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.
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