НЕКОТОРЫЕ ЗАМЕЧАНИЯ, КАСАЮЩИЕСЯ ВЗАИМОСВЯЗИ АУТОФАГИИ, КЛЕТОЧНОГО СТАРЕНИЯ И ОГРАНИЧЕНИЯ КЛЕТОЧНОЙ ПРОЛИФЕРАЦИИ

В обзоре кратко описываются основные типы аутофагии — макроаутофагия, микроаутофагия и шаперон-опосредованная аутофагия. Анализируются данные о характере влияния аутофагии на возникновение некоторых патологических процессов и старение у различных организмов. Отмечается, что такое влияние, как правило (хоть и не всегда), является положительным. Рассматриваются результаты исследований данного феномена в экспериментах на мышах, нематодах, дрозофилах, бактериях, дрожжах и культурах клеток высших организмов. Подчеркивается очевидная связь активации аутофагии с ограничением клеточной пролиферации, которую авторы считают основной причиной накопления с возрастом различных дефектов (наиболее важные из них — повреждения ДНК) в клетках и тканях, что приводит к увеличению вероятности смерти, т.е. к старению. Заключается, что изучение роли аутофагии в процессе старения наиболее целесообразно проводить на моделях хронологического старения дрожжей или “стационарного старения” клеточных культур. 

1. Rubinsztein D.C., Mariño G., Kroemer G. Autophagy and aging // Cell. 2011. Vol. 146. N 5. P. 682–695.

2. Mortimore G.E., Lardeux B.R., Adams C.E. Regulation of microautophagy and basal protein turnover in rat liver. Effects of short-term starvation // J. Biol. Chem. 1988. Vol. 263. N 5. P. 2506–2512.

3. Vicencio J.M., Galluzzi L., Tajeddine N., Ortiz C., Criollo A., Tasdemir E., Morselli E., Ben Younes A., Maiuri M.C., Lavandero S., Kroemer G. Senescence, apoptosis or autophagy? When a damaged cell must decide its path — A mini-review // Gerontology. 2008. Vol. 54. N 2. P. 92–99.

4. Yen W.-L., Klionsky D.J. How to live long and prosper: Autophagy, mitochondria, and aging // Physiology (Bethesda). 2008. Vol. 23. P. 248–262.

5. Massey A.C., Kiffin R., Cuervo A.M. Autophagic defects in aging. Looking for an “emergency exit”? // Cell Cycle. 2006. Vol. 5. N 12. P. 1292–1296.

6. Levine B., Mizushima N., Virgin H.W. Autophagy in immunity and inflammation // Nature. 2011. Vol. 469. N 7330. P. 323–335.

7. Gottlieb R.A., Carreira R.S. Autophagy in health and disease. 5. Mitophagy as a way of life // Am. J. Physiol. Cell Physiol. 2010. Vol. 299. N 2. P. C203–C210.

8. Madeo F., Tavernarakis N., Kroemer G. Can autophagy promote longevity? // Nat. Cell Biol. 2010. Vol. 12. N 9. P. 842–846.

9. 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. N 7. P. 1507–1513.

10. Khokhlov A.N., Wei L., Li Y., He J. Teaching cytogerontology in Russia and China // Adv. Gerontol. 2012. Vol. 25. N 3. P. 513–516.

11. Khokhlov A.N., Klebanov A.A., Karmushakov A.F., Shilovsky G.A., Nasonov M.M., Morgunova G.V. Testing of geroprotectors in experiments on cell cultures: choosing the correct model system // Moscow Univ. Biol. Sci. Bull. 2014. Vol. 69. N 1. P. 10–14.

12. Khokhlov A.N. What will happen to molecular and cellular biomarkers of aging in case its program is canceled (provided such a program does exist)? // Adv. Gerontol. 2014. Vol. 4. N 2. P. 150–154.

13. Bjedov I., Toivonen J.M., Kerr F., Slack C., Jacobson J., Foley A., Partridge L. Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster // Cell Metab. 2010. Vol. 11. N 1. P. 35–46.

14. Morselli E., Maiuri M.C., Markaki M., Megalou E., Pasparaki A., Palikaras K., Criollo A., Galluzzi L., Malik S.A., Vitale I., Michaud M., Madeo F., Tavernarakis N., Kroemer G. Caloric restriction and resveratrol promote longevity through the Sirtuin-1-dependent induction of autophagy // Cell Death. Dis. 2010. Vol. 1. e10.

