GHK and DNA: Resetting the human genome to health
Open accessAbstract
During human aging there is an increase in the activity of inflammatory, cancer promoting, and tissue destructive genes plus a decrease in the activity of regenerative and reparative genes. The human blood tripeptide GHK possesses many positive effects but declines with age. It improves wound healing and tissue regeneration (skin, hair follicles, stomach and intestinal linings, and boney tissue), increases collagen and glycosaminoglycans, stimulates synthesis of decorin, increases angiogenesis, and nerve outgrowth, possesses antioxidant and anti-inflammatory effects, and increases cellular stemness and the secretion of trophic factors by mesenchymal stem cells. Recently, GHK has been found to reset genes of diseased cells from patients with cancer or COPD to a more healthy state. Cancer cells reset their programmed cell death system while COPD patients’ cells shut down tissue destructive genes and stimulate repair and remodeling activities. In this paper, we discuss GHK’s effect on genes that suppress fibrinogen synthesis, the insulin/insulin-like system, and cancer growth plus activation of genes that increase the ubiquitin-proteasome system, DNA repair, antioxidant systems, and healing by the TGF beta superfamily. A variety of methods and dosages to effectively use GHK to reset genes to a healthier state are also discussed.
AI snapshot
Written from the paper’s full text.
TL;DR
This review/analysis argues that the human tripeptide GHK can reset age-related gene expression toward a healthier state, based on Connectivity Map gene-expression data and prior in vitro/in vivo studies. It reports broad GHK effects on fibrinogen, ubiquitin-proteasome, DNA repair, antioxidant, insulin/IGF-1, TGF-beta/COPD, and cancer-related genes, and proposes possible clinical dosing.
Key findings
- In Broad Institute Connectivity Map data, GHK altered expression of 31.2% of 13,424 genes by ≥50% (the abstract says 32.1%); among UPS genes, 41 were increased and 1 suppressed, and among DNA repair genes, 47 were increased and 5 suppressed.
- GHK increased 14 antioxidant genes and suppressed 2 prooxidant genes; it increased NF-κB2 by 103%, TLE1 by 762%, and IL18BP by 295%.
- In the insulin/IGF-1-like system, GHK stimulated 3 genes and suppressed 6; in cancer-related analyses, it increased 6 of 12 caspase genes and altered 31 other genes in a manner expected to inhibit cancer growth.
- In COPD fibroblasts, GHK recapitulated TGF-beta-induced gene expression patterns, organized the actin cytoskeleton, elevated integrin beta1, and restored collagen I contraction and remodeling; estimated human dosing was 100–200 mg GHK, or about 140 μg per injection with 10 treatments/day when scaled from a rat bone-fracture peptide mixture.
Methods
- Design: gene-expression analysis of GHK signatures from the Broad Connectivity Map (retrieved March 5, 2013), plus review of prior GHK in vitro and in vivo studies.
- Data: three GHK signatures on the GeneChip HT Human Genome U133A Array; two profiles used the PC3 cell line and one used MCF7; 22,277 probe sets represented 13,424 genes.
- Analysis: GenePattern with MAS5 and background correction; ComparativeMarkerSelectionViewer was used for fold changes, which were converted to percentages and averaged across probe sets per gene; a ratio of 1.66 was used to estimate gene-level effects.
Limitations
- Stated: “There is still not enough information to translate gene profiling data into biological effects”; the paper also notes it was not clear how one simple molecule could accomplish so much.
- Evident: the findings rely on Connectivity Map cell-line signatures (PC3, MCF7) and prior studies, not new clinical trials; proposed human dosages are extrapolated from animal experiments and cell-culture responses.
- Evident: the abstract and Methods report slightly different percentages (32.1% vs 31.2%) for genes affected by GHK, indicating some inconsistency in reporting.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
0 of 68 cited sources checked · 0 supported · 0 flagged
- Findingown data
The number of genes stimulated or suppressed by GHK with a change greater than or equal to 50% is 31.2%.
“The number of genes stimulated or suppressed by GHK with a change greater than or equal to 50% is 31.2%.”
Quote in the paperSubstantial claim - Findingcitation
GHK increased or decreased gene expression by more than 50% in 32.1% of human genes.
“GHK increased or decreased gene expression (UP or DOWN more than 50%) in 32.1% of the human genes [7].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [7] source
Not checked in the free run.
