Epitalon 50mg

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Epitalon is a short peptide composed of four amino acids, initially studied for its role in cellular aging and circadian rhythm mechanisms. Its primary functions focus on cellular renewal, regulation of the cell cycle, and maintenance of overall homeostasis. Research indicates that Epitalon participates in intracellular signaling pathways, exerting regulatory effects on the cellular life cycle. Its mechanisms involve telomere-related regulation, rhythmic gene expression, and the stability of cell cycle signaling. By influencing key regulatory pathways, it contributes to the long-term functional maintenance of cells. In studies of aging mechanisms, circadian rhythm regulation, and cellular homeostasis, Epitalon is regarded as a significant research tool, holding fundamental importance for understanding long-term regulation at the cellular level.

The peptide will be provided as lyophilized powder to ensure maximum stability.

What is Epitalon?

Epitalon is a synthetic tetrapeptide. It is an anti-aging drug and a telomerase activator. It has an inhibitory effect on the development of spontaneous tumors in mice and also has the function of preventing aging. When administered nasally, it can increase the activity of neurons. It can also be used in the treatment of cancer, geriatric diseases, and retinitis pigmentosa.

Epitalon helps cells replicate telomeres by activating telomerase, thus maintaining the health and replication ability of cells. This is of great significance for anti-aging and maintaining tissue function. In addition, Epitalon can also regulate the circadian rhythms of melatonin and cortisol, which may be helpful for improving sleep and maintaining the normal function of the biological clock.

In medical research, Epitalon has shown potential in many aspects, including extending the lifespan of experimental animals and improving visual function. As a polypeptide substance, Epitalon has broad application prospects in the fields of anti-aging, regenerative medicine, and the treatment of chronic diseases.

▎Epitalon Structure

Sequence: Ala-Glu-Asp-Gly

Molecular Formula: C₁₄H₂₂N₄O₉

Molecular Weight: 390.35 g/mol

CAS Number: 307297-39-8

PubChem CID: 219042

Synonyms: Epithalon

Epitalon Research

What is the research background of Epitalon?

In the 1980s, a group of Russian researchers led by Vladimir Khavinson first discovered Epitalon1^[1]. Epitalon is a synthetic short peptide composed of four amino acids: alanine, glutamic acid, aspartic acid, and glycine. Its synthesis is based on the natural peptide epithalamion extracted from the pineal gland. Epitalon is believed to have antioxidant effects comparable to those of melatonin and may have the benefit of extending lifespan^[2]. Researchers have found that Epitalon can stimulate the activity of telomerase. Telomerase is an enzyme that can protect and extend the telomeres at the ends of chromosomes. As people age, telomeres shorten, which is associated with age-related diseases and a shorter lifespan. By stimulating telomerase activity, Epitalon may help extend telomeres, thereby slowing down the aging process and preventing aging-related diseases ^[1]. Some studies have shown that Epitalon may be involved in regulating the expression of CCL11 and HMGB1 genes and act as an activator of the expression of these genes. At the same time, the dipeptide vilon (Lys-Glu) and the tetrapeptide Epitalon (Ala-Glu-Asp-Gly) may exert their anti-aging effects by inhibiting these genes. Together, Epitalon and vilon are known to regulate gene expression and protein synthesis, promoting a reduction in mortality and a slowdown in pathological development in the elderly^[3]. Currently, the research on Epitalon mainly focuses on the animal experiment stage, and its long-term effectiveness and safety in humans have not been fully determined. Although some animal studies have achieved encouraging results, such as in rodents, Epitalon is associated with a longer lifespan and better health, the applicability of these results in humans still requires further research^[1].

What is the mechanism of action of Epitalon in the field of anti-aging?

Reducing the level of reactive oxygen species:

Reactive oxygen species (ROS) play an important role in the aging process of oocytes. Excessive ROS will cause oxidative damage to oocytes, affecting their quality and developmental potential. Studies have shown that Epitalon can reduce the rate of cytoplasmic fragmentation of oocytes caused by aging and the content of intracellular reactive oxygen species ^[2]. As an antioxidant, Epitalon can neutralize intracellular ROS and reduce its damage to oocytes. Specifically, it may be achieved in the following two ways: First, directly scavenging ROS. Epitalon may have the ability to directly react with ROS and convert it into harmless substances. Second, enhancing the activity of antioxidant enzymes. Epitalon may stimulate the activity of intracellular antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), etc. These enzymes can help scavenge ROS and maintain the intracellular redox balance.

