Livagen
Also known as: KEDA, Lys-Glu-Asp-Ala, tetrapeptide KEDA, lyvagen
Short synthetic peptide bioregulator (tetrapeptide)
What it is
Livagen (Lys-Glu-Asp-Ala) is a synthetic tetrapeptide bioregulator derived from liver tissue analysis. Its primary studied mechanism involves epigenetic remodeling of chromatin: it induces deheterochromatinization (decondensation) of total heterochromatin, activates ribosomal gene synthetic processes by decondensing nucleolus organizer regions (NORs) of acrocentric chromosomes, and releases genes repressed by age-related heterochromatinization of euchromatic regions (PMID 12533768, PMID 16705247, PMID 15085253). Livagen also induces decondensation of pericentromeric structural heterochromatin of chromosomes 1 and 9 (PMID 15085253, PMID 16705247). In biochemical studies, Livagen inhibited enkephalin-degrading enzymes in human serum in vitro, with an IC50 of 20 µM; it did not interact with mu- or delta-opioid receptors. Tissue culture studies indicate tissue-specific stimulation of liver explant growth, consistent with its derivation from liver polypeptide preparations (PMID 11713572, PMID 12096446). Livagen is reported to be weakly hydrolyzed by peptide hydrolases of the small intestine. In hepatocyte cultures, it increased protein synthesis particularly in old animals. In vivo (rat), Livagen administration per os for two weeks reduced digestive enzyme activity in young animals while increasing it toward youthful levels in old animals.
Class: Short synthetic peptide bioregulator (tetrapeptide)
What it's studied for
- Chromatin reactivation / epigenetic modulation in aging Human observational
- Livagen induced activation of ribosomal genes, decondensation of pericentromeric structural heterochromatin, and release of age-repressed genes in lymphocytes from old people (75–88 yr). PMID 12533768 Khavinson et al., Bulletin of Experimental Biology and Medicine (2002)
- Livagen (with Epitalon and Vilon) activated synthetic processes via deheterochromatinization of NORs, induced unrolling of total heterochromatin, and released heterochromatinization-repressed genes in lymphocytes of old individuals (75–88 yr). PMID 16705247 Lezhava et al., Georgian Medical News (2006)
- Livagen induced activation of ribosome genes, decondensation of densely packed chromatin fibrils, deheterochromatinization of facultative chromatin, and decondensation of pericentromeric structural chromatin of chromosomes 1 and 9 in leukocytes of subjects aged 75–88 years. PMID 15085253 Khavinson et al., Bulletin of Experimental Biology and Medicine (2004)
- Livagen induced reactivation (deheterochromatinization) of chromatin and modified heterochromatinized chromosomal regions in cultured lymphocytes of aged individuals (80–91 yr); it decreased CoCl2-induced chromosomal aberrations. PMID 17460203 Lezhava & Jokhadze, Annals of the New York Academy of Sciences (2007)
- Livagen (Lys-Glu-Asp-Ala) induced deheterochromatinization of total heterochromatin and satellite stalks of acrocentric chromosomes, activating ribosomal gene synthetic processes, but did not deheterochromatinize pericentromeric structural heterochromatin in lymphocytes from individuals aged 75–88 years. PMID 37042594 Lezhava et al., Georgian Medical News (2023)
- Hepatoprotection and liver function support Mixed
- KEDA (Livagen) demonstrated hepatoprotective, immunoprotective, and antioxidant effects in experimental liver pathology models (fibrosis, acute and chronic hepatitis) in animals and in vitro; maximal effect observed in aging. PMID 32362099 Kuznik et al., Advances in Gerontology (2020)
- Livagen stimulated structural and functional homeostasis of cell populations in organotypic liver culture (rat), stabilizing morphological integrity and reinforcing cellular and intracellular regeneration. PMID 12577697 Riadnova et al., Advances in Gerontology (2002)
- Livagen increased protein synthesis in hepatocyte monolayer cultures from rats of different ages; highest effect observed in old animals; in old rats it increased the amplitude of protein synthesis fluctuations. PMID 15926314 Brodskiy et al., Izvestiia Akademii nauk (2001)
- Genomic instability correction in atherosclerosis Human observational
- Livagen (alone and combined with cobalt ions) promoted normalization of altered genomic indicators (chromosomal aberrations, aneuploidy, polyploidy) in lymphocytes from atherosclerosis patients of two age groups; identified as potentially efficacious in prevention of atherosclerosis. PMID 25541832 Dzhokhadze et al., Georgian Medical News (2014)
- Genomic instability correction in hypertrophic cardiomyopathy (HCM) Human observational
