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<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">cardiovascular</journal-id><journal-title-group><journal-title xml:lang="ru">Кардиоваскулярная терапия и профилактика</journal-title><trans-title-group xml:lang="en"><trans-title>Cardiovascular Therapy and Prevention</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1728-8800</issn><issn pub-type="epub">2619-0125</issn><publisher><publisher-name>«SILICEA-POLIGRAF» LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.15829/1728-8800-2017-6-133-138</article-id><article-id custom-type="elpub" pub-id-type="custom">cardiovascular-725</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>ОБЗОРЫ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>REVIEWS</subject></subj-group></article-categories><title-group><article-title>ИЗУЧЕНИЕ ДОЛГОЖИТЕЛЬСТВА: СОВРЕМЕННЫЙ СТАТУС ПРОБЛЕМЫ И ПЕРСПЕКТИВЫ. Часть 2</article-title><trans-title-group xml:lang="en"><trans-title>THE STUDY OF LONGEVITY: RECENT UPDATES AND FURTHER DIRECTION. PART 2</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>Котовская</surname><given-names>Ю. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Kotovskaya</surname><given-names>Yu. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Доктор медицинских наук, профессор, зав. кафедрой кардиологии и персонифицированной медицины ФПК МР МИ, РУДН; руководитель лаборатории сердечно-сосудистого старения ОСП “Российский геронтологический научно-клинический центр”</p></bio><bio xml:lang="en"/><email xlink:type="simple">kotovskaya@bk.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>Ткачева</surname><given-names>О. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Tkacheva</surname><given-names>О. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Доктор медицинских наук, профессор, директор, ОСП “Российский геронтологический научно-клинический центр”</p></bio><bio xml:lang="en"/><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Рунихина</surname><given-names>Н. К.</given-names></name><name name-style="western" xml:lang="en"><surname>Runikhina</surname><given-names>N. К.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Доктор медицинских наук, заместитель директора, ОСП “Российский геронтологический научно-клинический центр”</p></bio><bio xml:lang="en"/><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Каштанова</surname><given-names>Д. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kashtanova</surname><given-names>D. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Аспирант отдела изучения процессов старения и профилактики возраст-ассоциированных заболеваний, ОСП “Российский геронтологический научно-клинический центр”;  м.н.с. лаборатории биологии старения и биоинформатики, Государственный научно- исследовательский центр профилактической медицины</p></bio><bio xml:lang="en"/><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Бойцов</surname><given-names>С. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Boytsov</surname><given-names>S. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Доктор медицинских наук, профессор, чл.-корр. РАН, директор</p></bio><bio xml:lang="en"/><xref ref-type="aff" rid="aff-4"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГАОУ ВО “Российский университет дружбы народов” Министерства образования и науки Российской Федерации; &#13;
ФГБОУ ВО “Российский научно-исследовательский медицинский университет им. Н.И. Пирогова” Министерства здравоохранения Российской Федерации</institution></aff><aff xml:lang="en"><institution>Peoples’ Friendship University of Russia; &#13;
