For half a century, Russian scientists such as Vladimir Anisimov and Vladimir Khavinson have been developing small peptides that can extend lifespan and at the same time reduce or prevent the aging phenomena that occur in old age. Epitalon, perhaps one of their most successful discoveries, has been in vogue outside of Russia for several years in the longevity scene. If you peruse the impressive biomedical literature on Epitalon, you’ll understand why.  |  By Willem Koert

If both their genetic characteristics and living conditions are perfect, people can live up to about 120 years old. Reaching such a high age is, however, reserved for only a few. The life span of the average human is about 75-80 years, 30 to 40 percent less than the maximum achievable human life span.

The aim of the research project that Vladimir Anisimov, affiliated with the Petrov Research Institute of Oncology in Saint Petersburg, started in the 1970s is to reduce the gap between the average and the maximum life span. A key role in this is the administration of peptides that Anisimov and his collaborators call ‘bioregulators’.[1]

Most of the bioregulators that the Russians are studying are small peptides. They are chains of 2, 3 or 4 amino acids. The Russians synthesize them, but suspect them to be bioidentical to peptides present and active in the body. The best way of administration is by injection, but administration via a nebulizer or a capsule is also an option. And all bioregulatory peptides are able to reach the cell nucleus and interact with the DNA there. In this interaction, the peptides in old cells can ‘rejuvenate’ the DNA.

The DNA contains a collection of instructions to manufacture proteins that collectively form and function cells. As a cell has divided more often and has aged, the cell can no longer read parts of those instructions properly and can no longer produce proteins properly. The bioregulators created by Anisimov and his collaborator Vladimir Khavinson at the Institute of Bioregulation and Gerontology in St. Petersburg are making the inactive parts of ancient DNA accessible again. Bioregulating peptides allow old DNA to function as young DNA again.[2]

Animisov, Khavinson and colleagues have demonstrated these effects in a variety of organisms – in nematodes, insects, mice, rats, monkeys and humans. They even found them in plants.[3]

‘Anyone can live to be 120 years old’

“Nobody would want to live a long and unhealthy life”, Khavinson explained the Russian research project at a conference on longevity in 2017.[4] “The main goal for us now must be to allow people to stay healthy for as long as possible into their old age.”

“We have come to the conclusion that it is possible to restore it to a normal level with the use of peptide bioregulators and have found an optimal way to maintain natural peptide production of a sufficient quantity.”

In combination with a healthy lifestyle, with a healthy diet and a lot of exercise, the Russian peptides should be able to ensure that in the near future everyone can live to 120 years old in optimal health, Khavinson concluded. “The trials have already started.”

Gray market

We have not heard much about these trials since then. Perhaps commercial parties with sufficient finances to set up such trials were not interested. That is hard to imagine, when you know that Khavinson and Anisimov have managed to extend lifespan by up to 60 percent in animal models. On the other hand, the bioregulatory peptides developed by the Russians may not be patentable. Perhaps this explains the lack of interest.

Anyway, the Russian bioregulators are not officially on the market in the EU and the USA. They are available in the gray circuit. This also applies to Epitalon, the bioregulator that this blog is about [structure shown below].

Ala-Glu-Asp-Gly

Epitalon is a peptide consisting of 4 amino acids. The sequence is alanine-glutamic acid-asparagine-glycine. In the early 1990s, the Russians discovered this tetrapetide in an extract of epiphyses from the brains of cows. This extract is marketed in Russia as Epitalimin.

Anisimov has been experimenting with extracts from cow epiphyses since 1973. If he injected old rats with it, the animals lived fifty percent longer.[5] Anisimov achieved similar results with other lab animals, such as fruit flies and mice.[6]

The subjects, who all struggled with various aging symptoms, received 6 short cycles over 3 years. The researcher then followed the subjects for another 9 years. During this period, the subjects treated with the extract had a 28 percent lower risk of death than subjects who had received a placebo. Epitalimin even reduced the risk of death from heart attacks, heart failure and respiratory diseases by 50 percent.