- Livagen (alone and with cobalt chloride) was tested in lymphocyte cultures from HCM patients and relatives; showed protective action on functional genome parameters, though Epitalon was reported most effective for reducing chromosomal instability. PMID 24423684 Dzhokhadze et al., Georgian Medical News (2013)
- Combined Livagen and cobalt ions increased frequency of large-sized NORs and associative activity of acrocentric chromosomes in lymphocytes from HCM patients and relatives, suggesting decondensation of heterochromatinized chromatin and release of inactivated genes. PMID 25341254 Georgian Medical News (2014)
- Genomic instability correction in ductal breast cancer Human observational
- Livagen (with cobalt ions) reduced DNA single-strand breaks, chromosomal abnormalities, and sister chromatid exchanges in lymphocyte cultures from ductal breast cancer patients, demonstrating a protective effect on all studied genomic parameters. PMID 28574395 Jokhadze et al., Georgian Medical News (2017)
- Radiation adaptive response modulation in aged individuals Human observational
- Corrective activity of Livagen was observed in aged individuals (72–86 yr) in the context of radiation-induced adaptive response to low-dose gamma-rays and copper chloride-induced damage in PHA-stimulated lymphocytes. PMID 17921545 Dzhokhadze et al., Georgian Medical News (2007)
- Modulation of expression of chromosome fragile sites Human observational
- Livagen (and Epitalon) lessened heavy metal (nickel, zinc, cobalt) effects on expression of chromosome fragile sites in peripheral blood lymphocytes; statistically reliable reduction was observed only in the young age group (20–38 yr). PMID 18830022 Dzhokhadze et al., Georgian Medical News (2008)
- Inhibition of enkephalin-degrading enzymes / opioid system modulation In vitro only
- Livagen inhibited enkephalin-degrading enzymes in human serum in vitro (IC50 = 20 µM), more efficiently than puromycin, leupeptin, and D-PAM. No interaction was observed with mu- or delta-opioid receptors in rat brain membrane fraction. PMID 12942748 Kost et al., Izvestiia Akademii nauk (2003)
- Tissue-specific stimulation of liver explant growth Animal studies only
- Livagen (a cytogen) stimulated growth of liver explants in organotypic cultures of rat tissues in a tissue-specific manner. PMID 11713572 Khavinson, Bulletin of Experimental Biology and Medicine (2001)
- Livagen exerted tissue-specific effects in organ-typical culture of rat tissues (cerebral cortex, liver, thymus) across different ages. PMID 12096446 Khavinson et al., Advances in Gerontology (2002)
- Modulation of digestive enzyme activity Animal studies only
- Livagen is weakly hydrolyzed by small intestinal peptide hydrolases. In vitro it reduced glycil-L-leucinedipeptidase activity in small intestine by 50%. After two weeks of per os administration in rats, digestive enzyme activity decreased in young animals and increased toward youthful levels in old animals. PMID 16075683 Timofeeva et al., Advances in Gerontology (2005)
- Anti-aging / longevity-associated epigenetic activity Animal studies only
- Motifs of short-chain epigenetically active peptides (including those structurally related to Livagen) were discovered in proteins of the long-lived African mole rat (Heterocephalus glaber) but not in short-lived rodent species, suggesting a link between these peptides and longevity. PMID 28948547 Khavinson et al., Bulletin of Experimental Biology and Medicine (2017)
Community-reported dosing
| Route | Dose | Frequency / Duration | Population / context | Source tier |
|---|---|---|---|---|
| In vitro | IC50 = 20 µM (enkephalin-degrading enzyme inhibition in human serum in vitro) | Not stated (in vitro assay) | in_vitro | Research PMID 12942748 |
| Per os (oral) | Not specified (per os administration) | Two weeks | animal | Research PMID 16075683 |
| In vitro | Reduction of glycil-L-leucinedipeptidase activity by 50% (in vitro concentration not specified) | Not stated (in vitro) | in_vitro | Research PMID 16075683 |
| Not specified (experimental liver pathology models in animals and in vitro) | Not specified | Not specified | animal | Research PMID 32362099 |
| Organotypic liver culture (in vitro) | Not specified | Not specified | in_vitro | Research PMID 12577697 |
| In vitro (hepatocyte monolayer culture) | Not specified | Not specified | in_vitro | Research PMID 15926314 |
| In vitro (organotypic tissue culture) | Not specified (concentrations described as varied) | Not specified | in_vitro | Research PMID 12096446 |
Tier key: Research = PMID-cited study · [C] = scraped community source · [S] = model-synthesized from aggregate community reports (softer evidence). How we source.
