Skip to main content

Advertisement

Log in

Peptide bioregulation of aging: results and prospects

  • Research Article
  • Published:
Biogerontology Aims and scope Submit manuscript

Abstract

The review comprises the results of author’s long-term investigation in the mechanisms of aging and a role of peptide bioregulators in prevention of age-related pathology. A number of small peptides have been isolated from different organs and tissues and their analogues (di-, tri-, tetrapeptides) were synthesized from the amino acids. It was shown that long-term treatment with some peptide preparations increased mean life span by 20–40%, slow down the age-related changes in the biomarkers of aging and suppressed development of spontaneous and induced by chemical or radiation carcinogens tumorigenesis in rodents. Possible mechanisms of the biological effects of small peptides are discussed in the paper. The results of clinical applications of peptide preparation during the period of 6–12 years are presented as well.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Alexandrov VA, Bespalov VG, Morozov VG, Khavinson VKh, Anisimov VN (1996) Study of the postnatal effects of chemopreventive agents on ethylnitrosourea-induced transplacental carcinogenesis in rats. II. Influence of low-molecular-weight polypeptide factors from the thymus, pineal glands, bone marrow, anterior hypothalamus, brain cortex and brain white substance. Carcinogenesis 17:1931–1934

    Article  PubMed  Google Scholar 

  • Anisimov VN (2008) Molecular and physiological mechanisms of aging, vol 1 & 2. Nauka Publ, St. Petersburg

    Google Scholar 

  • Anisimov VN, Khavinson VKh (1991) Effect of polypeptide pineal preparation on life span and spontaneous tumor incidence in the elderly female rats. Dokl Akad Nauk SSSR 319:250–253

    PubMed  Google Scholar 

  • Anisimov VN, Khavinson VKh (1993) Using of polypeptide pineal preparation in oncology: twenty-year experience of studies on epithalamin. Vopr Onkol 39:131–142

    PubMed  Google Scholar 

  • Anisimov VN, Khavinson VKh (2003) Small peptide-associated modulation of aging and longevity. In: Rattan SIS (ed) Modulating aging and longevity. Kluwer, Dordrecht, pp 279–301

    Google Scholar 

  • Anisimov VN, Khavinson VKh (2005) Pineal peptides as modulators of aging. In: Rattan SIS (ed) Aging interventions and therapies. World Scientific, Singapore, pp 127–146

  • Anisimov VN, Khavinson VKh (2009) Use of peptide bioregulators for cancer prevention. Results of 35-year research and prospects. Vopr Onkol 55:291–304

    PubMed  Google Scholar 

  • Anisimov VN, Danetskaya EV, Morozov VG, Khavinson VKh (1980) Inhibitory effect of polypeptide thymic factor on development of mammary adenocarcinomas induced by 7, 12-dimethylbenz(a)anthracene in female rats. Dokl Akad Nauk SSSR 250:1485–1487

    PubMed  Google Scholar 

  • Anisimov VN, Khavinson VKh, Morozov VG (1982a) Carcinogenesis and aging. IV. Effect of low-molecular-weight factors of thymus, pineal gland and anterior hypothalamus on immunity, tumor incidence and lifespan of C3H/Sn mice. Mech Aging Dev 19:245–258

    Article  PubMed  Google Scholar 

  • Anisimov VN, Miretski GI, Morozov VG, Khavinson VKh (1982b) Effect of polypeptide factors of thymus and pineal gland on radiation carcinogenesis. Bull Exp Biol Med 94:80–82

    Article  Google Scholar 

  • Anisimov VN, Morozov VG, Khavinson VKh (1987) Effect of polypeptide factors of thymus, bone marrow, pineal gland and vessels on life span and tumor development in mice. Dokl Acad Nauk SSSR 293:1000–1004

    Google Scholar 

  • Anisimov VN, Loktionov AS, Khavinson VKh, Morozov VG (1989) Effect of low-molecular-weight factors of thymus and pineal gland on lifespan and spontaneous tumour development in female mice of different age. Mech Aging Dev 49:245–257

