<?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="en"><front><journal-meta><journal-id journal-id-type="publisher-id">donstu</journal-id><journal-title-group><journal-title xml:lang="en">Advanced Engineering Research (Rostov-on-Don)</journal-title><trans-title-group xml:lang="ru"><trans-title>Advanced Engineering Research (Rostov-on-Don)</trans-title></trans-title-group></journal-title-group><issn pub-type="epub">2687-1653</issn><publisher><publisher-name>Don State Technical University</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.12737/3509</article-id><article-id custom-type="elpub" pub-id-type="custom">donstu-292</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="en"><subject>TECHNICAL SCIENCES</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ТЕХНИЧЕСКИЕ НАУКИ</subject></subj-group></article-categories><title-group><article-title>STOCHASTIC SIMULATION MODELING OF CELL TELOMERE SHORTENING MECHANISMS IN AGEING AND DISTURBANCE DEVELOPMENT PROCESSES</article-title><trans-title-group xml:lang="ru"><trans-title>Стохастическое имитационное моделирование механизмов укорочения теломер клеток в процессах старения и развития патологических отклонений</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>Бутов</surname><given-names>Александр Александрович</given-names></name><name name-style="western" xml:lang="en"><surname>Butov</surname><given-names>Alexander Alexandrovich</given-names></name></name-alternatives><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Карев</surname><given-names>Михаил Андреевич</given-names></name><name name-style="western" xml:lang="en"><surname>Karev</surname><given-names>Mikhail Andreyevich</given-names></name></name-alternatives><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Хрусталёв</surname><given-names>Сергей Александрович</given-names></name><name name-style="western" xml:lang="en"><surname>Khrustalev</surname><given-names>Sergey Alexandrovich</given-names></name></name-alternatives><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Ульяновский государственный университет, Россия</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Ulyanovsk State University, Russia</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2014</year></pub-date><pub-date pub-type="epub"><day>30</day><month>03</month><year>2014</year></pub-date><volume>14</volume><issue>1</issue><fpage>98</fpage><lpage>109</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Butov A.A., Karev M.A., Khrustalev S.A., 2014</copyright-statement><copyright-year>2014</copyright-year><copyright-holder xml:lang="ru">Бутов А.А., Карев М.А., Хрусталёв С.А.</copyright-holder><copyright-holder xml:lang="en">Butov A.A., Karev M.A., Khrustalev S.A.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" 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://www.vestnik-donstu.ru/jour/article/view/292">https://www.vestnik-donstu.ru/jour/article/view/292</self-uri><abstract><p>Some issues of applying the stochastic simulation modeling to the description and stud ying of DNA’s end structures (telomeres) shortening mechanisms are considered. The aim of this research is to study — on the base of the st ochastic and simulation modeling — processes in the cells leading to the telomeres’ length shortening, and as a co nse quence, to decreasing the proliferative capacity, and developing pathologies including oncologic one s. The mat hematical model is described in the semimartingale terms. The analysis of the modeling results is bas ed on their comparison to the biological expe riments data. The formed cell distribution in accordance to their telomeres’ length is compared with the e x perimental data obtained through the tests performed with human fibroblast - culture using Levy — Prokhorov metric. The study results can be used in bi omedical research on ageing, and on developing var ious pathologies, as well as in solving a number of problems in the field of gero n tology.</p></abstract><trans-abstract xml:lang="ru"><p>Рассматриваются вопросы применения стохастического имитационного моделирования к описанию и иссл едованию механизмов укорочения концевых структур ДНК — теломер. Целью настоящей работы является исследов а ние на основе стохастического и имитационного мод елирования протекающих в клетк ах явлений , которые приводят к уменьшению длины теломер и, как следствие, к снижению пролиферативного потенци ала и возникновению патологий, в том числе онкологических. М атематическ ая модел ь описывается в сем имартингальных терминах. Анализ резул ь татов модел ирова ния ос нован на сопоставлени и со статистическими данными биологических экспериментов. Построенные распределения клеток по длинам их теломер соп оставлялись с экспериментальными данными, полученны ми на культурах фибробластов человека с использ ованием мет рики Леви — Прохорова. Результаты работы могут найти применение в медико - биологических и сследованиях старения и возникновения различных патологий, а также при решении ряда вопросов в обл а сти геронтол о гии.