Livagen is a short “bioregulatory” peptide (sequence: Lys–Glu–Asp–Ala; alias KEDA) studied for its ability to loosen age‑condensed chromatin and normalize gene activity in older cells. In human lymphocyte experiments, Livagen de‑heterochromatinized DNA and reactivated ribosomal genes; in other models it modulated digestive enzymes and protected endogenous enkephalins by inhibiting their breakdown—without binding opioid receptors. Livagen is an experimental research compound, not an approved drug. (PubMed)
Fast Answer / Executive Summary (40–60 words)
Livagen is a tetrapeptide bioregulator (KEDA: Lys–Glu–Asp–Ala) investigated for epigenetic effects—specifically, opening compacted chromatin to restore youthful gene expression in aging cells. Studies in human lymphocytes and animal models report chromatin decondensation, improved protein synthesis rhythms, hepatoprotective and immunomodulatory effects, and potent inhibition of enkephalin‑degrading enzymes (without receptor agonism). Research use only; not medical advice. (PubMed)
Entity Properties (Research/Educational)
(Standardize names early: “Livagen,” sometimes misspelled “Lyvagen,” is the KEDA tetrapeptide; we use “Livagen (KEDA)” throughout.)
| Property | Value |
|---|---|
| Aliases / Synonyms | Livagen; KEDA tetrapeptide; “liver peptide bioregulator” |
| Family / Pathway | Ultrashort peptide bioregulator; epigenetic remodeling (chromatin de‑heterochromatinization); enzyme modulation (e.g., enkephalinase) |
| Sequence (AA) | Lys–Glu–Asp–Ala (K–E–D–A) |
| Molecular Formula / Weight | C18H31N5O9; ~461.5 Da (PubChem CID 87919683 for H‑Lys‑Glu‑Asp‑Ala‑OH) |
| CAS (if applicable) | No validated CAS on PubChem for KEDA. Do not use 195875‑84‑4—that CAS belongs to tesofensine, not Livagen. |
| Typical Diluent(s) | Bacteriostatic water (0.9% benzyl alcohol) or sterile saline (research handling) |
| Example Concentrations (educational) | 20 mg vial + 2 mL diluent → 10 mg/mL; a 5 mg research dose volume would be 0.5 mL (50 “units” on a U‑100 insulin syringe). |
| Storage | Lyophilized: frozen, protected from light (≤ –20 °C preferred). After reconstitution: aliquot, refrigerate short‑term; minimize freeze–thaw; solutions are less stable than powders. |
Chemical identity per PubChem; note the widespread misattribution of CAS 195875‑84‑4 to Livagen—PubChem assigns that CAS to tesofensine. (PubChem)
Stability guidance summarized from peer‑reviewed pharmaceutical reviews on peptide/protein lyophilization and solution stability. (PMC)
Core Concepts & Key Entities
What is Livagen, and how is it studied? Livagen (KEDA) is an ultrashort tetrapeptide derived from peptide‑bioregulator research in gerontology. In cultured lymphocytes from older adults, Livagen activated ribosomal genes and decondensed age‑tightened chromatin, a hallmark mechanism proposed to restore more youthful transcriptional activity. (PubMed)
How does Livagen relate to epigenetics and outcomes? The peptide’s defining action is remodeling heterochromatin—reversing age‑related chromatin compaction (de‑heterochromatinization) that represses transcription. Independent teams report selective remodeling of constitutional and facultative heterochromatin in elders’ lymphocytes with Livagen and related peptides, reinforcing a mechanistic link between chromatin structure and functional rejuvenation. (PubMed)
Which adjacent entities matter? In the bioregulator family, Epitalon (AEDG), Vilon (KE), and Thymalin frequently appear alongside Livagen. Epitalon activates telomerase and extended telomeres in human cell studies; Vilon and Thymalin exhibit immune‑modulatory effects in preclinical and clinical contexts. Positioning Livagen among these clarifies overlap (immune and gene‑regulatory effects) and differences (e.g., telomeres vs. chromatin focus). (PubMed)
Key mechanisms tied to outcomes (evidence‑first):
- Chromatin opening & gene reactivation: In human lymphocytes from older donors, Livagen activated ribosomal genes and relaxed pericentromeric heterochromatin—changes consistent with restoring protein‑synthetic capacity. (PubMed)
- Protein synthesis rhythms in aging liver cells: In rat hepatocyte cultures, Livagen increased the amplitude of protein‑synthesis oscillations in old animals’, suggesting a partial “youthful” reset of hepatic protein metabolism. (PubMed)
- Digestive enzyme modulation & oral stability signal: Rat studies found Livagen weakly hydrolyzed by intestinal peptidases and able to normalize GI enzyme activity in opposite directions by age (down in young, up in old). (PubMed)
- Endogenous opioid system support (without receptor agonism): Livagen inhibited enkephalin‑degrading enzymes with an IC50 ≈ 20 µM (vs. ≈ 500 µM for Epitalon) and did not bind μ/δ opioid receptors—consistent with preserving natural analgesic peptides rather than acting as an opioid. (PubMed)
- Hepatoprotective & immunomodulatory signals: In animal models of hepatitis and liver fibrosis, the liver tetrapeptide KEDA (Livagen) normalized immune/antioxidant status and liver function, with strongest effects in aged cohorts. (PubMed)