- Findingnone given
GHK strongly suppresses the gene for the beta chain of fibrinogen (FGB).
“GHK strongly suppresses the gene for the beta chain of fibrinogen.”
Quote in the paperSubstantial claim - Findingown data
Our analysis found that GHK increased gene expression in 6 of the 12 human caspase genes that activate apoptosis.
“Our analysis of GHK's actions found that it increased gene expression in 6 of the 12 human caspase genes that activate apoptosis.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [7] source
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- Findingown data
Mice treated with GHK:Cu(2+) and ascorbic acid appeared to remain very healthy and active.
“The mice treated in this manner appeared to remain very healthy and active, in contrast to the toxicities of current cancer chemotherapy.”
Quote in the paperSubstantial claim
- Findingcitation
GHK:Cu(2+) and ascorbic acid strongly suppressed sarcoma 180 in mice.
“In a recent paper, we used their basic method but with GHK : Cu(2+) and ascorbic acid, which strongly suppressed sarcoma 180 in mice without any evident distress to the animals [7].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [7] source
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- Findingcitation
GHK:Cu(2+) and ascorbic acid caused no evident distress to the mice.
“which strongly suppressed sarcoma 180 in mice without any evident distress to the animals [7].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [7] source
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- Findingown data
GHK was primarily stimulatory for DNA repair genes (47 UP, 5 DOWN).
“GHK was primarily stimulatory for DNA repair genes (47 UP, 5 DOWN).”
Quote in the paperSubstantial claim - Findingnone given
In wound healing experiments, the addition of copper strongly enhanced healing.
“In wound healing experiments, the addition of copper strongly enhanced healing.”
Quote in the paperNot a substantial claim - Premisecitation
Fibrinogen is an excellent predictor of mortality especially in patients with cardiovascular complications.
“Fibrinogen is an excellent predictor of mortality especially in patients with cardiovascular complications [11, 12].”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
GHK resets genes of diseased cells from patients with cancer or COPD to a more healthy state.
“Recently, GHK has been found to reset genes of diseased cells from patients with cancer or COPD to a more healthy state.”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
The Connectivity Map selected GHK from 1,309 bioactive molecules as the best choice to reset diseased gene patterns to a healthier pattern for aggressive metastatic colon cancer.
“The gene analysis computer program selected GHK from 1,309 bioactive molecules as the best choice to reset the diseased gene patterns to a healthier pattern.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [8] source
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- Interpretationcitation
GHK and securinine may have a therapeutic effect on metastasis-prone patients.
“and suggested that they may have a therapeutic effect on the metastasis-prone patients.”
Quote in the paperSubstantial claim - Premisecitation
Addition of GHK or TGF beta restored collagen I contraction and remodeling by fibroblasts derived from COPD lungs compared to fibroblasts from former smokers without COPD.
“Furthermore, addition of GHK or TGF beta restored collagen I contraction and remodeling by fibroblasts derived from COPD lungs compared to fibroblasts from former smokers without COPD.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [10] source
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- Premisecitation
In rats, injecting GHK intraperitoneally 10 times daily lowered the necessary dosage by approximately 100-fold compared to earlier studies.
“two subsequent tissue repair studies in rats found that injecting GHK intraperitoneally 10 times daily lowered the necessary dosage by approximately 100-fold in contrast to our earlier studies [38, 65].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [38] 2010, Experimental Biology and Medicine
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- cites [65]
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- Interpretationreasoning
Therapies using GHK might provide health benefits to the elderly.
“These results, combined with GHK's broad spectrum of positive actions on many systems that maintain human health, suggest that therapies using GHK might provide health benefits to the elderly.”
Quote in the paperSubstantial claim- Rests on an assumption: GHK declines with age.
- Rests on an assumption: The primary cause of human aging and its attendant diseases is changes in the activity of the human genome.
- Rests on an assumption: Gene profiling data can be used to predict beneficial biological actions based on documented in vivo activity of GHK.
- Interpretationnone given
GHK altered gene expression in 84 genes (caspases, cytokines, and DNA repair genes) in a manner expected to suppress cell growth.
“GHK altered gene expression in 84 genes (caspases, cytokines, and DNA repair genes) in a manner that would be expected to suppress cell growth.”
