<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">vestnik-bio-msu</journal-id><journal-title-group><journal-title xml:lang="ru">Вестник Московского университета. Серия 16. Биология</journal-title><trans-title-group xml:lang="en"><trans-title>Vestnik Moskovskogo universiteta. Seriya 16. Biologiya</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">0137-0952</issn><publisher><publisher-name>Lomonosov Moscow State University,  School of Biology</publisher-name></publisher></journal-meta><article-meta><article-id custom-type="elpub" pub-id-type="custom">vestnik-bio-msu-318</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>Геронтология</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>Gerontology</subject></subj-group></article-categories><title-group><article-title>ИНТЕРПРЕТАЦИЯ ДАННЫХ О ВЛИЯНИИ БИОЛОГИЧЕСКИ АКТИВНЫХ ПРЕПАРАТОВ НА ЖИЗНЕСПОСОБНОСТЬ КУЛЬТИВИРУЕМЫХ КЛЕТОК РАЗНОГО ПРОИСХОЖДЕНИЯ С ПОЗИЦИЙ ГЕРОНТОЛОГИИ</article-title><trans-title-group xml:lang="en"><trans-title>INTERPRETATION OF DATA ABOUT THE IMPACT OF BIOLOGICALLY ACTIVE COMPOUNDS ON VIABILITY OF CULTURED CELLS OF VARIOUS ORIGIN FROM A GERONTOLOGICAL POINT OF VIEW</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Моргунова</surname><given-names>Г. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Morgunova</surname><given-names>G. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>аспирантка сектора эволюционной цитогеронтологии биологического факультета МГУ. Тел.: 8-495-939-15-90</p></bio><email xlink:type="simple">morgunova@mail.bio.msu.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Клебанов</surname><given-names>А. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Klebanov</surname><given-names>A. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>научный сотрудник сектора эволюционной цитогеронтологии биологического факультета МГУ. Тел.: 8-495-939-15-90</p></bio><email xlink:type="simple">klebanov@mail.bio.msu.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Хохлов</surname><given-names>А. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Khokhlov</surname><given-names>A. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>докт. биол. наук, зав. сектором эволюционной цитогеронтологии биологического факультета МГУ. Тел.: 8-495-939-15-90</p></bio><email xlink:type="simple">khokhlov@mail.bio.msu.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru">Сектор эволюционной цитогеронтологии, биологический факультет, Московский государственный университет имени М.В. Ломоносова; Россия, 119234, Москва, Ленинские горы, д. 1, стр. 12<country>Россия</country></aff><aff xml:lang="en">Evolutionary Cytogerontology Sector, School of Biology, Lomonosov Moscow State University, Leninskiye gory 1-12, Moscow, 119234, Russia<country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2016</year></pub-date><pub-date pub-type="epub"><day>23</day><month>05</month><year>2016</year></pub-date><volume>0</volume><issue>2</issue><fpage>3</fpage><lpage>7</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Моргунова Г.В., Клебанов А.А., Хохлов А.Н., 2016</copyright-statement><copyright-year>2016</copyright-year><copyright-holder xml:lang="ru">Моргунова Г.В., Клебанов А.А., Хохлов А.Н.</copyright-holder><copyright-holder xml:lang="en">Morgunova G.V., Klebanov A.A., Khokhlov A.N.</copyright-holder><license license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://vestnik-bio-msu.elpub.ru/jour/article/view/318">https://vestnik-bio-msu.elpub.ru/jour/article/view/318</self-uri><abstract><p>Рассматриваются проблемы, возникающие при интерпретации данных, полученных при испытании потенциальных геропротекторов в цитогеронтологических экспериментах. Подчеркивается, что такие препараты/физические факторы должны влиять на процессы, приводящие к увеличению с возрастом вероятности смерти многоклеточных организмов (главным образом — человека, старение которого интересует геронтологов в первую очередь). При этом, по