Successful stimulation of fibroblast to produce more collagen and GAGs endogenously will in effect rejuvenate aging skin. Wrinkles will disappear and skin thickness will increase. There is currently much research in this area of skin care.
Currently, two approaches have been clinically proven to be successful:
A. Stimulate the central hormonal system to increase Growth Hormone secretion. Growth hormone is the master hormone that will in turn promote fibroblasts to produce more collagen throughout the body.
B. Stimulate selected parts of the body, such as the face or neck, to produce more collagen through exposing the area topically to certain nutrients called Secretagogues.
Let us take at look at these two approaches more closely.
Human growth hormone (hGH) is a small protein molecule, which contains 191 amino acids in a single polypeptide chain. It is the most common hormone secreted by the anterior pituitary gland. For some reason unknown, the amount of growth hormone secreted starts to slow after peaking in the late teens. The measurable level of hGH in our body decreases 14 percent every ten years into old age after peaking. This reduced level of secretion occurs over a period of time, with concurrent signs of aging appearing. Daily secretion from the pituitary gland diminishes with age to the extent that a 60-year-old man secretes only 25 percent of the hGH secreted by a 20 year old adult.
A landmark study conducted by the late Dr. Rudman and published in the prestigious New England Journal of Medicine showed that the effects of six months of human growth hormone injection on lean body mass, skin thickness, and adipose-tissue mass were equivalent to 10 to 20 years of reversed aging. Specifically, skin thickness, as measured from 4 different sites, increased by 7.1% during this period on subjects in the study.
Since that study, many people have undergone growth hormone injections as a way to regain their youthfulness. Thicker skin is just one of many benefits. Growth hormone injections were approved by the FDA in the mid 1990s for treatment of adult growth hormone deficiency syndrome. Growth hormone is a drug requiring close supervision by a qualified physician. As with most drugs, side effects can and do occur with growth hormone injections, including fluid retention and carpal tunnel syndrome.
Many have tried to apply this hormone topically. Human growth hormone, like collagen, is too large a molecule to be absorbed by direct application onto the skin. It is therefore not suitable for dermatological use.
A secretagogue (pronounced se-cre'-ta-gog) is a natural amino acid chain (called a peptide) that acts to promote the production and or release of the target chemical in question, whether it be a hormone or an enzyme. The goal for a growth hormone secretagogue, for example, is to encourage the pituitary gland to release growth hormone. While hGH causes the body to act as if the pituitary has released growth hormone, a secretagogue actually causes the release of it. The ultimate result is similar. However, secretagogues are generally less potent and sold over the counter as nutritional supplements rather than as a drug. As far as hGH is concerned, numerous nutrients can acts as secretagogues, including amino acids such as glutamine, lysine, and arginine. Specialized short chain peptides also act as secretagogues to enhance growth hormone release from the pituitary gland. Oral intake of such secretagogues will lead to enhanced growth hormone levels, which in turn will lead to more collagen synthesis. With secretagogues, injection of human growth hormone can therefore be avoided.
Secretagogues typically come in the oral or topical forms, depending on the end result desired. Oral secretagogues are designed to stimulate hGH release centrally, while Topical Secretatogues (TS) are designed to stimulate collagen synthesis locally.
A topical secretagogue (TS), when applied to the skin, acts locally to stimulate the growth of collagen and GAGs. Such topical secretagogues (TS) include fibroblast growth factors (FGFs), transforming growth factors (TGFs), and insulin growth factors (IGF).
Most TS normally consist a fragment chain of active amino acids called a peptide chain. Not all the amino acids in a long chain hormone such as hGH or Collagen is active. Normally, only part of the overall chain is responsible for the majority of its overall action. The key is to identify the active portion of the peptide chain. Because of its small size, such peptides can be topically applied and absorbed into the skin with relative ease.
Successful isolation of such peptide fragments has been carried out both in the research and clinical setting. They are produced by targeted cleaving of "precursor proteins," such as those of collagen, fibronectin, and elastin. They also have an important feedback role on their own neo-synthesis system and thus contribute to tissue replacement. Such peptides are selective natural messengers than can be applied to the skin and causes an immediate recognition by the cell to produce collagen.
Several such short chain peptide secretagogues have been extensively researched. One of the most effective is a short peptide chain consisting of 5 key amino acids: Lysyl, Threonyl, Threonly, Lysyl, and Serine. This penta-peptide is derived from a fragment of the C-terminal portion of collagen I. It has been studied in detail by Katayama et al.
