The potential of GHK as an anti-aging peptide
Open accessAbstract
GHK (glycyl-L-histidyl-L-lysine) is a naturally occurring peptide found in human serum with levels averaging 200 ng/ml at age 20 but declining to an average of 80 ng/ml by age 60. The molecule has a very high affinity for copper and forms the chelate GHK-Cu. The peptide as well as its Cu (II) chelate have anti-inflammatory and tissue remodeling properties. GHK-Cu has been shown to promote skin remodeling, wound healing and regeneration, and has prominent antioxidant and anti-inflammatory effects in in vitro and in vivo studies. In addition, preliminary observations suggest GHK can partially reverse cognitive impairment in aging mice by targeting anti-inflammatory and epigenetic pathways. The evidence as presented provides the rationale to further investigate this naturally occurring peptide in preclinical and clinical aging studies.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
21 of 50 cited sources checked · 2 supported · 0 flagged · accuracy not yet measured
- Premisecitation
At low concentrations, GHK-Cu stimulates the migration of macrophages and mast cells.
“GHK-Cu at low concentrations is a powerful attractant for capillary cells that build new blood vessels, and a powerful migration stimulant for macrophages and mast cells that remove damaged cellular debris and secrete proteins important for wound contraction and tissue healing [8–9].”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [8]
- cites [9] source
The Introduction says GHK-Cu is a potent chemotactic agent for monocytes/macrophages and mast cells, supporting the migration claim. It does not specify that this effect occurs at low concentrations; the paper’s dose-response results concern connective-tissue accumulation, not migration. (LLM, conf=0.84)
Experimental — accuracy not yet measured
- Premisecitation
GHK-Cu increases the expression of bFGF and VEGF in irradiated human dermal fibroblasts at a concentration of 1 nM.
“GHK-Cu at a concentration of 1nM increases the expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) in irradiated human dermal fibroblasts, both of which aid blood vessel formation and blood flow into damaged tissues [4–6].”
Quote in the paperSubstantial claim1 of 3 sources checked- cites [4] source
- cites [5] source
The sections on FGF signaling and repair discuss angiogenesis and wound healing, but do not address GHK-Cu treatment. Searches for GHK-Cu, irradiated dermal fibroblasts, and the 1 nM concentration found no passage reporting the claimed increase in bFGF or VEGF expression. (LLM, conf=0.76)
Experimental — accuracy not yet measured - cites [6] source
- Premisecitation
Copper is an important trace element in the production of collagen and elastin.
“Since copper is an important trace element that plays a key factor in the production of collagen and elastin, GHK-Cu can be a natural supplement for copper in the connective tissue synthesis [10–11].”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [10] source
- cites [11] source
The Results section ('GHK-Cu increases extracellular matrix deposition in wound chambers'; page unavailable) reports increased collagen in wounds treated with the copper-containing complex GHK-Cu. It does not establish that copper alone is an important trace element for collagen production, and the passages found do not address elastin production (searched: 'elastin' and 'elastin synthesis copper connective tissue'). (LLM, conf=0.83)
Experimental — accuracy not yet measured
- Premisecitation
At low concentrations, GHK-Cu attracts capillary cells that form new blood vessels.
“GHK-Cu at low concentrations is a powerful attractant for capillary cells that build new blood vessels, and a powerful migration stimulant for macrophages and mast cells that remove damaged cellular debris and secrete proteins important for wound contraction and tissue healing [8–9].”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [8]
- cites [9] source
The Discussion describes GHK-Cu as a potent chemoattractant for endothelial cells, and the Introduction reports that it can trigger angiogenesis in vivo. The paper does not say that the attraction occurs at low concentrations; its dose results concern connective-tissue accumulation, not endothelial-cell attraction. (LLM, conf=0.86)
Experimental — accuracy not yet measured
- Premisecitation
GHK is a naturally occurring peptide present in human serum.
“GHK (glycyl-L-histidyl-L-lysine) is a naturally occurring peptide originally found in human serum and shown to stimulate growth in hepatoma cells [1].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [1] source
The References (page not specified) identify GHK as a human-plasma tripeptide, and Figure 8 (p. 938) shows that GHK can be released from SPARC by digestion. Our copy does not establish that GHK is present in human serum specifically; plasma and serum are not interchangeable for this claim. (LLM, conf=0.78)
Experimental — accuracy not yet measured
- Premisecitation
NF-κB p65 and p38 MAPK signaling pathways are key regulators of inflammation and pro-inflammatory responses.
“Both signaling pathways are key regulators of inflammation and pro-inflammatory responses, which are considered targets for developing anti-inflammatory therapeutic agents [23–26].”
Quote in the paperSubstantial claim2 of 4 sources checked- cites [23] source
The Introduction identifies p65 (RelA) as an NF-κB family member, and the section on pro-inflammatory gene induction calls NF-κB a central mediator of that process. The Concluding Remarks describe NF-κB signaling as a potential anti-inflammatory therapeutic target. The passages found do not support the corresponding claim about p38 MAPK. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [24] source
- cites [25] source
- cites [26] source
The Introduction and Results and Discussion discuss mTOR, nitric oxide signaling, and vascular inflammation, but do not identify NF-κB p65 or p38 MAPK as regulators of inflammatory responses or targets for anti-inflammatory agents. Searches for both pathways and anti-inflammatory therapeutic agents found no passage addressing the attributed claim. Page numbers were unavailable in our copy. (LLM, conf=0.74)
Experimental — accuracy not yet measured
- Findingcitation
GHK-treated aged mice find the escape hole significantly faster in trials 4 and 5 than saline-treated mice in a Box Maze spatial navigation task.