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>стохастическое имитационное моделирование</kwd><kwd>семимартингал</kwd><kwd>компенсатор</kwd><kwd>ДНК</kwd><kwd>теломера</kwd><kwd>теломераза</kwd><kwd>старение</kwd><kwd>канцерогенез</kwd><kwd>оксидативный стресс</kwd><kwd>свободные радикалы</kwd></kwd-group><kwd-group xml:lang="en"><kwd>stochastic simulation modeling</kwd><kwd>semimartingale</kwd><kwd>compensator</kwd><kwd>DNA</kwd><kwd>telomere</kwd><kwd>telomerase</kwd><kwd>aging</kwd><kwd>ca rcinogene sis</kwd><kwd>oxidative stress</kwd><kwd>free radicals.</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Министерства образования и науки РФ</funding-statement><funding-statement xml:lang="en">Ministry of Education and Science of the Russian Federation</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Blackburn, E.-H. Telomeres and telomerase: their mechanisms of action and the effects of altering their functions / E.-H. Blackburn // FEBS Letters. — 2005. — Vol. 579. — Pp. 859‒862.</mixed-citation><mixed-citation xml:lang="en">Blackburn, E.-H. Telomeres and telomerase: their mechanisms of action and the effects of altering their functions / E.-H. Blackburn // FEBS Letters. — 2005. — Vol. 579. — Pp. 859‒862.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Blasco, M.-A. Telomere length, stem cells and aging / M.-A. Blasco // Nature Chemical Biology. — 2007. — Vol. 3. — Pp. 640‒649.</mixed-citation><mixed-citation xml:lang="en">Blasco, M.-A. Telomere length, stem cells and aging / M.-A. Blasco // Nature Chemical Biology. — 2007. — Vol. 3. — Pp. 640‒649.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Proteins induced by telomere dysfunction and DNA damage represent biomarkers of human aging and disease / H. Jiang [et al.] // Proceedings of the National Academy of Sciences of the United States of America. — 2008. — Vol. 105. — Pp. 11299‒11304.</mixed-citation><mixed-citation xml:lang="en">Proteins induced by telomere dysfunction and DNA damage represent biomarkers of human aging and disease / H. Jiang [et al.] // Proceedings of the National Academy of Sciences of the United States of America. — 2008. — Vol. 105. — Pp. 11299‒11304.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Sex hormones, acting on the TERT gene, increase telomerase activity in human primary hematopoietic cells / R.-T. Calado [et al.] // Blood. — 2009. — Vol. 114. — Pp. 2236‒2243.</mixed-citation><mixed-citation xml:lang="en">Sex hormones, acting on the TERT gene, increase telomerase activity in human primary hematopoietic cells / R.-T. Calado [et al.] // Blood. — 2009. — Vol. 114. — Pp. 2236‒2243.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Calado, R.-T. Telomere Diseases / R.-T. Calado, N.-S. Young // The New England Journal of Medicine. — 2009. — Vol. 361. — P. 2353‒2365.</mixed-citation><mixed-citation xml:lang="en">Calado, R.-T. Telomere Diseases / R.-T. Calado, N.-S. Young // The New England Journal of Medicine. — 2009. — Vol. 361. — P. 2353‒2365.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Proctor, C.-J. Modelling telomere shortening and the role of oxidative stress / C.-J. Proctor, T.-B.-L. Kirkwood // Mechanisms of Ageing and Development. — 2002. — Vol. 123. — Pp. 351‒363.</mixed-citation><mixed-citation xml:lang="en">Proctor, C.-J. Modelling telomere shortening and the role of oxidative stress / C.-J. Proctor, T.-B.-L. Kirkwood // Mechanisms of Ageing and Development. — 2002. — Vol. 123. — Pp. 351‒363.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Sozou, P.-D. A stochastic model of cell replicative senescence based on telomere shortening, oxidative stress, and somatic mutations in nuclear and mitochondrial DNA / P.-D. Sozou, T.-B.-L. Kirkwood // Journal of Theoretical Biology. — 2001. — Vol. 213. — Pp. 573‒586.</mixed-citation><mixed-citation xml:lang="en">Sozou, P.-D. A stochastic model of cell replicative senescence based on telomere shortening, oxidative stress, and somatic mutations in nuclear and mitochondrial DNA / P.-D. Sozou, T.-B.-L. Kirkwood // Journal of Theoretical Biology. — 2001. — Vol. 213. — Pp. 573‒586.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Rubelj, I. Stochastic mechanism of cellular aging — abrupt telomere shortening as a model for stochastic nature of cellular aging / I. Rubelj, Z. Vondracek // Journal of Theoretical Biology. — 1999. — Vol. 197. — Pp. 425‒438.</mixed-citation><mixed-citation xml:lang="en">Rubelj, I. Stochastic mechanism of cellular aging — abrupt telomere shortening as a model for stochastic nature of cellular aging / I. Rubelj, Z. Vondracek // Journal of Theoretical Biology. — 1999. — Vol. 197. — Pp. 425‒438.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Wein, L.-M. Estimation of replicative senescence via a population dynamics model of cells in culture / L.