Epitalon: Telomere Lengthening and Anti-Aging

By Cocer Peptides      1 month ago 

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Introduction

With the continuous development of life sciences, research into the mechanisms of aging has become increasingly in-depth, and finding effective anti-aging methods has become an important topic in the scientific community. Telomeres, as protective structures at the ends of chromosomes, are closely related to cellular aging. Epitalon, a synthetic short peptide with anti-aging effects, has attracted attention in recent years.

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Telomere Lengthening Related Content

(1) Structure and Function of Telomeres

Telomeres are highly conserved repetitive nucleotide sequences at the ends of chromosomes, composed of simple DNA tandem repeat sequences and associated proteins. Telomeres play a crucial role in maintaining the integrity of gene structure and chromosomal stability. During each cell division, telomeres gradually shorten due to the limitations of DNA replication mechanisms. When telomeres shorten to a certain extent, cells enter the senescence or apoptosis stage, hence telomeres are metaphorically referred to as the “cellular clock of life.”

Figure 1 Epitalon decreased the intracellular ROS level.

(2) Methods of Telomere Lengthening

Telomerase pathway

Telomerase is a ribonucleoprotein complex with reverse transcriptase activity. It can use its own RNA as a template to synthesize telomere repeat sequences and add them to the ends of chromosomes, thereby maintaining telomere length. In normal human cells, telomerase activity is low or absent, and telomeres gradually shorten with each cell division. However, in many tumor cells, telomerase is reactivated, enabling tumor cells to proliferate indefinitely and achieve immortality. In pediatric primary metastatic medulloblastoma, some tumor cells control telomere elongation through telomerase activation. Approximately 10.7% of metastatic medulloblastomas induce telomerase activation via TERT promoter mutations and UTSS hypermethylation, thereby achieving telomere elongation.

ALT pathway

In addition to the telomerase pathway, there is a telomerase-independent mechanism known as the alternation lengthening of telomeres (ALT) pathway. This pathway is primarily triggered by ATRX inactivation and plays a significant role in some tumor cells. In pediatric primary metastatic medulloblastoma, approximately 32.1% of cases achieve telomere elongation through the ALT mechanism, with 30% of samples exhibiting ATRX nuclear deletions, thereby activating the ALT pathway.

(3) Epitalon and the Mechanism of Telomere Elongation

Epitalon's Effect on Telomerase

Epitalon is a synthetic short peptide composed of four amino acids (alanine, glutamic acid, aspartic acid, and glycine), based on the natural peptide Epithalamion extracted from the pineal gland. Research suggests that Epitalon may influence telomere length by stimulating telomerase activity. A group of Russian researchers first discovered in the 1980s that Epitalon can stimulate telomerase, the enzyme responsible for protecting and extending telomeres at the ends of chromosomes. Although there is currently no conclusive evidence that Epitalon can directly extend telomeres in humans, some experiments have shown that it can increase telomerase activity. Increased telomerase activity means that more telomere repeat sequences can be synthesized and added to the ends of chromosomes, potentially slowing the rate of telomere shortening and even achieving telomere elongation.

Figure 2 Epitalon protected the function of mitochondria during post-ovulatory oocyte aging in vitro.  

Epitalon's regulation of intracellular signaling pathways

Intracellular signaling pathways form a complex network that interacts to regulate cellular processes such as growth, proliferation, and aging. Epitalon may indirectly influence telomere elongation by regulating these signaling pathways. For example, it may affect pathways related to cell cycle regulation, enhancing the protective mechanisms for telomeres during cell division. Additionally, as an antioxidant, Epitalon reduces the production of reactive oxygen species (ROS) within cells. The accumulation of ROS can cause DNA damage, thereby affecting telomere stability. By lowering ROS levels, Epitalon helps maintain the normal structure and function of telomeres, creating favorable conditions for telomere elongation.

