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Hydrogels for Osteochondral
Tissue Engineering
Journal of Biomedical

(March 2020)
Anti-Wrinkle Activity
& Transdermal Delivery
of GHK Peptide
Journal of Peptide Science
(March 2020)
Pulsed Glow Discharge
to GHK-Cu Determination
International Journal
of Mass Spectrometry

(March 2020)
Protective Effects of GHK-Cu
in Pulmonary Fibrosis
Life Sciences
(January 2020)
Anti-Wrinkle Benefits
of GHK-Cu Stimulating
Skin Basement Membrane
International Journal of Molecular Sciences
(January 2020)
Structural Analysis
Molecular Dynamics of
Skin Protective
TriPeptide GHK
Journal of Molecular Structure
(January 2020)
In Vitro / In Vivo Studies
pH-sensitive GHK-Cu in
Superabsorbent Polymer
GHK Enhances
Stem Cells Osteogenesis
Acta Biomaterialia
Antibacterial GHK-Cu
Nanoparticles for
Wound Healing
Particle & Particle (2019)
Effect of GHK-Cu
on Stem Cells and
Relevant Genes
OBM Geriatrics
GHK Alleviates
Neuronal Apoptosis Due
to Brain Hemorrhage
Frontiers in Neuroscience
Endogenous Antioxidant
International Journal of Pathophysiology and Pharmacology (2018)
Regenerative and
Protective Actions of
GHK-Cu Peptide
International Journal of
Molecular Sciences
Skin Regenerative and
Anti-Cancer Actions
of Copper Peptides
GHK-Cu Accelerates
Scald Wound Healing
Promoting Angiogenesis
Wound Repair and

GHK Peptide Inhibits
Pulmonary Fibrosis
by Suppressing TGF-β1
Frontiers in Pharmacology
Skin Cancer Therapy
with Copper Peptides
The Effect of Human
Peptide GHK Relevant to
Nervous System Function
and Cognitive Decline
Brain Sciences (2017)
Effects of Tripeptide
GHK in Pain-Induced
Aggressive Behavior
Bulletin of Experimental
Biology & Medicine
GHK-Cu Elicits
In Vitro Alterations
in Extracellular Matrix
Am Journal of Respiratory
and Critical Care Medicine

Selected Biomarkers &
Copper Compounds
Scientific Reports

GHK-Cu on Collagen,
Elastin, and Facial Wrinkles
Journal of Aging Science
Tri-Peptide GHK-Cu
and Acute Lung Injury

Effect of GHK Peptide
on Pain Sensitivity
Experimental Pharmacology

New Data of the
Cosmeceutical and
TriPeptide GHK
SOFW Journal
GHK Peptide as a
Natural Modulator of
Multiple Cellular Pathways
in Skin Regeneration
BioMed Research (2015)
Resetting Skin Genome
Back to Health
Naturally with GHK
Textbook of Aging Skin
GHK-Cu May Prevent
Oxidative Stress in Skin
by Regulating Copper and
Modifying Expression of
Numerous Antioxidant Genes Cosmetics (2015)
GHK Increases
TGF-β1 in
Human Fibroblasts

Acta Poloniae

The Human Skin Remodeling Peptide Induces Anti-Cancer
Expression and DNA Repair Analytical Oncology
Resetting the
Human Genome to Health
BioMed Research
Enhanced Tropic Factor Secretion of Mesenchymal
Stem Cells with GHK
Acta Biomater
Anxiolytic (Anti-Anxiety)
Effects of GHK Peptide
Bulletin of Experimental
Biology & Medicine
Lung Destruction and
its Reversal by GHK
Genome Medicine
TriPeptide GHK Induces
Programmed Cell Death
of Neuroblastoma
Journal of Biotechnology
Stem Cell
Recovering Effect
of GHK in Skin
Peptide Science
Skin Penetration of
Copper Tripeptide in Vitro
Journal of International
Inflammation Research
Possible Therapeutics
for Colorectal Cancer
Journal of Clinical and
Experimental Metastasis
Methods of Controlling
Differentiation and
Proliferation of Stem Cells
Effects of
Copper Tripeptide
on Irradiated Fibroblasts
American Medical Association
Avoid Buying Fake Copper Peptides Dangerous

Why Do Children Have Such Beautiful Skin?

Children have the most beautiful skin. Soft, firm, elastic, and blemish-free. When children's skin is damaged, scars are usually removed with a week or two.

The reason children's skin remains so healthy is a process call "skin remodeling". It is the same process that that removes scars and damaged skin during wound repair. Damaged skin is removed and slowly replaced with normal, blemish free skin. In young children this process functions efficiently and skin damage is rapidly removed. But in adults this process slows drastically and various skin lesions may persist for years or decades.