“Mice treated with GHK were able to find the escape hole significantly faster in trials 4 and 5 compared to mice treated with saline (Figure 2) as assessed by a Box Maze spatial navigation learning task [27] at the end of the treatment period.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [27] source
The cited paper’s Basic Science sections discuss wound healing in older mice, not a Box Maze spatial-navigation task. Searches for the Box Maze and for GHK-treated versus saline-treated mice found no passage addressing the task or the reported results for trials 4 and 5. (LLM, conf=0.75)
Experimental — accuracy not yet measured
- Premisecitation
GHK-Cu promotes bone healing.
“Moreover, GHK-Cu promotes bone healing and enhances osteoblastic cell attachment, potentially through the increase in collagen synthesis [14–15].”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [14]
- cites [15] source
- Premisecitation
GHK-Cu activates the synthesis of matrix compounds in vivo that are needed for resistant new tissue.
“It is also involved in the activation of the synthesis of matrix compounds in vivo, which are critical for the formation of a resistant new tissue [12–13].”
Quote in the paperSubstantial claim1 of 2 sources checked - Premisecitation
GHK-Cu enhances osteoblastic cell attachment.
“Moreover, GHK-Cu promotes bone healing and enhances osteoblastic cell attachment, potentially through the increase in collagen synthesis [14–15].”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [14]
- cites [15] source
The paper’s introductory passage says GHK-Cu can enhance attachment of an implant to bone, and its References list a study on osteoblastic cell attachment. The paper does not itself state or test that GHK-Cu enhances osteoblastic cell attachment; its own ACL-reconstruction results concern graft and bone-tunnel healing. (LLM, conf=0.83)
Experimental — accuracy not yet measured
- Interpretationcitation
The observation that GHK might target an epigenetic pathway increases its potential as an anti-aging peptide.
“In addition, the novel observation that GHK might target an epigenetic pathway further enhances its potential as an anti-aging peptide [32].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [32] source
The ‘Aging processes can be targeted with repurposed drugs’ section discusses epigenetic pathways in aging, and the REVIEW section identifies phenylbutyrate as a drug targeting histone deacetylation. Searches for GHK, copper tripeptide, and epigenetic activity found no passage connecting GHK to an epigenetic pathway or assessing its anti-aging potential. (LLM, conf=0.76)
Experimental — accuracy not yet measured
- Interpretationcitation
GHK-Cu can serve as a natural copper supplement for connective tissue synthesis.
“Since copper is an important trace element that plays a key factor in the production of collagen and elastin, GHK-Cu can be a natural supplement for copper in the connective tissue synthesis [10–11].”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [10] source
- cites [11] source
The Abstract says GHK binds copper to form GHK-Cu, and the wound-chamber results report increased collagen and extracellular-matrix deposition after GHK-Cu injection. The paper does not establish that GHK-Cu acts as a copper supplement for connective-tissue synthesis or address copper’s role in elastin production. Page numbers are unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measured
- Interpretationcitation
GHK is a potential treatment for pulmonary fibrosis.
“In a bleomycin-induced fibrosis mouse model, treatment with GHK showed reduced inflammatory cell infiltration and interstitial thickness with reduced TNF-α and IL-6 expression, suggesting GHK as a potential treatment for pulmonary fibrosis [21].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [21] source
The Abstract (page not provided) reports that GHK-Cu reduced inflammatory-cell infiltration and TNF-α and IL-6 production in mice with lipopolysaccharide-induced acute lung injury. It proposes GHK-Cu as a potential treatment for ALI/ARDS, not pulmonary fibrosis. The paper does not report a bleomycin-induced fibrosis model or a reduction in interstitial thickness. (LLM, conf=0.88)
Experimental — accuracy not yet measured
- Premisecitation
Articular injection of 0.3 mg/ml GHK-Cu improves some healing outcomes in a rat model of anterior cruciate ligament reconstruction.
“Articular injection of 0.3 mg/ml GHK-Cu enhances some of the healing outcomes in a rat model of anterior cruciate ligament reconstruction (ACLR), and the treatment of GHK-Cu encapsulated in liposome significantly fasten burn wound healing in mice with scald wound [7, 16].”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [7]
- cites [16] source
The Introduction reports that GHK-Cu promoted wound healing in rats, supporting only the broad healing effect. Neither the Introduction nor the Conclusion reports a 0.3 mg/ml articular injection or healing outcomes after anterior cruciate ligament reconstruction; the Conclusion instead discusses a different peptide mixture used for rat bone fractures. No page numbers were available in our copy. (LLM, conf=0.78)
Experimental — accuracy not yet measured
- Premisecitation
Liposome-encapsulated GHK-Cu accelerates burn wound healing in mice with scald wounds.
“Articular injection of 0.3 mg/ml GHK-Cu enhances some of the healing outcomes in a rat model of anterior cruciate ligament reconstruction (ACLR), and the treatment of GHK-Cu encapsulated in liposome significantly fasten burn wound healing in mice with scald wound [7, 16].”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [7]
- cites [16] source
The Introduction reports that GHK-Cu promotes wound healing in animals, including mice. Section 8, “Formulation and Delivery,” discusses incorporation into niosomes, but neither passage reports liposome-encapsulated GHK-Cu accelerating healing of scald burns in mice. (LLM, conf=0.86)
Experimental — accuracy not yet measured
- Findingown data
GHK-Cu pretreatment has a robust antioxidant effect in WI-38 cells treated with 150 uM hydrogen peroxide, reducing ROS levels to almost 60%.