15. Meléndez A., Tallóczy Z., Seaman M., Eskelinen E.L., Hall D.H., Levine B. Autophagy genes are essential for dauer development and life-span extension in C. elegans // Science. 2003. Vol. 301. N 5638. P. 1387–1391.

16. Juhász G., Érdi B., Sass M., Neufeld T.P. Atg7-dependent autophagy promotes neuronal health, stress tolerance, and longevity but is dispensable for metamorphosis in Drosophila // Genes Dev. 2007. Vol. 21. N 23. P. 3061–3066.

17. Simonsen A., Cumming R.C., Brech A., Isakson P., Schubert D.R., Finley K.D. Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult Drosophila // Autophagy. 2008. Vol. 4. N 2. P. 176–184.

18. Hara T., Nakamura K., Matsui M., Yamamoto A., Nakahara Y., Suzuki-Migishima R., Yokoyama M., Mishima K., Saito I., Okano H., Mizushima N. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice // Nature. 2006. Vol. 441. N 7095. P. 885–889.

19. Komatsu M., Waguri S., Chiba T., Murata S., Iwata J., Tanida I., Ueno T., Koike M., Uchiyama Y., Kominami E., Tanaka K. Loss of autophagy in the central nervous system causes neurodegeneration in mice // Nature. 2006. Vol. 441. N 7095. P. 880–884.

20. Masiero E., Sandri M. Autophagy inhibition induces atrophy and myopathy in adult skeletal muscles // Autophagy. 2010. Vol. 6. N 2. P. 307–309.

21. 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. N 1. P. 14–20.

22. Khokhlov A.N. Impairment of regeneration in aging: appropriateness or stochastics? // Biogerontology. 2013. Vol. 14. N 6. P. 703–708.

23. Cuervo A.M., Bergamini E., Brunk U.T., Dröge W., Ffrench M., Terman A. Autophagy and aging: the importance of maintaining “clean” cells // Autophagy. 2005. Vol. 1. N 3. P. 131–140.

24. Cuervo A.M., Dice J.F. How do intracellular proteolytic systems change with age? // Front. Biosci. 1998. Vol. 3. P. d25–d43.

25. Stefanova N.A., Kolosova N.G. Evolution of Alzheimer’s disease pathogenesis conception // Moscow Univ. Biol. Sci. Bull. 2016. Vol. 71. N 1. P. 4–10.

26. Ravikumar B., Vacher C., Berger Z., Davies J.E., Luo S., Oroz L.G., Scaravilli F., Easton D.F., Duden R., O’Kane C.J., Rubinsztein D.C. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease // Nat. Genet. 2004. Vol. 36. N 6. P. 585–595.

27. Gewirtz D.A. Autophagy and senescence. A partnership in search of definition // Autophagy. 2013. Vol. 9. N 5. P. 808–812.

28. Goehe R.W., Di X., Sharma K., Bristol M.L., Henderson S.C., Valerie K., Rodier F., Davalos A.R., Gewirtz D.A. The autophagy-senescence connection in chemotherapy: must tumor cells (self) eat before they sleep? // J. Pharmacol. Exp. Ther. 2012. Vol. 343. N 3. P. 763–778.

29. Degenhardt K., Mathew R., Beaudoin B., Bray K., Anderson D., Chen G., Mukherjee C., Shi Y., Gélinas C., Fan Y., Nelson D.A., Jin S., White E. Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis // Cancer Cell. 2006. Vol. 10. N 1. P. 51–64.

30. Morgunova G.V., Klebanov A.A., Khokhlov A.N. Interpretation of data about the impact of biologically active compounds on viability of cultured cells of various origin from a gerontological point of view // Moscow Univ. Biol. Sci. Bull. 2016. Vol. 71. N 2. P. 67–70.

31. Campisi J. Aging, cellular senescence, and cancer // Annu. Rev. Physiol. 2013. Vol. 75. P. 685–705.

32. Hayflick L., Moorhead P.S. The serial cultivation of human diploid cell strains // Exp. Cell Res. 1961. Vol. 25. N 3. P. 585–621.

33. Hayflick L. The limited in vitro lifetime of human diploid cell strains // Exp. Cell Res. 1965. Vol. 37. N 3. P. 614–636.

