COPPER PEPTIDES IN SKIN-AGEING
Authors : Dr. Pallavi Ailawadi .
Skin ageing is a part of a natural human “aging mosaic” which becomes evident and follows different trajectories in different organs, tissues and cells with time. While the aging signs of internal organs are masked from the ambient “eyes,” the skin provides first obvious marks of the passing time. Aged skin appears as thin and atrophic, finely wrinkled and dry and might show signs of photodamage such as thickened epidermis, mottled discoloration, deep wrinkles, laxity, dullness and roughness.
Skin ageing is a complex biological process influenced by combination of multiple endogenous and exogenousfactors which together lead to cumulative structural and physiological alterations and progressive changes in the skin.
The ageing of skin is due to slowing of the epidermal turnover rate and cell cycle lengths leading to aslower wound healing, along with alteration in distribution and content of collagen (collagen 1) due to increased collagen degradation by various matrix metalloproteinases, serine, and other proteases. Glycosaminoglycans (GAGs), which are among the primary dermal skin matrix constituents may be associated with abnormal elastotic material and thus be unable to function effectively.
The biosynthesis and breakdown of collagen, elastin, and GAGs exists in a dynamic balance in young healthy skin. However in the ageing skin, their productionis reduced while the rate of breakdown is increased, which leads to wrinkle formation and loss of elasticity.
Ageing, a basic biological process is not preventable. Various medical and surgical modalities have been invented for the anti-ageing armamentarium, of which peptides are the newest ammunition.
Peptides are short chains of amino acids and these are known to have multiple biological functions. Their role in skin and hair care has been known for decades but these have become the new buzzword in cosmeceuticals over the last 5 years. Amongst the various peptides available, copper peptides have become an integral component of the anti-ageing formulations
Copper peptide GHK-Cu is a naturally occurring complex of copper (Cu) with three amino acids forming the Cu-glycyl-L-histidyl-L-lysine (Cu-GHK) tripeptide, which is the physiologically most active Cu peptide. In the human body, these are found in trace amounts in blood plasma, saliva and urine. The plasma level of these Cu complexes decrease with age, from about 200 µg/ml at age 20 to 80 µg/ml at the age of 60.
These have various functions in the body including promotionof wound healing, antioxidant and anti-inflammatory effects, stimulationof collagen and GAG synthesis in skin fibroblasts and angiogenesis. Recent studies revealed its ability to modulate expression of a large number of human genes, generally reversing gene expression to a healthier state1.
GHK peptide has anti-inflammatory properties. Even though an exact mechanism remains unclear, in a recent study GHK and its copper complexes decreased TNF-alpha-dependent IL-6 secretion in normal human dermal fibroblasts.Because of the anti-inflammatory properties, Cu peptides could replace corticosteroids or non-steroidal anti-inflammatory drugs in treatment of inflammatory skin conditions and reduction of UV induced erythema. 2
It has also been seen that GHK-Cu stimulates proliferation of keratinocytesand increases expression of integrins and p63 protein in the epidermal stem cells. Since p63 is considered to be an important marker of stem cell and anti-senescence protein, the authors concluded that GHK-copper is able to recover epidermal stem cells and increase their ability to repair tissue.3
Cu peptides have also been found to promote the production of GAGs like hyaluronic acid4 as well as neutralize free radicals.
All the above mentioned functions of Cu-GHK makes many signs of aging less noticeable and slows down the aging process. They can help prevent expression lines and wrinkles from developing prematurely.
Several controlled facial studies confirmed anti-aging, firming and anti-wrinkle activity of GHK-Cu.Abdulghani et al. established that facial cream containing GHK-Cu increased collagen in photoaged skin of 20 female volunteers, performing better than vitamin C and retinoic acid.5
Leyden et al. conducted a 12-week facial study of GHK-Cu containing face and eye cream, reporting significant improvement of skin laxity, clarity and appearance, reduced fine lines and the depths of wrinkles and increased skin density and thickness comparing to placebo. GHK-Cu eye cream performed better than vitamin K cream.6
Apart from the anti-ageing benefits, clinical studies have found that Cu-peptides also remove damaged collagen and elastin from the skin and scar tissue and thus help in better scar remodeling.