“We have also found that pretreatment of GHK-Cu has a robust antioxidant effect in WI-38 cells treated with 150uM of hydrogen peroxide, decreasing the ROS level to almost 60 percent (Figure 1).”
Quote in the paperSubstantial claim - Premisecitation
GHK, without copper bound, quenches cytotoxic lipid peroxidation products such as 4-hydroxy-trans-2-nonenal and acrolein.
“Without being bound to copper, GHK has been shown to be a quencher of cytotoxic end products of lipid peroxidation such as α,β−4-hydroxy-trans-2-nonenal and acrolein, which can be associated with severe pathologies such as diabetes and neurodegenerative disease [18–19].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [18] source
- cites [19]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation
GHK-Cu has more prominent antioxidant and anti-inflammatory effects than GHK in vitro and in vivo.
“Compared with GHK, its copper (II)-chelated form shows a more prominent antioxidant and anti-inflammatory effect in both in vitro and in vivo studies.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [22] source
- Premisecitation
GHK-Cu pretreatment decreases LPS-induced ROS levels in RAW 264.7 macrophage cells.
“Pretreatment of RAW 264.7 macrophage cells with GHK-Cu has been shown to significantly decrease ROS levels induced by lipopolysaccharide (LPS), increase levels of SOD activities and total GSH, and decrease levels of TNF-α and IL-6 production through the suppression of NF-κB p65 and p38 MAPK signaling [22].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [22] source
- Premisecitation
GHK-Cu pretreatment decreases TNF-α and IL-6 production in RAW 264.7 macrophage cells.
“Pretreatment of RAW 264.7 macrophage cells with GHK-Cu has been shown to significantly decrease ROS levels induced by lipopolysaccharide (LPS), increase levels of SOD activities and total GSH, and decrease levels of TNF-α and IL-6 production through the suppression of NF-κB p65 and p38 MAPK signaling [22].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [22] source
- Interpretationown data
GHK can partially reverse cognitive impairment in aging mice.
“In addition, preliminary observations suggest GHK can partially reverse cognitive impairment in aging mice by targeting anti-inflammatory and epigenetic pathways.”
Quote in the paperSubstantial claim - Premisecitation
At 10 uM, GHK reduces tert-butyl hydroperoxide-induced ROS in Caco-2 cells by almost 50%.
“With a concentration as low as 10uM, the addition of GHK can reduce the tert-butyl hydroperoxide-induced reactive oxygen species (ROS) level in Caco-2 cells by almost 50-percent.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [18] source
- cites [19]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation
GHK-Cu decreases TNF-α and IL-6 production by suppressing NF-κB p65 and p38 MAPK signaling.
“Pretreatment of RAW 264.7 macrophage cells with GHK-Cu has been shown to significantly decrease ROS levels induced by lipopolysaccharide (LPS), increase levels of SOD activities and total GSH, and decrease levels of TNF-α and IL-6 production through the suppression of NF-κB p65 and p38 MAPK signaling [22].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [22] source
- Interpretationreasoning
GHK may trigger an epigenetic pathway that contributes to the amelioration of cognitive impairment in aging mice.
“Immunohistochemistry of brain tissues from mice treated with GHK showed evidence of decreased inflammation and increased labeling of histone deacetylase 2, suggesting that in addition to an anti-inflammatory effect, GHK may be triggering an epigenetic pathway in the amelioration of cognitive impairment in aging mice.”
Quote in the paperSubstantial claim - Interpretationcitation
GHK-Cu is useful for developing novel anti-inflammatory therapies.
“In the LPS-induced acute lung injury mouse model, treatment of GHK-Cu also significantly suppressed TNF-α and IL-6 expression with a significant decrease of both NF-κB p65 and p38 MAPK signaling, suggesting that GHK-Cu is useful for the development of novel anti-inflammatory therapies [22].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [22] source
- May combine two claims. 9
May combine two claims.
PremisecitationIn a bleomycin-induced fibrosis mouse model, GHK reduces inflammatory cell infiltration and interstitial thickness and lowers TNF-α and IL-6 expression.
“In a bleomycin-induced fibrosis mouse model, treatment with GHK showed reduced inflammatory cell infiltration and interstitial thickness with reduced TNF-α and IL-6 expression, suggesting GHK as a potential treatment for pulmonary fibrosis [21].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [21] source
The lung-damage Results section (page unavailable) reports that GHK-Cu mitigated lung pathology, including immune-cell infiltration and alveolar wall thickening. The cytokine Results section reports lower TNF-α and IL-6 in treated mice. But this was an LPS-induced acute lung injury model, not a bleomycin-induced fibrosis model, so the cited paper does not establish GHK as a potential treatment for pulmonary fibrosis. (LLM, conf=0.89)
Experimental — accuracy not yet measured
May combine two claims.
InterpretationcitationThe ability of GHK and its Cu chelate to promote skin remodeling, wound healing and regeneration, and their antioxidant and anti-inflammatory effects, will help enhance healthy aging.
“The ability of GHK and its Cu chelate to promote skin remodeling, wound healing and regeneration, and its prominent antioxidant and anti-inflammatory effects are qualities that will help enhance healthy aging [28–31].”
