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Testing of geroprotectors in experiments on cell cultures: Choosing the correct model system

  • Gerontology
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Abstract

We believe that cytogerontological models, such as the Hayflick model, though very useful for experimental gerontology, are based only on certain correlations and do not directly apply to the gist of the aging process. Thus, the Hayflick limit concept cannot explain why we age, whereas our “stationary phase aging” model appears to be a “gist model,” since it is based on the hypothesis that the main cause of both various “age-related” changes in stationary cell cultures and similar changes in the cells of aging multicellular organism is the restriction of cell proliferation. The model is applicable to experiments on a wide variety of cultured cells, including normal and transformed animal and human cells, plant cells, bacteria, yeasts, mycoplasmas, etc. The results of relevant studies show that cells in this model die out in accordance with the Gompertz law, which describes exponential increase of the death probability with time. Therefore, the “stationary phase aging” model may prove effective in testing of various geroprotectors (anti-aging factors) and geropromoters (pro-aging factors) in cytogerontological experiments. It should be emphasized, however, that even the results of such experiments do not always agree with the data obtained in vivo and therefore cannot be regarded as final but should be verified in studies on laboratory animals and in clinical trials (provided this complies with ethical principles of human subject research).

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References

  1. Hayflick, L., Progress in cytogerontology, Mech. Ageing Dev., 1979, vol. 9, no. 5–6, pp. 393–408.

    Article  PubMed  CAS  Google Scholar 

  2. Khokhlov, A.N., Proliferatsiya i starenie (Cell Proliferation and Aging), Itogi Nauki i Tekhniki VINITI AN SSSR. Ser. Obshchie Problemy Fiziko-Khimicheskoi Biologii (Advances in Science and Technology, VINITI Akad. Sci. USSR, Ser. General Problems of Physicochemical Biology), Moscow: VINITI, 1988, vol. 9.

    Google Scholar 

  3. Khokhlov, A.N., Results and perspectives of cytogerontologic studies in modern time, Tsitologiia, 2002, vol. 44, no. 12, pp. 1143–1148.

    PubMed  CAS  Google Scholar 

  4. Khokhlov, A.N., Cytogerontology at the beginning of the third millennium: from “correlative” to “gist” models, Russ. J. Dev. Biol., 2003, vol. 34, no. 5, pp. 321–326.

    Article  Google Scholar 

  5. Khokhlov, A.N., Gerontological studies on cell cultures: from organism to cell and back, Probl. Staren. Dolgolet., 2008, vol. 17, no. 4, pp. 451–456.

    Google Scholar 

  6. Khokhlov, A.N., Testing geroprotectors in cell culture experiments: pros and cons, Probl. Staren. Dolgolet., 2009, vol. 18, no. 1, pp. 32–36.

    Google Scholar 

  7. Khokhlov, A.N., Does aging need its own program, or is the program of development quite sufficient for it? Stationary cell cultures as a tool to search for anti-aging factors, Curr. Aging Sci., 2013, vol. 6, no. 1, pp. 14–20.

    Article  PubMed  CAS  Google Scholar 

  8. Hayflick, L. and Moorhead, P.S., The serial cultivation of human diploid cell strains, Exp. Cell Res., 1961, vol. 25, no. 3, pp. 585–621.

    Article  PubMed  CAS  Google Scholar 

  9. Hayflick, L., The limited in vitro lifetime of human diploid cell strains, Exp. Cell Res., 1965, vol. 37, no. 3, pp. 614–636.

    Article  PubMed  CAS  Google Scholar 

  10. Rattan, S.I.S., “Just a fellow who did his job...,” an interview with Leonard Hayflick, Biogerontology, 2000, vol. 1, no. 1, pp. 79–87.

    Article  Google Scholar 

  11. Campisi, J., Cellular senescence: putting the paradoxes in perspective, Curr. Opin. Genet. Dev., 2011, vol. 21, no. 1, pp. 107–112.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  12. Sikora, E., Arendt, T., Bennett, M., and Narita, M., Impact of cellular senescence signature on ageing research, Ageing Res. Rev., 2011, vol. 10, no. 1, pp. 146–152.