-M. Wein, J.-T. Wu // Experimental Gerontology. — 2001. — Vol. 36. — Pp. 79‒88.</mixed-citation><mixed-citation xml:lang="en">Wein, L.-M. Estimation of replicative senescence via a population dynamics model of cells in culture / L.-M. Wein, J.-T. Wu // Experimental Gerontology. — 2001. — Vol. 36. — Pp. 79‒88.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Arino, O. Mathematical modeling of the loss of telomere sequences / O. Arino, M. Kimmel, G.-F. Webb // Journal of Theoretical Biology. — 1995. — Vol. 177. — Pp. 45‒57.</mixed-citation><mixed-citation xml:lang="en">Arino, O. Mathematical modeling of the loss of telomere sequences / O. Arino, M. Kimmel, G.-F. Webb // Journal of Theoretical Biology. — 1995. — Vol. 177. — Pp. 45‒57.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Tan, Z. Simulated shortening of proliferation-restricting telomeres during clonal proliferation and senescence of human cells / Z. Tan // Experimental Gerontology. — 2001. — Vol. 36. — Pp. 89‒97.</mixed-citation><mixed-citation xml:lang="en">Tan, Z. Simulated shortening of proliferation-restricting telomeres during clonal proliferation and senescence of human cells / Z. Tan // Experimental Gerontology. — 2001. — Vol. 36. — Pp. 89‒97.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Zglinicki, T. Stress, DNA damage and ageing — an integrative approach / T. Zglinicki, A. Burkle, T.-B.-L. Kirkwood // Experimental Gerontology. — 2001. — Vol. 36. — Pp. 1049‒1062.</mixed-citation><mixed-citation xml:lang="en">Zglinicki, T. Stress, DNA damage and ageing — an integrative approach / T. Zglinicki, A. Burkle, T.-B.-L. Kirkwood // Experimental Gerontology. — 2001. — Vol. 36. — Pp. 1049‒1062.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Blagoev, K. B. Telomere exchange and asymmetric segregation of chromosomes can account for the unlimited proliferative potential of ALT cell populations / K. B. Blagoev, E. H. Goodwin // DNA Repair. — 2008. — Vol. 7. — Pp. 199‒204.</mixed-citation><mixed-citation xml:lang="en">Blagoev, K. B. Telomere exchange and asymmetric segregation of chromosomes can account for the unlimited proliferative potential of ALT cell populations / K. B. Blagoev, E. H. Goodwin // DNA Repair. — 2008. — Vol. 7. — Pp. 199‒204.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Qi, Q. Mathematical modelling of telomere Dynamics / Q. Qi // Thesis submitted to The University of Nottingham for the degree of Doctor of Philosophy. — Nottingham, 2011. — 210 p.</mixed-citation><mixed-citation xml:lang="en">Qi, Q. Mathematical modelling of telomere Dynamics / Q. Qi // Thesis submitted to The University of Nottingham for the degree of Doctor of Philosophy. — Nottingham, 2011. — 210 p.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Grasman, J. Stochastic modelling of length dependent telomere shortening in Corvus monedula / J. Grasman, H.-M. Salomons, S. Verhulst // Journal of Theoretical Biology. — 2011. — Vol. 282. — Pp. 1‒6.</mixed-citation><mixed-citation xml:lang="en">Grasman, J. Stochastic modelling of length dependent telomere shortening in Corvus monedula / J. Grasman, H.-M. Salomons, S. Verhulst // Journal of Theoretical Biology. — 2011. — Vol. 282. — Pp. 1‒6.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Kapitanov, G. A. Mathematical Model of Cancer Stem Cell Lineage Population Dynamics with Mutation Accumulation and Telomere Length Hierarchies / G. A. Kapitanov // Mathematical Modelling of Natural Phenomena. — 2012. — Vol. 7. — Pp. 136‒165.</mixed-citation><mixed-citation xml:lang="en">Kapitanov, G. A. Mathematical Model of Cancer Stem Cell Lineage Population Dynamics with Mutation Accumulation and Telomere Length Hierarchies / G. A. Kapitanov // Mathematical Modelling of Natural Phenomena. — 2012. — Vol. 7. — Pp. 136‒165.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Tchirkov, A. Role of oxidative stress in telomere shortening in cultured fibroblasts from normal individuals and patients with ataxia-elangiectasia / A. Tchirkov, P. M. Lansdorp // Human Molecular Genetics. — 2003. — Vol. 12. — Pp. 227‒232.</mixed-citation><mixed-citation xml:lang="en">Tchirkov, A. Role of oxidative stress in telomere shortening in cultured fibroblasts from normal individuals and patients with ataxia-elangiectasia / A. Tchirkov, P. M. Lansdorp // Human Molecular Genetics. — 2003. — Vol. 12. — Pp. 227‒232.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Accumulation of short telomeres in human fibroblasts prior to replicative senescence / U.-M. Martens [et al.] // Experimental Cell Research. — 2000. — Vol. 256. — Pp. 291‒299.</mixed-citation><mixed-citation xml:lang="en">Accumulation of short telomeres in human fibroblasts prior to replicative senescence / U.-M. Martens [et al.] // Experimental Cell Research. — 2000. — Vol. 256. — Pp. 291‒299.</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>
