▎Livagen Research

What is the research background of Livagen?

The Free Radical Theory of Aging: In the 1950s, Harman proposed the free radical theory of aging, suggesting that free radicals produced during cellular metabolism would attack biomolecules, leading to cell damage and aging. This theory provided a theoretical basis for the research of anti-aging substances and prompted scientists to search for substances that could scavenge free radicals or enhance the antioxidant capacity of cells.

The Discovery of Peptide Substances: With the continuous in-depth study of biology, scientists have found that peptide substances play an important role in cell signaling, metabolic regulation, and other aspects. Some peptide substances have functions such as antioxidant, anti-inflammatory, and promoting cell repair, which provides a new direction for the development of new anti-aging drugs.

The Research and Development of Livagen: Against this background, Russian scientists developed Livagen based on their research on peptide substances. They extracted bioactive peptide fragments from animal tissues and finally obtained Livagen after a series of screenings and optimizations. Studies have shown that Livagen can regulate the metabolic process of cells and enhance the antioxidant capacity of cells, thereby delaying cell aging.

What is the mechanism of action of Livagen?

1. Effects on the Digestive System

Regulating the Activity of Digestive Enzymes: Studies have shown that Livagen (Lys-Glu-Asp-Ala) is a weakly hydrolyzable peptide. The peptide hydrolases in the small intestine can hardly hydrolyze Livagen to a very small extent^[1]. Under in vitro conditions, Livagen can reduce the activity of glycyl-L-leucine dipeptidase in the small intestine by 50%. After orally administering Livagen to rats for two weeks, the activity of digestive enzymes in young animals decreased, while that in old animals increased. It is worth mentioning that in most cases, the enzyme activity of old rats after receiving Livagen was close to the level of young animals in the control group^[1].

2. Effects on Enkephalin Degrading Enzymes in Serum

Inhibiting Enkephalin Degrading Enzymes: The effects of the new peptide bioregulators Livagen and Epitalon (Ala-Glu-Asp-Gly) on the endogenous opioid system were studied, especially their ability to change the activity of enkephalin degrading enzymes in serum and interact with opioid receptors in the membrane fraction of brain cells. The activity of enkephalinase was determined in vitro by measuring the hydrolysis rate of ⊃3;H-Leu-enkephalin in the presence of the test peptides. Livagen and Epitalon inhibited the enkephalin degrading enzymes in human serum. Compared with well-known peptidase inhibitors such as puromycin, leupeptin, and D-PAM, Livagen was proven to be more effective. The dose-inhibition effect curves of Livagen and Epitalon were plotted, and their IC₅₀ values were 20 and 500 μM respectively ^{[2, 3]}.

3. Protective Effects on the Liver

As a Potential Hepatoprotective Agent: The use of many drugs in the elderly is often the cause of liver dysfunction. Therefore, with the increase of age, the risks of liver fibrotic induration, acute and chronic hepatitis increase. This is the reason for searching for new, effective, and harmless hepatoprotective agents. Some studies have shown that the hepatic polypeptide complex (Ventvil) and the KEDA tetrapeptide (Lys-Glu-Asp-Ala, Livagen) have hepatoprotective, immunoprotective, and anti-aging properties. In animal and in vitro experimental models of liver pathology (liver fibrotic induration, acute and chronic hepatitis), Ventvil and the KEDA peptide showed high efficiency. Ventvil and the KEDA peptide have a consistent effect - normalizing the immune and antioxidant status and restoring liver function during hepatitis. Studies have shown that during the aging process, the maximum hepatoprotective and immunoprotective effects of the peptides have been verified^[4].

4. Effects on the Chromatin of Lymphocytes

Activating the Chromatin of Lymphocytes: The effects of the synthetic peptide Livagen on the activity of ribosomal genes, the parameters of heterochromatin denaturation, the polymorphism of structural C heterochromatin, and the variability of facultative heterochromatin in the lymphocytes of the elderly were studied. Livagen induced the activation of ribosomal genes, the depolymerization of the constitutive heterochromatin around the centromere, and the release of genes that were inhibited due to the condensation of age-related euchromatin regions in the chromosomes. The results showed that Livagen led to the deheterochromatization (activation) of chromatin in the chromosomes of the elderly, which was achieved by modifying the heterochromatin and the heterochromatinized regions in the chromosomes^[5].

What are the applications of Livagen?

Research on Cellular Aging

Livagen can affect the activity of key enzymes involved in the cell repair or stress response pathways. For example, it interacts with epigenetic regulators and influences the changes in chromatin structure and gene expression patterns, thereby regulating the process of cellular aging. Oxidative damage accumulates over time and leads to cellular aging-related dysfunctions. The effect of Livagen on the oxidative stress pathway is one of the research hotspots, and it can delay cellular aging by regulating the relevant pathways.

Effects on Liver Diseases

With the increase of age, the use of many drugs by the elderly often leads to liver dysfunction, thus increasing the risks of liver fibrosis, acute and chronic hepatitis. In this situation, it is crucial to find new, effective, and harmless hepatoprotective agents. Some studies have shown that the hepatic polypeptide complex (Ventvil) and the KEDA tetrapeptide (Lys-Glu-Asp-Ala, namely Livagen) have hepatoprotective, immunoprotective, and anti-aging properties. In animal experimental models of liver pathology (liver fibrosis, acute and chronic hepatitis) and in vitro experiments, Ventvil and the KEDA peptide showed high efficiency. Ventvil and the KEDA peptide have a synergistic effect, which can normalize the immune and antioxidant status and restore liver function during hepatitis. Moreover, during the aging process, the hepatoprotective and immunoprotective effects of these peptides reach their maximum^[4].

