7 replies to this topic

[kevin]

From Google newsgroup sci.life-extension I read this thread which indicates the russians have been quietly researching a peptide called epithalamin which has some interesting anti-aging properties..

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Effects of pineal peptide preparation Epithalamin on free-radical processes in humans and animals.

Full Text
Anisimov VN, Arutjunyan AV, Khavinson VK.

Saint-Petersburg Institute of Bioregulation and Gerontology, St. Petersburg, Russia. aging@mail.ru

OBJECTIVES: The review on our own data on the effect of the pineal peptide preparation Epithalamin on free radical processes in rodents and humans is presented in this paper. RESULTS: The activity of Cu, Zn-superoxide dismutase (SOD) was found decreased in the brain of aged rats (30 months old) by 46.8% as compared to young animals. Concentration of Schiff's bases in the brain also went down with age (by 13.6%), while the level of dien conjugates (DC) and protein peroxidation (PPO) remained unchanged. General antioxidation activity (AOA) in the brain also remained stable with age. The liver of aged rats showed significant increase of Schiff's bases (by 27.1%) and PPO products (by 109.2%) and considerable decrease of SOD activity. The level of DC and general AOA in the liver remained unchanged with age. Considerable elevation of protein and lipid peroxidation products contents was registered in the blood serum of aged rats. At the same time, general AOA and SOD activity remarkably decreased. The results obtained evidence from both significant age-related alterations in the activity of free radical processes in animal organism and organic peculiarities of their dynamics. Application of peptide drug epithalamin suppressed significantly the intensity of peroxide chemoluminescence in the blood serum (2.8-fold) and lipid peroxide oxidation (LPO) expressed in the considerably decreased DC contents (4,1-fold). The contents of Schiff's bases showed only a tendency towards decrease (by 14.4%, p > 0.05) and PPO level remained unchanged. Epithalamin administration was followed by considerable (by 36.6%, p < 0.01) increase of general AOA and increased SOD activity (by 19.7%) in males. Epithalamin decreased significantly the contents of conjugated hydroperoxides and ketodienes in tissues of D.melanogaster females, increased catalase activity in drosophila males and females, and increased SOD activity in males of D.melanogaster by 41%. Humans reveal significant age-related decrease of antioxidation defence indices. CONCLUSION: Epithalamin administration to patients with age-related pathology eliminates imbalance in prooxidation and antioxidation systems.

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Neuroendocrinol Lett. 2002;23 Suppl 3:11-144. Related Articles, Links
Peptides and Ageing.

Khavinson VKh.

Saint Petersburg Institute of Bioregulation and Gerontology, 3 Dinamo Pr, Saint Petersburg, 197110, Russia. ibg@medport.ru