мнению авторов, соединения, активность которых направлена на лечение возрастных болезней, вряд ли можно относить к геропротекторам. Отмечается, что на модельных системах, использующих культивируемые клетки, исследователи, как правило, оценивают их жизнеспособность, критерии которой в значительной степени зависят от концепции старения, разделяемой экспериментаторами. При этом принципиально важно, на каких именно клетках проводятся такие эксперименты — нормальных или трансформированных клетках многоклеточных организмов, одноклеточных эукариотических или прокариотических организмах и др. В частности, биологически активные соединения, уменьшающие жизнеспособность культивируемых раковых клеток, могут продлевать жизнь экспериментальным животным и человеку, как и препараты, увеличивающие жизнеспособность культивируемых нормальных клеток. Анализируются различные проблемы с интерпретацией данных тестирования потенциальных геропротекторов, полученных на модели Хейфлика, модели “стационарного старения”, клеточно-кинетической модели и в экспериментах по оценке эффективности клонирования. Обсуждаемые подходы проиллюстрированы на примере результатов геронтологических исследований известного ингибитора mTOR — рапамицина. Заключается, что факторы, обеспечивающие замедление “стационарного старения” (хронологического старения) культивируемых клеток, по-видимому, являются наиболее перспективными геропротекторами, хотя конкретные механизмы их действия могут сильно различаться.</p></abstract><trans-abstract xml:lang="en"><p>Problems related to the interpretation of data obtained during testing of potential geroprotectors in cytogerontological experiments are considered. It is emphasized that such compounds/physical factors should influence on the processes leading to the age-related increase of death probability of multicellular organisms (primarily — of man, in whose aging gerontologists are mainly interested). However, in the authors’ opinion, compounds which cure age-related diseases unlikely could be classified as geroprotectors. It is noted, that, in the model systems using cultured cells, researchers, as a rule, evaluate their viability criteria of which, to a great extent, depend on the aging theory shared by the experimenters. Besides, it is very important what cells are used in the studies — normal or transformed cells of multicellular organisms, unicellular eukaryotic or prokaryotic organisms, etc. In particular, biologically active compounds which decrease the viability of cultured cancer cells may increase the life span of experimental animals and humans, as well as compounds which increase the viability of normal cultured cells. Various problems with interpretation of data obtained with the Hayflick model, the stationary phase aging model, and the cell kinetics model, as well as in experiments on evaluation of cell colony-forming efficiency are analyzed. The approaches discussed are illustrated on the example of the results from gerontological investigations of a famous mTOR inhibitor, rapamycin. It is assumed that factors retarding the stationary phase aging (chronological aging) of cultured cells are, apparently, the most promising geroprotectors although the specific mechanisms of their action may vary considerably.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>цитогеронтология</kwd><kwd>жизнеспособность клеток</kwd><kwd>старение</kwd><kwd>репликативное старение</kwd><kwd>“стационарное старение”</kwd><kwd>возрастные болезни</kwd><kwd>геропротекторы</kwd><kwd>геропромоторы</kwd><kwd>обзор.</kwd></kwd-group><kwd-group xml:lang="en"><kwd>cytogerontology</kwd><kwd>cell viability</kwd><kwd>aging</kwd><kwd>senescence</kwd><kwd>replicative aging</kwd><kwd>stationary phase aging</kwd><kwd>age-related diseases</kwd><kwd>geroprotectors</kwd><kwd>geropromoters</kwd><kwd>review</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Vilenchik M.M., Khokhlov A.N., Grinberg K.N. Study of spontaneous DNA lesions and DNA repair in human diploid fibroblasts aged in vitro and in vivo // Studia biophysica. 