    Article  PubMed  CAS  Google Scholar 

  13. Campisi, J., Aging, cellular senescence, and cancer, Annu. Rev. Physiol., 2013, vol. 75, pp. 685–705.

    Article  PubMed  CAS  Google Scholar 

  14. Olovnikov, A.M., Redumera as the missing link in the understanding of human aging, Clin. Gerontol., 2005, vol. 11, no. 1, pp. 50–69.

    Google Scholar 

  15. Olovnikov, A.M., Hypothesis: lifespan is regulated by chronomere DNA of the hypothalamus, J. Alzheimer’s Dis., 2007, vol. 11, no. 2, pp. 241–252.

    CAS  Google Scholar 

  16. Olovnikov, A.M., Role of paragenome in development, Russ. J. Dev. Biol., 2007, vol. 38, no. 2, pp. 104–123.

    Article  Google Scholar 

  17. Khokhlov, A.N., Does aging need an own program or the existing development program is more than enough?, Russ. J. Gen. Chem., 2010, vol. 80, no. 7, pp. 1507–1513.

    Article  CAS  Google Scholar 

  18. Khokhlov, A.N., From Carrel to Hayflick and back, or what we got from the 100-year cytogerontological studies, Biophysics, 2010, vol. 55, no. 5, pp. 859–864.

    Article  Google Scholar 

  19. Macieira-Coelho, A., Cell division and aging of the organism, Biogerontology, 2011, vol. 12, no. 6, pp. 503–515.

    Article  PubMed  Google Scholar 

  20. Khokhlov, A.N., Wei, L., Li, Y., and He, J., Teaching cytogernotology in Russia and China, Adv. Gerontol., 2012, vol. 25, no. 3, pp. 513–516.

    PubMed  CAS  Google Scholar 

  21. Wei, L., Li, Y., He, J., and Khokhlov, A.N., Teaching the cell biology of aging at the Harbin Institute of Technology and Moscow State University, Moscow Univ. Biol. Sci. Bull., 2012, vol. 67, no. 1, pp. 13–16.

    Article  Google Scholar 

  22. Olovnikov, A.M., The principle of marginotomy in the template synthesis of polynucleotides, Dokl. Akad. Nauk SSSR, 1971, vol. 201, no. 6, pp. 1496–1499.

    PubMed  CAS  Google Scholar 

  23. Olovnikov, A.M., A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon, J. Theor. Biol., 1973, vol. 41, no. 1, pp. 181–190.

    Article  PubMed  CAS  Google Scholar 

  24. Olovnikov, A.M., Telomeres, telomerase and aging; origin of the theory, Exp. Gerontol., 1996, vol. 31, no. 4, pp. 443–448.

    Article  PubMed  CAS  Google Scholar 

  25. Mikhelson, V.M., Replicative mosaicism might explain the seeming contradictions in the telomere theory of aging, Mech. Ageing. Dev., 2001, vol. 122, no. 13, pp. 1361–1365.

    Article  PubMed  CAS  Google Scholar 

  26. Vilenchik, M.M., Khokhlov, A.N., and Grinberg, K.N., Study of spontaneous DNA lesions and DNA repair in human diploid fibroblasts aged in vitro and vivo, Stud. Biophys., 1981, vol. 85, no. 1, pp. 53–54.

    CAS  Google Scholar 

  27. Khokhlov, A.N., Stationary cell cultures as a tool for gerontological studies, Ann. N.Y. Acad. Sci., 1992, vol. 663, pp. 475–476.

    Article  PubMed  CAS  Google Scholar 

  28. Khokhlov, A.N., Cell proliferation restriction: is it the primary cause of aging?, Ann. N.Y. Acad. Sci., 1998, vol. 854, p. 519.