34. Akimov S.S., 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.

35. Khokhlov A.N. Evolution of the term “cellular senescence” and its impact on the current cytogerontological research // Moscow Univ. Biol. Sci. Bull. 2013. Vol. 68. N 4. P. 158–161.

36. Khokhlov A.N., Morgunova G.V., Ryndina T.S., Coll F. Pilot study of a potential geroprotector, “Quinton Marine Plasma”, in experiments on cultured cells // Moscow Univ. Biol. Sci. Bull. 2015. Vol. 70. N 1. P. 7–11.

37. Khokhlov A.N., Morgunova G.V. On the constructing of survival curves for cultured cells in cytogerontological experiments: a brief note with three hierarchy diagrams // Moscow Univ. Biol. Sci. Bull. 2015. Vol. 70. N 2. P. 67–71.

38. Jeyapalan J.C., Sedivy J.M. Cellular senescence and organismal aging // Mech. Aging Dev. 2008. Vol. 129. N 7–8. P. 467–474.

39. White E., Lowe S.W. Eating to exit: autophagy-enabled senescence revealed // Genes Dev. 2009. Vol. 23. N 7. P. 784–787.

40. Young A.R., Narita M., Ferreira M., Kirschner K., Sadaie M., Darot J.F., Tavaré S., Arakawa S., Shimizu S., Watt F.M., Narita M. Autophagy mediates the mitotic senescence transition // Genes Dev. 2009. Vol. 23. N 7. P. 798–803.

41. Fabrizio P., Longo V.D. The chronological life span of Saccharomyces cerevisiae // Aging Cell. 2003. Vol. 2. N 2. P. 73–81.

42. Khokhlov A.N. Which aging in yeast is “true”? // Moscow Univ. Biol. Sci. Bull. 2016. Vol. 71. N 1. P. 11–13.

43. Alvers A.L., Wood M.S., Hu D., Kaywell A.C., Dunn W.A. Jr., Aris J.P. Autophagy is required for extension of yeast chronological life span by rapamycin // Autophagy. 2009. Vol. 5. N 6. P. 847–849.

44. Kaeberlein M., Burtner C.R., Kennedy B.K. Recent developments in yeast aging // PLOS Genet. 2007. Vol. 3. N 5. e84.

45. Herman P.K. Stationary phase in yeast // Curr. Opin. Microbiol. 2002. Vol. 5. N 6. P. 602–607.

46. Matecic M., Smith D.L., Jr., Pan X., Maqani N., Bekiranov S., Boeke J.D., Smith J.S. A microarray-based genetic screen for yeast chronological aging factors // PLOS Genet. 2010. Vol. 6. N 4. e1000921.

47. Nyström T. Stationary-phase physiology // Annu. Rev. Microbiol. 2004. Vol. 58. P. 161–181.

48. Khokhlov A.N. Decline in regeneration during aging: appropriateness or stochastics? // Russ. J. Dev. Biol. 2013. Vol. 44. N 6. P. 336–341.

49. Morgunova G.V., Kolesnikov A.V., Klebanov A.A., Khokhlov A.N. Senescence-associated β-galactosidase — a biomarker of aging, DNA damage, or cell proliferation restriction? // Moscow Univ. biol. Sci. bull. 2015. Vol. 70. N 4. P. 165–167.

50. Shram S.I., Shilovskii G.A., Khokhlov A.N. Poly(ADPribose)-polymerase-1 and aging: experimental study of possible relationship on stationary cell cultures // Bull. Exp. Biol. Med. 2006. Vol. 141. N 5. P. 628–632.

51. Khokhlov A.N. On the immortal hydra. Again // Moscow Univ. Biol. Sci. Bull. 2014. Vol. 69. N 4. P. 153–157.

52. Chera S., Buzgariu W., Ghila L., Galliot B. Autophagy in Hydra: A response to starvation and stress in early animal evolution // BBA–Mol. Cell Res. 2009. Vol. 1793. N 9. P. 1432–1443.

53. Alayev A., Berger S.M., Kramer M.Y., Schwartz N.S., Holz M.K. The combination of rapamycin and resveratrol blocks autophagy and induces apoptosis in breast cancer cells // J. Cell Biochem. 2015. Vol. 116. N 3. P. 450–457.