1. World Population Prospects: The 2008 Revision Population Division of the Department of Economic and Social Affairs of the United Nations Secretariat. June 2009.
2. Федеральная служба государственной статистики (Росстат). Численность населения Российской Федерации по полу и возрасту на 1 января 2013 года. Статистический бюллетень. М., 2013.
3. http://www.gks.ru/bgd/regl/b13_13/IssWWW.exe/Stg/d4/26-03.htm
4. Butler RN, Miller RA, Perry D et al. New model of health promotion and disease prevention for the 21st century. BMJ 2008; 337: a399.
5. Goldman DP, Cutler D, Rowe JW et al. Substantial Health And Economic Returns From Delayed Aging May Warrant A New Focus For Medical Research. Health Affairs 2013; 32 (10): 1698–705.
6. Dirks AJ, Hofer T, Marzetti E et al. Mitochondrial DNA mutations, energy metabolism and apoptosis in aging muscle. Ageing Res Rev 2006; 5: 179–95.
7. Kritchevsky D. Diet, lipid metabolism, and aging. Fed Proc 1979; 38: 2001–6.
8. Roberts-Thomson IC, Whittingham S, Youngchaiyud U, Mackay IR. Ageing, immune response, and mortality. Lancet 1974; 2: 368–70.
9. Koga H, Kaushik S, Cuervo AM. Protein homeostasis and aging: The importance of exquisite quality control. Ageing Res Rev 2011; 10: 205–15.
10. Wei M, Fabrizio P, Hu J et al. Life span extension by calorie restriction depends on Rim15 and transcription factors downstream of Ras/PKA, Tor, and Sch9. PLoS Genet 2008; 4: e13. [PMC free article] [PubMed].
11. McCay CM, Crowell MF, Maynard LA. The effect of retarded growth upon the length of life span and upon the ultimate body size. J Nutr 1935; 10: 63–79.
12. Lee CK, Klopp RG, Weindruch R, Prolla TA. Gene expression profile of aging and its retardation by caloric restriction. Science 1999; 285: 1390–3.
13. Bordone L, Guarente L. Calorie restriction, SIRT1 and metabolism: understanding longevity. Nat Rev Mol Cell Biol 2005; 6: 298–305.
14. Fontana L, Partridge L, Longo VD. Extending healthy life span – from yeast to humans. Science 2010; 328: 321–6.
15. McCay CM, Crowell MF, Maynard LA. The effect of retarded growth upon the length of life span and upon the ultimate body size. 1935. Nutrition 1989; 5: 155–171, discussion 172.
16. Colman RJ, Anderson RM, Johnson SC et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 2009; 325: 201–4.
17. Lin SJ, Kaeberlein M, Andalis AA et al. Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration. Nature 2002; 418: 344–8.
18. Nisoli E, Tonello C, Cardile A et al. Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science 2005; 310: 314–7.
19. Powers RW, Kaeberlein M, Caldwell SD et al. Extension of chronological life span in yeast by decreased TOR pathway signaling. Genes Dev 2006; 20: 174.
20. Qin W, Chachich M, Lane M et al. Calorie restriction attenuates Alzheimer's disease type brain amyloidosis in Squirrel monkeys (Saimiri sciureus). J Alzheimers Dis 2006; 10: 417–22.
21. Lane MA, Tilmont EM, de Angelis H et al. Short-term calorie restriction improves disease-related markers in older male rhesus monkeys (Macaca mulatta). Mech Ageing Dev 2000; 112: 185–96.
22. Hansen BC, Bodkin NL. Primary prevention of diabetes mellitus by prevention of obesity in monkeys. Diabetes 1993; 42: 1809–14.
23. Kemnitz JW. Calorie Restriction and Aging in Nonhuman Primates. ILAR Journal 2011; 52: 66–77.
24. Edwards AG, Donato AJ, Lesniewski LA et al. Life-long caloric restriction elicits pronounced protection of the aged myocardium: a role for AMPK. Mech Ageing Dev 2010; 131: 739–42.
25. Csiszar A, Labinskyy N, Jimenez R et al. Anti-oxidative and anti-inflammatory vasoprotective effects of caloric restriction in aging: role of circulating factors and SIRT1. Mech Ageing Dev 2009; 130: 518–27.
