GHK

GHK is a tripeptide with the amino acid sequence glycyl-histidyl-lysine. It occurs naturally in human plasma, saliva, and urine. Plasma levels of GHK are approximately 200 ng/mL at the age of 20 years, but decline to 80 ng/mL by the age of 60 years, a decline that coincides with a significant decrease in the regenerative capacity of organisms. Scientific studies have shown that GHK contributes to wound healing, infection control, hair growth, cancer, cognitive health and facial beauty.

What is the difference between GHK and GHK-Cu?

GHK with or without copper affects a large number of genes involved in an organism’s response to stress and injury (tissue remodeling, antioxidant, anti-inflammatory, anti-pain, anti-anxiety, vascular growth, nerve growth, anti-cancer) actions. GHK sequences are contained in collagen molecules and are naturally released from the SPARC proteins and GHK as a result of proteolytic breakdown after injury.

Copper is a transition metal that is essential to all eukaryotes from microbes to humans. Because it can be converted from the oxidized Cu(II) to the reduced Cu(I) form, it serves as an important cofactor in a variety of biochemical reactions involving electron transfer. More than a dozen enzymes utilize changes in the oxidation state of copper to catalyze important biochemical reactions, including cellular respiration, antioxidant defense, detoxification, coagulation, and connective tissue formation. Copper is required for iron metabolism, oxygenation, neurotransmission, embryonic development and many other important biological processes.

GHK Research

1. GHK inhibits fibrinogen synthesis

Fibrinogen consists of three polypeptide chains; alpha, beta and gamma.GHK strongly inhibits the fibrinogen beta chain gene. Lack of sufficient FGB effectively prevents fibrinogen synthesis because equal amounts of all three polypeptide chains are required to produce fibrinogen.

GHK also inhibits the production of the inflammatory cytokine interleukin 6 (IL-6), a major positive regulator of fibrinogen synthesis, by interacting with the fibrinogen gene. In a cell culture system, GHK inhibited IL-6 secretion in skin fibroblasts and IL-6 gene expression in SZ95 sebocytes. In summary, the effect of GHK on the FGB gene coupled with its effect on IL-6 production implies an inhibition of overall fibrinogen production. 2.

2. GHK activates the ubiquitin/proteasome system (UPS).

The UPS removes damaged proteins, and the higher activity of the UPS appears to delay the effects of aging. GHK stimulates gene expression of 41 UPS genes while suppressing only 1 UPS gene.

3. GHK activates DNA repair genes

DNA damage is rapidly repaired in young and healthy cells; however, as we age, DNA damage begins to accumulate. Resetting the activity of DNA repair genes reduces the deleterious effects of aging.GHK primarily stimulates DNA repair genes (47 UP, 5 DOWN).4. GHK acts as an antioxidant.

4. GHK as an antioxidant

Toxic end products of free radicals and lipid peroxidation are associated with atherosclerosis, cancer, cataracts, diabetes, kidney disease, Alzheimer’s disease, and other serious pathological conditions of aging. gHK stimulates 14 antioxidant genes and inhibits two pro-oxidant genes. 5.

5. GHK Suppresses Insulin and Insulin-like Genes

The insulin family is recognized as a negative regulator of longevity. Higher levels of insulin and insulin-like proteins shorten life span. GHK stimulates 3 genes and represses 6 genes in this system.

The insulin/IGF-1-like receptor pathway is a contributor to the biological aging process in many organisms. Gene expression data suggest that GHK inhibits this system, as 6 of the 9 affected insulin/IGF-1 genes are repressed. Insulin/IGF-1-like signaling is conserved from nematodes to humans. In vitro experiments have shown that reducing mutations in insulin/IGF-1 signaling has been shown to slow the degenerative aging process and extend lifespan in many organisms, including mice and potentially humans. reductions in IGF-1 signaling have also been suggested to contribute to the “anti-aging” effects of caloric restriction. 6.

6. GHK Repairs Tissues via the TGF Superfamily

The most explored role of GHK is the repair of damaged tissues (skin, hair follicles, stomach and intestinal lining, and bone tissue) through the use of copper peptide-containing creams or by inducing systemic healing.

Campbell et al. found that the reset of gene expression in fibroblasts from COPD patients by GHK fits into the category of tissue repair through the TGF beta superfamily. Campbell et al. also found that GHK directly increases the activity of TGF beta and other family members, thereby activating the repair process.

7. Cancer-controlling genes

Caspases, growth regulator genes and DNA repair genes are important for cancer suppression. 2010, Hong et al. identified 54 genes associated with aggressive, metastatic human colon cancer. The Broad Institute’s linkage map was used to find compounds that reverse the differential expression of these genes. The results showed that two wound healing and skin remodeling molecules, 1 micromolar of GHK and 18 micromolar of luteolin, significantly reversed the differential expression of these genes and suggested that they may have therapeutic benefits for patients susceptible to metastasis.

Conclusion

The tripeptide GHK has many positive effects that diminish with age. It improves wound healing and tissue regeneration (skin, hair follicles, stomach and intestinal lining, and bone tissue), increases collagen and glycosaminoglycans, stimulates the synthesis of core proteoglycans, increases angiogenesis and nerve growth, has antioxidant and anti-inflammatory properties, and increases the secretion of trophic factors by cytosolic and mesenchymal stem cells. Recently, GHK has even been found to reset the genes of diseased cells in patients with cancer or COPD to a healthier state.