N. I. Pirogov Russian National Research Medical University— SD “Russian Gerontological Scientific-Clinical Center”</institution></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>ФГБОУ ВО “Российский научно-исследовательский медицинский университет им. Н.И. Пирогова” Министерства здравоохранения Российской Федерации</institution></aff><aff xml:lang="en"><institution>N. I. Pirogov Russian National Research Medical University— SD “Russian Gerontological Scientific-Clinical Center”</institution></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>ФГБОУ ВО “Российский научно-исследовательский медицинский университет им. Н.И. Пирогова” Министерства здравоохранения Российской Федерации ; &#13;
ФГБУ “Государственный научно- исследовательский центр профилактической медицины” Министерства здравоохранения Российской Федерации</institution></aff><aff xml:lang="en"><institution>N. I. Pirogov Russian National Research Medical University— SD “Russian Gerontological Scientific-Clinical Center”; &#13;
Russian Cardiological Research-and-Production Complex of the Ministry of Health</institution></aff></aff-alternatives><aff-alternatives id="aff-4"><aff xml:lang="ru"><institution>ФГБУ “Государственный научно- исследовательский центр профилактической медицины” Министерства здравоохранения Российской Федерации</institution></aff><aff xml:lang="en"><institution>Russian Cardiological Research-and-Production Complex of the Ministry of Health</institution></aff></aff-alternatives><pub-date pub-type="collection"><year>2017</year></pub-date><pub-date pub-type="epub"><day>20</day><month>12</month><year>2017</year></pub-date><volume>16</volume><issue>6</issue><fpage>133</fpage><lpage>138</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Котовская Ю.В., Ткачева О.Н., Рунихина Н.К., Каштанова Д.А., Бойцов С.А., 2017</copyright-statement><copyright-year>2017</copyright-year><copyright-holder xml:lang="ru">Котовская Ю.В., Ткачева О.Н., Рунихина Н.К., Каштанова Д.А., Бойцов С.А.</copyright-holder><copyright-holder xml:lang="en">Kotovskaya Y.V., Tkacheva О.N., Runikhina N.К., Kashtanova D.A., Boytsov 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://cardiovascular.elpub.ru/jour/article/view/725">https://cardiovascular.elpub.ru/jour/article/view/725</self-uri><abstract><p>Несмотря на глобальные демографические тенденции увеличения продолжительности жизни, долгожительство и сверхдолгожительство остаются во многом недостаточно изученной и понятой популяцией. Необходимы широкомасштабные исследования для понимания того, что значит дожить до 100-летнего возраста. Большое количество исследований было посвящено предикторам долгожительства, поиску путей старения, которые могли бы стать терапевтическими мишенями с целью не только собственно продления жизни, но и обеспечения ее качества, оказания медико-социальной гериатрической помощи. Программа “100-летний гражданин”, проводимая ведущими научными коллективами РФ, направлена на получение медицинской, научной и социальной информации, уникальной для страны.</p></abstract><trans-abstract xml:lang="en"><p>Regardless the global demographic tendencies of life duration increase, longevity and super longevity remain quite understudied and non-fully understood population. Broader studies needed to understand, what it means to live by 100-year old. Lots of studies are about the longevity predictors and ways of ageing, that could be therapeutical targets not simply for life duration, but life quality as well, and medical-social geriatrics. The program “A Centenarian”, being conducted by leading scientific groups inRussia, is approaching a country unique medical, scientific and social data. </p></trans-abstract><kwd-group xml:lang="ru"><kwd>долгожительство</kwd><kwd>старение</kwd><kwd>программы “100-летний гражданин”</kwd><kwd>комплексная гериатрическая оценка</kwd></kwd-group><kwd-group xml:lang="en"><kwd>longevity</kwd><kwd>ageing</kwd><kwd>a centenarian</kwd><kwd>complex geriatrician assessment</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">Vergani C, Lucchi T, Caloni M, et al. I405V polymorphism of the cholesteryl ester transfer protein (CETP) gene in young and very old people. Arch Gerontol Geriatr 2006; 43(2): 213-21. DOI: 10.1016/j.archger.2005.10.008</mixed-citation><mixed-citation