1981. Vol. 85. N 1. P. 53–54.</mixed-citation><mixed-citation xml:lang="en">Vilenchik M.M., Khokhlov A.N., Grinberg K.N. Study of spontaneous DNA lesions and DNA repair in human diploid fibroblasts aged in vitro and in vivo // Studia biophysica. 1981. Vol. 85. N 1. P. 53–54.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Khokhlov A.N. Stationary cell cultures as a tool for gerontological studies // Ann. N.Y. Acad. Sci. 1992. Vol. 663. P. 475–476.</mixed-citation><mixed-citation xml:lang="en">Khokhlov A.N. Stationary cell cultures as a tool for gerontological studies // Ann. N.Y. Acad. Sci. 1992. Vol. 663. P. 475–476.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Khokhlov A.N. Cell proliferation restriction: is it the primary cause of aging? // Ann. N.Y. Acad. Sci. 1998. Vol. 854. P. 519.</mixed-citation><mixed-citation xml:lang="en">Khokhlov A.N. Cell proliferation restriction: is it the primary cause of aging? // Ann. N.Y. Acad. Sci. 1998. Vol. 854. P. 519.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Khokhlov A.N. From Carrel to Hayflick and back, or what we got from the 100-year cytogerontological studies // Biophysics. 2010. Vol. 55. N 5. P. 859–864.</mixed-citation><mixed-citation xml:lang="en">Khokhlov A.N. From Carrel to Hayflick and back, or what we got from the 100-year cytogerontological studies // Biophysics. 2010. Vol. 55. N 5. P. 859–864.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Khokhlov A.N. Impairment of regeneration in aging: appropriateness or stochastics? // Biogerontology. 2013. Vol. 14. N 6. P. 703–708.</mixed-citation><mixed-citation xml:lang="en">Khokhlov A.N. Impairment of regeneration in aging: appropriateness or stochastics? // Biogerontology. 2013. Vol. 14. N 6. P. 703–708.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Khokhlov A.N. Decline in regeneration during aging: appropriateness or stochastics? // Russ. J. Dev. Biol. 2013. Vol. 44. N 6. P. 336–341.</mixed-citation><mixed-citation xml:lang="en">Khokhlov A.N. Decline in regeneration during aging: appropriateness or stochastics? // Russ. J. Dev. Biol. 2013. Vol. 44. N 6. P. 336–341.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Khokhlov A.N. On the immortal hydra. Again // Moscow Univ. Biol. Sci. Bull. 2014. Vol. 69. N 4. P. 153–157.</mixed-citation><mixed-citation xml:lang="en">Khokhlov A.N. On the immortal hydra. Again // Moscow Univ. Biol. Sci. Bull. 2014. Vol. 69. N 4. P. 153–157.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Hayflick L. Entropy explains aging, genetic determinism explains longevity, and undefined terminology explains misunderstanding both // PLoS Genet. 2007. Vol. 3. N 12. e220.</mixed-citation><mixed-citation xml:lang="en">Hayflick L. Entropy explains aging, genetic determinism explains longevity, and undefined terminology explains misunderstanding both // PLoS Genet. 2007. Vol. 3. N 12. e220.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Hayflick L. The cell biology of aging // J. Invest. Dermatol. 1979. Vol. 73. N 1. P. 8–14.</mixed-citation><mixed-citation xml:lang="en">Hayflick L. The cell biology of aging // J. Invest. Dermatol. 1979. Vol. 73. N 1. P. 8–14.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Hayflick L. Aging under glass // Mutation Research/ DNAging. 1991. Vol. 256. N 2–6. P. 69–80.</mixed-citation><mixed-citation xml:lang="en">Hayflick L. Aging under glass // Mutation Research/ DNAging. 1991. Vol. 256. N 2–6. P. 69–80.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Cristofalo V.J., Allen R.G., Pignolo R.J., Martin B.G., Beck J.C. Relationship between donor age and the replicative lifespan of human cells in culture: A reevaluation // Proc. Natl. Acad. Sci. USA. 1998. Vol. 95. N 18. P. 10614–10619.