Safety signals
- Cobalt ions (CoCl2) used in combination with Livagen caused significant increases in chromosomal aberrations in old donors compared to control (P < 0.05); Livagen alone decreased CoCl2-induced aberrations from 4.2±0.7% to 3.4±0.6%. PMID 17460203
- No adverse effects or toxicity signals for Livagen itself are explicitly reported in any reviewed abstract; however, no formal toxicology or safety studies are described. PMID 32362099
Frequently asked
What is Livagen and what is it used for?
Livagen (Lys-Glu-Asp-Ala) is a synthetic tetrapeptide bioregulator originally derived from liver tissue analysis. Published research has primarily studied it for its ability to reactivate chromatin in aged cells — specifically by inducing decondensation (deheterochromatinization) of heterochromatin and activating ribosomal genes in lymphocytes from elderly individuals (PMID 12533768, PMID 16705247). It has also been studied for hepatoprotective effects in animal models and in vitro, inhibition of enkephalin-degrading enzymes in vitro, and correction of genomic instability in conditions such as atherosclerosis and breast cancer lymphocytes. Most human-relevant research has used ex vivo lymphocyte cultures, not in vivo human administration.
What dose of Livagen should I take?
I'm not a medical professional and can't recommend a protocol for you specifically. What research has shown: The reviewed published abstracts do not report any clinical dosing protocol for human in vivo use of Livagen. Animal studies used oral (per os) administration for two weeks but did not specify the dose. In vitro enzyme inhibition studies reported an IC50 of 20 µM. No human dosing data are available in the reviewed literature.
Can I combine Livagen with other peptides or compounds?
I can't recommend combining compounds — that's a prescribing decision. Here's what has been studied individually: Several abstracts examined Livagen alongside cobalt ions (CoCl2) in ex vivo lymphocyte cultures. Cobalt ions alone significantly increased chromosomal aberrations in aged donors; Livagen reduced these cobalt-induced aberrations. Livagen was also studied alongside Epitalon and Vilon in chromatin reactivation experiments, with each peptide showing somewhat distinct selective effects on chromosome regions (PMID 37042594, PMID 16705247). No human clinical combination data exist in the reviewed literature.
Is Livagen safe for human use?
The reviewed published abstracts do not include formal human clinical safety or toxicology studies for Livagen. Human-relevant research used ex vivo lymphocyte cultures rather than direct human administration (PMID 12533768, PMID 17460203). Kuznik et al. describe Livagen as 'harmless' in the context of liver protection in animal/in vitro models, but this characterization was not derived from a formal human safety study. No contraindications or adverse effects are explicitly reported in the reviewed literature. Consult a licensed healthcare provider before considering use.
How does Livagen affect the liver?
Livagen has been studied in liver-related contexts in animals and in vitro. In an organotypic rat liver culture, Livagen stimulated structural and functional homeostasis of liver cell populations and reinforced cellular and intracellular regeneration. In hepatocyte monolayer cultures, it increased protein synthesis across ages, with the greatest effect in old animals. A review reported hepatoprotective, immunoprotective, and antioxidant effects in experimental liver fibrosis and hepatitis models in animals and in vitro, with the maximal effect in aging. After two weeks of oral administration in rats, digestive enzyme activity in old animals increased toward youthful levels. No human liver clinical data are available in the reviewed abstracts.
Does Livagen affect the opioid system?
In vitro, Livagen inhibited enkephalin-degrading enzymes in human serum with an IC50 of 20 µM — more potently than known peptidase inhibitors such as puromycin, leupeptin, and D-PAM. However, Livagen did not interact with mu- or delta-opioid receptors in rat brain membrane fractions. These findings are from in vitro and animal studies only; no human in vivo opioid system data are available in the reviewed abstracts.
Can Livagen help with aging or longevity?
Livagen has been studied primarily in the context of age-related chromatin changes. Research in lymphocyte cultures from elderly individuals (75–91 years old) showed that Livagen can induce decondensation of heterochromatin and reactivation of genes that become silenced with aging (PMID 12533768, PMID 16705247, PMID 15085253). A separate study found structural motifs similar to epigenetically active short peptides in proteins of the long-lived African mole rat, suggesting a possible longevity-related relevance. However, no human clinical trial demonstrating anti-aging outcomes from Livagen administration exists in the reviewed literature. These findings should be interpreted cautiously.
Where can I buy Livagen?
I don't recommend vendors or sources. Please consult a licensed provider.
Can Livagen treat cancer?