xml:lang="en">Vergani C, Lucchi T, Caloni M, et al. I405V polymorphism of the cholesteryl ester transfer protein (CETP) gene in young and very old people. Arch Gerontol Geriatr 2006; 43(2): 213-21. DOI: 10.1016/j.archger.2005.10.008</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Sanders AE, Wang C, Katz M, et al. Association of a functional polymorphism in the cholesteryl ester transfer protein (CETP) gene with memory decline and incidence of dementia. JAMA 2010; 303(2): 150-8. DOI: 10.1001/jama.2009.1988</mixed-citation><mixed-citation xml:lang="en">Sanders AE, Wang C, Katz M, et al. Association of a functional polymorphism in the cholesteryl ester transfer protein (CETP) gene with memory decline and incidence of dementia. JAMA 2010; 303(2): 150-8. DOI: 10.1001/jama.2009.1988</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Atzmon G, Rincon M, Schechter CB, et al. Lipoprotein genotype and conserved pathway for exceptional longevity in humans. PLoS Biol 2006; 4(4): e113. DOI: 10.1371/journal.pbio.0040113</mixed-citation><mixed-citation xml:lang="en">Atzmon G, Rincon M, Schechter CB, et al. Lipoprotein genotype and conserved pathway for exceptional longevity in humans. PLoS Biol 2006; 4(4): e113. DOI: 10.1371/journal.pbio.0040113</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Pollin TI, Damcott CM, Shen H, et al. A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection. Science 2008; 322(5908): 1702-5. DOI: 10.1126/science.1161524 5. Atzmon G, Pollin TI, Crandall J, et al. Adiponectin levels and genotype: a potential regulator of life span in humans. J Gerontol A Biol Sci Med Sci 2008; 63(5): 447-53.</mixed-citation><mixed-citation xml:lang="en">Pollin TI, Damcott CM, Shen H, et al. A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection. Science 2008; 322(5908): 1702-5. DOI: 10.1126/science.1161524 5. Atzmon G, Pollin TI, Crandall J, et al. Adiponectin levels and genotype: a potential regulator of life span in humans. J Gerontol A Biol Sci Med Sci 2008; 63(5): 447-53.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Atzmon G, Barzilai N, Surks MI, et al. Genetic predisposition to elevated serum thyrotropin is associated with exceptional longevity. J Clin Endocrinol Metab 2009; 94(12): 4768-75. DOI: 10.1210/jc.2009-0808</mixed-citation><mixed-citation xml:lang="en">Atzmon G, Barzilai N, Surks MI, et al. Genetic predisposition to elevated serum thyrotropin is associated with exceptional longevity. J Clin Endocrinol Metab 2009; 94(12): 4768-75. DOI: 10.1210/jc.2009-0808</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Atzmon G, Barzilai N, Hollowell JG, et al. Extreme longevity is associated with increased serum thyrotropin. J Clin Endocrinol Metab 2009; 94(4): 1251-4. DOI: 10.1210/jc.2008-325</mixed-citation><mixed-citation xml:lang="en">Atzmon G, Barzilai N, Hollowell JG, et al. Extreme longevity is associated with increased serum thyrotropin. J Clin Endocrinol Metab 2009; 94(4): 1251-4. DOI: 10.1210/jc.2008-325</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Rozing MP, Houwing-Duistermaat JJ, Slagboom PE, et al. Familial longevity is associated with decreased thyroid function. J Clin Endocrinol Metab 2010; 95(11): 4979-84. DOI: 10.1210/jc.2010-0875</mixed-citation><mixed-citation xml:lang="en">Rozing MP, Houwing-Duistermaat JJ, Slagboom PE, et al. Familial longevity is associated with decreased thyroid function. J Clin Endocrinol Metab 2010; 95(11): 4979-84. DOI: 10.1210/jc.2010-0875</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Tabatabaie V, Surks MI. The aging thyroid. Curr Opin Endocrinol Diabetes Obes 2013; 20(5): 455-9. DOI: 10.1097/01.med.0000433055.99570.52</mixed-citation><mixed-citation xml:lang="en">Tabatabaie V, Surks MI. The aging thyroid. Curr Opin Endocrinol Diabetes Obes 2013; 20(5): 455-9. DOI: 10.1097/01.med.0000433055.99570.52</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Brown-Borg HM, Borg KE, Meliska CJ, et al. Dwarf mice and the ageing process. Nature 1996; 384(6604): 33. DOI: 10.1038/384033a0</mixed-citation><mixed-citation xml:lang="en">Brown-Borg HM, Borg KE, Meliska CJ, et al. Dwarf mice and the ageing process. Nature 1996; 384(6604): 33. DOI: 10.1038/384033a0</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Samaras TT, Elrick H. Height, body size, and longevity: is smaller better for the human body? West J Med 2002; 176(3): 206-8.