Livagen 20mg

▎Livagen Structure

▎Livagen Research

Molecular Background

Livagen is a synthetic tetrapeptide bioregulator with the specific amino acid sequence lysine-glutamic acid-aspartic acid-alanine (Lys-Glu-Asp-Ala)^[1].

Research Progress

Teimuraz Lezhava investigated the bioregulatory peptides Livagen— (Lys-Glu-Asp-Ala) and Epitalon—(Ala-Glu-Asp-Gly)—as well as the individual and combined effects of the metal ions nickel, cobalt, and zinc on chromatin condensation levels, chromosome aberration rates, and sister chromatid exchange rates in cultured lymphocytes from healthy individuals aged 20–40 and 71–86. In the cultured cells examined, the analysis described differences in chromatin condensation between the donor age groups. In these cultured lymphocyte samples, Livagen and Epitalon were associated with changes in chromatin openness and measures of de-heterochromatinization; these observations do not establish the same effects in living individuals. The study also reported changes in the frequency of metal-ion-associated chromosomal aberrations in cultured lymphocytes following experimental exposure to Livagen or Epitalon^[1].

Fig1. Influence of Livagen and Epitalon on the frequency of cells with chromosome aberrations (% of the total number of cells) induced by heavy metals in lymphocyte cultures of middle-aged people (* p < 0.05)^[1].

In T. Lezhava’s study, on the one hand, the epigenetic modification of condensed "old" chromatin was determined, and on the other hand, the influence of peptide bioregulators (Ala-Glu-Asp-Gly-Epitalon; Lys-Glu-Asp-Ala-Livagen; Ala-Glu-Asp-Pro - Cortagen and Lys-Glu - Vilon) on condensed chromatin in lymphocytes from old individuals. The researchers used molecular-cytogenetic methods: differential scanning calorimetry; activity of ribosomal genes of acrocentric chromosome satellite stalks-NORs; polymorphism of structural pericentromeric C-heterochromatin; variability of the facultative heterochromatin (sister chromatid exchanges - SCE) in the culture of lymphocytes from 75-88-year-old individuals. The study described differences in chromatin condensation in cultures prepared from older donors. The authors proposed that chromatin condensation may be associated with reduced activity of certain genes in the tested lymphocyte cultures. These measurements did not establish effects on disease outcomes. The authors reported changes in total heterochromatin condensation, acrocentric chromosome satellite regions, and ribosomal gene activity, while pericentromeric structural heterochromatin did not show comparable changes under the tested conditions. The data were interpreted as suggesting region-dependent responses to the studied peptides (Ala-Glu-Asp-Gly; Lys-Glu-Asp-Ala; Ala-Glu-Asp-Pro and Lys-Glu) in the cell-culture model^[3].

The functional characteristics of chromosomes (level of total heterochromatin, chromosome instability, and sister chromatid exchanges [SCEs]) were studied in cultured lymphocytes derived from 80- to 91-year-old and 18- to 30-year-old (control group) individuals under the single and combined effect of CoCl(2) and bioregulator Livagen by Teimuraz Lezhava.  The authors described differences in chromosome heterochromatinization (condensation of eu- and heterochromatin regions) between the donor age groups and discussed possible changes in gene activity. Livagen exposure was associated with changes in heterochromatin measurements in cultured lymphocytes from older donors. The study reported differences in the frequency of chromosomal aberrations in cultured lymphocytes exposed to CoCl(2) compared with the control group (P < 0.05). Under the reported culture conditions, the CoCl(2)-associated measurement was 3.4 +/- 0.6% in the Livagen-exposed samples (control group 4.2 +/- 0.7%). The authors also reported differences in SCE distribution across chromosomes with Co(2+) exposure alone and with Livagen: pericentromeric heterochromatin was more sensitive to the effect of CoCl(2) (15.4 +/- 1.8% SCE), while SCE were mostly registered in telomeric heterochromatin under the combined effect of CoCl(2) and Livagen 12.0 +/- 1.2% SCE (control group 4.5 +/- 0.6% and 2.8 +/- 0.5% SCE, respectively)^[2].

Research Limitations

Research by N. M. Timofeeva found that, under in vitro conditions, Livagen was reported to reduce glycyl-L-leucine dipeptidase activity in small-intestinal enzyme preparations by approximately 50%. In a separate rat experiment, digestive enzyme activity decreased in younger animals and increased in older animals following experimental exposure to Livagen; in several measures, values in older rats approached those of younger control animals. These preclinical observations do not establish safety or efficacy in humans^[4].

The cited Livagen research includes in vitro studies using human-derived lymphocyte cultures and a limited number of animal experiments; these findings are preclinical. Although these cell-culture models allow observation of chromatin condensation, chromosome aberrations, and sister chromatid exchanges, they cannot establish clinical effects or safety in humans. Such experiments do not fully reproduce physiological regulation, systemic metabolism, or tissue barriers, and the available studies do not provide a basis for human use^[1].

COCER Peptides presents Livagen exclusively for controlled laboratory research. Not for human use, veterinary use, self-administration, or clinical application. The studies above describe preclinical findings in cell cultures or animals only; they do not establish human safety, clinical efficacy, or regulatory approval, and they are not instructions for use.

▎Relevant Citations

References

[1] Lezhava T, Jokhadze T, Monaselidze J, et al. Epigenetic Variations in Chromatin Caused by the Combination of Bioregulators with Heavy Metals During Aging[J]. International Journal of Peptide Research and Therapeutics, 2022,28(4).

DOI:10.1007/s10989-022-10427-9.

[2] Lezhava T, Jokhadze T. Activation of pericentromeric and telomeric heterochromatin in cultured  lymphocytes from old individuals[J]. Ann N Y Acad Sci, 2007,1100:387-399.

DOI:10.1196/annals.1395.043.

[3] Lezhava T, Jokhadze T, Monaselidze J, et al. EPIGENETIC MODIFICATION UNDER THE INFLUENCE OF PEPTIDE BIOREGULATORS ON THE "OLD" CHROMATIN[J]. Georgian Med News, 2023(335):79-83.

PMID:37042594

[4] Timofeeva N M, Khavinson V K, Malinin V V, et al. [Effect of peptide Livagen on activity of digestive enzymes in gastrointestinal  tract and non-digestive organs in rats of different ages][J]. Adv Gerontol, 2005,16:92-96.

PMID:16075683

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