(4) Experimental Evidence for Epitalon's Role in Telomere Elongation

In vitro cell experiments

In in vitro cell culture experiments, adding Epitalon to the culture medium resulted in enhanced telomerase activity in some cells. Researchers added Epitalon at a concentration of 0.1 mM to the cell culture medium. After a period of cultivation, it was found that the expression levels of telomerase-related genes in the cells had increased, indicating that Epitalon may promote the synthesis or activation of telomerase. Additionally, measurements of telomere length showed that, compared to the control group without Epitalon, the telomere shortening rate in the experimental group was significantly slowed, and in some cells, a slight telomere lengthening was observed.

Animal experiments  

In animal experiments, Epitalon was administered to experimental animals (such as mice) via injection or oral administration, and their tissue cells were analyzed. The results showed that telomerase activity in some tissues (such as the liver and kidneys) was enhanced, and telomere length remained relatively stable. In studies of mouse liver cells, it was found that mice treated with Epitalon had significantly higher telomerase activity in liver cells compared to the untreated group, and after continuous observation over several months, the degree of telomere shortening in liver cells was significantly lower than in the untreated group. This further demonstrates that Epitalon has a positive effect on telomere elongation in animals.

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Anti-Aging-Related Content

(1) Mechanisms of Aging

Oxidative Stress and Aging

As age increases, the redox balance within cells is disrupted, leading to the accumulation of reactive oxygen species (ROS). ROS possess strong oxidative properties, capable of oxidizing cellular biomolecules such as proteins, lipids, and DNA, resulting in damage to cellular structure and function. Oxidized proteins may lose their normal biological activity, oxidized lipids may impair cellular membrane fluidity and stability, and DNA oxidative damage may lead to gene mutations and cellular dysfunction, all of which accelerate the aging process of cells and the organism.

Cellular Aging and Apoptosis

Cell senescence and apoptosis are important events in the aging process. When cells are exposed to various stress factors (such as oxidative stress, DNA damage, etc.), they enter a senescent state. Characteristics of senescent cells include cell cycle arrest, metabolic changes, and the secretion of specific cytokines. Meanwhile, apoptosis is a programmed cell death process that plays a crucial role in maintaining tissue homeostasis. However, as age increases, the regulatory mechanisms of apoptosis may become disrupted, and either excessive or insufficient apoptosis can lead to tissue functional decline, ultimately manifesting as organismal aging.

Telomere Shortening and Aging

As mentioned earlier, telomere shortening is one of the key markers of aging. As cells continue to divide, telomeres gradually shorten. When telomeres reach a critical length, cells cease division and enter a senescent state. Telomere shortening may also trigger DNA damage response reactions within cells, further accelerating cellular aging and apoptosis, thereby influencing the overall aging process of the organism.

Figure 3 Effect of Epitalon on early apoptosis in post-ovulatory aging oocytes.

(2) The Anti-Aging Mechanism of Epitalon

Antioxidant Activity

Epitalon is an effective antioxidant with antioxidant capacity comparable to melatonin. It can directly scavenge ROS within cells, reducing oxidative damage to biomolecules caused by ROS. In an in vitro experiment using mouse oocytes, adding 0.1 mM Epitalon to the culture medium resulted in a significant reduction in intracellular ROS levels. The reduction in ROS helps maintain cellular membrane integrity, normal protein function, and DNA stability, thereby delaying cellular aging. Additionally, Epitalon may enhance the cell's own antioxidant capacity by regulating the activity of intracellular antioxidant enzyme systems (such as superoxide dismutase and catalase), thereby further alleviating oxidative stress-induced cellular damage.

Regulating mitochondrial function

Mitochondria are the energy powerhouses of cells, and their functional state is closely related to cellular aging. With age, mitochondrial function gradually declines, manifested by reduced mitochondrial membrane potential, decreased ATP production, and increased ROS generation. Epitalon can increase mitochondrial membrane potential and mitochondrial DNA copy number, thereby improving mitochondrial function. In an in vitro aging experiment using mouse oocytes, oocytes treated with Epitalon exhibited significantly higher mitochondrial membrane potential and increased mitochondrial DNA copy numbers after 12 and 24 hours of aging compared to the untreated group. This indicates that Epitalon can maintain normal mitochondrial function and reduce cellular aging caused by mitochondrial dysfunction. Improved mitochondrial function also helps maintain cellular energy metabolism balance, providing sufficient energy for normal physiological activities and delaying cellular aging.