Skin remodeling causes changes such as smoothing the skin, reducing wrinkles, the repair of sun damage, the removal of skin blemishes and imperfections, all of which give the skin a more youthful appearance.




Why Our Skin Seems to Get Older and Have More Problems as We Pass Age 45

For many years when I started my research on human aging, I collected blood samples from people between age 18 and 80. I measured changes in many factors important in blood clotting, since unexpected blood clots become much more common as we get older. I also used the blood samples to measure how well the blood supported the metabolism and survival of cells in culture. Younger blood usually worked better than blood from older individuals but this difference became more noticeable after age 45. Ultimately, this work led to the discovery of skin remodeling copper peptides. Much of the skin's loss of renewal with time appears to be due to a lower level on the copper-peptide GHK-copper in the blood.

So what we need is much more help after age 45.

As we get older, our skin becomes thinner and accumulates various blemishes, lesions and imperfections. The structural proteins are progressively damaged causing collagen and elastin to lose their resiliency. The skin’s water-holding proteins and sugars diminish, the dermis and epidermis thin, the capillary network becomes disorganized, and the subcutaneous fat cells diminish in number. These effects are further intensified by decades of exposure to ultraviolet rays, irritants, allergens, and various environmental toxins. The result is a dry, wrinkled, inelastic skin populated by unsightly lesions.

The good news is that, even though the levels of skin remodeling copper peptides decrease in the body, we can apply certain types of copper-peptides to the surface of the skin and help the skin become more like a biologically younger skin. GHK-copper was the first such copper peptide that I found and works fairly well. But in my opinion, the newer types of copper peptides that I have been developing at Skin Biology should, in time, prove to be a more effective system for helping skin act younger.

Remodeling copper peptides are the only signal that fills all the requirements for skin remodeling.


Requirements for Skin Remodeling Signals

1. Must stop inflammatory actions in the skin
Increase the activity of the copper-protein antioxidant systems such as superoxide dismutase and ceruloplasmin.
Copper-proteins are the primary antioxidants in the human body.
Suppress scar forming actions of TGF-beta.
Block skin damaging action of Interleukin 1
2. Activate removal of damaged skin
Increase activity of metalloproteinases that remove damaged cells and proteins.
3. Increase production of skin proteins
Increase synthesis of collagen, elastin, proteoglycans
4. Rebuild the skin's microcirculation
Increase new capillary formation (angiogenesis)
5. Increase production of new skin cells
Increase the size of vellus-producing hair follicles. These produce new skin cells.


Remodeling - Skin Removal and Replacement

Restoration to a biologically younger skin morphology requires two linked processes: (1) the removal of damaged proteins and aberrant skin lesions, and (2) their replacement with normal, blemish free skin. This process is similar to the remodeling phase of wound healing in which scar tissue is removed over several years to slowly restore the skin to its original state.

Various skin renewal methods have been developed that produce a limited type of skin restoration but all have drawbacks. Retinoic acid slowly remodels skin but at the price of chronic irritation and redness.

Chemicals such as vitamin C and melatonin increase skin collagen but skin also needs rebuilding of elastin, water-holding proteoglycans, and the blood microcirculation. Peptides (amino peptides, etc.) that are similar in action to TGF-beta 1 and fibronectin binding peptides, are the newest gimmick in the cosmetic industry. But such peptides were tested extensively for uses in wound healing but produced unacceptable skin thickening, hardening, and scarring. It is not enough to push more protein into the skin; the damaged skin components must be removed.

Controlled skin damage (i.e., lasers, peels, dermabrasion) works well only if there is a vigorous post therapy regenerative response by the damaged skin.

The good news today is that certain types of copper peptides possess all the necessary biochemical actions that can, in a morphological sense, restore skin to a younger state without causing skin irritation. Such types of copper peptides are increasingly used in cosmetic skin care products such as Neutrogena Active Copper line and Skin Biology's second generation copper peptides. These copper peptides also are used to improve post-treatment skin recovery after dermatological skin renewal procedures, such as chemical peels, laser resurfacing, and dermabrasion. Unlike many other purported skin improvement therapies where the "science" of the products is just not credible, the skin remodeling actions of such types of copper peptides are documented by numerous well-controlled, published studies from leading laboratories and universities.


The Key to Youthful Skin is Skin Remodeling

Vigorous skin renewal and skin remodeling is the key to maintaining a youthful skin. Children have wonderful skin with a high natural self regeneration and a beautiful color and texture. When a child's skin is damaged, the wounds heal rapidly and scars and skin lesions are quickly removed.