Quote in the paperSubstantial claim - Interpretationreasoning
The effects of GHK on the FGB gene plus its effects on IL-6 production imply a suppression of overall fibrinogen production.
“In summary, the effects of GHK on the FGB gene plus its effects on IL-6 production imply a suppression of overall fibrinogen production.”
Quote in the paperSubstantial claim - Premisecitation
A mixture of GHK, transferrin, and somatostatin was sufficient to promote branching in serum-free organ culture.
“The mixture of GHK, transferrin, and somatostatin was sufficient to promote branching in the absence of serum in organ culture, all of which could be added to the misting solution [64].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [64] source
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- Interpretationown data
GHK altered the pattern of gene expression in 31 other genes in a manner expected to inhibit cancer growth.
“In 31 other genes, GHK altered the pattern of gene expression in a manner that would be expected to inhibit cancer growth.”
Quote in the paperSubstantial claim - Premisecitation
Hong et al. identified 54 genes associated with aggressive, metastatic human colon cancer.
“In 2010, Hong et al. identified 54 genes associated with aggressive, metastatic, human colon cancer [8].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [8] source
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- Interpretationown data
GHK should have a positive effect on the ubiquitin proteasome system.
“Thus, it should have a positive effect on this system [13, 14, 46].”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
Matalka et al. demonstrated that GHK at 1 to 10 nanomolar reactivated the apoptosis system, as measured by caspases 3 and 7.
“Matalka et al. demonstrated that GHK, at 1 to 10 nanomolar, reactivated the apoptosis system, as measured by caspases 3 and 7”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [9] source
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- Premisecitation
Mutations that reduce insulin/IGF-1 signaling decelerate degenerative aging and extend lifespan in many organisms, including mice and possibly humans.
“In vitro experiments show that mutations that reduce insulin/IGF-1 signaling have been shown to decelerate the degenerative aging process and extend lifespan in many organisms, including mice and possibly humans.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [63] source
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- Interpretationown data
The gene expression data suggests that GHK suppresses the insulin/IGF-1 system.
“The gene expression data suggests that GHK suppresses this system as 6 of 9 of the affected insulin/IGF-1 genes are suppressed.”
Quote in the paperSubstantial claim- Rests on an assumption: The insulin/IGF-1-like receptor pathway is a contributor to biological aging in many organisms.
- Interpretationown data
GHK's stimulation of DNA repair genes suggests increased DNA repair activity.
“GHK was stimulatory for DNA repair genes (47 stimulated, 5 suppressed) suggesting an increased DNA repair activity.”
Quote in the paperSubstantial claim- Rests on an assumption: Resetting activity of DNA repair genes can diminish deleterious effects of aging.
- Premisecitation
A mixture including Gly-His-Lys (0.5 μg/kg), dalargin (1.2 μg/kg), and thymogen (0.5 μg/kg) was given to rats to heal bone fractures.
“This mixture of small molecules included Gly-His-Lys (0.5 μg/kg), dalargin (1.2 μg/kg) (an opioid-like synthetic drug), and the biological peptide thymogen (0.5 μg/kg) (L-glutamyl-L-tryptophan) to heal bones.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [38] 2010, Experimental Biology and Medicine
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- cites [65]
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- Premisecitation
GHK possesses antioxidant activities in cell culture and in vivo.
“GHK also possesses antioxidant activities in cell culture and in vivo.”
Quote in the paperSubstantial claim0 of 4 sources checked - Premisecitation
Treatment of rats, mice, and pigs with GHK effectively activates systemic healing throughout the animal.
“The treatment of rats, mice, and pigs with GHK was shown to effectively activate systemic healing throughout the animal.”
Quote in the paperSubstantial claim0 of 9 sources checked- cites [37]
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- cites [38] 2010, Experimental Biology and Medicine
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- cites [39] source
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- cites [40] source
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- cites [43] source
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- cites [44] source
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- Premisecitation
GHK has a very high affinity for Cu(2+) (pK of association = 16.4).
“GHK has a very high affinity for Cu(2+) (pK of association = 16.4) and can easily obtain copper from the blood's albumin bound Cu(2+) (pK of association = 16.2) [3].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [3] source
Not checked in the free run.
- Interpretationnone given
GHK is a potential treatment for a variety of disease conditions associated with aging.
“GHK, abundantly available at low cost in bulk quantities, is a potential treatment for a variety of disease conditions associated with aging.”
