Overview
Overview
Livagen (Lys-Glu-Asp-Ala) is a synthetic tetrapeptide bioregulator studied for its effects on peptidase inhibition and epigenetic modulation in aging tissues[1][4]. Preclinical research demonstrates Livagen strongly inhibits enkephalin-degrading enzymes[1] and induces heterochromatin decondensation with gene reactivation in aged cells[4]. No standardized human dosing exists; this educational protocol presents a once-daily subcutaneous approach based on analogy with similar peptide bioregulators.
- Category
- Longevity
- Routes
- subcutaneous
Mechanism
Livagen
Mechanism of action
Mechanism of action
Livagen’s mechanisms involve peptidase inhibition and epigenetic modulation. The peptide strongly inhibits enkephalin-degrading enzymes (IC50 ≈ 20 μM) in human serum [1] , which may prolong endogenous enkephalin activity. Notably, this occurs without direct opioid receptor binding [1] . In aging cells, Livagen has been shown to induce heterochromatin decondensation and reactivate ribosomal genes [4] . Preclinical studies in rat liver organ cultures demonstrated enhanced cellular structure and regenerative processes [3] , while oral administration in aged rats shifted digestive enzyme activities toward youthful patterns [2] .
Key research findings
- 01
Chemistry/identity: Livagen is a synthetic tetrapeptide, Lys-Glu-Asp-Ala (KEDA), in the Khavinson short-peptide bioregulator series; PubMed-indexed reports describe it as derived from amino-acid analysis of liver peptide complexes and study it as a liver-associated bioregulator (According to PubMed: PMID 32362099; PMID 15926314). Note: KEDA = 4 residues, so 'tetrapeptide' is the precise descriptor.
- 02
In vitro (cultured human-derived lymphocytes): The most-replicated observation is that Livagen induces chromatin decondensation (de-heterochromatinization) and reactivation of ribosomal genes at nucleolar organizer regions in lymphocytes/leukocytes cultured from elderly donors (~75-91 years), including reported decondensation of pericentromeric structural heterochromatin on chromosomes 1 and 9 - interpreted by the authors as epigenetic/chromatin modulation. These are cell-culture observations, not clinical outcomes (According to PubMed: PMID 12533768, DOI 10.1023/a:1021924702103; PMID 15085253, DOI 10.1023/b:bebm.0000024393.40560.05; PMID 16705247; PMID 17460203, DOI 10.1196/annals.1395.043; PMID 37042594, 2023).
- 03
In vitro / animal model (liver): In rat hepatocyte and organotypic liver cultures, Livagen has been reported to raise protein-synthesis activity (largest effect in cells from old animals) and to support liver-tissue homeostasis and regenerative morphology in culture, with tissue-specific stimulation of liver-derived explants in organ-culture systems (According to PubMed: PMID 15926314; PMID 12577697; PMID 11713572, DOI 10.1023/a:1013058701974; PMID 12096446).
- 04
In vitro (human serum) / animal model (rat): Livagen is reported to be weakly hydrolyzed by intestinal peptidases and to modulate enzyme activity - inhibiting enkephalin-degrading enzymes in human serum (reported IC50 ~20 microM, with no measurable mu-/delta-opioid receptor binding) and shifting digestive-enzyme activity in aged rats toward younger-animal levels after oral administration (According to PubMed: PMID 12942748; PMID 16075683).
- 05
In vitro (cultured human-derived lymphocytes): Additional exploratory reports extended the same chromatin / genomic-stability assays (ribosomal-gene activity, chromosome aberrations, sister-chromatid exchanges, fragile-site expression) to lymphocyte cultures from further adult donor groups; these remain cell-culture observations, not clinical outcomes, and are described here without any therapeutic or disease-prevention claim (According to PubMed: PMID 17921545; PMID 18830022; PMID 24423684; PMID 25341254; PMID 25541832; PMID 28574395).
- 06
Research maturity (limitation): According to PubMed, no human clinical trials and no published pharmacokinetic studies of Livagen were identified (Clinical Trial/RCT filter returned zero records). The literature is concentrated in two affiliated programs - the St. Petersburg Institute of Bioregulation and Gerontology (Khavinson) and Tbilisi State University (Lezhava/Jokhadze) - largely in lower-impact and Russian-language journals, with limited independent replication. A related study supports the broader 'short-peptide epigenetic regulator' hypothesis but is not Livagen-specific (PMID 28948547, DOI 10.1007/s10517-017-3876-x).