    Article  PubMed  Google Scholar 

  • Anisimov VN, Bondarenko LA, Khavinson VKh (1990) The pineal peptides: interaction with indoles and the role in aging and cancer. In: Gupta D, Wollmann HA, Ranke MB (eds) Neuro-endocrinology: new frontiers. Brain Research Promotion, London–Tubingen, pp 317–325

    Google Scholar 

  • Anisimov VN, Bondarenko LA, Khavinson VKh (1992a) Effect of pineal peptide preparation (epithalamin) on lifespan and pineal and serum melatonin level in old rats. Ann NY Acad Sci 673:53–57

    Article  PubMed  Google Scholar 

  • Anisimov VN, Miretsky GI, Morozov VG, Pavelieva IA, Khavinson VKh (1992b) Effect of synthetic immunomodulator thymogen on radiation carcinogenesis in rats. Vopr Onkol 38:451–458

    PubMed  Google Scholar 

  • Anisimov VN, Khavinson VKh, Morozov VG (1994) Twenty years of study on effect of pineal peptide preparation: epithalamin in experimental gerontology and oncology. Ann NY Acad Sci 719:483–493

    Article  PubMed  Google Scholar 

  • Anisimov VN, Mylnikov SV, Oparina TI, Khavinson VKh (1997) Effect of melatonin and pineal peptide preparation epithalamin on lifespan and free radical oxidation in Drosophila melanogaster. Mech Aging Dev 97:81–91

    Article  PubMed  Google Scholar 

  • Anisimov VN, Khavinson VKh, Morozov VG (1998a) Effect of synthetic dipeptide Thymogen® (Glu-Trp) on lifespan and spontaneous tumor incidence in rats. Gerontologist 38:7–8

    Google Scholar 

  • Anisimov VN, Mylnikov SV, Khavinson VKh (1998b) Pineal peptide preparation epithalamin increases the lifespan of fruit flies, mice and rats. Mech Aging Dev 103:123–132

    Article  PubMed  Google Scholar 

  • Anisimov VN, Khavinson VKh, Morozov VG (2000) Immunomodulatory peptide L-Glu-L-Trp slows down aging and inhibits spontaneous carcinogenesis in rats. Biogerontology 1:55–59

    Article  PubMed  Google Scholar 

  • Anisimov VN, Arutjunyan AV, Khavinson VKh (2001a) Effects of pineal peptide preparation Epithalamin on free-radical processes in humans and animals. Neuro Endocrinol Lett 22:9–18

    PubMed  Google Scholar 

  • Anisimov VN, Khavinson VKh, Mikhalski AI, Yashin AI (2001b) Effect of synthetic thymic and pineal peptides on biomarkers of aging, survival and spontaneous tumour incidence in female CBA mice. Mech Aging Dev 122:41–68

    Article  PubMed  Google Scholar 

  • Anisimov VN, Khavinson VKh, Provinciali M, Alimova IN, Baturin DA, Popovich IG, Zabezhinski MA, Imyanitov EN, Mancini R, Franceschi C (2002a) Inhibitory effect of the peptide epitalon on the development of spontaneous mammary tumors in Her-2/NEU transgenic mice. Int J Cancer 101:7–10

    Article  PubMed  Google Scholar 

  • Anisimov VN, Khavinson VKh, Popovich IG, Zabezhinski MA (2002b) Inhibitory effect of peptide Epitalon on colon carcinogenesis induced by 1, 2-dimethylhydrazine in rats. Cancer Lett 183:1–8

    Article  PubMed  Google Scholar 

  • Anisimov VN, Khavinson VKh, Popovich IG, Zabezhinski MA, Alimova IN, Rosenfeld SV, Zavarzina NYu, Semenchenko AV, Yashin AI (2003) Effect of epitalon on biomarkers of aging, lifespan and spontaneous tumor incidence in female Swiss-derived SHR mice. Biogerontology 4:193–202

    Article  PubMed  Google Scholar 

  • Anisimov SV, Boheler KR, Khavinson VKh, Anisimov VN (2004a) Elucidation of the effect of brain cortex tetrapeptide Cortagen on gene expression in mouse heart by microarray. Neuro Endocrinol Lett 25:87–93