A technology has been developed for manufacturing of biologically active complex peptide preparations from extracts of different tissues. In particular, the pineal preparation (Epithalamin) augments the in vitro outgrowth of explants from the pineal gland but not from other tissues, the latter being stimulated by peptide preparations from respective tissues. Epithalamin increases melatonin production by the pineal gland of rats, improves immunological parameters in rats and mice, produces anticarcinogenic effects in different experimental models, stimulates antioxidant defenses, and restores the reproductive function in old rats. These effects are combined in the ability of Epithalamin to increase the lifespan in rats, mice, and fruit flies. Many of these effects are reproduced in clinical trials, which have demonstrated the geroprotector activity of Epithalamin in humans. Among the effects of the thymic preparation Thymalin, those related to its ability to stimulate immunity are the most prominent. This ability is associated with anticarcinogenic and geroprotector activities. Clinical trials of the peptide preparations obtained from other organs including the prostate, the cerebral cortex, and the eye retina, have demonstrated beneficial effects reflected by the improvement of the conditions of respective organs. Based on the data about the amino acid compositions of the peptide preparations, novel principles of the design of biologically active short peptides possessing tissue-specific activities has been developed. Dipeptides specific for the thymus and tetrapeptides specific for the heart, liver, brain cortex, and pineal glands stimulate the in vitro outgrowth of explants of respective organs. Interestingly, for eye retina and the pineal gland, a common tetrapeptide Ala-Glu-Asp-Gly (Epitalon) has been designed, probably reflecting the common embryonal origin of these two organs. Epitalon reproduces the effects of Epithalamin including those related to its geroprotector activity. In particular, Epitalon increases the lifespan of mice and fruit flies and restores the circadian rhythms of melatonin and cortisol production in old rhesus monkeys. At the same time, Epitalon prolongs the functional integrity of the eye retina in Campbell rats with hereditary Retinitis Pigmentosa and improves the visual functions in patients with pigmental retinal degeneration. Changes in gene expression were observed to be produced by the short peptide preparations. Therefore, the effects of Epitalon are suggested to be mediated by transcriptional machinery common for the pineal gland and the retina and, probably, for regulation of melatonin production in fruit flies. Based on three decades of studies of the peptide preparations, the peptide theory of ageing has been put forward. According this theory, ageing is an evolutionary determined biological process of changes in gene expression resulting in impaired synthesis of regulatory and tissue-specific peptides in organs and tissues, which provokes their structural and functional changes and the development of diseases. Correspondingly, correction of such disorders by means of stimulation of peptide production in the organism or through their delivery can promote the normalisation of disturbed body functions.

Publication Types:
Review
Review, Academic

PMID: 12374906 [PubMed - indexed for MEDLINE]
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Adv Gerontol. 2002;10:74-84. Related Articles, Links


Geroprotective effect of thymalin and epithalamin

[Article in Russian]

Khavinson VKh, Morozov VG.

St. Petersburg Institute of Bioregulation and Gerontology, 3, Dynamo Prospect, 197110, St. Petersburg, Russia. khavinson@gerontology.ru

Researchers of the St. Petersburg Institute of Bioregulation and Gerontology of the North-Western Branch of the Russian Academy of Medical Sciences and the Research Institute of Gerontology of the Ukrainian Academy of Medical Sciences (Kiev) clinically assessed the geroprotective effects of thymic and epiphyseal peptide bioregulators (Thymalin and Epithalamin, correspondingly) in 266 elderly and older persons during 6-8 years (the bioregulators were applied for the first 2-3 years of observation). The obtained results convincingly confirmed the ability of the bioregulators to normalize the basic functions of the human organism, i.e. to improve the indices of the cardiovascular, endocrine, immune, and nervous systems, homeostasis, and metabolism. The restoration of homeostasis in the patients was accompanied by a 2.0-2.4-fold decrease in acute respiratory disease incidence, reduced incidence ischemic heart disease clinical manifestations, hypertension, deforming osteoarthrosis, and osteoporosis, as compared to the control group. Such a significant improvement in the somatic state of the peptide-treated patients corresponded to a decrease in their mortality rate during the observation period: 2.0-2.1-fold among the Thymalin-treated patients, 1.6-1.8-fold--in the Epithalamin-treated group, and 2.5-fold--in the patients treated with Thymalin combined with Epithalamin, as compared to the control group. A separate group of patients was treated with Thymalin combined with Epithalamin annually for 6 years. We registered a 4.1-fold mortality decrease in this group as compared to the control level. The results of our research confirmed the conclusion on the high geroprotective efficacy of Thymalin and Epithalamin and the expediency of their application in medicine and social care as the means of health maintenance and age-related pathology prevention in persons over 60 years old enabling the prolongation of the active period of their lives.

Publication Types:
Review
Review, Tutorial

PMID: 12577695 [PubMed - indexed for MEDLINE]
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And it looks like they are getting ready to market the pharmaceutical

Epithalamin®

Maybe it will give the pill by Ceremedix a run...

[lordprovost]

See, I knew he couldn't have made that much cash by the age of 36, heh [lol]

http://www.crikey.co...815chelski.html

[kevin]

Biogerontology. 2003;4(4):193-202.

Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice.