Laboratory Research studies of this peptide have shown that the synthesis of collagen I, collagen III, and fibronectin are enhanced when this peptide is added to cultured human fibroblast tissue. Peptide chains from other locations within the collagen molecule do not yield similar effects. This peptide also has a more marked impact on low-density cultures of fibroblasts, similar to that of aging skin, than on higher density, confluent culture like that of younger skin.
Laboratory in vitro studies of this peptide showed that it is highly specific for interaction with fibroblasts and causes the increased stimulation of collagen synthesis by up to 320% as compared to the control group. It was also shown that at various concentrations, this peptide produces highly significant induction of the neo-synthesis of soluble collagen IV (important in the dermal-epidermal interface) by a factor of 2 to 4. At 2% concentration, GAG production was increased by 267% as well.
Ex Vivo studies using skin biopsy samples showed that this peptide produced major stimulation of the synthesis of collagen, with a maximum response of 117% at the 4% concentration. This was higher than with Vitamin C or other topical secretagogues such TGFb.
In a clinical double blind study, a panel of 35 female volunteers between the ages of 34 and 72 (mean age: 58 years) was given a cream containing 3% of this peptide for 6 months. They were instructed to apply the cream two times a day. No other anti-wrinkle, restorative, restructuring, or regenerating cosmetic products were used. The volunteers had no history of allergy or skin disorders.
After 6 months of treatment, imprints of the relief of the skin were obtained and the skin irregularities were analyzed by Image analysis. It was shown that a highly significant reduction in the deep and moderate wrinkles was obtained with those treated with this peptide as compared to the control group. The reduction in deep wrinkles increased with time. Specifically, surface area occupied by deep wrinkles was reduced by a mean of 68% over 6 months. Deep wrinkles are defined with a maximum depth of more than 200 mm. The surface are occupied by moderate wrinkles (defined as those of 150 to 200 mm in depth) was reduced by a mean of 51% over the same period.
Subjects also showed significant improvements in the density of the furrows. Furrows are the deepest wrinkles. Vectorization by image analysis was used to assign a length to these furrows and calculate the sum per unit area, with 28% reduction after 2 months, 31% reduction after 4 months, and 47% reduction after 6 months.
Roughness of the skin is also measured by image analysis. This provides a global approach to the concept of the smoothness of the surface by assigning to it a mean amplitude, which is the resultant of all the furrows and peaks. The results of the study showed a 10% reduction after 2 months and 16% after 6 months.
Self evaluation by the volunteers were conducted after 2, 4, and 6 months with the following results at the end of 6 months:
83% reported reduced wrinkles and lines (versus 45% for placebo)
92% increase in moisturizing effect (compared to 76% for placebo)
80% increase in smoothing effect (compared to 68% for placebo)
76% increase in skin suppleness (compared to 60% for placebo)
In summary, laboratory in vitro and ex vivo studies showed the use of the peptide showed 117% increase (compared to 42% increase for vitamin C) in synthesis of Collagen I and 327% increase for collagen IV (compare to 229% increase for vitamin C). Production of GAGs increased by 267%. The main support structures of the dermis and epidermis are therefore stimulated in a physiological manner.
Furthermore, an in vivo 6 month double blind clinical study showed:
68% reduction of deep wrinkle surface area
47% reduction of main furrows
51% reduction of moderate wrinkles
22% reduction of main wrinkle
The application of the proper topical peptide secretagogue has therefore shown to be effective in enhancing collagen and GAG production. Increased collagen and GAG production leads to thicker skin and diminishing wrinkles and fine lines. A good topical secretagogue should be considered a cornerstone of an overall anti-aging skin management system.
The mission of any successful anti-aging skin regimen must address, in addition to increased collagen synthesis, ways to limit the amount of oxidative damage caused by environmental pollutions and the sun's ultraviolet rays on our skin.
The following are key ingredients with antioxidant properties that should be topically applied in conjunction with a good water-based moisturizer to nourish the skin from the outside in and to prevent oxidative damage.
Used by the great Egyptian and Mayan civilizations, the extract of lupin, called lupaline, has been scientifically proven to be 10,000 more potent than the single use of Vitamin E, 5000 times more effective than Vitamin C, and 2 times more effective than Vitamin B. Lupaline helps to combat the signs of aging and reduces the damaging effects of free radical breakdown and environmental pollutions. This product is naturally derived from the synergetic combination of Lupin oil and the active fraction of wheat germ oil obtained by molecular distillation.