    PubMed  Google Scholar 

  • Anisimov VN, Popovich IG, Zabezhinski MA, Rosenfeld SV (2004b) Spontaneous mutagenesis, carcinogenesis and aging in SAM mice: effect of melatonin, epitalon and neuronal. In: Takeda T (ed) Proceedings of the 19th SAM meeting, Kyoto, pp 101–102

  • Brodsky VY, Khavinson VKh, Zolotarev YuA (2001) Rhythm of protein synthesis in cultures of hepatocytes of rats at different age. Izv Akad Nauk Ser Biol 5:517–521

    Google Scholar 

  • Dilman VM, Anisimov VN, Ostroumova MN, Khavinson VKh, Morozov VG (1979a) Increase in lifespan of rats following polypeptide pineal extract treatment. Exp Pathol 17:539–545

    Google Scholar 

  • Dilman VM, Anisimov VN, Ostroumova MN, Morozov VG, Khavinson VKh, Azarova MA (1979b) Study of the anti-tumor effect of polypeptide pineal extract. Oncology 36:274–280

    Article  PubMed  Google Scholar 

  • Djeridane Y, Khavinson VKh, Anisimov VN, Touitou Y (2003) Effect of synthetic pineal tetrapeptide (Ala-Glu-Asp-Gly) on melatonin secretion by the pineal gland of young and old rats. J Endocrinol Invest 26:211–215

    PubMed  Google Scholar 

  • Goncharova ND, Vengerin AA, Khavinson VKh, Lapin BA (2005) Pineal peptides restore the age-related disturbances in hormonal functions of the pineal gland and the pancreas. Exp Gerontol 40:51–57

    Article  PubMed  Google Scholar 

  • Khavinson VKh (2001) Tissue-specific effects of peptides. Bull Exp Biol Med 132:807–808

    Article  PubMed  Google Scholar 

  • Khavinson VKh (2002) Peptides and aging. Neuro Endocrinol Letter—special issue

  • Khavinson VKh (2004) US Patent N 6,727,227 B1 “Tetrapeptide revealing geroprotective effect, pharmacological substance on its basis, and the method of its application”, 27 April 2004

  • Khavinson VKh (2006) US Patent N 7,101,854 B2 “Tetrapeptide stimulating the functional activity of hepatocytes, pharmacological substance on its basis and the method of its application”, 5 Sept 2006

  • Khavinson VKh, Anisimov VN (2009) 35-years experience in study of peptide regulation of aging. Adv Gerontol 22:11–23

    PubMed  Google Scholar 

  • Khavinson VKh, Malinin VV (2005) Gerontological aspects of genome peptide regulation. Karger AG, Basel (Switzerland)

    Google Scholar 

  • Khavinson V, Morozov V (2003) Peptides of pineal gland and thymus prolong human life. Neuro Endocrinol Lett 24:233–240

    PubMed  Google Scholar 

  • Khavinson VKh, Mikhailova ON (2007) Health and aging in Russia. In: Robinson M (ed) Global health and global aging. Josse-Bass, San Francisco, pp 226–237

  • Khavinson VKh, Mylnikov SV (2000a) Effect of Epitalon on the age-specific changes in the time course of lipid peroxidation in Drosophila melanogaster. Bull Exp Biol Med 130:1116–1119

    PubMed  Google Scholar 

  • Khavinson VKh, Mylnikov SV (2000b) Effect of pineal tetrapeptide on antioxidant defense in Drosophila melanogaster. Bull Exp Biol Med 129:355–356

    Article  PubMed  Google Scholar 

  • Khavinson VKh, Chalisova NI, Okulov VB (1997) The neurite-stimulating effect of peptides from brain in dorsal root ganglion neuron organotypic culture. Prim Sensory Neuron 2:191–200