Furthermore,it has shown that Cu peptides and red LED light make a powerful combination. Red light alone maintains fibroblast activity and increased collagen synthesis. When used with copper peptides, collagen 1 expression increases even more.
Other copper peptides have also been shown to be beneficial in skin care including the tripeptide Cu-AHK and Cu-PCA and the pentapeptide Cu - glycine, L-histidine, L-lysine, L-serine, L-citrulline.
Synthetic GHK-Cu is used in cosmetics as a reparative and anti-aging ingredient. These are available in various formulations including lotions, creams and serums designed to reduce the appearance of fine lines and wrinkles. Apart from these, they have also been used in mesotherapydrug combinations for skin and hair.
Apart from mild burning or stinging and irritant dermatitis, no other known side effects of Cu peptides are known to exist. Even though no controlled studies have been done, literature doesn’t mention any harmful effects on pregnancy or lactation.
Cu-peptides have an impressive clinical pedigree going back to the 1970s. They are proven wound healers, can help hair growth and have been in skin care products for past 20 years. Today, they are regarded as one of the most potent skin regeneration actives, and much more is understood about how they work and how we can get the most out of them as an anti-aging active for skin and hair. However, due to the absence of concrete evidence and lack of long term studies, the actual efficacy of the complex is questionable.
References
References are available on request
Skin ageing is a part of a natural human “aging mosaic” which becomes evident and follows different trajectories in different organs, tissues and cells with time. While the aging signs of internal organs are masked from the ambient “eyes,” the skin provides first obvious marks of the passing time. Aged skin appears as thin and atrophic, finely wrinkled and dry and might show signs of photodamage such as thickened epidermis, mottled discoloration, deep wrinkles, laxity, dullness and roughness.
Skin ageing is a complex biological process influenced by combination of multiple endogenous and exogenousfactors which together lead to cumulative structural and physiological alterations and progressive changes in the skin.
The ageing of skin is due to slowing of the epidermal turnover rate and cell cycle lengths leading to aslower wound healing, along with alteration in distribution and content of collagen (collagen 1) due to increased collagen degradation by various matrix metalloproteinases, serine, and other proteases. Glycosaminoglycans (GAGs), which are among the primary dermal skin matrix constituents may be associated with abnormal elastotic material and thus be unable to function effectively.
The biosynthesis and breakdown of collagen, elastin, and GAGs exists in a dynamic balance in young healthy skin. However in the ageing skin, their productionis reduced while the rate of breakdown is increased, which leads to wrinkle formation and loss of elasticity.
Ageing, a basic biological process is not preventable. Various medical and surgical modalities have been invented for the anti-ageing armamentarium, of which peptides are the newest ammunition.
Peptides are short chains of amino acids and these are known to have multiple biological functions. Their role in skin and hair care has been known for decades but these have become the new buzzword in cosmeceuticals over the last 5 years. Amongst the various peptides available, copper peptides have become an integral component of the anti-ageing formulations
Copper peptide GHK-Cu is a naturally occurring complex of copper (Cu) with three amino acids forming the Cu-glycyl-L-histidyl-L-lysine (Cu-GHK) tripeptide, which is the physiologically most active Cu peptide. In the human body, these are found in trace amounts in blood plasma, saliva and urine. The plasma level of these Cu complexes decrease with age, from about 200 µg/ml at age 20 to 80 µg/ml at the age of 60.
These have various functions in the body including promotionof wound healing, antioxidant and anti-inflammatory effects, stimulationof collagen and GAG synthesis in skin fibroblasts and angiogenesis. Recent studies revealed its ability to modulate expression of a large number of human genes, generally reversing gene expression to a healthier state1.
