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 collagen
Collagen 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 lysinehydroxylysine-hydroxyproline.

The types of collagen

Collagen 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 - Cartilage
Type 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 I
Type VII - Epithelia (lining of GI tract, urinary tract, etc.)
Type VIII - Lining of blood vessels
Type XII - Found alongside and interacts with types I and III

The 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 quality
Having 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 degradation
Most 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 (see our Anti-Aging Treatments section).

Elastin: A neglected essential of skin youth

When 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 elastin
Elastin 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 aging

One simple test for skin aging is to check how long it takes for the skin to snap back after being pinchpulled 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, agerelated 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.
Retinoic acid
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.)
MMP inhibitors

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.)
Topical tropoelastin
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
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.)

Vitamin C for wrinkles and skin aging

Vitamin C is one of the most widely used skin care ingredients. The variety of skin rejuvenation / antiwrinkle products with vitamin C is staggering. Do these products work? Do their claims have any
substance? The situation is a little complicated. On one hand, vitamin C does possess definite,
scientifically validated merits for wrinkle reduction and skin rejuvenation. On the other hand, many vitamin
C products do not work.
Potentially, vitamin C can benefit skin in two important ways. Firstly, vitamin C is essential for the
synthesis of collagen, a key structural protein of the skin. Adding vitamin C to a culture of skin cells
(fibroblasts) dramatically increases the synthesis of collagen. Secondly, vitamin C is an antioxidant and
can help reduce skin damage caused by free radicals. So, when vitamin C is properly delivered into skin
cells, there is a good chance to reduce wrinkles and improve skin texture.
There are, however, some complicating circumstances often disregarded by manufacturers. First, vitamin
C is relatively unstable (unless it is in a dry form). In the presence of air or other oxidizing agents, vitamin
C is easily converted to oxidized forms. The oxidized vitamin C is not only incapable of boosting collagen
synthesis or scavenging free radicals but may actually promote free radical formation causing damage to
vital molecules such as proteins and DNA. In poorly prepared or poorly stored skin care products, vitamin
C may already be oxidized by the time you apply it to your skin. Second, only highly concentrated
preparations (10% or more) deliver enough vitamin C to the cells to be topically effective.
A number of skin care companies offer highly concentrated stabilized vitamin C products, which (at least
in theory) are supposed to be consistently effective. However, these products are usually quite expensive.
Furthermore, even stabilized vitamin C products may be at least somewhat oxidized by the time you use
them. When vitamin C oxidizes, it eventually acquires a yellowish tint indicating an advanced stage of
oxidation. Interestingly, some manufacturers add coloring to their vitamin C products, in which case it
becomes hard to spot advanced vitamin C oxidation. Whatever the motives for adding color may be, we
recommend avoiding vitamin C products that aren't colorless or white. Unfortunately, the lack of a tint
does not, by itself, guarantee the lack of oxidation because the initial product of vitamin C oxidation
(dehydroascorbic acid) is colorless. Only further oxidation produces a noticeable yellowish tint. Therefore,
when selecting a vitamin C product it is important to pick a trustworthy source and be careful about the
expiration date and proper storage.
If you are willing to invest a bit of extra time, you can easily make a vitamin C gel or serum on your own.
That way you ensure both freshness and potency - not to mention substantial cost savings. (For more
information on making your own skin care, including vitamin C formulations, see our article Do-It-Yourself
Anti-Aging Skin Care.)
Even when using an optimal formulation, not everyone will respond to vitamin C treatments. About 50% of
people show noticeable benefits. The chances are improved when vitamin C is a part of a comprehensive
regimen to rebuild collagen in your skin. (See our article on collagen.) Also, people who do not respond to
conventional vitamin C products may respond to its derivatives, such as magnesium ascorbyl phosphate,
ascorbyl palmitate and others. These vitamin C cousins not only boost collagen synthesis but also are
more stable and less irritating. (See our article on vitamin C derivatives.)
Finally, keep in mind that taking large amounts of vitamin C (or its derivatives) orally is of little benefit for
reducing wrinkles because you cannot obtain high enough concentration of vitamin C in the skin to
increase collagen production.

Antioxidant nutrients and skin protection

Free radical damage is one of the principal mechanisms of aging. Free radicals are highly and
indiscriminately reactive chemicals that can damage any structure in living cells. The most common
source of free radicals is normal burning of fuel that occurs in every cell every minute of every day.
(Generally, the more free radicals a species produces, the shorter its life span.) Skin suffers additional
free radical damage from sunlight and pollutants.
Topical antioxidants provide some protection against environmental damage to the skin and may be
somewhat effective in slowing down the skin aging. However, topical antioxidants are relatively unreliable.
Their effect depends on skin permeability, other ingredients in the cream and many other factors. It
appears that increasing oral intake of some antioxidants may additionally protect skin from free radicals.
Keep in mind, however, that relatively little solid research has been done specifically on skin benefits of
oral or topical antioxidants and much of the supporting evidence is indirect.
A very important chemical property for an oxidant is its solubility in water and fat (or oil). Basically, living
organisms have two types of internal media, watery extra- and intracellular space and oily membranes
that serve as partitions enclosing individual cells and various intracellular compartments. Water-soluble
antioxidants are effective mainly in extra- and intracellular fluid, whereas fat-soluble antioxidants protect
biological membranes. Both types of antioxidants are needed to create an effective shield against free
radicals for the entire body, and skin in particular.

Water soluble
Vitamin C
Cysteine
Methionine
Selenium
Glutathione

Solubility of antioxidants
Fat soluble
Water and fat soluble
Vitamin E
Vitamin A
Carotenes
Lycopene
Coenzyme Q10

Lipoic acid
Melatonin
Some polyphenols
Some flavonoids

Below we review some of the antioxidant nutrients and supplements which appear the most likely to
produce skin benefits.

Vitamin E
Vitamin E is a principal fat soluble antioxidant vitamin in the body. It protects cellular membranes,
lipoproteins and other "oily" structures. Skin is high in unsaturated fatty acids ("oily" molecules especially
susceptible to free radical damage), and can benefit from vitamin E protection (both oral and topical).

Flavonoids
Flavonoids are a diverse group of plant pigments with antioxidant properties. These substances are
responsible for color in many fruits, vegetables and flowers. In addition to providing color that attracts
insects or animals, these pigments protect plants from environmental stress. In addition to being potent
antioxidants, some flavonoids have antiallergic, anti-carcinogenic, anti-viral and anti-inflammatory activity.
Over 4,000 flavonoids have been characterized and classified, but only a few have been researched. As
far as skin benefits are concerned, two classes of flavonoids appear to be especially beneficial:
proanthocyanins (found in grapes and pine bark) and polyphenols (found in green tea).

Coenzyme Q10, Lipoic acid, Cysteine, Methionine

Coenzyme Q10, lipoic acid, cysteine and methionine are potent antioxidants. But they also play other
roles that are at least as important as their antioxidant activity. See also the article about conditionally
essential nutrients in this section.
For practical details on adding antioxidants to your diet for optimal skin health see Skin & Nutrition
Infopack