ИЗУЧЕНИЕ ДОЛГОЖИТЕЛЬСТВА: СОВРЕМЕННЫЙ СТАТУС ПРОБЛЕМЫ И ПЕРСПЕКТИВЫ. Часть 2

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.

1. 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

2. 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

3. 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

4. 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.

5. 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

6. 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

7. 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

8. 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

9. Brown-Borg HM, Borg KE, Meliska CJ, et al. Dwarf mice and the ageing process. Nature 1996; 384(6604): 33. DOI: 10.1038/384033a0

10. Samaras TT, Elrick H. Height, body size, and longevity: is smaller better for the human body? West J Med 2002; 176(3): 206-8.

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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

23. McLain JH, Alsterda AJ, Arora RR. Cholesteryl Ester Transfer Protein Inhibitors: Trials and Tribulations. J Cardiovasc Pharmacol Ther 2016 DOI: 10.1177/1074248416662349

24. 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

25. 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

26. 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

27. 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

28. 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

29. 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

30. 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

31. 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

32. 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

33. 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

34. 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.

35. 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

36. 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

37. 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

38. 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

39. 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

40. 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

41. 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

42. 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

43. 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.

44. 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

45. 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.

46. 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

47. 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

48. 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