    Article  Google Scholar 

  • Khavinson VKh, Anisimov VN, Zavarzina NYu, Zabezhinskii MA, Zimina OA, Popovich IG, Shtylik AV, Malinin VV, Morozov VG (2000a) Effect of vilon on biological age and lifespan in mice. Bull Exp Biol Med 130:687–690

    Article  PubMed  Google Scholar 

  • Khavinson VKh, Izmailov DM, Obukhova LK, Malinin VV (2000b) Effect of epitalon on the lifespan increase in Drosophila melanogaster. Mech Aging Dev 120:141–149

    Article  PubMed  Google Scholar 

  • Khavinson VKh, Morozov VG, Malinin VV, Kazakova TB, Korneva EA (2000c) Effect of peptide Lys-Glu on Interleukin-2 gene expression in lymphocytes. Bull Exp Biol Med 130:898–899

    PubMed  Google Scholar 

  • Khavinson VKh, Goncharova N, Lapin B (2001a) Synthetic tetrapeptide epitalon restores disturbed neuroendocrine regulation in senescent monkeys. Neuro Endocrinol Lett 22:251–254

    PubMed  Google Scholar 

  • Khavinson VKh, Morozov VG, Anisimov VN (2001b) Experimental studies of the pineal gland preparation Epithalamin. In: Bartsch C, Bartsch H, Blask DE, Cardinali DP, Hrushesky WJM, Mecke D (eds) The pineal gland and cancer. Springer-Verlag, Berlin, pp 294–306

    Google Scholar 

  • Khavinson VKh, Mylnikov SV, Oparina TI (2001c) Effect of peptides on generation of reactive oxygen species in subcellular fractions of Drosophila melanogaster. Bull Exp Biol Med 132:682–685

    Article  PubMed  Google Scholar 

  • Khavinson VKh, Egorova VV, Timofeeva NM, Malinin VV, Gordova LA, Gromova LV (2002a) Effect of vilon and epithalon on glucose and glycine absorption in various regions of small intestine in aged rats. Bull Exp Biol Med 133:494–496

    Article  PubMed  Google Scholar 

  • Khavinson VKh, Korneva EA, Malinin VV, Rybakina EG, Pivanovich IYu, Shanin SN (2002b) Effect of epitalon on interleukin-1ß signal transduction and the reaction of thymocyte blast transformation under stress. Neuro Endocrinol Lett 23:411–416

    PubMed  Google Scholar 

  • Khavinson V, Razumovsky M, Trofimova S, Grigorian R, Razumovskaya A (2002c) Pineal-regulating tetrapeptide epitalon improves eye retina condition in retinitis pigmentosa. Neuro Endocrinol Lett 23:365–368

    PubMed  Google Scholar 

  • Khavinson VKh, Rybakina EG, Malinin VV, Pivanovich IYu, Shanin SN, Korneva EA (2002d) Effects of short peptides on thymocyte blast transformation and signal transduction along the sphingomyelin pathway. Bull Exp Biol Med 133:497–499

    Article  PubMed  Google Scholar 

  • Khavinson VKh, Lezhava TA, Monaselidze JR, Jokhadze TA, Dvalis NA, Bablishvili NK, Trofimova SV (2003) Peptide Epitalon activates chromatin at the old age. Neuro Endocrinol Lett 24:329–333

    PubMed  Google Scholar 

  • Khavinson V, Bondarev I, Butyugov A (2004a) Epitalon peptide induces telomerase activity and telomere elongation in human somatic cells. Bull Exp Biol Med 135:590–592

    Article  Google Scholar 

  • Khavinson V, Bondarev I, Butyugov A, Smirnova T (2004b) Peptide promotes overcoming of the division limit in human somatic cell. Bull Exp Biol Med 137:613–616

    Google Scholar 

  • Khavinson V, Shataeva L, Chernova A (2005) DNA double-helix binds regulatory peptides similarly to transcription factors. Neuro Endocrinol Lett 26:237–241

    PubMed  Google Scholar 

  • Khavinson VKh, Soloviov AYu, Shataeva LK (2006) Molecular mechanism of interaction between oligopeptides and double-stranded DNA. Bull Exp Biol Med 141:457–461