In a normal cell, tiny organelles called mitochondria turn food molecules into energy. In the process, a free radical oxygen called superoxide is produced, which causes what is called oxidative stress damage. Superoxide dismutase (SOD) is an enzyme that revitalizes cells and reduces the rate of cell destruction. It neutralizes this most common, and possibly the most dangerous, free radical - superoxide. It converts the reactive oxygen species by converting superoxide radical into hydrogen peroxide, which is then changed into molecular oxygen and water.
SOD levels tend to decline with age, while free radical production increases. Its potential as an anti-aging treatment has been well documented. Compounds that mimic SOD have been shown to extend the lifespan of experimental worms by nearly 50 percent, according to researcher Simon Melov of the Buck Institute for Age Research in Novato, California.
Biologist William Orr of Southern Methodist University reported in 1997 that genetic engineering of fruit flies live longer. Flies that normally live about 45 days lived about 75 days when their cells produced more of the same two natural enzymes, called superoxide dismutase and catalase.
This is a traditional herbal oil that has been used for centuries for skin burns, cheoloids, and scars. It is extracted from the seeds that form in the hips of the wild rose of Chile - Rosa Affinis Rubiginosa, or commonly known in Chile as Rosa Mosqueta. It smoothes wrinkles by hydrating the skin and slows new signs of aging. Rose hip oil is extremely high in essential fatty acids such as Linoleic acid (45%), Linolenic acid (32%), Oleic acid (15%), and Palmitic acid. Fatty acids are essential building blocks of cellular membranes to allow efficient transportation of nutrients from the extracellular space into the intracellular environment where metabolism takes place. Besides non-saturated fatty acids, the presence of carotenoids, flavonoids, vitamin C, and, trans-retinoic acid has also been detected and these could be responsible for some of the pharmacological and therapeutic properties of Rosehip Seed Oil.
Extensive studies have shown rosehip seed oil to have a positive effect on scars, stretch marks, sunburn, and aging skin. Because of its high fatty acid content, Rosehip seed oil penetrates the skins upper layers very quickly, making it a good moisturizer.
Squalane is an excellent moisturizer and lubricant. It is highly compatible with skin lipids because human sebum is comprised of 25% squalane. Squalene is obtained by hydrogenation of natural oils. However, most people do not synthesize enough of this vital oil, which can lead to rough, dry aging skin.
Since squalane is a natural component of the human sebum, it acts as a mild liquid vehicle able to impart suppleness and smoothness to the skin without any unpleasant greasy feel. It readily forms emulsions with the human sebum.
Squalane assists in preventing water loss from the skin's surface. This in turn causes hydration of the skin and increases the percutaneous absorption of incorporated active substances. It helps to restore suppleness and smoothness to skin dried by frequent use of detergents or by sunburn.
Retinoic acid precursors and derivatives have been used effectively since the 1980s to stimulate the increased turnover of aging keratinocytes. Retenoids repair the skin's connective tissue as well as reduce pigmentation, increase blood supply, and normalize skin turnover.
The FDA approved topical retinoc acid in 1995 for improving the appearance of photo-aged skin. Retinol reduces fine facial wrinkles, hyper-pigmentation (age spots), and surface roughness associated with chronic sun exposure. The drug sloughs off dead skin, regenerates collagen, and allows cells in the top layer of the skin, which are always being replaced, to mature more normally than untreated sun-damaged cells.
There is evidence that retinol actually prevents sun damage. Researchers have found that even brief exposure to sunlight increases the activity of enzymes that break down the proteins collagen and elastin that provide structural support for the skin. Creams containing trans-retinoic-acid reduce the activation of these enzymes.
Side effects of retinoic acid for topical application include temporary peeling, redness, and blistering, and a permanent increase in sun sensitivity. Since retinol is only minimally absorbed, there is no systemic toxicity. The use of high dose retinol is contraindicated in patients receiving photosensitizing drugs such as thiazides, tetracyclines, fluoroquinolones, phenothiazines, and sulfonamides.
The use of retinoic acid is a mainstay of treatment and is the ingredient of choice in many beauty creams, and for good reasons. The dosage should be monitored closely to avoid over-treatment and side effects.
This is an amino acid that stimulates the contraction of collagen fiber. It also supplies the nutrients to protect the remaining elastin and fibroblasts against free radical attacks.
Ginkgo biloba has a long, colorful history. It is the oldest tree on Earth, with fossils showing it to be more than 200 million years old. In fact, it is that last survivor of an ancient family of trees.