Primary source: According to PubMed, Livagen has a real but narrow, preclinical research base (~19 indexed records spanning 2001-2023): the most-cited line is in vitro chromatin-decondensation and ribosomal-gene-reactivation work in lymphocytes cultured from elderly donors, supplemented by rat liver-culture and enzyme-modulation studies. The work is concentrated in two affiliated Russian/Georgian research groups publishing mostly in lower-impact journals, with no human clinical trials and no published pharmacokinetics identified, so despite the existence of citable mechanistic literature the data are limited and confidence in any longevity or functional benefit remains low.
Researched Effects
Researched benefits
Areas of active research and investigation. Results may vary and are based on preclinical or early clinical data.
Supports inhibition of enkephalin-degrading enzymes, potentially prolonging endogenous enkephalin signaling[1].
May modulate gene expression and chromatin structure in aging tissues[4].
Preclinical evidence suggests support for cellular homeostasis and regenerative capacity[3].
In aged rodents, oral dosing normalized digestive enzyme activity toward youthful levels[2].
Protocol Reference
Protocol reference
Commonly cited research range: 0.5–2 mg, daily.
Reference figures reported in the research literature — not a dosing recommendation. For interactive vial math and scheduling, see the Calculator and Schedule tabs.
Cited protocol & reconstitution guide
Source-backed reference fields by phase, including any volume fields authored in the cited guide.
Weeks 1–2
0.5 mg (500 mcg)
Weeks 3–4
1.0 mg (1000 mcg)
Weeks 5–6
1.5 mg (1500 mcg)
Weeks 7–12
2.0 mg (2000 mcg)
| Phase | Reference amount | Units / volume |
|---|---|---|
| Weeks 1–2 | 0.5 mg (500 mcg) | 7.5 units (0.075 mL) |
| Weeks 3–4 | 1.0 mg (1000 mcg) | 15 units (0.15 mL) |
| Weeks 5–6 | 1.5 mg (1500 mcg) | 22.5 units (0.225 mL) |
| Weeks 7–12 | 2.0 mg (2000 mcg) | 30 units (0.30 mL) |
Storage & Handling
Storage requirements(typical for most peptides)
Can be stored for extended periods. Protect from moisture.
Store in refrigerator door. Never freeze after reconstitution.
Label vials with reconstitution date. Discard if cloudy.
Reconstitution steps
- 01🌡️Draw 3.0 mL bacteriostatic water with a sterile syringe.
- 02🧴Inject slowly down the vial wall; avoid foaming.
- 03💉Gently swirl/roll until dissolved (do not shake).
- 04💧Label and refrigerate at 2–8 °C (35.6–46.4 °F), protected from light.
- 05🔄Important: This guide is for educational purposes only and is not medical advice. For research use only. Not for human consumption.
Additional storage notes
Store at −20 °C (−4 °F) in dry, dark conditions; minimize moisture exposure.
Refrigerate at 2–8 °C (35.6–46.4 °F); prepare aliquots if needed and avoid freeze–thaw .
Allow vials to reach room temperature before opening to reduce condensation uptake.
Clinical Evidence
Clinical evidence
Preclinical research reports immunomodulatory and gene-activating activity; human data are absent.
According to PubMed, Livagen has a real but narrow, preclinical research base (~19 indexed records spanning 2001-2023): the most-cited line is in vitro chromatin-decondensation and ribosomal-gene-reactivation work in lymphocytes cultured from elderly donors, supplemented by rat liver-culture and enzyme-modulation studies. The work is concentrated in two affiliated Russian/Georgian research groups publishing mostly in lower-impact journals, with no human clinical trials and no published pharmacokinetics identified, so despite the existence of citable mechanistic literature the data are limited and confidence in any longevity or functional benefit remains low.
- 01Chemistry/identity: Livagen is a synthetic tetrapeptide, Lys-Glu-Asp-Ala (KEDA), in the Khavinson short-peptide bioregulator series; PubMed-indexed reports describe it as derived from amino-acid analysis of liver peptide complexes and study it as a liver-associated bioregulator (According to PubMed: PMID 32362099; PMID 15926314). Note: KEDA = 4 residues, so 'tetrapeptide' is the precise descriptor.