    Article  Google Scholar 

  29. Akimov, S.S. and Khokhlov, A.N., Study of “stationary phase aging” of cultured cells under various types of proliferation restriction, Ann. N.Y. Acad. Sci., 1998, vol. 854, p. 520.

    Article  Google Scholar 

  30. Alinkina, E.S., Vorobyova, A.K., Misharina, T.A., Fatkullina, L.D., Burlakova, E.B., and Khokhlov, A.N., Cytogerontological studies of biological activity of oregano essential oil, Moscow Univ. Biol. Sci. Bull., 2012, vol. 67, no. 2, pp. 52–57.

    Article  Google Scholar 

  31. Yablonskaya, O.I., Ryndina, T.S., Voeikov, V.L., and Khokhlov, A.N., A paradoxical effect of hydrated C60-fullerene at an ultralow concentration on the viability and aging of cultured Chinese hamster cells, Moscow Univ. Biol. Sci. Bull., 2013, vol. 68, no. 2, pp. 63–68.

    Article  Google Scholar 

  32. Kapitanov, A.B. and Aksenov, M.Y., Ageing of procaryotes. Acholeplasma laidlawii as an object for cell ageing studies: a brief note, Mech. Ageing Dev., 1990, vol. 54, no. 3, pp. 249–258.

    Article  PubMed  CAS  Google Scholar 

  33. Khokhlov, A.N., Ushakov, V.L., Kapitanov, A.B., and Nadzharian, T.L., Effect of the geroprotector 2-ethyl-6-methyl-3-hydroxypyridine chlorhydrate on the cell proliferation of Acholeplasma laidlawii, Dokl. Akad. Nauk SSSR, 1984, vol. 274, no. 4, pp. 930–933.

    PubMed  CAS  Google Scholar 

  34. Khokhlov, A.N., Can cancer cells age? Stationary cell culture approach to the problem solution, in Visualizing of senescent cells in vitro and in vivo. Programme and abstracts, Warsaw, Poland, December 15–16, 2012, Warsaw, 2012, pp. 48–49.

    Google Scholar 

  35. Khokhlov, A.N., Prokhorov, L.Yu., Ivanov, A.S., and Archakov, A.I., Effects of cholesterol- or 7-ketocholesterol-containing liposomes on colony-forming ability of cultured cells, FEBS Lett., 1991, vol. 290, no. 1–2, pp. 171–172.

    Article  PubMed  CAS  Google Scholar 

  36. Maier, A.B., Maier, I.L., van Heemst, D., and Westendorp, R.G.J., Colony formation and colony size do not reflect the onset of replicative senescence in human fibroblasts, J. Gerontol. A Biol. Sci. Med. Sci., 2008, vol. 63, no. 7, pp. 655–659.

    Article  PubMed  Google Scholar 

  37. Khokhlov, A.N., Chirkova, E.Iu., and Nadzharian, T.L., DNA degradation in resting cultured Chinese hamster cells, Tsitologiia, 1984, vol. 26, no. 8, pp. 965–968.

    PubMed  CAS  Google Scholar 

  38. Khokhlov, A.N., Chirkova, E.Iu., and Chebotarev, A.N., Changes in the level of sister chromatid exchanges in cultured Chinese hamster cells undergoing limited proliferation, Tsitol. Genet., 1985, vol. 19, no. 2, pp. 90–92.

    PubMed  CAS  Google Scholar 

  39. Khokhlov, A.N., Chirkova, E.Yu., and Gorin, A.I., Strengthening of the DNA-protein complex during stationary phase aging of cell cultures, Bull. Exp. Biol. Med., 1986, vol. 101, no. 4, pp. 437–440.

    Article  Google Scholar 

  40. Khokhlov, A.N., Chirkova, E.Iu., and Chebotarev, A.N., Changes in the number of sister chromatid exchanges in cultured Chinese hamster cells with limited proliferation. Additional studies, Tsitol. Genet., 1987, vol. 21, no. 3, pp. 186–190.