GHK peptide has anti-inflammatory properties. Even though an exact mechanism remains unclear, in a recent study GHK and its copper complexes decreased TNF-alpha-dependent IL-6 secretion in normal human dermal fibroblasts.Because of the anti-inflammatory properties, Cu peptides could replace corticosteroids or non-steroidal anti-inflammatory drugs in treatment of inflammatory skin conditions and reduction of UV induced erythema. 2
It has also been seen that GHK-Cu stimulates proliferation of keratinocytesand increases expression of integrins and p63 protein in the epidermal stem cells. Since p63 is considered to be an important marker of stem cell and anti-senescence protein, the authors concluded that GHK-copper is able to recover epidermal stem cells and increase their ability to repair tissue.3
Cu peptides have also been found to promote the production of GAGs like hyaluronic acid4 as well as neutralize free radicals.
All the above mentioned functions of Cu-GHK makes many signs of aging less noticeable and slows down the aging process. They can help prevent expression lines and wrinkles from developing prematurely.
Several controlled facial studies confirmed anti-aging, firming and anti-wrinkle activity of GHK-Cu.Abdulghani et al. established that facial cream containing GHK-Cu increased collagen in photoaged skin of 20 female volunteers, performing better than vitamin C and retinoic acid.5
Leyden et al. conducted a 12-week facial study of GHK-Cu containing face and eye cream, reporting significant improvement of skin laxity, clarity and appearance, reduced fine lines and the depths of wrinkles and increased skin density and thickness comparing to placebo. GHK-Cu eye cream performed better than vitamin K cream.6
Apart from the anti-ageing benefits, clinical studies have found that Cu-peptides also remove damaged collagen and elastin from the skin and scar tissue and thus help in better scar remodeling.
Furthermore,it has shown that Cu peptides and red LED light make a powerful combination. Red light alone maintains fibroblast activity and increased collagen synthesis. When used with copper peptides, collagen 1 expression increases even more.
Other copper peptides have also been shown to be beneficial in skin care including the tripeptide Cu-AHK and Cu-PCA and the pentapeptide Cu - glycine, L-histidine, L-lysine, L-serine, L-citrulline.
Synthetic GHK-Cu is used in cosmetics as a reparative and anti-aging ingredient. These are available in various formulations including lotions, creams and serums designed to reduce the appearance of fine lines and wrinkles. Apart from these, they have also been used in mesotherapydrug combinations for skin and hair.
Apart from mild burning or stinging and irritant dermatitis, no other known side effects of Cu peptides are known to exist. Even though no controlled studies have been done, literature doesn’t mention any harmful effects on pregnancy or lactation.
Cu-peptides have an impressive clinical pedigree going back to the 1970s. They are proven wound healers, can help hair growth and have been in skin care products for past 20 years. Today, they are regarded as one of the most potent skin regeneration actives, and much more is understood about how they work and how we can get the most out of them as an anti-aging active for skin and hair. However, due to the absence of concrete evidence and lack of long term studies, the actual efficacy of the complex is questionable.
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| Copper peptide Cu-GHK Copper complexed with 3 amino acids |
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| Physiological effects of Copper Peptides |
References
- Pickart, L (2008). "The human tri-peptide GHK and tissue remodeling". J. Biomater. Sci. Polymer Edn. 19 (8): 969–988
- Gruchlik A., Jurzak M., Chodurek E., Dzierzewicz Z. Effect of Gly-Gly-His, Gly-His-Lys and their copper complexes on TNF-alpha-dependent IL-6 secretion in normal human dermal fibroblasts. Acta. Pol. Pharm. 2012 Nov-Dec;69(6):1303-6
- Kang, YA; Choi, HR; Na, JI; Huh, CH; Kim, MJ; Youn, SW; Kim, KH; Park, KC (Apr 2009). "Copper-GHK increases integrin expression and p63 positivity by keratinocytes".ArchDermatol Res 301 (4): 301–6.
- Wegrowski Y, Maquart FX, Borel JP. Stimulation of sulfated glycosaminoglycan synthesis by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+" Life Sci 1992; 51(13):1049-56.
- Abdulghani, AA; Sherr, S; Shirin, S; Solodkina, G; Tapia, EM; Gottlieb, AB (1998). "Effects of topical creams containing vitamin C, a copper-binding peptide cream and melatonin compared with tretinoin on the ultrastructure of normal skin - A pilot clinical, histologic, and ultrastructural study". Disease ManagClin Outcomes 1: 136–141.
References are available on request