Research Profile — Longevity and Anti-aging Research
GHK-Cu: Complete Copper Peptide Research Profile
Copper peptideGHK copper complexLamin
GHK-Cu is the copper(II) complex of the tripeptide Gly-His-Lys, representing one of the smallest biologically active peptides known. Despite having only three amino acids, GHK-Cu has demonstrated remarkable breadth of biological activity, with published studies documenting effects on wound healing, collagen synthesis, anti-inflammatory responses, and — most notably — massive-scale gene expression modulation. The Connectivity Map analysis by Campbell et al. (2012) published in Genome Medicine revealed that GHK-Cu modulates the expression of over 4,000 genes, representing approximately 6% of the human genome. The naturally declining levels of GHK-Cu with age (from ~200 ng/mL at age 20 to ~80 ng/mL at age 60) have made it a central compound in longevity and anti-aging research.
Technical Specifications
CAS Number
49557-75-7
Molecular Formula
C14H23CuN6O4
Molecular Weight
403.92 g/mol
Amino Acids
3
Sequence
Gly-His-Lys + Cu2+
Purity
≥99% (HPLC)
Appearance
Blue lyophilized powder
Salt Form
Copper(II) complex
Solubility
Soluble in water
Storage
-20°C lyophilized, 2-8°C reconstituted
Origin & Discovery
GHK-Cu is a naturally occurring copper complex of the tripeptide Glycyl-L-Histidyl-L-Lysine. It was first identified by Dr. Loren Pickart in the 1970s when he observed that albumin from young human blood (age 20-25) promoted liver cell growth more effectively than albumin from older blood (age 60-80). The active factor was identified as GHK-Cu, and subsequent research revealed that plasma levels of GHK-Cu decline significantly with age — from approximately 200 ng/mL at age 20 to 80 ng/mL by age 60.
Mechanism of Action
GHK-Cu operates through several interconnected mechanisms that are unusually broad for a tripeptide.
Copper Delivery: GHK-Cu serves as a bioavailable copper transport peptide, delivering Cu2+ ions to cells and tissues where copper is required as a cofactor for numerous enzymes including superoxide dismutase (SOD), lysyl oxidase (collagen cross-linking), and cytochrome c oxidase (mitochondrial electron transport).
Collagen Synthesis: GHK-Cu stimulates production of collagen types I and III, the primary structural proteins of skin, tendon, and bone. It also increases glycosaminoglycan (GAG) synthesis, which maintains tissue hydration and structural integrity.
Massive Gene Expression Modulation: The most striking finding is GHK-Cu's ability to modulate over 4,000 human genes (~6% of the genome). Analysis of the Connectivity Map data showed that GHK-Cu upregulates genes associated with stem cell markers, DNA repair, antioxidant defense, and ubiquitin-proteasome system function, while downregulating genes associated with inflammation, fibrosis, and tissue destruction. This pattern of gene expression changes reverses many age-associated gene expression signatures.
DNA Repair Gene Activation: GHK-Cu upregulates multiple DNA repair genes including GADD45A, XPC, and DDB2, suggesting enhancement of the cellular DNA damage response — a key mechanism in cancer prevention and aging.
Gene Expression & Anti-Aging Research
The most significant GHK-Cu research breakthrough came from computational analysis of the Connectivity Map (CMap) database. Pickart et al. (2015) analyzed the gene expression signature of GHK-Cu and found that it modulated 4,048 genes at a significance threshold of p<0.05. Campbell et al. (2012) published in Genome Medicine a systematic analysis showing that GHK-Cu's gene expression signature was the closest match to reversing the age-associated gene expression changes in the CMap database. Specifically, GHK-Cu upregulated 1,584 genes that decline with age and downregulated 917 genes that increase with age. The affected pathways included DNA repair, antioxidant response, ubiquitin-proteasome activity, stem cell maintenance, and inflammatory resolution. These findings position GHK-Cu as a uniquely broad-acting compound for aging research.
Citations
Pickart L, et al. (2015) "GHK-Cu gene expression modulation and anti-aging."
Campbell JD, et al. (2012) "Gene expression signature of GHK-Cu." Genome Med, 4(10), 84.
Wound Healing & Tissue Repair
Pickart et al. (2008) reviewed the wound healing properties of GHK-Cu, documenting enhanced collagen synthesis, increased angiogenesis, and improved wound contraction in animal models. Arul et al. (2007) demonstrated that GHK-Cu-loaded collagen matrices significantly accelerated wound closure in rat models, with enhanced granulation tissue formation and organized collagen deposition. The copper delivery function of GHK-Cu is particularly relevant to wound healing, as copper is required by lysyl oxidase for collagen cross-linking and by superoxide dismutase for antioxidant protection of healing tissue.
Citations
Pickart L, et al. (2008) "GHK-Cu wound healing review."
Arul V, et al. (2007) "GHK-Cu collagen matrices for wound healing."
Frequently Asked Questions
What is GHK-Cu?▼
GHK-Cu is the copper(II) complex of the tripeptide Glycyl-L-Histidyl-L-Lysine. It is a naturally occurring compound found in human plasma, saliva, and urine. It modulates over 4,000 human genes and declines with age from ~200 ng/mL at age 20 to ~80 ng/mL at age 60.
Why does GHK-Cu contain copper?▼
Copper(II) is an essential cofactor for numerous enzymes (SOD, lysyl oxidase, cytochrome c oxidase). The GHK tripeptide has high affinity for Cu2+ (log K = 16.44) and serves as a bioavailable copper delivery system. The copper complex is required for many of GHK-Cu's biological activities.