin physiologyHyaluronic acid has many functions throughout the body, especially in the connective tissue. In the skin, some of its known roles are the following:
Holding moistureIncreasing viscosity and reducing permeability of extracellular fluidContributing to mechanical resilience and suppleness of the skinRegulation of tissues repairRegulation of movement and proliferation of cellsRegulation of immune and inflammatory responsesIt is important to note that physiological effects of hyaluronic acid depend to a large degree on the size (molecular weight) of its chains. In particular, relatively small HA molecules (weighing less than about 20,000 Da) appear to trigger the early phases of wound healing, including activation of various types of immune cells and inflammatory responses. This is understandable. Considering that tissue injury would typically result in increased degradation of extracellular matrix (and HA in particular), it makes sense that the degradation fragments (i.e. small size HA fragments) would act as indicators of injury and trigger wound healing. On the other hand, large HA molecules appear to suppress local immune response and inflammation. By the similar logic, the predominance of large HA molecules sends a signal that the skin is intact and defense and/or repair are not required.
Hyaluronic acid and agingThe skin content of hyaluronic acid decreases with age (after peaking in adolescence or early adulthood). This contributes to the loss of moisture; the skin becomes thinner and less supple. The loss of HA may also impair the skin's ability to repair itself and possibly affects the synthesis and deposition pattern of other skin matrix components.
Can you boost hyaluronic acid in your skin?Reversing the age-related decline in the skin content of hyaluronic acid is an increasingly visible topic in skin care. It would complement other steps to preserve the health of the skin matrix (such as replenishing collagen and elastin). Unfortunately, as of the time of this writing, there is no simple, inexpensive and broadly effective way to preserve/restore HA levels in the skin. Below, we discuss what options are currently available or hold promise for the future.
Topical hyaluronic acidTopical hyaluronic acid in the form of gels, serums and so forth is widely available but its usefulness is limited.
HA can provide effective skin surface moisturizing, either alone or in combination with other moisturizing ingredients. However, there is a controversy whether concentrated HA formulas should be used as a moisturizer in dry climate. When air humidity is very low, HA may preferentially pull water from the skin rather than from the air, thus producing the opposite effect. The optimal use of HA as a moisturizer needs further research.
But can topical HA go beyond moisturizing? Can it penetrate into the dermis and help rebuild the skin matrix? Generally, large molecules do not penetrate the skin or do so in very small amounts. Most likely, medium-to-large size HA molecules (perhaps with molecular weight above 20,000 Da) won't penetrate sufficiently to have an impact on the skin matrix. However, small size HA (5,000 - 20,000 Da) may penetrate into the dermis in significant amounts. However, this may not necessarily be a good thing. Assuming small size HA molecules penetrate into the dermis, they are likely to trigger some elements of the wound healing response (as we discussed above), such as immune activation, inflammation, cell division, blood vessel growth, new skin matrix synthesis and so forth. The net effect might be either matrix degradation and accelerated skin aging or matrix remodeling and improved skin texture. Studies are required to answer this question.
Hyaluronic acid-based fillersConsidering that medium and large hyaluronic acid molecules cannot penetrate the skin in significant amounts, one alternative is to deliver HA via injection. This approach may improve localized imperfections (e.g. wrinkles, furrows, depressed scars) but cannot revitalize the skin overall. For details, see our article on HA-based fillers.
Stimulating synthesis of hyaluronic acidOne way to increase the skin content of HA would be to stimulate its synthesis in the skin. Unfortunately, there is little data on practically useful ways to do it. One approach to explore would be to provide the body with more building blocks for hyaluronic acid, such as glucosamine and N-acetyl-glucosamine. Research is needed to determine whether oral or topical administration of the HA building blocks increases its synthesis in the skin - particularly the synthesis of medium-to-large size molecules. (This approach has been shown to work for cartilage but each tissue is different.) Another approach is to find agents that stimulate the activity of hyaluronan synthases, the enzymes producing HA. Presumably, the ideal agent should preferentially activate HAS1 and HAS2, the enzymes producing high molecular weight HA. Unfortunately, no such agent suitable for practical use appears to be available as of the time of this writing.
Inhibiting the degradation of hyaluronic acidIf stimulating HA synthesis is problematic or insufficient, an alternative could be to inhibit its degradation. Plugging the drain instead of pouring more, so to speak. One way to do it would be to inhibit the HA-degrading enzyme hyaluronidase. Unfortunately, practically useful hyaluronidase inhibitors appear as hard to come by as hyaluronan synthase activators. There are a few leads, however. One candidate is escin, a saponin extracted from horse chestnut. In a few clinical trials, it was shown to strengthen veins and improve venous insufficiency, presumably via inhibiting hyaluronidase and elastase in vein walls. It may (or may not) be able to inhibit these matrix-degrading enzymes in the skin. The other candidate, surprisingly, is a variant of a well-known skin care ingredient ascorbyl palmitate. Ascorbyl palmitate is often considered inferior (as a skincare ingredient) to other common vitamin C derivatives because it is a poor activator of collagen synthesis. A variant (isomer) of ascorbyl palmitate called L-Ascorbic Acid 6-Hexadecanoate was shown to inhibit hyaluronidase in some species, including mammals. Whether this effect can be reproduced in the human skin remains to be seen. If it is, the skin care reputation of ascorbyl palmitate may get a boost.
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