Dozens of studies have led the Russians to the conclusion that Epitalon is the main active substance in Epitalimin – or at least can imitate the effects of other proteins in Epitalimin. For example, the researchers discovered that Epitalon stimulates the enzyme telomerase in cells in vitro. Telomerase lengthens the telomeres in the DNA of cells, theoretically allowing the cells to divide more often.[8]

Human cells [this does not include human stem cells] can divide anywhere from 40-60 times. Divide more often than not is not possible, pathologist Leonard Hayflick discovered in the 1960s.[9] In biology, this maximum number of cell divisions is called the Hayflick Limit. However, in 2004, Khavinson published a study in which exposure to Epitalon enabled human cells to divide an additional ten times.[10]

Cancer prevention

Molecular oncologists are cautious with agents that activate telomerase. In many cancer cell types, the genes that produce telomerase are turned on all the time. As a result, they can continue to divide themselves unbridled. With any phenomenon or agent that causes telomerase elongation, oncologists reflexively ask whether it can promote cancer cells.

In the case of Epitalon, this fear is not justified, Anisimov and Khavinson showed in their studies. Administration of Epitalon to mice genetically prone to cancer reduced tumor growth and extended lifespan by 40 percent.[11] In laboratory animals that age rapidly and have an increased risk of cancer, Epitalon reduced the risk of tumors developing.[12]

Human data

The Russians have published few human studies in English-language scientific journals in which test subjects were not given Epitalimin but Epitalon. There is a study in which injections of Epitalon in patients with retitinis pigmentosa protected the retina.[13] There is also a human study in which Epitalon restored the day-night rhythm and improved sleep in the elderly.[14] That’s all. There may be more studies, but we have not been able to find them.

More is known about Epitalimin. Epitalimin has been well researched and approved in Russia. In the decades that Russian doctors have used Epitalimin, no serious side effects have come to light. We have already mentioned above that Anisimov and Khavinson assume that Epitalon is the main active substance in Epitalimin. In their reviews they assume that what applies to Epitalimin also applies to Epitalon. Because we only have access to a fraction of the relevant Russian studies, we cannot say whether this is correct.

Cycles & dosages

Websites for peptide users list schedules for using Epitalon.[15] For example, a frequent schedule includes a daily subcutaneous injection of 10 milligrams of Epitalon for 10 consecutive days. An alternative is 2 injections of 5 milligrams of Epitalon daily for 10 days.

After a period of just under 6 months, this schedule can then be repeated. Users can therefore apply such an Epitalon treatment twice a year.

This treatment schedule seems to be taken from the publications of Anisimov and Khavinson.[16] However, that schedule refers to the extract Epitalimin, not Epitalon. We have not been able to find any Epitalon cycles intended for humans in the scientific literature.

In animal studies, the Russian scientists used Epitalon in a completely different way. They usually injected their test animals with a relatively low dose 5 days a week for a longer period of time.[17] [18] The human equivalent of the doses administered is – for an adult of normal body weight – approximately 30-40 micrograms of Epitalon per injection.

An alternative to injections is oral use. Medical research on other but comparable peptides shows that oral administration of a peptide requires 100 times the injectable dose to produce some bioactivity. Applying this rule of thumb, we arrive at 3-4 milligrams per daily dosage for use in a supplement. Webshops offer supplements that contain such amounts.

Real life effects and adverse effects

Judging by the experiences that Epitalon users share on internet forums, the anti-aging effects of Epitalon are not immediately visible. However, athletes notice that they recover faster, almost all users report an improvement in sleep.

Incidentally, users say that they have had their telomere length measured. They confirm that their telomere length is indeed increased by Epitalon. Remarkably, however, there is no noticeable and acute reversal of aging in these posts either. Although Epitalon may rejuvenate skin cells in vitro,[19] in real life Epitalon users do not notice that they look younger. A factor here may be the relatively young age of the users. People in their thirties and forties may not experience much from Epitalon cycles.

Finally, on social media, Epitalon users report surprisingly few side effects. A few mention red irritated injection sites. More frequent are the reports of intense dreams, which not everyone finds unpleasant.

[1] Anisimov VN, Khavinson VKh. Peptide bioregulation of aging: results and prospects. Biogerontology. 2010 Apr;11(2):139-49.

[2] Vanyushin BF, Khavinson VK (2016). Short Biologically Active Peptides as Epigenetic Modulators of Gene Activity. In: Doerfler W, Böhm P (eds). Epigenetics – A Different Way of Looking at Genetics, pp 69-90. Springer.