Reducing damage to your skin is not an adequate approach. You can hide from sunlight until you evolve into a mole but this will not keep your skin young and vibrant. Yes, avoiding UV light will reduce some types of skin damage as you age, but you will still end up with a pasty, grayish, lifeless, pale skin. Avoiding skin damage from ultraviolet light, allergens, detergents, damaging soaps, irritants, acne scars, airborne pollutants, chemical sunscreens and so forth but is only one part of a wider story.

As we age, a number of skin changes occur which require different types of skin care and treatments. These are four basic changes as we age.

Change 1. The rate of skin cell replacement is reduced, producing a thinner, more fragile skin. Skin is replaced every three weeks at age 20 but this increases to every nine weeks by age 50.

Change 2. Damaged protein accumulates in the skin. This damage can be the results of scars, sun damage, oxidative damage, and the cross-linking of skin proteins by sugars.

Change 3. After age 25, skin oil production starts to drop. This reduces acne but produces a dryer skin. This drop in oil production becomes more serious after age 45.

Change 4. The biosynthesis and breakdown of collagen, elastin, and the water-holding proteoglycans and GAGs exists in a dynamic balance in young healthy skin. However after age 25, the skin's production of collagen, elastin, the water-holding molecules is reduced while the breakdown of these factors is increased. This begins wrinkle formation and loss of elasticity. The problem become progressively more serious with passing years.

To understand skin renewal and remodeling, it is necessary to understand skin repair. The sequence of events producing skin renewal is very similar to the mechanisms involved in wound healing. The human body uses the same biochemical systems in many different ways.

1. Initially after skin damage or wounding, the body's damage control mechanisms serve to stop blood loss (if any), then to quickly cover the damaged skin with a layer of tough and protective scar tissue. A type of immune cell, called the neutrophil, quickly arrives in the damaged area. The neutrophils sterilize the damaged area by releasing very toxic oxygen radicals to kill bacteria. This neutrophil action is usually very brief and usually stops within a day. However, occasionally the damage is of a type that continues these neutrophil actions and the skin becomes chronically inflamed.

Also, a scar forming hormone called TGF-beta (transforming growth factor beta) is produced to stimulate scar production. Large amounts of scar-forming collagen are secreted into the damaged area. Many cosmetic companies have recently began selling skin creams with peptides said to have actions similar to TGF-beta. Such peptides were extensively tested for wound healing about 10 years ago but produced excessive skin hardening and scarring. See Are Very Expensive Skin Creams Worth the Price?

2. The tissue damage also causes the release of enzymes which, in turn, break down skin proteins into smaller fragments. Copper ions begin to accumulate within a few days and are complexed with peptides in the damaged area. If copper is deficient, then healing will be inadequate. No other metal ions are concentrated. The copper-peptides serve as chemical signals to the immune system that the skin is injured and needs repair.

3. The copper peptides then initiate the phase of healing called skin remodeling. In this phase, the scar tissue is removed and replaced with normal skin tissue.

4. As copper peptides accumulate, they act directly to protect the tissues by (1) stopping the production of, and sterilizing effects of, oxygen radicals and (2) suppressing scar formation by inhibiting the production of TGF-beta.

5. The copper peptides also attract a type of immune cell called a macrophage which arrives after the neutrophils have sterilized the tissue. The macrophage begins to ingest the skin debris produced by the damage and also secrete about 20 different growth factors needed for proper skin repair. These have names such as epidermal growth factor, fibroblast growth factor, platelet-derived growth factor and so on. Regranex Gel sold by McNeil Pharmaceutical and used for wound healing contains a macrophage-released growth factor, called platelet-derived growth factor. The macrophage action also helps remove chronically-damaged, abnormal skin such as spots and lesions from sun damage.

6. The copper peptides also stimulate the production of the scar removal systems by changing the synthesis of metalloproteinases (a family of at least 14 proteins that remove damaged proteins such as damaged collagen and elastin) and antiproteases. At the same time, the copper peptides stimulate the production of new proteins such as collagen and elastin to give the skin strength and elasticity, and other proteins and molecules such as proteoglycans and glycosaminoglycans (GAGs) that bind large amounts of water to moisturize the skin. The only true skin moisturization is via these water-holding molecules. The copper peptides also stimulate angiogenesis (new capillary formation) to reestablish new blood vessels to nourish and oxygenate the newly repaired skin.

7. Skin remodeling continues for a long period. The wounded area slowly improves as scar tissue is removed or reduced. Incomplete healing causes heavy scarring but complete healing produces minimal scarring. The old damaged protein is removed and replaced with new collagen and elastin fibers. This removes scar tissue and restores skin elasticity. This mechanism can also be used to reduce wrinkles.