Inhibiting apoptosis

Cell apoptosis plays a crucial role in the aging process. Excessive cell apoptosis can lead to the decline of tissue and organ functions. Epitalon regulates intracellular apoptosis-related signaling pathways to reduce the occurrence of cell apoptosis. In an in vitro aging experiment using mouse oocytes, after 24 hours of in vitro aging, the apoptosis rate of oocytes in the Epitalon-treated group was significantly lower than that in the untreated group. This can be attributed to Epitalon's ability to inhibit the activation of apoptosis signals through mechanisms such as reducing ROS levels and improving mitochondrial function, thereby reducing apoptosis and helping to maintain normal tissue and organ function, and delaying bodily aging.

(3) Experimental Evidence of Epitalon's Anti-Aging Effects

Protective effect on oocytes

In experiments investigating the effects of Epitalon on oocyte quality, it was found that Epitalon effectively protects oocytes from damage associated with post-ovulation aging. As post-ovulation time increases, the developmental potential of oocytes gradually decreases. When 0.1 mM Epitalon was added to the culture medium, oocyte quality was assessed after 6, 12, and 24 hours of culture. The results showed that Epitalon treatment significantly reduced the frequency of spindle defects and abnormal distribution of cortical granules, while increasing mitochondrial membrane potential and mitochondrial DNA copy number, and reducing oocyte apoptosis. This indicates that Epitalon can delay the in vitro aging process of oocytes, maintain their quality and developmental potential, and provide cellular-level evidence of Epitalon's anti-aging effects.

Effects on overall aging in animals

In animal experiments, after long-term administration of Epitalon via feeding or injection, improvements were observed in several aging-related indicators in mice. Compared to untreated control mice, Epitalon-treated mice exhibited denser, shinier fur, enhanced mobility, and a certain degree of lifespan extension. Pathological analysis of mouse tissues revealed that the cellular damage and aging levels in important organs such as the liver and kidneys of Epitalon-treated mice were significantly lower than those in the control group. This indicates that Epitalon not only exhibits anti-aging effects at the cellular level but also slows down the aging process at the organismal level, improving animal health and quality of life.

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Application Prospects of Epitalon

Potential Applications in the Medical Field

Anti-Aging Therapy

Based on Epitalon's research findings in telomere elongation and anti-aging, it could serve as a novel anti-aging drug. With the accelerating trend of population aging, the demand for anti-aging therapies is growing. Epitalon delays cellular aging through multiple mechanisms, offering new insights for developing treatments targeting age-related diseases such as cardiovascular diseases and neurodegenerative diseases. For neurodegenerative diseases, Epitalon may protect neurons from oxidative stress damage and maintain telomere length, thereby slowing down neuronal aging and death, improving disease symptoms, and enhancing patients' quality of life.

Improving Reproductive Health

In the field of reproductive medicine, Epitalon has a certain protective effect on oocytes. As women age, oocyte quality declines, increasing the risk of infertility and fetal developmental abnormalities. Epitalon can delay oocyte aging and improve oocyte quality, providing new supportive measures for assisted reproductive technologies such as in vitro fertilization. By adding Epitalon during in vitro oocyte culture, it is expected to improve fertilization rates and embryo development quality, thereby increasing the success rate of assisted reproduction and helping more infertile couples fulfill their desire to have children.

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Conclusion

Epitalon demonstrates significant potential in telomere elongation and anti-aging. Although there are still some issues that require further research and resolution, its significance in both scientific theory and social application cannot be overlooked. As research continues to deepen, it is believed that Epitalon will bring more surprises and breakthroughs to the field of human health.

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Sources

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

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

[3] Minasi S, Baldi C, Pietsch T, et al. Telomere elongation via alternative lengthening of telomeres (ALT) and telomerase  activation in primary metastatic medulloblastoma of childhood[J]. Journal of Neuro-Oncology, 2019,142(3):435-444.DOI:10.1007/s11060-019-03127-w.

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