    Article  PubMed  Google Scholar 

  • Khavinson VKh, Malinin VV, Grigoriev EI, Ryzhak GA (2007a) LV Patent N 13462 “Tetrapeptide regulating blood glucose level in diabetes mellitus”, 20 Feb 2007

  • Khavinson VKh, Morozov VG, Malinin VV, Grigoriev EI (2007b) US Patent N 7,189,701 B1 “Tetrapeptide stimulating the functional activity of neurons, pharmacological agent based thereon and method of use thereof”, 13 March 2007

  • Khavinson VKh, Gavrisheva NA, Malinin VV, Chefu SG, Trofimov EL (2007c) Effect of Pancragen on blood glucose level, capillary permeability and adhesion in rats with experimental diabetes mellitus. Bull Exp Biol Med 144:559–562

  • Khavinson VKh, Ryzhak GA, Grigoriev EI, Ryadnova IYu (2008a) EP Patent N 1 758 922 B1 “Peptide substance restoring function of respiratory organs”, 13 Feb 2008

  • Khavinson VKh, Ryzhak GA, Grigoriev EI, Ryadnova IYu (2008b) EP Patent N 1 758 923 B1 “Peptide substance restoring myocardium function”, 13 Feb 2008

  • Korkushko OV, Khavinson VKh, Shatilo VB, Magdich LV (2004) Effect of peptide preparation epithalamin on circadian rhythm of epiphyseal melatonin–producing function in elderly people. Bull Exp Biol Med 137:389–391

    Article  PubMed  Google Scholar 

  • Kossoy G, Zandbank J, Tendler E, Anisimov VN, Khavinson VKh, Popovich IG, Zabezhinski MA, Zusman I, Ben-Hur H (2003) Epitalon and colon carcinogenesis in rats: proliferative activity and apoptosis in colon tumors and mucosa. Int J Mol Med 12:473–477

    PubMed  Google Scholar 

  • Kossoy G, Anisimov VN, Ben-Hur H, Kossoy N, Zusman I (2006) Effect of the synthetic pineal peptide epitalon on spontaneous carcinogenesis in female C3H/He mice. In Vivo 20:253–257

    PubMed  Google Scholar 

  • Kozina LS, Arutjunyan AV, Khavinson VKh (2007) Antioxidant properties of geroprotective peptides of the pineal gland. Arch Gerontol Geriatr Suppl 1:213–216

    Article  Google Scholar 

  • Kvetnoy IM, Reiter RJ, Khavinson VKh (2000) Claude Bernard was right: hormones may be produced by “non-endocrine” cells. Neuro Endocrinol Lett 21:173–174

    PubMed  Google Scholar 

  • Labunets IF, Butenko GM, Khavinson VKh (2004a) Effect of bioactive factors of the pineal gland on thymus function and cell composition of the bone marrow and spleen in mice of different age. Bull Exp Biol Med 137:620–622

    Google Scholar 

  • Labunets IF, Butenko GM, Magdich LV, Korkushko OV, Khavinson VKh, Shatilo VB (2004b) Effect of epithalamin on circadian relationship between the endocrine function of the thymus and meiatonin–producing function of the pineal gland in elderly people. Bull Exp Biol Med 137:617–619

    Google Scholar 

  • Lezhava T (1984) Heterochromatization as a key factor in aging. Mech Aging Dev 28:279–288

    Article  PubMed  Google Scholar 

  • Lezhava T (2006) Human chromosomes and aging. From 80 to 114 years. Nova Biomedical, New York

    Google Scholar 

  • Morozov VG, Khavinson VKh (1991) US Patent N 5,070,076 “Thymus-Gland preparation and method for producing same”, 03 Dec 1991

  • Morozov VG, Khavinson VKh (1996) US Patent N 5,538,951 “Pharmaceutical preparation for the therapy of immune deficiency conditions”, 23 July 1996

  • Morozov VG, Khavinson VKh (1997) Natural and synthetic thymic peptides as therapeutics for immune dysfunction. Int J Immunopharmacol 19:501–505