Quote in the paperNot a substantial claim- Rests on an assumption: GHK is very safe and no issues have ever arisen during its use as a skin cosmetic or in human wound healing studies.
- Rests on an assumption: GHK is abundantly available at low cost in bulk quantities.
- Premisecitation
GHK at 1 micromolar and securinine at 18 micromolar significantly reversed the differential expression of the 54 genes associated with aggressive, metastatic human colon cancer.
“The results indicated that two wound healing and skin remodeling molecules, GHK at 1 micromolar and securinine at 18 micromolar, could significantly reverse the differential expression of these genes”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [8] source
Not checked in the free run.
- Interpretationreasoning
GHK would be expected to influence cells' gene expression to be more similar to that of a person of age 20-25.
“Thus, GHK would be expected to influence the cells' gene expression to be more similar to that of a person of age 20–25, an age when the afflictions of aging are very rare.”
Quote in the paperSubstantial claim - Interpretationown data
These results support the idea that GHK may help slow or suppress cancer growth.
“These results support the idea that GHK may help slow or suppress cancer growth.”
Quote in the paperSubstantial claim - Interpretationreasoning
GHK's gene data on FGB suppression combined with its actions on lowering IL-6 secretion appears sufficient to explain its lowering effect on fibrinogen.
“The gene data on GHK's suppression of FGB (the fibrinogen beta chain) combined with its actions on lowering IL-6 secretion on fibroblasts and sebocytes appears to be sufficient to explain its lowering effect on fibrinogen.”
Quote in the paperSubstantial claim- Rests on an assumption: A lack of adequate FGB will effectively stop fibrinogen synthesis because equal amounts of all three polypeptide chains are needed to produce fibrinogen.
- Premisecitation
GHK can easily obtain copper from the blood's albumin-bound Cu(2+) (pK of association = 16.2).
“GHK has a very high affinity for Cu(2+) (pK of association = 16.4) and can easily obtain copper from the blood's albumin bound Cu(2+) (pK of association = 16.2) [3].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [3] source
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- Premisecitation
Matalka et al. demonstrated that GHK at 1 to 10 nanomolar inhibited the growth of human SH-SY5Y neuroblastoma cells, human U937 histiocytic lymphoma cells, and human breast cancer cells.
“and inhibited the growth of human SH-SY5Y neuroblastoma cells, human U937 histiocytic lymphoma cells, and human breast cancer cells [9].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [9] source
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- Premisecitation
GHK accelerated the growth of healthy human NIH-3T3 fibroblasts.
“In contrast, the GHK accelerated the growth of healthy human NIH-3T3 fibroblasts.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [9] source
Not checked in the free run.
- Interpretationown data
An estimated 100-200 mg of GHK will produce therapeutic actions in humans.
“Based on our studies, in which GHK was injected intraperitoneally once daily to induce systemic wound healing throughout the body, we estimate about 100–200 mgs of GHK will produce therapeutic actions in humans.”
Quote in the paperSubstantial claim- Rests on an assumption: Most cultured cells respond maximally to GHK at 1 nanoM.
- Rests on an assumption: GHK has a half-life of about 0.5 to 1 hour in plasma.
- Interpretationreasoning
The anticancer actions of small copper peptides may be a side effect of the skin remodeling system.
“The anticancer actions of small copper peptides may be a side effect of this system.”
Quote in the paperNot a substantial claim- Rests on an assumption: On skin, GHK acts most strongly in the late stage of healing (remodeling), where cellular migration into the wound area is stopped and cellular debris is removed.
- Interpretationreasoning
GHK possibly inhibits the activity of the NF-κB protein.
“thus possibly inhibiting the activity of the NF-κB protein.”
Quote in the paperSubstantial claim - Interpretationown data
For human aging, simultaneously resetting hundreds to thousands of genes is needed to protect at-risk tissues and organs.
“But for human aging, our data suggests that we must think of simultaneously resetting hundreds to thousands of genes to protect at-risk tissues and organs.”
Quote in the paperSubstantial claim - Interpretationreasoning
GHK may be a step towards the gene resetting goal.
“GHK may be a step towards this gene resetting goal.”
Quote in the paperSubstantial claim
- May combine two claims. 16
May combine two claims.