</mixed-citation><mixed-citation xml:lang="en">Samaras TT, Elrick H. Height, body size, and longevity: is smaller better for the human body? West J Med 2002; 176(3): 206-8.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Kenyon C, Chang J, Gensch E, et al. A C. elegans mutant that lives twice as long as wild type. Nature 1993; 366(6454): 461-4. DOI: 10.1038/366461a0</mixed-citation><mixed-citation xml:lang="en">Kenyon C, Chang J, Gensch E, et al. A C. elegans mutant that lives twice as long as wild type. Nature 1993; 366(6454): 461-4. DOI: 10.1038/366461a0</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Sandhu MS, Heald AH, Gibson JM, et al. Circulating concentrations of insulin-like growth factor-I and development of glucose intolerance: a prospective observational study. Lancet 2002; 359(9319): 1740-5. DOI: 10.1016/S0140-6736(02)08655-5</mixed-citation><mixed-citation xml:lang="en">Sandhu MS, Heald AH, Gibson JM, et al. Circulating concentrations of insulin-like growth factor-I and development of glucose intolerance: a prospective observational study. Lancet 2002; 359(9319): 1740-5. DOI: 10.1016/S0140-6736(02)08655-5</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Burgers AM, Biermasz NR, Schoones JW, et al. Meta-analysis and dose-response metaregression: circulating insulin-like growth factor I (IGF-I) and mortality. J Clin Endocrinol Metab 2011; 96(9): 2912-20. DOI: 10.1210/jc.2011-1377</mixed-citation><mixed-citation xml:lang="en">Burgers AM, Biermasz NR, Schoones JW, et al. Meta-analysis and dose-response metaregression: circulating insulin-like growth factor I (IGF-I) and mortality. J Clin Endocrinol Metab 2011; 96(9): 2912-20. DOI: 10.1210/jc.2011-1377</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Pawlikowska L, Hu D, Huntsman S, et al. Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevity. Aging Cell 2009; 8(4): 460- 72. DOI: 10.1111/j.1474-9726.2009.00493.x</mixed-citation><mixed-citation xml:lang="en">Pawlikowska L, Hu D, Huntsman S, et al. Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevity. Aging Cell 2009; 8(4): 460- 72. DOI: 10.1111/j.1474-9726.2009.00493.x</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Suh Y, Atzmon G, Cho MO, et al. Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc Natl Acad Sci U S A 2008; 105(9): 3438-42. DOI: 10.1073/pnas.0705467105</mixed-citation><mixed-citation xml:lang="en">Suh Y, Atzmon G, Cho MO, et al. Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc Natl Acad Sci U S A 2008; 105(9): 3438-42. DOI: 10.1073/pnas.0705467105</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Tazearslan C, Huang J, Barzilai N, et al. Impaired IGF1R signaling in cells expressing longevity-associated human IGF1R alleles. Aging Cell 2011; 10(3): 551-4. DOI: 10.1111/j.1474-9726.2011.00697.х</mixed-citation><mixed-citation xml:lang="en">Tazearslan C, Huang J, Barzilai N, et al. Impaired IGF1R signaling in cells expressing longevity-associated human IGF1R alleles. Aging Cell 2011; 10(3): 551-4. DOI: 10.1111/j.1474-9726.2011.00697.х</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Guevara-Aguirre J, Balasubramanian P, Guevara-Aguirre M, et al. Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans. Sci Transl Med 2011; 3(70): 70ra13. DOI: 10.1126/scitranslmed.3001845</mixed-citation><mixed-citation xml:lang="en">Guevara-Aguirre J, Balasubramanian P, Guevara-Aguirre M, et al. Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans. Sci Transl Med 2011; 3(70): 70ra13. DOI: 10.1126/scitranslmed.3001845</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Milman S, Atzmon G, Huffman DM, et al. Low insulin-like growth factor-1 level predicts survival in humans with exceptional longevity. Aging Cell 2014; 13(4): 769- 71. DOI: 10.1111/acel.12213</mixed-citation><mixed-citation xml:lang="en">Milman S, Atzmon G, Huffman DM, et al. Low insulin-like growth factor-1 level predicts survival in humans with exceptional longevity. Aging Cell 2014; 13(4): 769- 71. DOI: 10.1111/acel.12213</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Atzmon G, Cho M, Cawthon RM, et al. Evolution in health and medicine Sackler colloquium: Genetic variation in human telomerase is associated with telomere length in Ashkenazi centenarians. Proc Natl Acad Sci U S A 2010; 107 Suppl 1: 1710-7. DOI: 10.1073/pnas.0906191106</mixed-citation><mixed-citation xml:lang="en">Atzmon G, Cho M, Cawthon RM, et al. Evolution in health and medicine Sackler colloquium: Genetic variation in human telomerase is associated with telomere length in Ashkenazi centenarians. Proc Natl Acad Sci U S A 2010; 107 Suppl 1: 1710-7. DOI: 10.1073/pnas.0906191106</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Han J, Atzmon G, Barzilai N, et al. Genetic variation in Sirtuin 1 (SIRT1) is associated with lipid profiles but not with longevity in Ashkenazi Jews. Transl Res 2015; 165(4): 480-1. DOI: 10.1016/j.trsl.2014.09.008</mixed-citation><mixed-citation xml:lang="en">Han J, Atzmon G, Barzilai N, et al. Genetic variation in Sirtuin 1 (SIRT1) is associated with lipid profiles but not with longevity in Ashkenazi Jews. Transl Res 2015; 165(4): 480-1. DOI: 10.1016/j.trsl.2014.09.008</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Gombar S, Jung HJ, Dong F, et al. Comprehensive microRNA profiling in B-cells of human centenarians by massively parallel sequencing. BMC Genomics 2012; 13: 353. DOI: 10.1186/1471-2164-13-353</mixed-citation><mixed-citation xml:lang="en">Gombar S, Jung HJ, Dong F, et al. Comprehensive microRNA profiling in B-cells of human centenarians by massively parallel sequencing. BMC Genomics 2012; 13: 353. DOI: 10.1186/1471-2164-13-353</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Barzilai N, Atzmon G, Schechter C, et al. Unique lipoprotein phenotype and genotype associated with exceptional longevity. JAMA 2003; 290(15): 2030-40. DOI: 10.1001/ jama.290.15.2030</mixed-citation><mixed-citation xml:lang="en">Barzilai N, Atzmon G, Schechter C, et al. Unique lipoprotein phenotype and genotype associated with exceptional longevity. JAMA 2003; 290(15): 2030-40. DOI: 10.1001/ jama.290.15.2030</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">McLain JH, Alsterda AJ, Arora RR. Cholesteryl Ester Transfer Protein Inhibitors: Trials and Tribulations. J Cardiovasc Pharmacol Ther 2016 DOI: 10.1177/1074248416662349</mixed-citation><mixed-citation xml:lang="en">McLain JH, Alsterda AJ, Arora RR. Cholesteryl Ester Transfer Protein Inhibitors: Trials and Tribulations. J Cardiovasc Pharmacol Ther 2016 DOI: 10.1177/1074248416662349</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">van der Tuin SJ, Kuhnast S, Berbee JF, et al. Anacetrapib reduces (V)LDL cholesterol by inhibition of CETP activity and reduction of plasma PCSK9. J Lipid Res 2015; 56(11): 2085-93. DOI: 10.1194/jlr.M057794</mixed-citation><mixed-citation xml:lang="en">van der Tuin SJ, Kuhnast S, Berbee JF, et al. Anacetrapib reduces (V)LDL cholesterol by inhibition of CETP activity and reduction of plasma PCSK9. J Lipid Res 2015; 56(11): 2085-93. DOI: 10.1194/jlr.M057794</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Roddy TP, McLaren DG, Chen Y, et al. Effects of anacetrapib on plasma lipids, apolipoproteins and PCSK9 in healthy, lean rhesus macaques. Eur J Pharmacol 2014; 740: 410-6. DOI: 10.1016/j.ejphar.2014.04.015</mixed-citation><mixed-citation xml:lang="en">Roddy TP, McLaren DG, Chen Y, et al. Effects of anacetrapib on plasma