Effects on the Genomic Parameters of Cancer Patients

It has been found that the genome of patients with ductal breast cancer is characterized by a high density of single-strand DNA breaks, a high frequency of chromosomal abnormalities, and an increased level of chromatin condensation. Using the oligopeptide bioregulator Livagen and cobalt ions as modifiers has a protective effect on the lymphocyte cultures of patients with ductal breast cancer, which can normalize all the studied parameters. This indicates that through the study of the lymphocytes of patients with ductal breast cancer, the curative effect of the treatment of breast cancer patients can be evaluated^[6].

Effects on the Lymphocytes of Patients with Hypertrophic Cardiomyopathy and Their Relatives

The effects of the peptide bioregulator Livagen (Lys-Glu-Asp-Ala) used alone and in combination with cobalt ions on the activity of nucleolar organizing regions (NORs) and the frequency of association of acrocentric chromosomes in the lymphocytes of patients with hypertrophic cardiomyopathy and their relatives were studied. The results showed that the combined action of Livagen and cobalt ions increased the frequency of NORs with a large score of 2 in patients and their relatives. These compounds also had a significant effect on the association activity of acrocentric chromosomes, manifested as a sharp increase in this index in both study groups.

In this case, the action of Livagen and cobalt ions was more effective. Since the activity of NORs and the frequency of association of acrocentric chromosomes depend on the condensation quality of the stalks of acrocentric chromosomes, it can be concluded that Livagen and cobalt ions have an effect on the lymphocytes of patients with hypertrophic cardiomyopathy and their relatives, causing the decondensation of heterochromatinized chromatin. This may be the condition for the release of inactivated genes during the condensation process in the individuals of the study group. These data provide new information on the protective effects of Livagen and Livagen + cobalt ions on the lymphocytes of patients with hypertrophic cardiomyopathy and their relatives and may contribute to the development of treatment methods^[7].

Effects on Enkephalin Degrading Enzymes in Serum

The effects of the new peptide bioregulators Livagen (Lys-Glu-Asp-Ala) and Epitalon (Ala-Glu-Asp-Gly) on the endogenous opioid system were studied, especially their ability to change the activity of enkephalin degrading enzymes in serum and interact with opioid receptors in the membrane fraction of brain cells. In vitro experiments determined the activity of enkephalinase by measuring the hydrolysis rate of ⊃3;H-Leu-enkephalin in the presence of Livagen and Epitalon. The results showed that Livagen and Epitalon inhibited the enkephalin degrading enzymes in human serum. Livagen was more effective than some well-known peptidase inhibitors such as puromycin, leupeptin, and D-PAM. The dose-inhibition effect curves of Livagen and Epitalon were plotted, and their IC₅₀ values were 20 and 500 μM respectively. The interaction between the peptides and opioid receptors was evaluated using the radioligand receptor method with [⊃3;H][D-Ala⊃2;, D-Leu⁵]-enkephalin. No interaction was observed between the μ or δ opioid receptors in the membrane fraction of the rat brain and the test peptides^{[2, 3]}.

In conclusion, by regulating gene expression and promoting protein synthesis, Livagen demonstrates significant effects in anti-aging, immunomodulation, and liver function protection. It can regulate the activity of digestive enzymes, inhibit enkephalin degrading enzymes, and delay cellular aging by activating key enzymes and influencing the oxidative stress pathway. In addition, Livagen also improves immune function and antioxidant status through its hepatoprotective effect and promotes the recovery of liver function in diseases such as hepatitis. It has potential application value in the prevention and treatment of related diseases and provides a new research direction for anti-aging and health maintenance.

About The Author

The above-mentioned materials are all researched, edited and compiled by Peptisource.

Scientific Journal Author

Vladimir Khavinson was a prominent Russian gerontologist and professor known for his pioneering research in peptide bioregulators and their role in slowing aging and improving healthspan. He served as the director of the St. Petersburg Institute of Bioregulation and Gerontology and was a corresponding member of the Russian Academy of Sciences. His research focused on the development of peptide-based therapies to enhance immune function, protect against oxidative stress, and promote longevity. Over four decades, he extracted and synthesized numerous peptide complexes, leading to the introduction of six peptide-based pharmaceuticals and 64 peptide food supplements into clinical practice. Khavinson's work has significantly contributed to the field of gerontology, particularly in understanding the mechanisms of aging and developing interventions to improve quality of life in older adults.

Vladimir Khavinson is a renowned Russian gerontologist and professor, famous for his groundbreaking research on peptide bioregulators and their role in retarding aging and enhancing healthspan. He held the position of director at the St. Petersburg Institute of Bioregulation and Gerontology and was a corresponding member of the Russian Academy of Sciences. His research was centered on the development of peptide-based therapies to boost immune function, resist oxidative stress, and facilitate longevity. During more than four decades of research, he extracted and synthesized a variety of peptide complexes, which promoted the clinical application of six peptide-based drugs and 64 peptide-based food supplements. Khavinson's work has made significant contributions to the field of gerontology, especially in understanding the mechanisms of aging and developing interventions to improve the quality of life of the elderly. Vladimir Khavinson is listed in the reference of citation [5].

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