</mixed-citation><mixed-citation xml:lang="en">Cristofalo V.J., Allen R.G., Pignolo R.J., Martin B.G., Beck J.C. Relationship between donor age and the replicative lifespan of human cells in culture: A reevaluation // Proc. Natl. Acad. Sci. USA. 1998. Vol. 95. N 18. P. 10614–10619.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Mikhelson V.M., Gamaley I.A. Telomere shortening is a sole mechanism of aging in mammals // Curr. Aging Sci. 2012. Vol. 5. N 3. P. 203–208.</mixed-citation><mixed-citation xml:lang="en">Mikhelson V.M., Gamaley I.A. Telomere shortening is a sole mechanism of aging in mammals // Curr. Aging Sci. 2012. Vol. 5. N 3. P. 203–208.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Khokhlov A.N., Prokhorov L.Yu., Ivanov A.S., Archakov A.I. Effects of cholesterol- or 7-ketocholesterolcontaining liposomes on colony-forming ability of cultured cells // FEBS Lett. 1991. Vol. 290. N 1-2. P. 171–172.</mixed-citation><mixed-citation xml:lang="en">Khokhlov A.N., Prokhorov L.Yu., Ivanov A.S., Archakov A.I. Effects of cholesterol- or 7-ketocholesterolcontaining liposomes on colony-forming ability of cultured cells // FEBS Lett. 1991. Vol. 290. N 1-2. P. 171–172.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Есипов Д.С., Горбачева Т.А., Хайруллина Г.А., Клебанов А.А., Нгуен Тхи Нгок Ту, Хохлов А.Н. Изучение накопления 8-оксо-2’-дезоксигуанозина в ДНК при “стационарном старении” культивируемых клеток // Усп. геронтол. 2008. Т. 21. № 3. С. 485–487.</mixed-citation><mixed-citation xml:lang="en">Есипов Д.С., Горбачева Т.А., Хайруллина Г.А., Клебанов А.А., Нгуен Тхи Нгок Ту, Хохлов А.Н. Изучение накопления 8-оксо-2’-дезоксигуанозина в ДНК при “стационарном старении” культивируемых клеток // Усп. геронтол. 2008. Т. 21. № 3. С. 485–487.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Khokhlov A.N. Cytogerontology at the beginning of the third millennium: from “correlative” to “gist” models // Russ. J. Dev. Biol. 2003. Vol. 34. N 5. P. 321–326.</mixed-citation><mixed-citation xml:lang="en">Khokhlov A.N. Cytogerontology at the beginning of the third millennium: from “correlative” to “gist” models // Russ. J. Dev. Biol. 2003. Vol. 34. N 5. P. 321–326.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Khokhlov A. N. The cell kinetics model for determination of organism biological age and for geroprotectors or geropromoters studies // Biomarkers of aging: expression and regulation. Proceeding / Ed. by F. Licastro and C.M. Caldarera. Bologna: CLUEB, 1992. P. 209–216.</mixed-citation><mixed-citation xml:lang="en">Khokhlov A. N. The cell kinetics model for determination of organism biological age and for geroprotectors or geropromoters studies // Biomarkers of aging: expression and regulation. Proceeding / Ed. by F. Licastro and C.M. Caldarera. Bologna: CLUEB, 1992. P. 209–216.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Nyström T. Aging in bacteria // Curr. Opin. Microbiol. 2002. Vol. 5. N 6. P. 596–601.</mixed-citation><mixed-citation xml:lang="en">Nyström T. Aging in bacteria // Curr. Opin. Microbiol. 2002. Vol. 5. N 6. P. 596–601.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Aging research in yeast: Subcell. Biochem. Vol. 57 / Eds. M. Breitenbach, S.M. Jazwinski, and P. Laun. Springer Netherlands, 2012. 368 pp.</mixed-citation><mixed-citation xml:lang="en">Aging research in yeast: Subcell. Biochem. Vol. 57 / Eds. M. Breitenbach, S.M. Jazwinski, and P. Laun. Springer Netherlands, 2012. 368 pp.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Khokhlov A.N. Which aging in yeast is “true”? // Moscow Univ. Biol. Sci. Bull. 2016. Vol. 71. N 1. P. 11–13.</mixed-citation><mixed-citation xml:lang="en">Khokhlov A.N. Which aging in yeast is “true”? // Moscow Univ. Biol. Sci. Bull. 2016. Vol. 71. N 1. P. 11–13.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Ушаков В.Л., Гусев М.В., Хохлов А.Н. Имеет ли смысл изучать механизмы старения на сине-зеленых водорослях? Критический обзор, часть 1 // Вестн. Моск. ун-та. Сер. 16. Биология. 1992. № 1. С. 3–15.