Quote in the paperSubstantial claim3 of 4 sources checked- cites [28] source
The Conclusion and Future Perspectives (page unavailable) discusses healthy aging and suggests that therapeutic modulation of reactive oxygen species is relevant to aging. It does not discuss GHK or its copper chelate, so it cannot support the attributed claims about their skin-remodeling, wound-healing, regenerative, antioxidant, or anti-inflammatory effects. (LLM, conf=0.76)
Experimental — accuracy not yet measured - cites [29] source
The Introduction discusses senescence, tissue deterioration, and aging, while the matching References passages concern regeneration and inflammation in other contexts. Searches for GHK, its copper chelate, and the claimed skin-remodeling, wound-healing, antioxidant, and anti-inflammatory effects found no passage attributing those effects to GHK or linking them to healthy aging. (LLM, conf=0.76)
Experimental — accuracy not yet measured - cites [30] source
Section 2.1 discusses antioxidant enzymes and aging, and Section 6.2 discusses exercise-related antioxidant responses. Neither addresses GHK, its copper chelate, or their effects on skin remodeling, wound healing, and regeneration; searches for GHK and the copper peptide found no pertinent passage in our copy. (LLM, conf=0.74)
Experimental — accuracy not yet measured - cites [31] source
May combine two claims.
PremisecitationGHK quenches hydroxyl and peroxyl radicals by ESR spectroscopy, and its hydroxyl radical quenching is stronger than that of glutathione.
“Moreover, GHK has been shown to be a quencher for hydroxyl and peroxyl radicals by ESR spectroscopy, with its ability to quench hydroxyl radicals much stronger than glutathione (GSH), making it a strong endogenous antioxidant [20].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [20] source
The Introduction describes GHK as a normal component of human plasma, and the Discussion reports anti-inflammatory and anti-fibrotic effects. Neither passage addresses hydroxyl or peroxyl radical quenching, ESR spectroscopy, or a comparison with glutathione; searches for those terms and antioxidant activity found no supporting passage in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measured
May combine two claims.
Findingown dataImmunohistochemistry of brain tissue from GHK-treated mice shows decreased inflammation and increased histone deacetylase 2 labeling.
“Immunohistochemistry of brain tissues from mice treated with GHK showed evidence of decreased inflammation and increased labeling of histone deacetylase 2, suggesting that in addition to an anti-inflammatory effect, GHK may be triggering an epigenetic pathway in the amelioration of cognitive impairment in aging mice.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationGHK is released from the protein SPARC when the extracellular matrix is degraded, and this release supports tissue remodeling by raising angiogenesis.
“The peptide is cleaved and released from its parent protein SPARC during the degradation of extracellular matrix, to aid in tissue remodeling by increasing levels of angiogenesis [2].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [2] source
May combine two claims.
PremisecitationGHK-Cu increases HUVEC proliferation by stimulating VEGF and FGF-2 expression, which promotes angiogenesis.
“It also increases HUVECs proliferation by stimulating VEGF and FGF-2 expressions, promoting angiogenesis that aids in wound healing [7].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [7]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
PremisecitationGHK-Cu pretreatment increases SOD activity and total GSH in RAW 264.7 macrophage cells.
“Pretreatment of RAW 264.7 macrophage cells with GHK-Cu has been shown to significantly decrease ROS levels induced by lipopolysaccharide (LPS), increase levels of SOD activities and total GSH, and decrease levels of TNF-α and IL-6 production through the suppression of NF-κB p65 and p38 MAPK signaling [22].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [22] source
May combine two claims.
PremisecitationIn an LPS-induced acute lung injury mouse model, GHK-Cu suppresses TNF-α and IL-6 expression and decreases NF-κB p65 and p38 MAPK signaling.
“In the LPS-induced acute lung injury mouse model, treatment of GHK-Cu also significantly suppressed TNF-α and IL-6 expression with a significant decrease of both NF-κB p65 and p38 MAPK signaling, suggesting that GHK-Cu is useful for the development of novel anti-inflammatory therapies [22].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [22] source
May combine two claims.
PremisecitationClinical studies show that GHK-Cu in skin cream leads to faster healing and better skin condition.
“In addition to wound healing studies in mice, clinical studies have been done on the effect of GHK-Cu on skin regeneration, which show a more rapid healing process and better skin conditions with GHK-Cu in the skin cream [3, 17].”
Quote in the paperSubstantial claim0 of 2 sources checked
The paper relies on this without support.
GHK has a very high affinity for copper(II) and forms the chelate GHK-Cu.
“The molecule has a very high affinity for copper (II) and forms the chelate GHK-Cu.”
The paper relies on this without support.
Plasma GHK level is about 200 ng/ml at age 20 and declines to 80 ng/ml by age 60.
“The plasma level of GHK is about 200 ng/ml at age 20 but declines to 80 ng/ml by age 60.”
The paper relies on this without support.
No studies have linked low serum GHK levels with specific aging processes or age-related disease.
“However, no studies have yet been reported linking low serum GHK levels with specific aging processes or age-related disease.”
The paper relies on this without support.
GHK is absorbed at high efficiency across the blood brain barrier into brains of rodents and nonhuman primates when delivered parenterally.
“Since GHK is absorbed at a high efficiency across the blood brain barrier into the brains of rodents and nonhuman primates when delivered parenterally, testing the effects of the peptide on neurological function is warranted.”
Cites
NF-κB signaling in inflammation
Liu, T., Zhang, L., Joo, D., & Sun, S.-C. (2017) · Signal Transduction and Targeted Therapy · doi:10.1038/sigtrans.2017.23 · Cited by 8,791 · cited 1× · see citing works
“Both signaling pathways are key regulators of inflammation and pro-inflammatory responses, which are considered targets for developing anti-inflammatory therapeutic agents [23-26].”