lipids, apolipoproteins and PCSK9 in healthy, lean rhesus macaques. Eur J Pharmacol 2014; 740: 410-6. DOI: 10.1016/j.ejphar.2014.04.015</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Girona J, Ibarretxe D, Plana N, et al. Circulating PCSK9 levels and CETP plasma activity are independently associated in patients with metabolic diseases. Cardiovasc Diabetol 2016; 15(1): 107. DOI: 10.1186/s12933-016-0428-z</mixed-citation><mixed-citation xml:lang="en">Girona J, Ibarretxe D, Plana N, et al. Circulating PCSK9 levels and CETP plasma activity are independently associated in patients with metabolic diseases. Cardiovasc Diabetol 2016; 15(1): 107. DOI: 10.1186/s12933-016-0428-z</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Lee RG, Crosby J, Baker BF, et al. Antisense technology: an emerging platform for cardiovascular disease therapeutics. J Cardiovasc Transl Res 2013; 6(6): 969-80. DOI: 10.1007/s12265-013-9495-7</mixed-citation><mixed-citation xml:lang="en">Lee RG, Crosby J, Baker BF, et al. Antisense technology: an emerging platform for cardiovascular disease therapeutics. J Cardiovasc Transl Res 2013; 6(6): 969-80. DOI: 10.1007/s12265-013-9495-7</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Milman S, Barzilai N. Dissecting the Mechanisms Underlying Unusually Successful Human Health Span and Life Span. Cold Spring Harb Perspect Med 2015; 6(1): a025098. DOI: 10.1101/cshperspect.a025098</mixed-citation><mixed-citation xml:lang="en">Milman S, Barzilai N. Dissecting the Mechanisms Underlying Unusually Successful Human Health Span and Life Span. Cold Spring Harb Perspect Med 2015; 6(1): a025098. DOI: 10.1101/cshperspect.a025098</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Mannick JB, Del Giudice G, Lattanzi M, et al. mTOR inhibition improves immune function in the elderly. Sci Transl Med 2014; 6(268): 268ra179. DOI: 10.1126/ scitranslmed.3009892</mixed-citation><mixed-citation xml:lang="en">Mannick JB, Del Giudice G, Lattanzi M, et al. mTOR inhibition improves immune function in the elderly. Sci Transl Med 2014; 6(268): 268ra179. DOI: 10.1126/ scitranslmed.3009892</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Anisimov VN, Egormin PA, Piskunova TS, et al. Metformin extends life span of HER-2/neu transgenic mice and in combination with melatonin inhibits growth of transplantable tumors in vivo. Cell Cycle 2010; 9(1): 188-97. DOI: 10.4161/ cc.9.1.10407</mixed-citation><mixed-citation xml:lang="en">Anisimov VN, Egormin PA, Piskunova TS, et al. Metformin extends life span of HER-2/neu transgenic mice and in combination with melatonin inhibits growth of transplantable tumors in vivo. Cell Cycle 2010; 9(1): 188-97. DOI: 10.4161/ cc.9.1.10407</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Anisimov VN, Berstein LM, Popovich IG, et al. If started early in life, metformin treatment increases life span and postpones tumors in female SHR mice. Aging (Albany NY) 2011; 3(2): 148-57. DOI: 10.18632/aging.100273</mixed-citation><mixed-citation xml:lang="en">Anisimov VN, Berstein LM, Popovich IG, et al. If started early in life, metformin treatment increases life span and postpones tumors in female SHR mice. Aging (Albany NY) 2011; 3(2): 148-57. DOI: 10.18632/aging.100273</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Martin-Montalvo A, Mercken EM, Mitchell SJ, et al. Metformin improves healthspan and lifespan in mice. Nat Commun 2013; 4: 2192. DOI: 10.1038/ncomms3192 34. Cabreiro F, Au C, Leung KY, et al. Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism. Cell 2013; 153(1): 228-39. DOI: 10.1016/j.cell.2013.02.035</mixed-citation><mixed-citation xml:lang="en">Martin-Montalvo A, Mercken EM, Mitchell SJ, et al. Metformin improves healthspan and lifespan in mice. Nat Commun 2013; 4: 2192. DOI: 10.1038/ncomms3192 34. Cabreiro F, Au C, Leung KY, et al. Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism. Cell 2013; 153(1): 228-39. DOI: 10.1016/j.cell.2013.02.035</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Holman RR, Paul SK, Bethel MA, et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008; 359(15): 1577-89. DOI: 10.1056/ NEJMoa0806470</mixed-citation><mixed-citation xml:lang="en">Holman RR, Paul SK, Bethel MA, et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008; 359(15): 1577-89. DOI: 10.1056/ NEJMoa0806470</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Anfossi G, Russo I, Bonomo K, et al. The cardiovascular effects of metformin: further reasons to consider an old drug as a cornerstone in the therapy of type 2 diabetes mellitus. Curr Vasc Pharmacol 2010; 8(3): 327-37.</mixed-citation><mixed-citation xml:lang="en">Anfossi G, Russo I, Bonomo K, et al. The cardiovascular effects of metformin: further reasons to consider an old drug as a cornerstone in the therapy of type 2 diabetes mellitus. Curr Vasc Pharmacol 2010; 8(3): 327-37.</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Libby G, Donnelly LA, Donnan PT, et al. New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care 2009; 32(9): 1620-5. DOI: 10.2337/dc08-2175</mixed-citation><mixed-citation xml:lang="en">Libby G, Donnelly LA, Donnan PT, et al. New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care 2009; 32(9): 1620-5. DOI: 10.2337/dc08-2175</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Ma SJ, Zheng YX, Zhou PC, et al. Metformin use improves survival of diabetic liver cancer patients: systematic review and meta-analysis. Oncotarget 2016 DOI: 10.18632/oncotarget.11033</mixed-citation><mixed-citation xml:lang="en">Ma SJ, Zheng YX, Zhou PC, et al. Metformin use improves survival of diabetic liver cancer patients: systematic review and meta-analysis. Oncotarget 2016 DOI: 10.18632/oncotarget.11033</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Rokkas T, Portincasa P. Colon neoplasia in patients with type 2 diabetes on metformin: A meta-analysis. Eur J Intern Med 2016; 33: 60-6. DOI: 10.1016/j.ejim.2016.05.027</mixed-citation><mixed-citation xml:lang="en">Rokkas T, Portincasa P. Colon neoplasia in patients with type 2 diabetes on metformin: A meta-analysis. Eur J Intern Med 2016; 33: 60-6. DOI: 10.1016/j.ejim.2016.05.027</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Anisimov VN, Bartke A. The key role of growth hormone-insulin-IGF-1 signaling in aging and cancer. Crit Rev Oncol Hematol 2013; 87(3): 201-23. DOI: 10.1016/j. critrevonc.2013.01.005</mixed-citation><mixed-citation xml:lang="en">Anisimov VN, Bartke A. The key role of growth hormone-insulin-IGF-1 signaling in aging and cancer. Crit Rev Oncol Hematol 2013; 87(3): 201-23. DOI: 10.1016/j. critrevonc.2013.01.005</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Karnevi E, Said K, Andersson R, et al. Metformin-mediated growth inhibition involves suppression of the IGF-I receptor signalling pathway in human pancreatic cancer cells. BMC Cancer 2013; 13: 235. DOI: 10.1186/1471-2407-13-235</mixed-citation><mixed-citation xml:lang="en">Karnevi E, Said K, Andersson R, et al. Metformin-mediated growth inhibition involves suppression of the IGF-I receptor signalling pathway in human pancreatic cancer cells. BMC Cancer 2013; 13: 235. DOI: 10.1186/1471-2407-13-235</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Quinn BJ, Dallos M, Kitagawa H, et al. Inhibition of lung tumorigenesis by metformin is associated with decreased plasma IGF-I and diminished receptor tyrosine kinase signaling. Cancer Prev Res (Phila) 2013; 6(8): 801-10. DOI: 10.1158/1940-6207. CAPR-13-0058-T</mixed-citation><mixed-citation xml:lang="en">Quinn BJ, Dallos M, Kitagawa H, et al. Inhibition of lung tumorigenesis by metformin is associated with decreased plasma IGF-I and diminished receptor tyrosine kinase signaling. Cancer Prev Res (Phila) 2013; 6(8): 801-10. DOI: 10.1158/1940-6207. CAPR-13-0058-T</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Muzumdar RH, Huffman DM, Atzmon G, et al. Humanin: a