Anisimov VN, Khavinson VK, Popovich IG, Zabezhinski MA, Alimova IN, Rosenfeld SV, Zavarzina NY, Semenchenko AV, Yashin AI.

Department of Carcinogenesis and Oncogerontology, N.N. Petrov Research Institute of Oncology, Pesochny-2, St. Petersburg, 197758, Russia (Author for correspondence; e-mail: aging@mail.ru; fax: +7-812-596-8947)

From the age of 3 months until their natural deaths, female outbred Swiss-derived SHR mice were subcutaneously injected on 5 consecutive days every month with 0.1 ml of normal saline (control) or with 1.0 microg/mouse ( approximately 30-40 microg/kg) of tetrapeptide Epitalon(®) (Ala-Glu-Asp-Gly) dissolved in 0.1 ml saline. There were 54 mice in each group. The results of this study show that treatment with Epitalon did not influence food consumption, body weight or mean life span of mice. However, it slowed down the age-related switching-off of estrous function and decreased the frequency of chromosome aberrations in bone marrow cells (by 17.1%, P < 0.05). It also increased by 13.3% the life span of the last 10% of the survivors (P < 0.01) and by 12.3% the maximum life span in comparison with the control group. We also found that treatment with Epitalon did not influence total spontaneous tumor incidence, but inhibited the development of leukemia (6.0-fold), as compared with the control group. The data obtained suggest a geroprotector activity of Epitalon and the safety of its long-term administration in mice.

PMID: 14501183 [PubMed - as supplied by publisher]

[treonsverdery]

Ala-Glu-Asp-Gly AEDG is one of the peptides Im verifying prior to genetically engineering it with barley

The Reader might want to volunteer to do rapid protocol work funded by me

Paramecium lifespan increases with melatonin, I will be trying this peptide on paramecium plus maybe daphnia http://imminst.org/f...f=142&t=2848&s=

Genscript.com tells me
Ala-Glu-Asp-Gly, 2 Mg, Crude peptide, the price will be $75 plus $30 for shipping and handling
A little nearer 40 If I use the university's sequencer place
The lifespan dosage with flies is 1 unit peptide:10 million unit nutrient

You the volunteer just count the quantity of daphnia alive in a tube every alternate day, ordinary daphnia lifespan is 90d thus more attention might be given d70+
N per tube might be 20. The living ones will be swimming.

The nice thing with Ala-Glu-Asp-Gly is that Amino acid substitutions in proteins which do not substantially alter biological and immunological activities have been known to occur and have been described, e.g., by Neurath et al., in "The Proteins", Academic Press, New York (1979), in particular in FIG. 6 at page 14. The most frequently observed amino acid substitutions are Ala/Ser, Val/lle, Asp/Glu, Thr/Ser, Ala/Gly, Ala/Thr, Ser/Asn, Ala/Val, Ser/Gly, Tyr/Phe, Ala/Pro, Lys/Arg, Asp/Asn, Leu/lle, Leu/Val, Ala/Glu, Asp/Gly

from http://www.uspto.gov

If AEDG is active, it may have many active versions that will be different than the planned commercial peptide like GDDG or AEGG The paramecium or daphnia will tell us

Write treonsverdery [alien] yahoo.com

also

Effect of epitalon on the lifespan increase in Drosophila melanogaster.
AU: Khavinson-V-Kh; Izmaylov-D-M {a}; Obukhova-L-K; Malinin-V-V
SO: Mechanisms-of-Ageing-and-Development. [print] December 1, 2000; 120 (1-3): 141-149.
Epitalon significantly increased the lifespan (LS) of imagoes[flies] by 11-16% when applied at unprecedented low concentrations - from 0.001 X 10-6 to 5 X 10-6 wt.% of culture medium for males and from 0.01 X 10-6 to 0.1 X 10-6 wt.% of culture medium for females. The increase in LS did not depend on the substance dose. Effective concentrations of epitalon were 16 000-80 000 000 times lower than those of melatonin

AEGG makes me think short peptides are like domain names

Edited by treonsverdery, 06 January 2004 - 09:54 AM.