Improving mitochondrial function:

Mitochondria play a key role in the energy metabolism and cell survival of oocytes. As oocytes age, mitochondrial function will gradually decline, manifested as a decrease in mitochondrial membrane potential and a reduction in the copy number of mitochondrial DNA. Epitalon can increase the mitochondrial membrane potential and the copy number of mitochondrial DNA^[2]. This helps to improve the energy supply of oocytes and maintain the normal physiological functions of cells. The specific mechanism of action may include: First, increasing the mitochondrial membrane potential. Maintaining the mitochondrial membrane potential is crucial for the normal function of mitochondria. Epitalon may increase the mitochondrial membrane potential by regulating the ion channels or transport proteins on the mitochondrial membrane, enhancing the energy production capacity of mitochondria. Second, increasing the copy number of mitochondrial DNA. Increasing the copy number of mitochondrial DNA can improve the synthesis ability of mitochondria and provide more energy for cells. Epitalon may increase the copy number of mitochondrial DNA by promoting the replication of mitochondrial DNA or reducing its degradation.

Reducing abnormal spindle morphology and abnormal exocytosis of cortical granules:

During the aging process of oocytes, the ratios of abnormal spindle morphology and abnormal exocytosis of cortical granules will increase, which will affect the fertilization and embryonic development ability of oocytes. Epitalon can reduce the ratios of abnormal spindle morphology and abnormal exocytosis of cortical granules^[2] . This may be due to the regulatory effect of Epitalon on the stability of the cytoskeleton and the cell membrane: First, stabilizing the spindle structure. The spindle is an important structure in the process of cell division, and its abnormal morphology will lead to abnormal chromosome segregation and affect the development of oocytes. Epitalon may stabilize the spindle structure by regulating the polymerization and depolymerization of tubulin, reducing the occurrence of abnormal morphology. Second, maintaining the stability of cortical granules. Cortical granules play an important role in the fertilization process of oocytes. Epitalon may maintain the stability of cortical granules by regulating the permeability of the cell membrane or calcium ion signaling, reducing the occurrence of abnormal exocytosis.

Reducing apoptosis signals:

During the aging process of oocytes, apoptosis signals will increase, leading to cell death. Epitalon can reduce the positive rate of Annexin V staining and the fluorescence intensity of γH2AX in in vitro aged oocytes^[2]. This indicates that Epitalon can reduce the apoptosis of oocytes. The specific mechanism may include: First, inhibiting the apoptosis signaling pathway. Epitalon may inhibit the transmission of apoptosis signals by regulating key proteins in the apoptosis signaling pathway, such as Bcl-2 family proteins and caspase family proteins, and reduce cell death. Second, maintaining genomic stability. γH2AX is one of the markers of DNA damage. Epitalon may maintain genomic stability by reducing DNA damage and reducing apoptosis signals.

Epitalon maintained normal spindle integrity and CGs distribution.

Source:PubMed^[2]

What is the specific mode of action of Epitalon in the treatment of neurodegenerative diseases?

Regulation of immune function:

Studies have shown that Epitalon can affect the immune response of mice under different stress conditions. In the face of immune-stimulating rotational stress and immunosuppressive combined stress, Epitalon can increase the proliferation activity of thymocytes ^[4]. This means that Epitalon may enhance the body's resistance to neurodegenerative diseases by regulating the immune system. The proliferation of thymocytes is closely related to the function of the immune system, and the immune system plays an important role in the occurrence and development of neurodegenerative diseases. For example, some neurodegenerative diseases may be related to the abnormal activation or dysfunction of the immune system. The promoting effect of Epitalon on the proliferation of thymocytes may help maintain the balance of the immune system, thereby alleviating the symptoms of neurodegenerative diseases.

Influence on the signal transduction pathway:

Epitalon has a regulatory effect on the interleukin-1β (IL-1β) signal transduction pathway. Specifically, Epitalon can increase the synergistic effect of IL-1β and affect the activity of the key enzyme in the ceramide signal transduction pathway in the cerebral cortex membrane, namely membrane neutral sphingomyelinase (nSMase)^[4]. IL-1β is an important cytokine involved in a variety of physiological and pathological processes. In neurodegenerative diseases, the abnormal expression of IL-1β may lead to neuroinflammation and neuronal damage. By regulating the IL-1β signal transduction pathway, Epitalon may reduce neuroinflammation and protect neurons from damage. In addition, changes in the activity of nSMase are also related to neurodegenerative diseases. The regulation of the activity of nSMase by Epitalon may help maintain the normal function of nerve cells.In conclusion, the mode of action of Epitalon in the treatment of neurodegenerative diseases may involve immune regulation and the regulation of the signal transduction pathway. However, the current research on Epitalon in the treatment of neurodegenerative diseases is still in the preliminary stage, and further research is needed to confirm its effectiveness and safety.