8. Skin renewal and hair follicles are closely linked. New skin is now thought to arise from the hair follicles. All skin remodeling chemicals or genes that activate skin remodeling also increase hair follicle size. But although skin remodeling improves hair follicle health, it does not create new follicles or grow hair in hairless areas.

Skin Remodeling Starts with Hair Follicles

Skin remodeling starts with the hair follicles. The body's signal for remodeling first activates the systems that break down damaged proteins and remove damaged skin lesion. Various proteins (proteolytic enzymes) start breaking down scars and damaged tissue . Then the signals enlarge the hair follicles in the skin area to be rebuilt. New skin cells arise from the hair follicle and migrate into the surrounding skin area.

This effect was first noted about 50 years ago during World War II. It was observed, in patients with severe burns and burn scars, that if hair follicles were observed to be developing at the edge of the burned skin, then there was an excellent prognosis that the burn scar would be replaced by healthy normal skin. If the follicles were absent or very small, then healing was likely to be inadequate and the burn scars would remain.

Later, in 1985, I found that copper peptides not only stimulated healing of wounds but also increased the size of the hair follicles near the wounds. The copper peptides were not hair growth stimulators, per se, but did increase the hair follicle size and vitality.

In recent years, it has been established that genetic modifications in mice that stimulate skin remodeling also increase hair follicle size (Fuchs 1998). Genes such as sonic hedgehog (Sato et al 2001, Nanba et al 2003, Oro et al 2003. Mill eta al 2003), catinin (Huelsken 2001, Van Mater et al 2003), Wnt (Stenn 2001) and Noggin (Botchkarev 2001) all enhance hair follicles then produce remodeling.


Example of Reversing Skin Aging by Skin Remodeling

The application of copper-peptide complexes to the skin's surface creates an environment that helps the skin tighten its barrier and increase its collagen and elastin density. The photo on the left (SEE BELOW) is an ultrasound scan of the skin of a woman (aged 59) before treatment with a cream containing peptide-copper complexes. On the right is the same skin after one month of treatment with the complexes. The white-yellow colored areas are the ultrasonic reflections from skin that is more dense because of closer cellular binding and increased amounts of collagen and elastin. This effect is opposite to the usual thinning and loosening of skin during aging.

Ultrasound scan of the skin of a women aged 59 before and after treatment with copper peptides.

This skin regeneration can be enhanced by also using (1) exfoliating agents such as alpha hydroxy acids, beta-hydroxy acids, and retinoic acid or by (2) methods that mildly damage skin such as laser re-surfacing or chemical peels. This is followed by a natural rebuilding of the skin that removes imperfections, rebuilds collagen and elastin fibers that tighten skin, and increases the amount of glycosamoinoglycans, the moisture-holding proteins that give skin its firmness.


How Skin Remodeling Copper Peptides Reverse Aging Effects

At age 20, your skin is thick, collagen and elastin strands are free and elastic (green), there is a rich blood supply through the skin (red and blue), and thick layer of subcutaneous fat cells (round balls).

By age 50, your skin thins and accumulates numerous small lesions, collagen and elastin fibers are broken and cross-linked, the skin's blood supply is diminished, and the layer of fat cells narrows. This produces wrinkles, sagging, and a less protective skin.

Skin remodeling copper peptides help reverse many effects of aging. They help remove minor skin lesions, re-thicken your skin, collagen and elastin are rebuilt, the skin's blood supply is improved, and subcutaneous fat is increased. This produces a skin biology more like young skin again.

Metalloproteinase Activation to Remove Damaged Protein and Skin Lesions

Skin remodeling is the process that removes damaged proteins from the skin so that they can be replaced with new healthy protein. Proteins accumulate damage from many causes - sun damage, cross-linking by sugars, free radical injuries and so on. The metalloproteinases, a family of at least 14 proteins, act in the skin to remove damaged proteins such as damaged collagen and elastin.

Remodeling copper-peptide complexes are potent activators of metalloproteinases (Alain et al 1999). The old damaged protein is removed and replaced with new collagen and elastin fibers. This removes scar tissue and restores skin elasticity and reduces wrinkles. The activation of such proteins may explain the potent scar reduction properties of strong copper peptide creams. (For more information, see

There is much confusion on the role of metalloproteinases on skin health. Some dermatologists are of the opinion that their effect is totally negative, but in reality metalloproteinases are part of the system that removes old and damaged proteins from the skin. The critical factor is the balance of protein production to metalloproteinase activation.

Questions or Advice?

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