- Genome‑stabilizing context in vascular disease: Chromatin‑modifying bioregulators including Livagen improved genomic instability markers in patients with atherosclerosis, hinting at broader cardiometabolic relevance. (PubMed)
- Peptide transport & delivery considerations: Reviews of ultrashort peptide transport highlight uptake via peptide transporters (e.g., POT/LAT families) and relative stability of some tetrapeptides in GI and tissue homogenates—mechanistic context for observed bioactivity patterns in preclinical work. (PMC)
Bottom line: Livagen’s most distinctive contribution is epigenetic—“opening” parts of aging chromatin so key genes resume work, which in turn links to immune, hepatic, and neuropeptide outcomes reported in preclinical studies. It remains investigational and is not an approved therapy. (PubMed)
Step‑by‑Step / How‑To (Educational; Research Handling Only)
How do researchers typically handle Livagen? Researchers generally reconstitute lyophilized Livagen with sterile diluent, calculate target concentrations, administer per study design, and store aliquots to preserve integrity. Below is a practical, copy‑ready framework for lab use (not medical guidance).
1) Confirm identity & plan your concentration
Verify sequence (KEDA), formula (C18H31N5O9), and purity from supplier documentation. For easy math, many labs target 10 mg/mL (e.g., 20 mg + 2 mL). Record batch, lot, and date for traceability. (Identity per PubChem.) (PubChem)
2) Reconstitute gently
Using sterile technique, inject bacteriostatic water down the vial wall; swirl—don’t shake—until dissolved. Avoid foaming. If the study requires higher concentration (e.g., 20 mg/mL), reduce diluent proportionally and annotate all calculations.
3) Dose calculation & measurement
At 10 mg/mL, 1 mL contains 10 mg. Example: 5 mg target → 0.5 mL. For small volumes, U‑100 insulin syringes (in research) read “units” where 50 units ≈ 0.5 mL. Double‑check math and labels; have a second person verify critical steps.
4) Administration modality (study‑dependent)
Preclinical protocols often use subcutaneous or intraperitoneal routes; in vitro work applies defined media concentrations. Choose route/vehicle per study aims, species, and ethics approvals. (No human treatment claims; this is investigational use only.)
5) Storage & stability best practices
Lyophilized: store frozen, protected from light; solutions degrade faster—aliquot and keep cold; minimize freeze–thaw. Reviews in pharmaceutical science consistently show powders are more stable than solutions and advocate cold, dry storage for longevity. (PMC)
Comparison / Alternatives (“Livagen vs. other bioregulators”)
How does Livagen compare to Epitalon, Thymalin, and Vilon? Livagen emphasizes chromatin remodeling in immune/hepatic contexts; Epitalon emphasizes telomerase/telomeres; Thymalin and Vilon emphasize immune regulation. This table pinpoints outcome‑relevant differences using peer‑reviewed signals:
| Feature | Livagen (KEDA) | Epitalon (AEDG) | Thymalin (thymic complex) | Vilon (KE) |
|---|---|---|---|---|
| Primary mechanism | Chromatin de‑heterochromatinization; ribosomal gene activation; enzyme modulation | Telomerase activation & telomere elongation in human somatic cells | Thymic‑derived immune regulation; clinical use reports in immunopathologies | Chromatin effects; immune‑modulation in models |
| Signature evidence | Human lymphocyte studies show decondensed heterochromatin & rDNA activation; rat work shows protein‑synthesis rhythm improvement in aged hepatocytes | Human cell work shows telomerase induction & telomere elongation | Reviews and clinical experience summarize immune status normalization in older/immunocompromised groups | Studies report reactivation of chromatin in lymphocytes from older adults |
| Neuropeptide angle | Potently inhibits enkephalin‑degrading enzymes; no μ/δ receptor binding | Inhibits enkephalinases far less potently than Livagen | Not a focus | Not a focus |
| Where it “leans” | Epigenetic cellular renewal; immune/liver outcomes | Genomic stability; circadian/endocrine context | Immune resilience; clinical adjunct contexts | Immune/epigenetic |
| Representative sources | Khavinson 2002; Timofeeva 2005; Brodskii 2001; Kost 2003 | Khavinson 2003 (Bull Exp Biol Med) | Kuznik 2021 (review/overview) | Lezhava 2006; Khavinson 2004 |
Citations: Livagen chromatin/protein: (PubMed); Epitalon telomerase: (PubMed); Thymalin immune: (PMC); Vilon chromatin: (PubMed); Livagen enkephalinase: (PubMed)
Templates / Checklist / Example
Copy‑ready checklist: Responsible Livagen Research Use
- Verify identity: Confirm sequence (KEDA), purity, and lot; archive COA and supplier details. (PubChem)
- Standardize naming: Use “Livagen (KEDA: Lys–Glu–Asp–Ala)” and avoid mis‑CAS (195875‑84‑4 = tesofensine) in your records. (PubChem)
- Define aim & endpoints: Pre‑specify hypotheses (e.g., chromatin markers, enzyme assays, immune readouts). Align sampling with mechanism. (PubMed)
- Choose route & model: Match route (e.g., SC/IP; in vitro media dosing) to the question; comply with IACUC/IRB as applicable.