I can't suggest treatments for medical conditions. Please speak with a licensed healthcare provider. For context, one observational study found that Livagen reduced DNA single-strand breaks, chromosomal abnormalities, and sister chromatid exchanges in ex vivo lymphocyte cultures from ductal breast cancer patients. This is preliminary laboratory research, not evidence of clinical efficacy as a cancer treatment.
Is Livagen the same as KEDA?
Yes. Multiple reviewed abstracts use the names interchangeably. 'KEDA' is the abbreviation for the amino acid sequence Lys-Glu-Asp-Ala, which is the tetrapeptide sequence of Livagen (PMID 32362099, PMID 25541832). It has also been referred to as 'lyvagen' in some publications.
How is Livagen administered in studies?
The reviewed abstracts describe two primary research administration contexts: (1) direct application to ex vivo lymphocyte or tissue cultures in vitro (PMID 12533768, PMID 17460203, PMID 12577697, PMID 15926314); and (2) oral (per os) administration in rats for two weeks. No injectable human administration protocols are described in the reviewed abstracts. Specific reconstitution methods, concentrations, or formulation details are not reported in the reviewed literature.
References
- [1] PMID 12533768 — Livagen induced activation of ribosomal genes, decondensation of pericentromeric structural heterochromatin, and release of age-repressed genes in lymphocytes f
- [2] PMID 16705247 — Livagen (with Epitalon and Vilon) activated synthetic processes via deheterochromatinization of NORs, induced unrolling of total heterochromatin, and released h
- [3] PMID 15085253 — Livagen induced activation of ribosome genes, decondensation of densely packed chromatin fibrils, deheterochromatinization of facultative chromatin, and deconde
- [4] PMID 17460203 — Livagen induced reactivation (deheterochromatinization) of chromatin and modified heterochromatinized chromosomal regions in cultured lymphocytes of aged indivi
- [5] PMID 37042594 — Livagen (Lys-Glu-Asp-Ala) induced deheterochromatinization of total heterochromatin and satellite stalks of acrocentric chromosomes, activating ribosomal gene s
- [6] PMID 32362099 — KEDA (Livagen) demonstrated hepatoprotective, immunoprotective, and antioxidant effects in experimental liver pathology models (fibrosis, acute and chronic hepa
- [7] PMID 12577697 — Livagen stimulated structural and functional homeostasis of cell populations in organotypic liver culture (rat), stabilizing morphological integrity and reinfor
- [8] PMID 15926314 — Livagen increased protein synthesis in hepatocyte monolayer cultures from rats of different ages; highest effect observed in old animals; in old rats it increas
- [9] PMID 25541832 — Livagen (alone and combined with cobalt ions) promoted normalization of altered genomic indicators (chromosomal aberrations, aneuploidy, polyploidy) in lymphocy
- [10] PMID 24423684 — Livagen (alone and with cobalt chloride) was tested in lymphocyte cultures from HCM patients and relatives; showed protective action on functional genome parame
- [11] PMID 25341254 — Combined Livagen and cobalt ions increased frequency of large-sized NORs and associative activity of acrocentric chromosomes in lymphocytes from HCM patients an
- [12] PMID 28574395 — Livagen (with cobalt ions) reduced DNA single-strand breaks, chromosomal abnormalities, and sister chromatid exchanges in lymphocyte cultures from ductal breast
- [13] PMID 17921545 — Corrective activity of Livagen was observed in aged individuals (72–86 yr) in the context of radiation-induced adaptive response to low-dose gamma-rays and copp
- [14] PMID 18830022 — Livagen (and Epitalon) lessened heavy metal (nickel, zinc, cobalt) effects on expression of chromosome fragile sites in peripheral blood lymphocytes; statistica
- [15] PMID 12942748 — Livagen inhibited enkephalin-degrading enzymes in human serum in vitro (IC50 = 20 µM), more efficiently than puromycin, leupeptin, and D-PAM. No interaction was
- [16] PMID 11713572 — Livagen (a cytogen) stimulated growth of liver explants in organotypic cultures of rat tissues in a tissue-specific manner.
- [17] PMID 12096446 — Livagen exerted tissue-specific effects in organ-typical culture of rat tissues (cerebral cortex, liver, thymus) across different ages.
- [18] PMID 16075683 — Livagen is weakly hydrolyzed by small intestinal peptide hydrolases. In vitro it reduced glycil-L-leucinedipeptidase activity in small intestine by 50%. After t
- [19] PMID 28948547 — Motifs of short-chain epigenetically active peptides (including those structurally related to Livagen) were discovered in proteins of the long-lived African mol