Findingown dataGHK stimulated gene expression in 41 UPS genes while suppressing only 1 UPS gene.
“GHK stimulated gene expression in 41 UPS genes while suppressing only 1 UPS gene.”
- Also stated in: § 3.2. Ubiquitin Proteasome System · plain
“In our screening of UPS genes with a percent change of at least ±50%, GHK increased gene expression in 41 UPS genes while suppressing 1 UPS gene.”
Quote in the paperSubstantial claim- Also stated in: § 3.2. Ubiquitin Proteasome System · plain
May combine two claims.
FindingcitationIn DNA repair genes, GHK increased expression of 47 genes and decreased expression of 5 genes.
“In DNA repair genes there was an increase (47 UP, 5 DOWN) [7].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [7] source
Not checked in the free run.
May combine two claims.
Findingown dataGHK increases expression of NF-κB2 by 103%, TLE1 by 762%, and IL18BP by 295%.
“GHK increases the expression of the oxidative/inflammatory gene NF-κB2 103% but also increases the expression of two inhibitors of NF-κB, TLE1 by 762% and IL18BP by 295%”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataAmong 13,424 available genes in the Broad Institute data, GHK stimulates 14 antioxidant genes and suppresses two prooxidant genes.
“Among the 13,424 available genes in the Broad Institute data, we were able to identify 14 antioxidant genes in which GHK stimulates as well as two prooxidant genes that GHK suppresses.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataGHK stimulates 3 genes in the insulin and insulin-like system and suppresses 6 genes.
“GHK stimulates 3 genes in this system and suppresses 6 genes.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationGHK increases cellular stemness and the secretion of trophic factors by mesenchymal stem cells.
“increases cellular stemness and the secretion of trophic factors by mesenchymal stem cells”
Quote in the paperSubstantial claim0 of 4 sources checkedMay combine two claims.
PremisecitationIn cells derived from damaged lungs of COPD patients, incubation with 10 nanomolar GHK recapitulated TGF beta-induced gene expression patterns, organized actin cytoskeleton, elevated integrin, and restored collagen contraction and remodeling by lung fibroblasts.
“When cells derived from the damaged areas of the lungs of COPD patients were incubated with 10 nanomolar GHK, the tripeptide recapitulated TGF beta induced genes expression patterns which led to the organization of the actin cytoskeleton and elevated the expression of integrin. This restored proper collagen contraction and remodeling by lung fibroblasts [10].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [10] source
Not checked in the free run.
May combine two claims.
PremisecitationGHK increases collagen and glycosaminoglycans and stimulates synthesis of decorin.
“increases collagen and glycosaminoglycans, stimulates synthesis of decorin”
Quote in the paperSubstantial claim0 of 4 sources checkedMay combine two claims.
PremisecitationGHK possesses antioxidant and anti-inflammatory effects.
“possesses antioxidant and anti-inflammatory effects”
Quote in the paperSubstantial claim0 of 4 sources checkedMay combine two claims.
PremisecitationDuring human aging, inflammatory, cancer-promoting, and tissue-destructive gene activity increases, while regenerative and reparative gene activity decreases.
“During human aging there is an increase in the activity of inflammatory, cancer promoting, and tissue destructive genes plus a decrease in the activity of regenerative and reparative genes.”
- Also stated in: § 1. Introduction · plain
“During aging there is an increase in the activity of inflammatory, cancer promoting, and tissue destructive genes plus a decrease in the activity of regenerative and reparative genes [1].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [1] source
Not checked in the free run.
- Also stated in: § 1. Introduction · plain
May combine two claims.
PremisecitationIn three human cancer cell lines, incubation with 1 to 10 nanomolar GHK reactivated apoptosis and inhibited cell growth.
“When three lines of human cancer cells (SH-SY5Y neuroblastoma cells, U937 histolytic cells, breast cancer cells) were incubated in culture with 1 to 10 nanomolar GHK, the programmed cell death system (apoptosis) was reactivated and cell growth inhibited [9].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [9] source
Not checked in the free run.
May combine two claims.
PremisecitationGHK improves wound healing and tissue regeneration in skin, hair follicles, stomach and intestinal linings, and boney tissue.
“It improves wound healing and tissue regeneration (skin, hair follicles, stomach and intestinal linings, and boney tissue)”
Quote in the paperSubstantial claim0 of 4 sources checkedMay combine two claims.