    Article  PubMed  Google Scholar 

  • Morozov VG, Khavinson VKh (2000) US Patent N 6,136,788 “Pharmaceutical preparation for the therapy of immune deficiency conditions”, 24 Oct 2000

  • Pliss GB, Melnikov AS, Malinin VV, Khavinson VKh (2001a) Inhibitory effect of peptide vilon on the development of induced rat urinary bladder tumors in rats. Bull Exp Biol Med 131:558–560

    Article  PubMed  Google Scholar 

  • Pliss GB, Melnikov AS, Malinin VV, Khavinson VKh (2001b) Effect of vilon and epitalon on development of induced bladder tumors in rats. Vopr Onkol 47:601–607

    PubMed  Google Scholar 

  • Pliss GB, Melnikov AS, Malinin VV, Khavinson VKh (2005) Effect of vilon (Lys-Glu) on neoplasis induced by 1,2-dimethylhydrazine in mice. Vopr Onkol 51:466–469

    PubMed  Google Scholar 

  • Popovich IG, Voitenkov BO, Anisimov VN, Ivanov VT, Mikhaleva II, Zabezhinski MA, Alimova IN, Baturin DA, Zavarzina NYu, Rosenfeld SA, Semenchenko AV, Yashin AI (2003) Effect of delta-sleep inducing peptide-containing preparations Deltaran on biomarkers of aging, life span and spontaneous tumor incidence in female SHR mice. Mech Aging Dev 124:721–731

    Article  PubMed  Google Scholar 

  • Riadnova IYu, Shataeva LK, Khavinson VKh (2000) DNA–protein interaction studied in model systems. Polym Scis Ser A 42:551–556

    Google Scholar 

  • Sibarov DA, Kovalenko RI, Malinin VV, Khavinson VKh (2002) Epitalon influences pineal secretion in stress-exposed rats in the daytime. Neuro Endocrinol Lett 23:452–454

    PubMed  Google Scholar 

  • Turchaninova LN, Kolosova LI, Malinin VV, Moiseeva AB, Nozdrachev AD, Khavinson VKh (2000) Effect of tetrapeptide Cortagen on regeneration of sciatic nerve. Bull Exp Biol Med 130:1172–1174

    PubMed  Google Scholar 

  • Vinogradova IA, Bukalev AV, Zabezhinski MA, Semenchenko AV, Khavinson VKh, Anisimov SV (2007) Effect of Ala-Glu-Asp-Gly peptide on lifespan and development of spontaneous tumors in female rats exposed to different illumination regimens. Bull Exp Biol Med 144:825–830

    Article  PubMed  Google Scholar 

  • Vinogradova IA, Bukalev AV, Zabezhinski MA, Semenchenko AV, Khavinson VKh, Anisimov SV (2008) Geroprotective effect peptide Ala-Glu-Asp-Gly in male rats maintained at various regimens of illumination. Bull Exp Biol Med 145:455–460

    Article  Google Scholar 

  • Voitenkov VB, Popovich IG, Arutiunian AV, Oparina TI, Prokopenko VM (2008) Effect of delta-sleep inducing peptide on free-radical processes in the brain and liver of mice during various light regimens. Adv Gerontol 21(1):53–55

    PubMed  Google Scholar 

Download references

Acknowledgments

The author expresses his sincere gratitude to our colleagues from the St. Petersburg Institute of Bioregulation and Gerontology and from another research institutes over Russia, Ukraine and Belorussia as well as foreign colleagues Professors J. Atzpodien (Germany), K. R. Boheler (USA), C. Franceschi (Italy), E. Lakatta (USA), T. A. Lezhava (Georgia), J. Martinez (France), M. Passeri (Italy), Y. Touitou (France), A. I. Yashin (USA), I. Zusman (Israel) for their significant contribution into our research work.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Vladimir N. Anisimov.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Anisimov, V.N., Khavinson, V.K. Peptide bioregulation of aging: results and prospects. Biogerontology 11, 139–149 (2010). https://doi.org/10.1007/s10522-009-9249-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10522-009-9249-8

Keywords

Navigation