BackgroundFibroblast growth factors, their receptors and signaling
Powers, C. J., McLeskey, S. W., & Wellstein, A. (2000) · Endocrine-related cancer · doi:10.1677/erc.0.0070165 · Cited by 1,332 · see citing works
Kaminska, B. (2005) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2005.08.017 · Cited by 1,285 · cited 1× · see citing works
“Both signaling pathways are key regulators of inflammation and pro-inflammatory responses, which are considered targets for developing anti-inflammatory therapeutic agents [23-26].”
BackgroundSenescence and aging: Causes, consequences, and therapeutic avenues
McHugh, D., & Gil, J. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201708092 · Cited by 1,233 · cited 1× · see citing works
“The ability of GHK and its Cu chelate to promote skin remodeling, wound healing and regeneration, and its prominent antioxidant and anti-inflammatory effects are qualities that will help enhance healthy aging [28-31].”
BackgroundROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age‐Related Diseases
Davalli, P., Mitic, T., Caporali, A., Lauriola, A., & D’Arca, D. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/3565127 · Cited by 1,059 · cited 1× · see citing works
“The ability of GHK and its Cu chelate to promote skin remodeling, wound healing and regeneration, and its prominent antioxidant and anti-inflammatory effects are qualities that will help enhance healthy aging [28-31].”
BackgroundThe p38 MAPK inhibitors for the treatment of inflammatory diseases and cancer
Yong, H.-Y., Koh, M.-S., & Moon, A. (2009) · Expert Opinion on Investigational Drugs · doi:10.1517/13543780903321490 · Cited by 422 · cited 1× · see citing works
“Both signaling pathways are key regulators of inflammation and pro-inflammatory responses, which are considered targets for developing anti-inflammatory therapeutic agents [23-26].”
BackgroundCross-linking of collagen and elastin. Properties of lysyl oxidase
Siegel, R. C., Pinnell, S. R., & Martin, G. R. (1970) · Biochemistry · doi:10.1021/bi00825a004 · Cited by 345 · cited 1× · see citing works
“Since copper is an important trace element that plays a key factor in the production of collagen and elastin, GHK-Cu can be a natural supplement for copper in the connective tissue synthesis [10-11].”
BackgroundChronic wound repair and healing in older adults: current status and future research
Gould, L., Abadir, P., Brem, H., Carter, M., Conner‐Kerr, T., Davidson, J., DiPietro, L., Falanga, V., Fife, C., Gardner, S., et al. (2015) · Wound Repair and Regeneration · doi:10.1111/wrr.12245 · Cited by 291 · cited 1× · see citing works
“The ability of GHK and its Cu chelate to promote skin remodeling, wound healing and regeneration, and its prominent antioxidant and anti-inflammatory effects are qualities that will help enhance healthy aging [28-31].”
BackgroundSPARC is a source of copper-binding peptides that stimulate angiogenesis
Lane, T. F., Iruela-Arispe, M. L., Johnson, R. S., & Sage, E. H. (1994) · The Journal of cell biology · doi:10.1083/jcb.125.4.929 · Cited by 249 · cited 1× · see citing works
“The peptide is cleaved and released from its parent protein SPARC during the degradation of extracellular matrix, to aid in tissue remodeling by increasing levels of angiogenesis [2].”
BackgroundThe human tri-peptide GHK and tissue remodeling
Pickart, L. (2008) · Journal of Biomaterials Science, Polymer Edition · doi:10.1163/156856208784909435 · Cited by 218 · cited 1× · see citing works
“Received: 06 March 2020 / Accepted: 09 March 2020 modeling and wound healing abilities for nearly four decades [3].”
BackgroundSantos, A. L., Sinha, S., & Lindner, A. B. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/1941285 · Cited by 168 · cited 1× · see citing works
“The ability of GHK and its Cu chelate to promote skin remodeling, wound healing and regeneration, and its prominent antioxidant and anti-inflammatory effects are qualities that will help enhance healthy aging [28-31].”
BackgroundGHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration
Pickart, L., Vasquez-Soltero, J. M., & Margolina, A. (2015) · BioMed Research International · doi:10.1155/2015/648108 · Cited by 144 · see citing works
Siméon, A., Wegrowski, Y., Bontemps, Y., & Maquart, F.-X. (2000) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2000.00166.x · Cited by 119 · cited 1× · see citing works
“It is also involved in the activation of the synthesis of matrix compounds in vivo, which are critical for the formation of a resistant new tissue [12-13].”
BackgroundMaquart, F. X., Bellon, G., Chaqour, B., Wegrowski, J., Patt, L. M., Trachy, R. E., Monboisse, J. C., Chastang, F., Birembaut, P., & Gillery, P. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116842 · Cited by 110 · cited 1× · see citing works
“Since copper is an important trace element that plays a key factor in the production of collagen and elastin, GHK-Cu can be a natural supplement for copper in the connective tissue synthesis [10-11].”
BackgroundHDAC inhibitors: A new promising drug class in anti-aging research
Pasyukova, E. G., & Vaiserman, A. M. (2017) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2017.08.008 · Cited by 99 · cited 1× · see citing works
“In addition, the novel observation that GHK might target an epigenetic pathway further enhances its potential as an anti-aging peptide [32].”
Background(1973) · doi:10.1016/0006-291x(73)91459-9 · Cited by 89 · cited 1× · see citing works
“GHK (glycyl-L-histidyl-L-lysine) is a naturally occurring peptide originally found in human serum and shown to stimulate growth in hepatoma cells [1].”