PremisecitationGHK increases angiogenesis and nerve outgrowth.
“increases angiogenesis, and nerve outgrowth”
Quote in the paperSubstantial claim0 of 4 sources checkedMay combine two claims.
PremisecitationThe total peptide dosage was about 2.2 μg/kg, equivalent to about 140 μg per injection in humans with 10 treatments per day.
“The total peptide dosage is about 2.2 μg/kg or, if scaled for the human body, about 140 μg per injection with 10 treatments per day [38, 65].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [38] 2010, Experimental Biology and Medicine
Not checked in the free run.
- cites [65]
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May combine two claims.
PremisecitationGHK suppresses IL-6 secretion in skin fibroblasts and IL-6 gene expression in SZ95 sebocytes.
“In cell culture systems, GHK suppresses IL-6 secretion in skin fibroblasts and IL-6 gene expression in SZ95 sebocytes [19, 20].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [19]
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- cites [20] 2012, Acta Poloniae Pharmaceutica
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May combine two claims.
PremisecitationTreatment of human fibroblasts with GHK recapitulated TGF beta-induced gene expression patterns, led to organization of actin cytoskeleton and elevated integrin beta1.
“Treatment of human fibroblasts with GHK recapitulated TGF beta-induced gene expression patterns, led to the organization of the actin cytoskeleton and elevated the expression of integrin beta1.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [10] source
Not checked in the free run.
The paper relies on this without support.
GHK declines with age.
“The human blood tripeptide GHK possesses many positive effects but declines with age.”
The paper relies on this without support.
The primary cause of human aging and its attendant diseases is changes in the activity of the human genome.
“It now becomes increasingly clear that the primary cause of human aging and its attendant diseases is changes in the activity of the human genome.”
The paper relies on this without support.
Resetting activity of DNA repair genes can diminish deleterious effects of aging.
“Resetting activity of DNA repair genes can diminish deleterious effects of aging.”
The paper relies on this without support.
Caspase, growth regulatory, and DNA repair genes are important in cancer suppression.
“Caspase, growth regulatory, and DNA repair genes are important in cancer suppression.”
The paper relies on this without support.
Gene profiling data can be used to predict beneficial biological actions based on documented in vivo activity of GHK.
“However, based on the documented activity of GHK in vivo, we can predict the following beneficial actions from our gene profiling data.”
The paper relies on this without support.
A lack of adequate FGB will effectively stop fibrinogen synthesis because equal amounts of all three polypeptide chains are needed to produce fibrinogen.
“A lack of adequate FGB will effectively stop fibrinogen syntheses since equal amounts of all three polypeptide chains are needed to produce fibrinogen.”
The paper relies on this without support.
The insulin/IGF-1-like receptor pathway is a contributor to biological aging in many organisms.
“The insulin/IGF-1-like receptor pathway is a contributor to the biological aging process in many organisms.”
The paper relies on this without support.
Steroids added to COPD inhalation solutions suppress lung inflammation in the short term but inhibit lung repair.
“Often steroids are added to the solution to suppress the lung inflammation, while this provides short-term help, it also inhibits lung repair.”
The paper relies on this without support.
DMSO and GHK or GHK:Cu(2+) have always worked well together on wound healing.
“DMSO and GHK or GHK : Cu(2+) has always worked well together on wound healing.”
The paper relies on this without support.
DMSO has been used in the past as a treatment for COPD, so there should be few safety issues.
“DMSO has been used in the past as a treatment for COPD, so there should be few safety issues.”
The paper relies on this without support.
GHK is very safe and no issues have ever arisen during its use as a skin cosmetic or in human wound healing studies.
“The molecule is very safe and no issues have ever arisen during its use as a skin cosmetic or in human wound healing studies.”
The paper relies on this without support.
Most cultured cells respond maximally to GHK at 1 nanoM.
“Most cultured cells respond maximally to GHK at 1 nanoM.”
The paper relies on this without support.
GHK has a half-life of about 0.5 to 1 hour in plasma.
“GHK has a half-life of about 0.5 to 1 hour in plasma”
The paper relies on this without support.
GHK is abundantly available at low cost in bulk quantities.
“GHK, abundantly available at low cost in bulk quantities, is a potential treatment for a variety of disease conditions associated with aging.”
The paper relies on this without support.