novel central regulator of peripheral insulin action. PLoS One 2009; 4(7): e6334. DOI: 10.1371/journal. pone.0006334</mixed-citation><mixed-citation xml:lang="en">Muzumdar RH, Huffman DM, Atzmon G, et al. Humanin: a novel central regulator of peripheral insulin action. PLoS One 2009; 4(7): e6334. DOI: 10.1371/journal. pone.0006334</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Richmond RL, Law J, Kay-Lambkin F. Physical, mental, and cognitive function in a convenience sample of centenarians in Australia. J Am Geriatr Soc 2011; 59(6): 1080-6. DOI: 10.1111/j.1532-5415.2011.03404.x</mixed-citation><mixed-citation xml:lang="en">Richmond RL, Law J, Kay-Lambkin F. Physical, mental, and cognitive function in a convenience sample of centenarians in Australia. J Am Geriatr Soc 2011; 59(6): 1080-6. DOI: 10.1111/j.1532-5415.2011.03404.x</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Andersen-Ranberg K, Schroll M, Jeune B. Healthy centenarians do not exist, but autonomous centenarians do: a population-based study of morbidity among Danish centenarians. J Am Geriatr Soc 2001; 49(7): 900-8.</mixed-citation><mixed-citation xml:lang="en">Andersen-Ranberg K, Schroll M, Jeune B. Healthy centenarians do not exist, but autonomous centenarians do: a population-based study of morbidity among Danish centenarians. J Am Geriatr Soc 2001; 49(7): 900-8.</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">Inagaki H, Gondo Y, Hirose N, et al. Cognitive function in Japanese centenarians according to the Mini-Mental State Examination. Dement Geriatr Cogn Disord 2009; 28(1): 6-12. DOI: 10.1159/000228713</mixed-citation><mixed-citation xml:lang="en">Inagaki H, Gondo Y, Hirose N, et al. Cognitive function in Japanese centenarians according to the Mini-Mental State Examination. Dement Geriatr Cogn Disord 2009; 28(1): 6-12. DOI: 10.1159/000228713</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Silver MH, Jilinskaia E, Perls TT. Cognitive functional status of age-confirmed centenarians in a population-based study. J Gerontol B Psychol Sci Soc Sci 2001; 56(3): P134-40.</mixed-citation><mixed-citation xml:lang="en">Silver MH, Jilinskaia E, Perls TT. Cognitive functional status of age-confirmed centenarians in a population-based study. J Gerontol B Psychol Sci Soc Sci 2001; 56(3): P134-40.</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Poon LW, Martin P, Bishop A, et al. Understanding centenarians’ psychosocial dynamics and their contributions to health and quality of life. Curr Gerontol Geriatr Res 2010 DOI: 10.1155/2010/680657</mixed-citation><mixed-citation xml:lang="en">Poon LW, Martin P, Bishop A, et al. Understanding centenarians’ psychosocial dynamics and their contributions to health and quality of life. Curr Gerontol Geriatr Res 2010 DOI: 10.1155/2010/680657</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">Jopp D, Rott C. Adaptation in very old age: exploring the role of resources, beliefs, and attitudes for centenarians’ happiness. Psychol Aging 2006; 21(2): 266-80. DOI: 10.1037/0882-7974.21.2.266</mixed-citation><mixed-citation xml:lang="en">Jopp D, Rott C. Adaptation in very old age: exploring the role of resources, beliefs, and attitudes for centenarians’ happiness. Psychol Aging 2006; 21(2): 266-80. DOI: 10.1037/0882-7974.21.2.266</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Kato K, Zweig R, Schechter CB, et al. Positive attitude toward life, emotional expression, self-rated health, and depressive symptoms among centenarians and near-centenarians. Aging Ment Health 2016; 20(9): 930-9. DOI: 10.1080/13607863.2015.1056770</mixed-citation><mixed-citation xml:lang="en">Kato K, Zweig R, Schechter CB, et al. Positive attitude toward life, emotional expression, self-rated health, and depressive symptoms among centenarians and near-centenarians. Aging Ment Health 2016; 20(9): 930-9. DOI: 10.1080/13607863.2015.1056770</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>