BackgroundFibroblast growth factors: key players in epithelial morphogenesis, repair and cytoprotection
Steiling, H., & Werner, S. (2003) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2003.08.003 · Cited by 86 · see citing works
Siméon, A., Monier, F., Emonard, H., Gillery, P., Hornebeck, W., Maquart, F.-X., & Birembaut, P. (1999) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.1999.00606.x · Cited by 68 · cited 1× · see citing works
“It is also involved in the activation of the synthesis of matrix compounds in vivo, which are critical for the formation of a resistant new tissue [12-13].”
BackgroundGao, M., Chen, L., Yu, H., Sun, Q., Kou, J., & Yu, B. (2013) · International Immunopharmacology · doi:10.1016/j.intimp.2012.11.019 · Cited by 63 · cited 1× · see citing works
“Both signaling pathways are key regulators of inflammation and pro-inflammatory responses, which are considered targets for developing anti-inflammatory therapeutic agents [23-26].”
Background(1983) · PubMed · Cited by 63 · see citing works
The tri-peptide GHK-Cu complex ameliorates lipopolysaccharide-induced acute lung injury in mice
Park, J.-R., Lee, H., Kim, S.-I., & Yang, S.-R. (2016) · Oncotarget · doi:10.18632/oncotarget.11168 · Cited by 60 · cited 2× · see citing works
“7 macrophage cells with GHK-Cu has been shown to significantly decrease ROS levels induced by lipopolysaccharide (LPS), increase levels of SOD activities and total GSH, and decrease levels of TNF-α and IL-6 production through the suppression of NF-κB p65 and p38 MAPK signaling [22].”
BackgroundMethodPollard, J. D., Quan, S., Kang, T., & Koch, R. J. (2005) · Archives of Facial Plastic Surgery · doi:10.1001/archfaci.7.1.27 · Cited by 58 · see citing works
Wang, X., Liu, B., Xu, Q., Sun, H., Shi, M., Wang, D., Guo, M., Yu, J., Zhao, C., & Feng, B. (2017) · Wound Repair and Regeneration · doi:10.1111/wrr.12520 · Cited by 54 · cited 2× · see citing works
“It also increases HUVECs proliferation by stimulating VEGF and FGF-2 expressions, promoting angiogenesis that aids in wound healing [7].”
Background(1984) · PubMed · Cited by 53 · see citing works
Zhou, X.-M., Wang, G.-L., Wang, X.-B., Liu, L., Zhang, Q., Yin, Y., Wang, Q.-Y., Kang, J., & Hou, G. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00904 · Cited by 41 · cited 1× · see citing works
“In a bleomycin-induced fibrosis mouse model, treatment with GHK showed reduced inflammatory cell infiltration and interstitial thickness with reduced TNF-α and IL-6 expression, suggesting GHK as a potential treatment for pulmonary fibrosis [21].”
MethodBeretta, G., Artali, R., Regazzoni, L., Panigati, M., & Facino, R. M. (2007) · Chemical Research in Toxicology · doi:10.1021/tx700185s · Cited by 30 · see citing works
Pohunková, H., Stehí, J., Váchal, J., čech, O., & Adam, M. (1996) · Biomaterials · doi:10.1016/0142-9612(95)00310-x · Cited by 28 · cited 1× · see citing works
“Moreover, GHK-Cu promotes bone healing and enhances osteoblastic cell attachment, potentially through the increase in collagen synthesis [14-15].”
BackgroundFu, S., Cheuk, Y., Chiu, W. V., Yung, S., Rolf, C. G., & Chan, K. (2015) · Journal of Orthopaedic Research · doi:10.1002/jor.22831 · Cited by 25 · cited 1× · see citing works
“3 mg/ml GHK-Cu enhances some of the healing outcomes in a rat model of anterior cruciate ligament reconstruction (ACLR), and the treatment of GHK-Cu encapsulated in liposome significantly fasten burn wound healing in mice with scald wound [7, 16].”
BackgroundBeretta, G., Arlandini, E., Artali, R., Anton, J. M. G., & Maffei Facino, R. (2008) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2008.02.012 · Cited by 25 · see citing works
(1995) · PubMed · Cited by 18 · see citing works
Sakuma, S., Ishimura, M., Yuba, Y., Itoh, Y., & Fujimoto, Y. (2018) · Europe PMC (PubMed Central) · Cited by 15 · see citing works
Sleep-deprived cognitive impairment in aging mice is alleviated by rapamycin
(2019) · Aging Pathobiology and Therapeutics · doi:10.31491/apt.2019.12.002 · Cited by 10 · cited 1× · see citing works
“Mice treated with GHK were able to find the escape hole significantly faster in trials 4 and 5 compared to mice treated with saline (Figure 2) as assessed by a Box Maze spatial navigation learning task [27] at the end of the treatment period.”
MethodSelf-citationThe rationale for testing drug combinations in aging intervention studies
Sharma, K., Wang, J., Jiang, Z., Klug, J., Darvas, M., M. Imai, D., Snider, T., Niedernhofer, L., & Ladiges, W. (2019) · Aging Pathobiology and Therapeutics · doi:10.31491/apt.2019.12.001 · Cited by 4 · cited 1× · see citing works
“There is also the possibility that GHK could be extremely useful combined with other antiaging drugs as a cocktail [33] to robustly enhance healthy aging.”