26. Guodong Zhao,Song Guo, Mehmet Somel, Philipp Khaitovich. Evolution of Human Longevity Uncoupled from Caloric Restriction Mechanisms. PLoS One 2014; 9 (1): e84117; doi: 10.1371/journal.pone.0084117
27. Strom A, Jensen RA. Mortality from circulatory diseases in Norway 1940–1945. Lancet 1951; 258: 126–9.
28. Hindhede M. The effects of food restriction duringwar on mortality in Copenhagen. JAMA 1921; 74: 381–2.
29. Kagawa Y. Impact of Westernization on the nutrition of Japanese: changes in physique, cancer, longevity and centenarians. Prev Med 1978; 7: 205–17.
30. Lefevre M, Redman LM, Heilbronn LK et al. Caloric restriction alone and with exercise improves CVD risk in healthy non-obese individuals. Atherosclerosis 2009; 203: 206–13.
31. Heilbronn LK, de Jonge L, Frisard MI et al. Pennington CALERIE Team. Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: a randomized controlled trial. JAMA 2006; 295: 1539–48.
32. Larson-Meyer DE, Heilbronn LK, Redman LM et al. Effect of calorie restriction with or without exercise on insulin sensitivity, beta-cell function, fat cell size, and ectopic lipid in overweight subjects. Diabetes Care 2006; 29: 1337–44.
33. Redman LM, Heilbronn LK, Martin CK et al. Effect of calorie restriction with or without exercise on body composition and fat distribution [published online ahead of print January 2, 2007]. J Clin Endocrinol Metab 2007; doi:10.1210/jc.2006-2184.
34. Racette SB, Weiss EP, Villareal DT et al. Washington University School of Medicine CALERIE Group. One year of caloric restriction in humans: feasibility and effects on body composition and abdominal adipose tissue. J Gerontol A Biol Sci Med Sci 2006; 61: 943–50.
35. Weiss EP, Racette SB, Villareal DT et al. Improvements in glucose tolerance and insulin action induced by increasing energy expenditure or decreasing energy intake: a randomized controlled trial. Am J Clin Nutr 2006; 84: 1033–42.
36. Villareal DT, Fontana L,Weiss EP et al. Bone mineral density response to caloric restriction-induced weight loss or exercise-induced weight loss: a randomized controlled trial. Arch Intern Med 2006; 166: 2502–10.
37. Weiss EP, Racette SB, Villareal DT et al. Lower extremity muscle size and strength and aerobic capacity decrease with caloric restriction but not with exercise-induced weight loss [published online ahead of print 2006]. J Appl Physiol 2006; doi:10.1152/ japplphysiol.00853.2006
38. Персон С.А. Основоположник клинической медицины Томас Сиденхем. Клин. медицина. 1965; 43 (11). / Person S.A. Osnovopolozhnik klinicheskoi meditsiny Tomas Sidenkhem. Klin. meditsina. 1965; 43 (11). [in Russian]
39. Lakatta E, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part I: aging arteries: a «set up» for vascular disease. Circulation 2003; 107: 139–46.
40. Tanaka H, Dinenno FA, Monahan KD et al. Aging, habitual exercise, and dynamic arterial compliance. Circulation 2000; 102: 1270–5.
41. Blacher J, Guerin AP, Pannier B et al. Impact of aortic stiffness on survival in end-stage renal disease. Circulation 1999; 99: 2434–9.
42. Laurent S, Boutouyrie P, Asmar R et al. Aortic Stiffness Is an Independent Predictor of All-Cause and Cardiovascular Mortality in Hypertensive Patients. Hypertension 2001; 37: 1236–41.
43. Cruickshank K, Riste L, Anderson SG et al. Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function? Circulation 2002; 106: 2085–90.
44. Орлова Я.А. Нуралиев Э.Ю. Балдина О.Н. и др. Скорость пульсовой волны – предиктор развития сердечно-сосудистых осложнений у мужчин с ИБС. Кардиологич. вестн. 2007; 2 (1): 17–22. / Orlova Ia.A. Nuraliev E.Iu. Baldina O.N. i dr. Skorost' pul'sovoi volny – prediktor razvitiia serdechno-sosudistykh oslozhnenii u muzhchin s IBS. Kardiologich. vestn. 2007; 2 (1): 17–22. [in Russian]
45. Singer J, Trollor JN, Crawford J et al The association between pulse wave velocity and cognitive function: the Sydney Memory and Ageing Study. PLoS One 2013; 8 (4): e61855; doi: 10.1371/journal.pone.0061855
46. Donato AJ, Walker AE, Magerko KA et al. Life-long caloric restriction reduces oxidative stress and preserves nitric oxide bioavailability and function in arteries of old mice. Aging Cell 2013; 12 (Issue 5): 772–83.