- 02In vitro (cultured human-derived lymphocytes): The most-replicated observation is that Livagen induces chromatin decondensation (de-heterochromatinization) and reactivation of ribosomal genes at nucleolar organizer regions in lymphocytes/leukocytes cultured from elderly donors (~75-91 years), including reported decondensation of pericentromeric structural heterochromatin on chromosomes 1 and 9 - interpreted by the authors as epigenetic/chromatin modulation. These are cell-culture observations, not clinical outcomes (According to PubMed: PMID 12533768, DOI 10.1023/a:1021924702103; PMID 15085253, DOI 10.1023/b:bebm.0000024393.40560.05; PMID 16705247; PMID 17460203, DOI 10.1196/annals.1395.043; PMID 37042594, 2023).
- 03In vitro / animal model (liver): In rat hepatocyte and organotypic liver cultures, Livagen has been reported to raise protein-synthesis activity (largest effect in cells from old animals) and to support liver-tissue homeostasis and regenerative morphology in culture, with tissue-specific stimulation of liver-derived explants in organ-culture systems (According to PubMed: PMID 15926314; PMID 12577697; PMID 11713572, DOI 10.1023/a:1013058701974; PMID 12096446).
- 04In vitro (human serum) / animal model (rat): Livagen is reported to be weakly hydrolyzed by intestinal peptidases and to modulate enzyme activity - inhibiting enkephalin-degrading enzymes in human serum (reported IC50 ~20 microM, with no measurable mu-/delta-opioid receptor binding) and shifting digestive-enzyme activity in aged rats toward younger-animal levels after oral administration (According to PubMed: PMID 12942748; PMID 16075683).
- 05In vitro (cultured human-derived lymphocytes): Additional exploratory reports extended the same chromatin / genomic-stability assays (ribosomal-gene activity, chromosome aberrations, sister-chromatid exchanges, fragile-site expression) to lymphocyte cultures from further adult donor groups; these remain cell-culture observations, not clinical outcomes, and are described here without any therapeutic or disease-prevention claim (According to PubMed: PMID 17921545; PMID 18830022; PMID 24423684; PMID 25341254; PMID 25541832; PMID 28574395).
- 06Research maturity (limitation): According to PubMed, no human clinical trials and no published pharmacokinetic studies of Livagen were identified (Clinical Trial/RCT filter returned zero records). The literature is concentrated in two affiliated programs - the St. Petersburg Institute of Bioregulation and Gerontology (Khavinson) and Tbilisi State University (Lezhava/Jokhadze) - largely in lower-impact and Russian-language journals, with limited independent replication. A related study supports the broader 'short-peptide epigenetic regulator' hypothesis but is not Livagen-specific (PMID 28948547, DOI 10.1007/s10517-017-3876-x).
Evidence maturity varies by compound; much peptide research is preclinical (in vitro or animal-model). Where human data are limited, findings should be read as research observations, not clinical conclusions.
References
Literature references
Published research articles and sources related to Livagen.
- 01Biology Bulletin (Springer) — Effects of Livagen and Epitalon on Enkephalin-Degrading Enzymes from Human Serum View Source
- 02PubMed — Effect of peptide Livagen on activity of digestive enzymes in gastrointestinal tract and non-digestive organs in rats of different ages View Source
- 03PubMed — Functional morphology of an organotypic liver culture exposed to the peptide Livagen View Source
- 04ResearchGate / Neuroendocrinology Letters — Peptides and Ageing: heterochromatin decondensation and gene reactivation View Source
- 05CDC — Preventing Unsafe Injection Practices (clinical safety and sharps disposal) View Source
- 06MedlinePlus — Subcutaneous (SQ) injections: technique, site rotation, and skin preparation View Source
- 07PMC — Subcutaneous Drug Injection Review: pharmacologic considerations of the subcutaneous route View Source
- 08CDC (Subcut Injection PDF) — Vaccine Administration: Subcutaneous injection technique and site guidance View Source
- 09Immunize.org — How to Administer Intramuscular and Subcutaneous Vaccine Injections (no aspiration guidance) View Source
- 10NCBI Bookshelf — Best practices for injection: asepsis, preparation, and administration View Source
- 11Pure Lab Peptides — Livagen (20 mg) product page (quality and batch documentation) View Source
Observed Effects
Observed effects in cited research
Reported
- No human clinical administration studies have been reported; observed effect profile in humans is unknown.