- Calculate concentrations: Plan an easy concentration (e.g., 10 mg/mL) and prepare a dosing sheet to prevent arithmetic errors.
- Reconstitute cleanly: Swirl, don’t shake; label with concentration/date; document any pH/vehicle adjustments.
- Aliquot & store: Aliquot to minimize freeze–thaw; powders at ≤ –20 °C; solutions cold, brief storage; document excursions. (PMC)
- Monitor effects: Track predefined markers: chromatin assays (NOR, C‑bands), enzyme activity, or cytokines (depending on model). (PubMed)
- Note safety signals: Record injection‑site reactions (animal work), behavior changes, or unexpected lab deviations.
- Report transparently: Disclose that Livagen is investigational; provide exact lot/concentration/protocol details for reproducibility.
FAQs (NLP‑friendly, answer‑first)
1) What is Livagen?
Livagen is a tetrapeptide bioregulator (KEDA: Lys–Glu–Asp–Ala) studied for epigenetic effects in aging cells. In human lymphocyte models, it de‑heterochromatinized compacted DNA and reactivated ribosomal genes; in rat studies, it modulated digestive enzymes and improved protein‑synthesis rhythms in aged hepatocytes. (PubMed)
2) How does Livagen work?
Livagen works by remodeling chromatin—opening age‑compacted regions so key genes can be transcribed again. This underpins reported changes in rDNA activity, heterochromatin structure, and enzyme regulation. Its enzyme‑inhibition of enkephalinases may elevate natural analgesic peptides without opioid receptor binding. (PubMed)
3) Is there clinical evidence for Livagen?
Clinical‑grade trials for Livagen are limited; most evidence is preclinical or ex vivo. Related bioregulators (e.g., Thymalin) have broader clinical literature on immune modulation, while Epitalon shows human‑cell telomerase effects. Livagen itself has human cell studies and animal data supporting epigenetic and hepatic/immune endpoints. (PMC)
4) Does Livagen affect pain or mood?
Livagen affects the endogenous opioid system by inhibiting enkephalin‑degrading enzymes (IC50 ≈ 20 µM) in vitro, which can preserve natural enkephalins; crucially, it does not bind μ/δ opioid receptors in rat brain membranes. Translational significance remains to be established in controlled trials. (PubMed)
5) Is Livagen orally active?
Livagen appears unusually resistant to intestinal hydrolysis in rats, where small‑intestine peptidases did not significantly degrade it; age‑dependent enzyme normalization was observed after oral administration in animal models. Human oral bioavailability hasn’t been established. (PubMed)
6) How should Livagen be stored for research?
Store Livagen lyophilized at cold temperatures and protect from light; after reconstitution, aliquot and keep cold, minimizing freeze–thaw. Pharmaceutical reviews consistently show peptides are far more stable as dry powders than in solution. (PMC)
Next Steps
If you’re exploring Livagen as a research tool, anchor your protocol to its core mechanism (chromatin remodeling) and pick measurable endpoints accordingly. For a step‑by‑step setup, see our internal guide to practical calculations in the Livagen 20 mg dosage protocol (educational only). (peptidedosages.com)
When sourcing for laboratory work, use reputable suppliers that provide COAs and consistency across lots; one option for research‑use material is PureLabPeptides’s Livagen (20 mg) listing. (Research use only; no medical claims).
- Order (research only): Livagen 20 mg — PureLabPeptides
Key takeaway: Livagen’s value proposition is epigenetic—selectively “opening” aging chromatin to restore gene activity, with preclinical signals across immune, hepatic, and neuropeptide pathways—but rigorous clinical validation is still ahead. (PubMed)