</mixed-citation><mixed-citation xml:lang="en">Ушаков В.Л., Гусев М.В., Хохлов А.Н. Имеет ли смысл изучать механизмы старения на сине-зеленых водорослях? Критический обзор, часть 1 // Вестн. Моск. ун-та. Сер. 16. Биология. 1992. № 1. С. 3–15.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Хохлов А.Н., Ушаков В.Л., Капитанов А.Б., Наджарян Т.Л. Влияние геропротектора хлоргидрата 2-этил-6-метил-3-оксипиридина на пролиферацию клеток Acholeplasma laidlawii // Докл. АН СССР. 1984. Т. 274. № 4. С. 930–933.</mixed-citation><mixed-citation xml:lang="en">Хохлов А.Н., Ушаков В.Л., Капитанов А.Б., Наджарян Т.Л. Влияние геропротектора хлоргидрата 2-этил-6-метил-3-оксипиридина на пролиферацию клеток Acholeplasma laidlawii // Докл. АН СССР. 1984. Т. 274. № 4. С. 930–933.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Kapitanov A.B., Aksenov M.Y. Ageing of procaryotes. Acholeplasma laidlawii as an object for cell ageing studies: a brief note // Mech. Ageing Dev. 1990. Vol. 54. N 3. P. 249–258.</mixed-citation><mixed-citation xml:lang="en">Kapitanov A.B., Aksenov M.Y. Ageing of procaryotes. Acholeplasma laidlawii as an object for cell ageing studies: a brief note // Mech. Ageing Dev. 1990. Vol. 54. N 3. P. 249–258.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Powers R.W. III, Kaeberlein M., Caldwell S.D., Kennedy B.K., Fields S. Extension of chronological life span in yeast by decreased TOR pathway signaling // Genes Dev. 2006. Vol. 20. N 2. P. 174–184.</mixed-citation><mixed-citation xml:lang="en">Powers R.W. III, Kaeberlein M., Caldwell S.D., Kennedy B.K., Fields S. Extension of chronological life span in yeast by decreased TOR pathway signaling // Genes Dev. 2006. Vol. 20. N 2. P. 174–184.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Harrison D.E., Strong R., Sharp Z.D., Nelson J.F., Astle C.M., Flurkey K., Nadon N.L., Wilkinson J.E., Frenkel K., Carter C.S., Pahor M., Javors M.A., Fernandez E., Miller R.A. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice // Nature. 2009. Vol. 460. N 7253. P. 392–395.</mixed-citation><mixed-citation xml:lang="en">Harrison D.E., Strong R., Sharp Z.D., Nelson J.F., Astle C.M., Flurkey K., Nadon N.L., Wilkinson J.E., Frenkel K., Carter C.S., Pahor M., Javors M.A., Fernandez E., Miller R.A. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice // Nature. 2009. Vol. 460. N 7253. P. 392–395.</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Miller R.A., Harrison D.E., Astle C.M. et al. Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction // Aging Cell. 2014. Vol. 13. N 3. P. 468–477.</mixed-citation><mixed-citation xml:lang="en">Miller R.A., Harrison D.E., Astle C.M. et al. Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction // Aging Cell. 2014. Vol. 13. N 3. P. 468–477.</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Rubinsztein D.C., Mariño G., Kroemer G. Autophagy and aging // Cell. 2011. Vol. 146. N 5. P. 682–695.</mixed-citation><mixed-citation xml:lang="en">Rubinsztein D.C., Mariño G., Kroemer G. Autophagy and aging // Cell. 2011. Vol. 146. N 5. P. 682–695.</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Blagosklonny M.V. Aging and immortality: quasiprogrammed senescence and its pharmacologic inhibition // Cell Cycle. 2006. Vol. 5. N 18. P. 2087–2102.</mixed-citation><mixed-citation xml:lang="en">Blagosklonny M.V. Aging and immortality: quasiprogrammed senescence and its pharmacologic inhibition // Cell Cycle. 2006. Vol. 5. N 18. P. 2087–2102.</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Neff F., Flores-Dominguez D., Ryan D.P. et al. Rapamycin extends murine lifespan but has limited effects on aging // J. Clin. Invest. 2013. Vol. 123. N 8. P. 3272–3291.</mixed-citation><mixed-citation xml:lang="en">Neff F., Flores-Dominguez D., Ryan D.P. et al. Rapamycin extends murine lifespan but has limited effects on aging // J. Clin. Invest. 2013. Vol. 123. N 8. P. 3272–3291.</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