[johnross47]

Biogerontology. 2003;4(4):193-202.

Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice.

Anisimov VN, Khavinson VK, Popovich IG, Zabezhinski MA, Alimova IN, Rosenfeld SV, Zavarzina NY, Semenchenko AV, Yashin AI.

Department of Carcinogenesis and Oncogerontology, N.N. Petrov Research Institute of Oncology, Pesochny-2, St. Petersburg, 197758, Russia (Author for correspondence; e-mail: aging@mail.ru; fax: +7-812-596-8947)

From the age of 3 months until their natural deaths, female outbred Swiss-derived SHR mice were subcutaneously injected on 5 consecutive days every month with 0.1 ml of normal saline (control) or with 1.0 microg/mouse ( approximately 30-40 microg/kg) of tetrapeptide Epitalon(®) (Ala-Glu-Asp-Gly) dissolved in 0.1 ml saline. There were 54 mice in each group. The results of this study show that treatment with Epitalon did not influence food consumption, body weight or mean life span of mice. However, it slowed down the age-related switching-off of estrous function and decreased the frequency of chromosome aberrations in bone marrow cells (by 17.1%, P < 0.05). It also increased by 13.3% the life span of the last 10% of the survivors (P < 0.01) and by 12.3% the maximum life span in comparison with the control group. We also found that treatment with Epitalon did not influence total spontaneous tumor incidence, but inhibited the development of leukemia (6.0-fold), as compared with the control group. The data obtained suggest a geroprotector activity of Epitalon and the safety of its long-term administration in mice.

PMID: 14501183 [PubMed - as supplied by publisher]

http://www.demogr.mp...pitalon-SHR.pdf

it also decreased the average lifespan of the epitalon treated group

[Mind]

Is there any reason to bio-chemical reason to suggest that Epitalon has different lifespan effects in mice vs. humans? Is this a dead end for rejuvenation, or another case where a substance (in this case a peptide) does not work well in isolation - is not a magic bullet - but perhaps might play a role in a more comprehensive life extension therapy? I know, big questions here, but I don't have enough knowledge to properly evaluate it myself.

[AgeVivo]

epitalon is generally considered a hoax in biogerontology. sorry guys.

[Logic]

epitalon is generally considered a hoax in biogerontology. sorry guys.

Care to expand on this statement AgeVivo?

It certainly is not by people taking it:
http://www.longecity...ad/page__st__90

It also seems to be antimetastatic:

http://www.ncbi.nlm....pubmed/16634527

Effect of the synthetic pineal peptide epitalon on spontaneous carcinogenesis in female C3H/He mice.

Kossoy G, Anisimov VN, Ben-Hur H, Kossoy N, Zusman I.

Source

Koret School of Veterinary Medicine, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot, Israel.

Abstract

The potential preventive effect of the synthetic pineal peptide Epitalon (Ala-Glu-Asp-Gly) on spontaneous tumorigenesis in mice was studied. One-year-old female C3H/He mice were kept for 6.5 months under standard conditions. Epitalon was injected at a dose of 0.1 microg, 5 times a week. Long-term exposure to Epitalon in small doses did not show any toxic effect. Treatment with Epitalon decreased the number of tumor-bearing mice with malignant tumors and prevented the development of metastases. Spontaneous tumors of the reproductive organs (mammary glands and ovaries) were predominant in both groups of mice (control and experimental). The mammary gland tumors were different variants of invasive ductal carcinomas. In the ovaries, granulosa-cell tumors were found. Tumors were in the minority in other organs and had benign characteristics. In control mice, metastases were found in 3 out of 9 tumor-bearing mice, all of them being from tumors of the reproductive organs. Treatment with Epitalon slowed down the development of metastases from spontaneous tumors, and no metastases were found in the experimental mice. These data highlight the antimetastatic effect of Epitalon as part of its oncostatic properties.