Research into ginkgo's effects on humans shows that it speeds up the flow of blood and oxygen through the body and brain. It increases the manufacture of adenosine triphosphate (ATP), which is sometimes described as the "universal energy molecule." Additionally, ginkgo keeps the brain arteries from clogging up with blood platelets by keeping the arteries flexible so that the platelets don't collect together on the artery walls. It helps the nerve cells transmit signals from one to another. Ginkgo is a vasodilator, which means it dilates the blood vessels, especially tiny capillaries. This increased circulation helps protect the nerves from the damage that can result from a reduced supply of blood and oxygen, as often occurs with age. Promotion of circulation to the skin enhances nutrients delivered to the cells.
Used for thousands of years in Asia as a longevity tonic, ginseng's dermatological properties include its use as remedy for boils, bruises, sores, and swelling. Ginseng is a root. The active components are called ginsenosides and are reported to be responsible for the revitalization and reactivation of epidermal cells. Important constituents include saponins, mucin, and Vitamin B.
Vitamin C is a water soluble vitamin that is a potent anti-oxidant. Vitamin C serum - a form of vitamin that can be absorbed by skin cells - is an important ingredient. Topical Vitamin C is capable of controlling inflammatory responses associated with UV exposure, which is seen as the cause of damage that eventually leads to wrinkling and skin cancer. It also acts as an antioxidant and promotes collagen synthesis.
A natural form of Vitamin E, tocopherol acts as an antioxidant to reduce free radical damage released from pollution, stress, and modern day diet. It is very effective in combating the lipid peroxidation effect of sun damage and environmental pollution. Vitamin E, together with green tea and chamomile, are also popular soothing ingredients used to assuage the effects of acid-induced exfoliation.
See below for a more detailed description.
In addition to topically applied anti-oxidants listed above, oral intake of the optimum level of antioxidants will fortify the skin cells internally.
The skin is constantly fighting a battle between pro-oxidants, such as free radicals, and antioxidants, which the body makes. Unfortunately, the amount of antioxidants your body produces to fight these pro-oxidants is generally insufficient. A diet rich in antioxidants will help. However, fortifying the body with oral supplementation will further reduce the aging effects of oxidants commonly found in our environment, which include the sun's rays, pollution, poor diet, and stress.
500 - 3,000 mg of Vitamin C
300 - 800 IU of Vitamin E
5,000 - 15,000 IU of Beta Carotene (which is converted to Vitamin A in the body)
100 - 200 mcg of Selenium
500 - 1,000 mg of Magnesium
500 mg of Calcium
100 - 200 mcg of Chromium
The skin is one of the key ways our body eliminates waste (the lungs and kidneys are the other ways) after being processed by the liver. Excessive toxins will accumulate in our body, some of which are deposited on the skin in the form of pigments, fats, and other pathologies.
In addition to the topical application and oral intake of optimum amount of antioxidants mentioned above, it is important to rid the body of toxins built up through the years. You will notice that people whose body is detoxified generally have healthier and younger looking skin. This is no accident.
Detoxification is therefore a key element in restoring youthful skin. Some natural herbs and nutritional factors specific for detoxification include:
A. Silymarin. A special extract of milk thistle (Silybum marianum) is known as silymarin. These compounds protect the liver from damage and enhance the detoxification process.
Silymarin prevents damage to the liver by acting as an antioxidant. It is much more effective than Vitamin E and Vitamin C. Numerous research studies have demonstrated its protective effect on the liver. Experimental liver damage in animals is produced by extremely toxic chemicals such as carbon tetrachloride, amanita toxin, galactosamine, and praseodymium nitrate. Silymarin has been shown to protect the liver against these toxins.
B. Herbal Teas. Accumulation of unwanted food particles in our digestive system is a major source of toxins. Promotion of colon cleansing through loosening the bowl movement on a regular basis is an important component of any detoxification program. This can be accomplished through the use of teas, powders, extracts, or enemas. Herbal teas can be made and consumed readily throughout the day, as they are mild and gentle. As there are different styles in preparing teas, experimentation may be done until finding a suitable tea. Cleansing powders are usually encapsulated to ensure easier swallowing. They are best taken with meals and digestive enzymes. On the other hand, herbal extracts may be used when certain herbs are needed. However, herbal extracts with alcohol content should be avoided.
C. Digestive Enzymes. Intestinal motility decreases with age. Healthy digestion is a prerequisite to healthy skin for the simple reason that undigested food can be turned into toxins, which eventually will find its way in part into the skin. Taking the proper amount of digestive enzymes to promote faster than normal digestion and reduced transit time in the gastro-intestinal tract will prevent stasis of toxins.