BackgroundSelf-citation
Flagged first, then by citations
Cited by
Sorted by citations
Unambiguous discrimination of all 20 proteinogenic amino acids and their modifications by nanopore
Wang, K., Zhang, S., Zhou, X., Yang, X., Li, X., Wang, Y., Fan, P., Xiao, Y., Sun, W. J., Zhang, P., et al. (2023) · Nature Methods · doi:10.1038/s41592-023-02021-8 · Cited by 196 · see citing works
“GHK (glycyl-l-histidyl-l-lysine) is a naturally occurring tripeptide that is widely found in human serum 41 .”
BackgroundLiuzzi, G. M., Petraglia, T., Latronico, T., Crescenzi, A., & Rossano, R. (2023) · Nutrients · doi:10.3390/nu15081913 · Cited by 101 · see citing works
Research Progress on Bioactive Factors against Skin Aging
He, X., Gao, X., Guo, Y., & Xie, W. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25073797 · Cited by 62 · see citing works
“…is a peptide that occurs naturally in human blood serum and is widely used in the field of skin care, where in vitro and in vivo studies have shown that GHK-Cu promotes skin remodeling, wound healing, and regeneration, and has significant antioxidant and anti-inflammatory effects [59].”
BackgroundBioactive peptides in cosmetic formulations: Review of current in vitro and ex vivo evidence
van Walraven, N., Fitzgerald, R. J., Danneel, H.-J., & Amigo‐Benavent, M. (2025) · Peptides · doi:10.1016/j.peptides.2025.171440 · Cited by 17 · see citing works
Potential Wound Healing of PLGA Nanoparticles Containing a Novel L ‐Carnitine–GHK Peptide Conjugate
Ramezanpour, S., Tavatoni, P., Akrami, M., Nigjeh, M. N., & Shiri, P. (2022) · Journal of Nanomaterials · doi:10.1155/2022/6165759 · Cited by 14 · see citing works
“Some important properties of the peptide that have been reported in this field include displaying antiinflammatory effects; attracting endothelial cells to the injured area; modulating the activity of both metalloproteinases and their inhibitors; stimulating collagen and glycosaminoglycan and its ability to modulate t…”
BackgroundHu, D., Zhang, X., Gong, S., Ma, W., Cheng, B., Yang, J., Yan, L., Li, B., Qiu, T., & Wang, X. (2025) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2025.114982 · Cited by 14 · see citing works
Greco, V., Lanza, V., Tomasello, B., Николаевна, Н. И., Cairns, W. R. L., Sciuto, S., & Rizzarelli, E. (2025) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.4c00545 · Cited by 12 · see citing works
Local and Systemic Peptide Therapies for Soft Tissue Regeneration: A Narrative Review
Cushman, C. J., Ibrahim, A. F., Smith, A. D., Hernandez, E. J., MacKay, B., & Zumwalt, M. (2024) · The Yale Journal of Biology and Medicine · doi:10.59249/tknm3388 · Cited by 12 · see citing works
“GHK-Cu tripeptide is released naturally from human tissues in response to injury, with average serum levels of 200ng/mL at age 20, decreasing to 80ng/mL by the age of 60 [82].”
BackgroundOgórek, K., Nowak, K., Wadych, E., Ruzik, L., Timerbaev, A. R., & Matczuk, M. (2025) · Molecules · doi:10.3390/molecules30010136 · Cited by 9 · see citing works
Min, J.-H., Sarlus, H., & Harris, R. A. (2024) · Metallomics · doi:10.1093/mtomcs/mfae019 · Cited by 9 · see citing works
“130 –132 This leaves a system such as the CNS with already extremely low metal ion turnover more vulnerable to fluctuations of especially zinc and copper that result from aging, inflammation, environmental toxins, and trauma that lead to protein aggregation and neurodegeneration.”
BackgroundAnxiety and Risk of Vascular Dementia in an Elderly Community Sample: The Role of Sex
Santabárbara, J., Villagrasa, B., López‐Antón, R., de la Cámara, C., Gracia‐García, P., & Lobo, A. (2020) · Brain Sciences · doi:10.3390/brainsci10050265 · Cited by 9 · see citing works
“Recent research of cellular ageing indicates that the human plasma peptide Gly-His-Lys, which has powerful anti-anxiety effects, is related to the suppression of several molecules that favor accelerated cellular ageing [36,37].”
BackgroundErat, A., & Addor, G. (2025) · Cosmetics · doi:10.3390/cosmetics12050202 · Cited by 9 · see citing works
Zhou, X., Guo, Y., Gao, Z., Lv, G., Wang, X., Zhang, M., & Zhou, Y. (2025) · Acta Biomaterialia · doi:10.1016/j.actbio.2025.08.043 · Cited by 7 · see citing works
GHK peptide prevents sleep deprived learning impairment in aging mice
Rosenfeld, M., Nickel, K., & Ladiges, W. (2023) · Aging Pathobiology and Therapeutics · doi:10.31491/apt.2023.03.109 · Cited by 7 · see citing works
Self-citationInternet marketing of dietary supplements for improving memory and cognitive abilities
Fuentes, J. B., Amidžić, M., Banović, J., & Torović, L. D. (2024) · PharmaNutrition · doi:10.1016/j.phanu.2024.100379 · Cited by 6 · see citing works
Mao, S., Huang, J., Li, J., Sun, F., Zhang, Q., Cheng, Q., Zeng, W., Lei, D., Wang, S., & Yao, J. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1551843 · Cited by 6 · see citing works
(2023) · doi:10.1101/2023.11.20.567908 · Cited by 4 · see citing works
Self-citationLu, W., Kang, S., Liu, S., Wang, Y., & Wang, H. (2026) · Systems Microbiology and Biomanufacturing · doi:10.1007/s43393-026-00447-7 · Cited by 2 · see citing works
Intranasal GHK peptide enhances resilience to cognitive decline in aging micePreprint
Tucker, M., Keely, A., Park, J. Y., Rosenfeld, M., Wezeman, J., Mangalindan, R., Ratner, D., & Ladiges, W. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.11.16.567423 · Cited by 1 · see citing works
“The peptide is clinically approved as a topical application for age-related skin conditions, and promoted mainly as a skin rejuvenation drug [13].”