The research progress of Epitalon

The impact on the quality of oocytes

Delaying the aging of oocytes:

In vitro experimental studies have found that Epitalon can reduce the level of intracellular reactive oxygen species (ROS) in aged mouse oocytes after ovulation. Over time, the developmental potential of oocytes will gradually decrease after ovulation in vivo or in vitro. As a synthetic short peptide, Epitalon acts similarly to melatonin and is an effective antioxidant, which may have the benefit of extending lifespan. Treatment with Epitalon significantly reduced the frequency of spindle defects and abnormal distribution of cortical granules during 12 hours and 24 hours of aging, and at the same time increased the mitochondrial membrane potential and the copy number of mitochondrial DNA, thereby reducing the apoptosis of oocytes during 24 hours of in vitro aging. These results indicate that Epitalon can delay the aging process of oocytes in vitro by regulating mitochondrial activity and ROS levels^[2].

Improving the quality of oocytes:

Adding 0.1 mM of Epitalon to the in vitro culture medium can reduce the rate of cytoplasmic fragmentation in the parthenogenetic activation of oocytes caused by in vitro aging after ovulation, reduce the ratios of abnormal spindle morphology and abnormal exocytosis of cortical granules, increase the mitochondrial membrane potential and the copy number of mitochondrial DNA, and reduce the positive rate of Annexin V staining and the fluorescence intensity of γH2AX in in vitro aged oocytes. This indicates that Epitalon can improve the disorder of organelles during the in vitro aging process of oocytes and improve the quality of oocytes (Xue Yue).

The impact on the differentiation of nerve cells

Studies have found that the AEDG peptide (Epitalon) can increase the synthesis of neurogenic differentiation markers in human gingival mesenchymal stem cells, such as Nestin, GAP43, β Tubulin III, and Doublecortin. Molecular modeling methods show that Epitalon preferentially binds to H1/6 and H1/3 histones, which may be one of the mechanisms for increasing the transcription of these neuronal differentiation genes^[5].

The regulatory effect on the nervous system

Regulating neuronal activity:

Through research on rats, it has been found that intranasal infusion of Epitalon (2 ng) can significantly activate the neural activity of the cerebral cortex of rats within a few minutes, and the firing frequency of neurons is increased by 2 - 2.5 times^[6]. In some recordings, complex responses consisting of several stages were also observed. The increase in the spontaneous activity of neurons by Epitalon is caused by a higher frequency of already active units and the participation of previously silent cells. At least the first stage of the action of Epitalon can be explained by the direct effect of this peptide on the cells of the motor cortex.

Stress protection effect:

Epitalon has a stress protection effect on mice exposed to different stress conditions. Experiments have shown that Epitalon increases the proliferation activity of thymocytes. Whether it is enhanced under immune-stimulating rotational stress or inhibited under immunosuppressive combined stress, Epitalon can play a regulatory role (Vladimir Kh Khavinson, 2002). At the same time, Epitalon can also increase the synergistic effect of interleukin-1β (IL-1β) and has an impact on the changes in the activity of sphingomyelinase (nSMase) in the cerebral cortex membrane induced by stress. This indicates that Epitalon has a stress protection effect at the level of IL-1β signal transduction in the sphingomyelin pathway and at the level of target thymocyte proliferation in nerve tissues.

The impact on the endocrine function of non-human primates:

In elderly rhesus monkeys, Epitalon can reduce the basal levels of glucose and insulin and increase the basal nighttime melatonin level. At the same time, Epitalon can reduce the area under the plasma glucose response curve, increase the "disappearance" rate of glucose, and normalize the plasma insulin kinetics in response to the administration of glucose. This indicates that Epitalon is a promising factor for restoring age-related endocrine dysfunction in primates^[7].

The potential application of Epitalon in the treatment of nervous system diseases

Alzheimer's disease: Alzheimer's disease is a common neurodegenerative disease, mainly characterized by a decline in cognitive function and memory loss. Current research shows that Alzheimer's disease is related to impaired neurogenic differentiation. The number of neural stem cells in the brains of Alzheimer's disease patients decreases, and their differentiation ability is also inhibited. Epitalon may promote the proliferation and differentiation of neural stem cells, increase the number of neurons, and improve the cognitive function of Alzheimer's disease patients. In addition, Epitalon may also regulate the release of neurotransmitters, improving the memory and learning ability of Alzheimer's disease patients^[8].