On skin, GHK acts most strongly in the late stage of healing (remodeling), where cellular migration into the wound area is stopped and cellular debris is removed.
“On skin, GHK seems to act most strongly in the late stage of healing, called remodeling, where cellular migration into the wound area is stopped and cellular debris is removed.”
The paper relies on this without support.
Most current theories and therapies to treat disease tend to target only one biochemical reaction or pathway.
“Most current theories and therapies to treat disease tend to target only one biochemical reaction or pathway.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
GHK-Cu is able to up- and down-regulate a significant number of human genes.
“This tool allowed researchers to investigate genome-wide effects of GHK and establish that GHK-Cu is able to up- and down-regulate a significant number of human genes.”
From Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data (2018) · cites this paper as [4]
Section 2.1 (Gene Expression Analysis; page unavailable) reports that GHK stimulated or suppressed expression of many human genes in cell-line profiles. It identifies the tested compound as GHK, not specifically GHK-Cu; Section 3.8 discusses experiments using a mixture of copper-free GHK and GHK-Cu, but does not establish that the genome-wide profiles tested GHK-Cu specifically. (LLM, conf=0.84)
Experimental — accuracy not yet measuredGHK modulates the expression of many genes.
“Importantly, GHK modulates the expression of many genes [5].”
From Ternary Cu(II) Complex with GHK Peptide and Cis-Urocanic Acid as a Potential Physiologically Functional Copper Chelate (2020) · cites this paper as [5]
GHK-Cu modulates expression of numerous genes associated with regulation of important biochemical pathways important for skin repair and regeneration.
“GHK-Cu modulates expression of numerous genes associated with regulation of important biochemical pathways important for skin repair and regeneration [12].”
From Skin Regenerative and Anti-Cancer Actions of Copper Peptides (2018) · cites this paper as [12]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Conflicting percentages of genes affected by GHK
MinorThe paper reports 32.1% of genes changing by more than 50%, but later reports only 31.2% changing by at least 50%. For the same gene data, the percentage meeting the broader "at least 50%" cutoff cannot be smaller.
“GHK's actions on gene expression were determined by the Broad Institute and, using their data, we determined that GHK increased or decreased gene expression (UP or DOWN more than 50%) in 32.1% of the human genes [7].”
“The number of genes stimulated or suppressed by GHK with a change greater than or equal to 50% is 31.2%.”
The citation lists haven’t been fetched yet
References 65 · Cited by 39
Research works printed but not linked: 5
- 2009, The human tripeptide GHK (Glycyl-L-Histidyl-L-Lysine), 301
- 2012, Acta Poloniae Pharmaceutica, 69, 1303
- 2000, Cellular and Molecular Biology, 46, 407
- 2010, Experimental Biology and Medicine, 4, 15
- 2006, Experimental Biology and Medicine, 3, 11
- Authors
- Pickart, L., Vasquez-Soltero, J. M., & Margolina, A.
- Affiliations
- Skin Biology, Research & Development Department, 4122 Factoria Boulevard SE, Suite No. 200, Bellevue, WA 98006, USA
- Corresponding author
- Pickart, Loren
- Venue
- BioMed Research International
- Publisher
- Wiley
- Published
- 2014
- Volume
- 2014
- Pages
- 1-10
- ISSN
- 1110-7243 (ISSN-L)
- 2314-6133
- 2314-6141
- PMC
- PMC4180391
- OpenAlex
- W2026022954
- Semantic Scholar
- d05c1b46834675cd3f1baaf6d1773e5725726c71
- Cited by
- 39
- References
- 65
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 5 · 2019: 2 · 2018: 6 · 2017: 2 · 2016: 1 · 2015: 4
- FWCI
- 2.27
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- BioMed Research International (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- gene expression regulation, human aging, wound healing, tissue regeneration, decorin, angiogenesis, neurite outgrowth, mesenchymal stem cells, tumor cell apoptosis, chronic obstructive pulmonary disease, fibrinogen synthesis, ubiquitin-proteasome system, DNA repair, antioxidant defense, TGF-beta superfamily, anti-inflammatory activity
- MeSH terms
- Aging, Chromosome Mapping, DNA, DNA-Binding Proteins, Humans, Oligopeptides, Genome, Human, Proteome, Pulmonary Disease, Chronic Obstructive
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 by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.
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 ›
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