    PubMed  CAS  Google Scholar 

  41. Khokhlov, A.N., Kirnos, M.D., and Vaniushin, B.F., The level of DNA methylation and “stationary-phaseaging” in cultured cells, Izv. Akad. Nauk SSSR, Ser. Biol., 1988, no. 3, pp. 476–478.

    Google Scholar 

  42. Prokhorov, L.Yu., Petushkova, N.A., and Khokhlov, A.N., Cytochrome P-450 and “stationary phase aging” of cultured cells, Age, 1994, vol. 17, no. 4, p. 162.

    Google Scholar 

  43. Shram, S.I., Shilovskii, G.A., and Khokhlov, A.N., Poly(ADP-ribose)-polymerase-1 and aging: experimental study of possible relationship on stationary cell cultures, Bull. Exp. Biol. Med., 2006, vol. 141, no. 5, pp. 628–632.

    Article  PubMed  CAS  Google Scholar 

  44. Esipov, D.S., Gorbacheva, T.A., Khairullina, G.A., Klebanov, A.A., Nguen Tkhi Ngok Tu, and Khokhlov, A.N., 8-oxo-2′-deoxyguanosine accumulation in DNA from “stationary phase aging” cultured cells, Adv. Gerontol., 2008, vol. 21, no. 3, pp. 485–487.

    PubMed  CAS  Google Scholar 

  45. Vladimorova, I.V., Shilovsky, G.A., Khokhlov, A.N., and Shram, S.I., “Age-related” changes of the poly(ADP-ribosyl)ation system in cultured Chinese hamster cells, in Visualizing of senescent cells in vitro and in vivo. Programme and abstracts, Warsaw, Poland, December 15–16, 2012, Warsaw, 2012, pp. 108–109.

    Google Scholar 

  46. Khokhlov, A.N., Evolutionary cytogerontology as a new branch of experimental gerontology, Age, 1994, vol. 17, no. 4, p. 159.

    Google Scholar 

  47. Khokhlov, A.N., The cell kinetics model for determination of organism biological age and for geroprotectors or geropromoters studies, in Biomarkers of Aging: Expression and Regulation. Proceeding, Licastro, F. and Caldarera, C.M., Eds., Bologna: CLUEB, 1992, pp. 209–216.

    Google Scholar 

  48. Carrel, A., Artificial activation of the growth in vitro of connective tissue, J. Exp. Med., 1912, vol. 17, no. 1, pp. 14–19.

    Article  Google Scholar 

  49. Carrel, A., Contributions to the study of the mechanism of the growth of connective tissue, J. Exp. Med., 1913, vol. 18, no. 3, pp. 287–289.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Evolutionary Cytogerontology Sector, School of Biology, Moscow State University, Moscow, 119992, Russia

    A. N. Khokhlov, A. A. Klebanov, A. F. Karmushakov, G. A. Shilovsky, M. M. Nasonov & G. V. Morgunova

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  1. A. N. Khokhlov
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  2. A. A. Klebanov
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  3. A. F. Karmushakov
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  4. G. A. Shilovsky
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  5. M. M. Nasonov
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  6. G. V. Morgunova
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Correspondence to A. N. Khokhlov.

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Original Russian Text © A.N. Khokhlov, A.A. Klebanov, A.F. Karmushakov, G.A. Shilovsky, M.M. Nasonov, G.V. Morgunova, 2014, published in Vestnik Moskovskogo Universiteta. Biologiya, 2014, No. 1, pp. 13–18.

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Khokhlov, A.N., Klebanov, A.A., Karmushakov, A.F. et al. Testing of geroprotectors in experiments on cell cultures: Choosing the correct model system. Moscow Univ. Biol.Sci. Bull. 69, 10–14 (2014). https://doi.org/10.3103/S0096392514020035

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  • DOI: https://doi.org/10.3103/S0096392514020035

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