[3] Fedoreyeva LI, Dilovarova TA, Ashapkin VV, Martirosyan YT, Khavinson VK, Kharchenko PN, Vanyushin BF. Short Exogenous Peptides Regulate Expression of CLE, KNOX1, and GRF Family Genes in Nicotiana tabacum. Biochemistry (Mosc). 2017 Apr;82(4):521-28.

[4] Thompson A. Humans may live to 120 in just 60 years time as new drugs interact with our DNA to slow ‘inner’ ageing, according to a leading expert. Daily Mail, 30 May 2017.

[5] Anisimov VN, Bondarenko LA, Khavinson VKh. Effect of pineal peptide preparation (epithalamin) on life span and pineal and serum melatonin level in old rats. Ann N Y Acad Sci. 1992 Dec 26;673:53-7.

[6] Anisimov VN, Mylnikov SV, Khavinson VK. Pineal peptide preparation epithalamin increases the lifespan of fruit flies, mice and rats. Mech Ageing Dev. 1998 Jun 15;103(2):123-32. 

[7] Korkushko OV, Khavinson VKh, Shatilo VB, Antonyuk-Shcheglova IA. Geroprotective effect of epithalamine (pineal gland peptide preparation) in elderly subjects with accelerated aging. Bull Exp Biol Med. 2006 Sep;142(3):356-9.

[8] Khavinson VKh, Bondarev IE, Butyugov AA. Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells. Bull Exp Biol Med. 2003 Jun;135(6):590-2.

[9] Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains. Exp Cell Res. 1961 Dec;25:585-621.

[10] Khavinson VKh, Bondarev IE, Butyugov AA, Smirnova TD. Peptide promotes overcoming of the division limit in human somatic cell. Bull Exp Biol Med. 2004 May;137(5):503-6.

[11] Anisimov VN, Khavinson VKh, Alimova IN, Semchenko AV, Yashin AI. Epithalon decelerates aging and suppresses development of breast adenocarcinomas in transgenic her-2/neu mice. Bull Exp Biol Med. 2002 Aug;134(2):187-90.

[12] Rosenfeld SV, Togo EF, Mikheev VS, Popovich IG, Khavinson VKh, Anisimov VN. Effect of epithalon on the incidence of chromosome aberrations in senescence-accelerated mice. Bull Exp Biol Med. 2002 Mar;133(3):274-6.

[13] Khavinson V, Razumovsky M, Trofimova S, Grigorian R, Razumovskaya A. Pineal-regulating tetrapeptide Epitalon improves eye retina condition in retinitis pigmentosa. Neuro Endocrinol Lett. 2002 Aug;23(4):365-8.

[14] Korkushko OV, Lapin BA, Goncharova ND, Khavinson VKh, Shatilo VB, Vengerin AA, Antoniuk-Shcheglova IA, Magdich LV. [Normalizing effect of the pineal gland peptides on the daily melatonin rhythm in old monkeys and elderly people]. Adv Gerontol. 2007;20(1):74-85.

[15] Epithalon dosage calculator and guide | What researchers must know. Peptides.org. Last visit: 29-8-2023.

[16] Khavinson V, Popovich I (2017). In Anti-aging Drugs: From Basic Research to Clinical Practice, ed. Vaiserman AM. The Royal Society of Chemistry, pp 496-513.

[17] Kossoy G, Anisimov VN, Ben-Hur H, Kossoy N, Zusman I. Effect of the synthetic pineal peptide Epitalon on spontaneous carcinogenesis in female C3H/He mice. In Vivo. 2006 Mar-Apr;20(2):253-7.

[18] Kossoy G, Zandbank J, Tendler E, Anisimov V, Khavinson V, Popovich I, Zabezhinski M, Zusman I, Ben-Hur H. Epitalon and colon carcinogenesis in rats: proliferative activity and apoptosis in colon tumors and mucosa. Int J Mol Med. 2003 Oct;12(4):473-7.

[19] Lin’kova NS, Drobintseva AO, Orlova OA, Kuznetsova EP, Polyakova VO, Kvetnoy IM, Khavinson VKh. Peptide Regulation of Skin Fibroblast Functions during Their Aging In Vitro. Bull Exp Biol Med. 2016 May;161(1):175-8.