BackgroundSelf-citation(2026) · doi:10.1016/j.bioactmat.2026.03.057 · Cited by 2 · see citing works
“The Glycyl-L-Histidyl-L-Lysine-Copper(II) complex (GHK-Cu 2+ ) is well recognized for its cyto-protective and regenerative properties [23], including anti-inflammatory effects and protection against free radical-induced damage [24,25].”
Duval, C., Qiu, J., Warrick, E., Sextius, P., Castiel‐Higounenc, I., Xiang, L. F., Bernerd, F., & Passeron, T. (2026) · Dermatology and Therapy · doi:10.1007/s13555-026-01807-w · Cited by 2 · see citing works
“Besides antiox‑ idant (AOX) and anti‑inflammatory effects, GHK exhibits potent tissue remodeling properties by stimulating collagen synthesis in fibroblasts and increasing keratinocyte proliferation [187, 188].”
Yuan, Y.-Y., Li, X., Han, M.-H., An, X., Lin, Y.-Q., & Liu, H.-B. (2026) · Food Research International · doi:10.1016/j.foodres.2026.119202 · Cited by 1 · see citing works
Jin, L., Sim, D. I., Kim, S. H., Han, S., Thein, W., & Na, D. H. (2025) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2025.107969 · Cited by 1 · see citing works
Hassoon, A. A., Szorcsik, A., & Gajda, T. (2025) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2025.112913 · Cited by 1 · see citing works
The Regenerative Potential of Glycyl- L- Histidyl- L- Lysine–Copperin Aesthetic Medicine
Mokhtar, J., Mohamad, B., Haddad, J., Said, A., Menon, A., Kreutz‐Rodrigues, L., Vyas, K. S., Cetrulo, C. L., & Lellouch, A. G. (2026) · Aesthetic Surgery Journal · doi:10.1093/asj/sjag169
Jiang, X., Li, J., Lu, Y., Ni, F., & Li, S. (2026) · International Journal of Peptide Research and Therapeutics · doi:10.1007/s10989-026-10862-y
“Well-recognized peptides, including GHK-Cu (glycyl-L-histidyl-L-lysine-copper), antimicrobial peptides (AMPs) and palmitoyl peptides, are known to alleviate skin inflammatory responses (Dou et al. 2020, Nguyen et al. 2020).”
Zheng, X., Wang, N., Ma, H., et al. (2026) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2026.179217
Xie, L.-H., Zhou, X., Wen, W.-Q., Wang, W., Gui, P., Li, L., & Wang, G.-H. (2026) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2026.125628
Mazzola, J., Rosenfeld, M., Tucker, M., Wezeman, J., Ladiges, W., & Liao, G. Y. (2026) · Research Square · doi:10.64898/2026.04.09.717524
“Evidence of blood-brain barrier (BBB) permeability and oxidative stress modulation further support its relevance to cognitive aging [14].”
Self-citationSkincare for All Ages: The Science, Advances and Future of Skincare from Infancy to Adulthood
Echeverry, A. (2026) · AAPS introductions in the pharmaceutical sciences · doi:10.1007/978-3-032-03596-7_3
Ye, H., Zhen, Y., Chen, S., Lin, Y., Xu, X., Yu, Y., Huang, X., Wang, Y., & Xie, J. (2025) · Journal of Liposome Research · doi:10.1080/08982104.2025.2584982
“…with the tripeptide sequence GhK, known for its therapeutic potential in skin inflammation, wound healing, and repair [13]. this combination facilitates the spon-taneous formation of anti-aging nanogels [14], combining the benefits of nanocarriers with intrinsic anti-aging properties.”
Koldiri, E., Rallis, E. A., & Kefala, V. (2024) · Review of Clinical Pharmacology and Pharmacokinetics - International Edition · doi:10.61873/yaok3799
- Authors
- Department of Comparative Medicine, S. O. M., Dou, Y., Lee, A., Zhu, L., Morton, J., & Ladiges, W.
- Affiliations
- University of Washington (US)
- Corresponding author
- Ladiges, Warren
- Venue
- Aging Pathobiology and Therapeutics
- Publisher
- Ant Publishing
- Published
- 2020-03-27
- Volume
- 2
- Issue
- 1
- Pages
- 58-61
- ISSN
- 2690-1803 (ISSN-L)
- PMC
- PMC8789089
- OpenAlex
- W3013536180
- Cited by
- 33
- References
- 33
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 6 · 2023: 4 · 2022: 1 · 2020: 1
- FWCI
- 0.83
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- Aging Pathobiology and Therapeutics (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG067193, AG057381, R56AG058543, R01AG057381)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Physiology › Biochemical effects in animals
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Keywords
- copper chelates, anti-aging, dermal remodeling, wound healing, tissue regeneration, antioxidant activity, anti-inflammatory activity, cognitive impairment, epigenetic mechanisms
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read under definition version 3 (extract-v3) on 2026-09-28.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-09-28.
Cited sources are checked by gpt-6-sol.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