- Occasional mild injection-site reactions (redness/itch) may occur with subcutaneous administration.
Research Considerations
Research considerations
Research Use Only - not for human or veterinary therapeutic use. Current evidence is limited to in vitro and/or animal-model research; human data are minimal or absent. Consult a licensed healthcare professional for any clinical decisions.
Factors noted in the research literature; not patient-specific medical advice.
Regulatory Status
Regulatory status
RUO
Comparisons
Comparisons
| Compound | Mechanism | Route | Status |
|---|---|---|---|
| Livagenthis | A synthetic tetrapeptide bioregulator (Lys-Glu-Asp-Ala) studied for peptidase modulation and epigenetic/chromatin effects (e.g., heterochromatin decondensation) in aging cell models. | subcutaneous | Investigational / RUO |
| NAD+ | An essential coenzyme central to cellular energy metabolism (redox reactions) and mitochondrial function, and a substrate for sirtuins and PARPs in DNA-repair and signaling pathways. | subcutaneous | Investigational / RUO |
| Prostamax | A synthetic tetrapeptide bioregulator (Lys-Glu-Asp-Pro) derived from prostate peptide-complex research, studied for tissue-specific regulatory effects on prostate tissue. | intramuscular | Investigational / RUO |
| SNAP-8 | A synthetic acetylated octapeptide (an extended Argireline analog) studied for topical reduction of muscle contraction by interfering with SNARE-complex formation at the neuromuscular junction. | subcutaneous | Investigational / RUO |
| SS-31 | A mitochondria-targeted tetrapeptide that selectively binds cardiolipin in the inner mitochondrial membrane, stabilizing electron-transport-chain organization and reducing reactive oxygen species. | subcutaneous | Investigational / RUO |
| LL-37 | The sole human cathelicidin-derived cationic antimicrobial peptide (37 residues), studied for broad-spectrum antimicrobial activity, immune modulation, and roles in wound healing and angiogenesis. | subcutaneous | Investigational / RUO |
| Mazdutide | A long-acting dual agonist of GLP-1 and glucagon receptors, combining GLP-1 appetite/glycemic signaling with glucagon-mediated energy expenditure. | subcutaneous | Investigational / RUO |
Attributes shown for research comparison only; not a statement of efficacy or therapeutic equivalence.
FAQ
Frequently asked questions
Livagen is a synthetic tetrapeptide, Lys-Glu-Asp-Ala (KEDA), in the Khavinson short-peptide bioregulator series. PubMed-indexed reports describe it as derived from amino-acid analysis of liver peptide complexes and study it as a liver-associated bioregulator (e.g., PMID 32362099). On this platform it is handled strictly as a Research Use Only material.
The most-replicated observation is in vitro: in lymphocytes cultured from elderly donors, Livagen has been reported to decondense heterochromatin and reactivate ribosomal genes, which the authors interpret as epigenetic/chromatin modulation (According to PubMed: PMID 12533768, DOI 10.1023/a:1021924702103; PMID 15085253, DOI 10.1023/b:bebm.0000024393.40560.05). These are cell-culture observations, not clinical outcomes.
It is preclinical. The human-relevant work is in vitro on cultured human-derived lymphocytes; other studies use rat hepatocytes, organotypic liver cultures, and whole rats. According to PubMed, no human clinical trials of Livagen were identified (the Clinical Trial/RCT filter returned zero records).
It is real and citable but limited. The literature is concentrated in two affiliated programs (the St. Petersburg Institute of Bioregulation and Gerontology and Tbilisi State University), largely in lower-impact or Russian-language journals, with limited independent replication and no published pharmacokinetics. It is best read as early, exploratory mechanistic research.
No validated human dosing exists. Amounts and concentrations reported in the research vary by experimental model and are not human dosing guidance; consult the protocol reference and product documentation. This is not medical advice.
No controlled human safety or pharmacokinetic data were identified, so an observed-effects profile from rigorous research is not established. The reported findings come from in vitro and animal models only.
Store the lyophilized peptide desiccated and protected from light, refrigerate reconstituted solutions, and follow the protocol reference and product documentation. It is not an approved drug or consumer product and is handled as Research Use Only, not intended for human or veterinary use.
Research-use notice
Research Use Only. This educational content and calculation support is intended for private research documentation. It does not provide medical advice, human-use directions, or claims of safety or effectiveness.