Parkinson's disease: Parkinson's disease is a neurodegenerative disease mainly characterized by motor disorders. Its main pathological feature is the loss of dopaminergic neurons in the substantia nigra. The current treatment methods mainly relieve the symptoms by supplementing dopamine or inhibiting the degradation of dopamine, but these methods cannot stop the progression of the disease. Neural stem cell transplantation is a potential treatment method, but the source and differentiation ability of neural stem cells are still a problem. Epitalon may promote the proliferation and differentiation of neural stem cells, increase the number of dopaminergic neurons, and improve the motor function of Parkinson's disease patients^[8].

Stroke and brain injury: Stroke is a common cerebrovascular disease, and its main consequence is the death of neurons and neurological dysfunction. Brain injury may also lead to the loss of neurons and dysfunction. Neural stem cells play an important role in the repair and regeneration after stroke and brain injury. Epitalon may promote the proliferation and differentiation of neural stem cells, increase the number of neurons, and improve the neurological function of stroke and brain injury patients ^[8].

In conclusion, as a synthetic tetrapeptide, the core anti-aging mechanism of Epitalon lies in activating the expression of the telomerase reverse transcriptase subunit (TERT) gene, extending the length of telomeres and maintaining telomerase activity, thereby intervening in the core process of cellular aging. Its significance lies in the first realization of anti-aging intervention from the perspective of telomere biology, breaking through the limitation of traditional antioxidants that only target free radicals, and providing a new target for delaying age-related diseases such as Alzheimer's disease and cardiovascular diseases. Although its long-term safety (especially the risk of cancer) still needs to be verified in phase III clinical trials, as the research and development paradigm of the first telomerase activator-type anti-aging drug, it marks a revolutionary breakthrough in aging intervention from symptom improvement to molecular mechanism regulation and is expected to promote the extension of human healthy lifespan.

About The Author

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

Scientific Journal AuthorVladimir Khavinson is a prominent Russian biogerontologist and peptide bioregulator researcher. He is the Director of the St. Petersburg Institute of Bioregulation and Gerontology and a member of the Russian Academy of Medical Sciences. Khavinson has made significant contributions to the field of aging research and has authored numerous publications in reputable journals such as "Molecular Biology of Aging" and "Journal of Anti-Aging Medicine". His work primarily focuses on the development and application of peptide bioregulators to combat age-related diseases and improve healthspan. Khavinson's research has been influential in the field of gerontology, offering new insights and therapeutic approaches for healthy aging. Vladimir Khavinson is listed in the reference of citation [5].

▎Relevant Citations

[1] Teterin O, Gv S. Epitalon[Z]. 2023. https://www.researchgate.net/publication/370060637_Epitalon

[2] Yue X, Liu S, Guo J, et al. Epitalon protects of against post-ovulatory aging-related damage of mouse oocytes in vitro[J]. Aging-Us, 2022,14(7):3191-3202. DOI: 10.18632/aging.204007

[3] Khavinson V K, Kuznik B I, Tarnovskaia S I, et al. Peptides and CCL11 and HMGB1 as molecular markers of aging: literature review and own data[J]. Advances in Gerontology = Uspekhi Gerontologii, 2014,27(3):399-406. DOI:10.1134/S2079057015030078

[4] Khavinson V K, Korneva E A, Malinin V V, et al. Effect of epitalon on interleukin-1β signal transduction and the reaction of thymocyte blast transformation under stress[J]. Neuroendocrinology Letters, 2002,23(5-6):411-416.

[5] Khavinson V, Diomede F, Mironova E, et al. AEDG Peptide (Epitalon) Stimulates Gene Expression and Protein Synthesis during Neurogenesis: Possible Epigenetic Mechanism[J]. Molecules, 2020,25(3).DOI:10.3390/molecules25030609.

[6] Sibarov D A, Vol'Nova A B, Frolov D S, et al. Intranasal epitalon infusion modulates neuronal activity in the rat neocortex.[J]. Rossiiskii Fiziologicheskii Zhurnal Imeni I.M. Sechenova, 2006,92(8):949-956. https://pubmed.ncbi.nlm.nih.gov/17217245/

[7] Goncharova N D, Vengerin A A, Khavinson V K, et al. Pineal peptides restore the age-related disturbances in hormonal functions of the pineal gland and the pancreas[J]. Experimental Gerontology, 2005,40(1-2):51-57.DOI:10.1016/j.exger.2004.10.004.

[8] Zhou H, Wang B, Sun H, et al. Epigenetic Regulations in Neural Stem Cells and Neurological Diseases[J]. Stem Cells International, 2018,2018.DOI:10.1155/2018/6087143.

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