47. Tipping the Scales: How obesity and unhealthy lifestyles have become a weighty problem for the North Carolina economy. Be Active North Carolina, 2008; p. 12 (Chenoweth & Associates).
48. Calle EE, Thun MJ, Petrelli JM et al. Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med 1999; 341: 1097–105.
49. Stevens J, Cai J, Pamuk ER et al. The effect of age on the association between body-mass index and mortality. N Engl J Med 1998; 338: 1–7.
50. Hoffmann J, Romey R, Fink C et al. Overexpression of Sir2 in the adult fat body is sufficient to extend lifespan of male and female Drosophila. Aging (Albany NY) 2013; 5 (4): 315–27.
51. Burnett C, Valentini S, Cabreiro F et al. Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature 2011; 477: 482–5.
52. Ludewig AH, Izrayelit Y, Park D et al. Pheromone sensing regulates Caenorhabditis elegans lifespan and stress resistance via the deacetylase SIR-2.1. Proc Natl Acad Sci 2013; 110: 5522–7.
53. Guarente L. Calorie restriction and sirtuins revisited. Genes Dev 2013; 27 (19): 2072–85.
54. Mouchiroud L, Houtkooper RH, Moullan N et al. The NAD(+)/Sirtuin Pathway Modulates Longevity through Activation of Mitochondrial UPR and FOXO Signaling. Cell 2013; 154 (2): 430–41.
55. Banerjee KK, Ayyub C, Ali SZ et al. dSir2 in the adult fat body, but not in muscles, regulates life span in a diet-dependent manner. Cell Rep 2012; 2: 1485–91.
56. Kim E-J, Um S-J. SIRT1: roles in aging and cancer. BMB Reports 2008; 41 (11): 751–6.
57. Stumpferl SW, Brand SE, Jiang JC et al. Natural genetic variation in yeast longevity. Genome Res 2012; 22: 1963–73.
58. Frye RA. Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem Biophys Res Commun 2000; 273793–8; doi: 10.1006/bbrc.2000.3000
59. Oberdoerffer P, Michan S, McVay et al. SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging. Cell 2008; 135 (5): 907–18.
60. Jarolim S, Millen J, Heeren G et al. A novel assay for replicative lifespan in Saccharomyces cerevisiae. FEMS Yeast Res 2004; 5: 169–77.
61. Viswanathan M, Kim SK, Berdichevsky A, Guarente L. A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span. Dev Cell 2005; 9: 605–15.
62. Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 2006; 5: 493–506.
63. Bass TM, Weinkove D, Houthoofd K et al. Effects of resveratrol on lifespan in Drosophila melanogaster and Caenorhabditis elegans. Mech Ageing Dev 2007; 128: 546–52.
64. Valenzano DR, Terzibasi E, Genade T et al. Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Curr Biol 2006; 16: 296–300.
65. Miller RA, Harrison DE, Astle CM et al. An Aging Interventions Testing Program: study design and interim report. Aging Cell 2013; 6: 565–75.
66. Kincaid B, Bossy-Wetzel E. Forever young: SIRT3 a shield against mitochondrial meltdown, aging, and neurodegeneration. Front Aging Neurosci 2013; 5: 48; doi: 10.3389/fnagi.2013.00048.
67. Palacios OM, Carmona JJ, Michan S et al. Diet and exercise signals regulate SIRT3 and activate AMPK and PGC-1alpha in skeletal muscle. Aging (Albany NY) 2009; 1771–83.
68. Tauriainen E, Luostarinen M, Martonen E et al. Distinct effects of calorie restriction and resveratrol on diet-induced obesity and fatty liver formation. J Nutr Metab 2011; doi: 525094.10.1155/2011/525094.
69. Hirschey MD, Shimazu T, Jing E et al. SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndrome. Mol Cell 2011; 44177–90.
70. Rose G, Dato S, Altomare K et al. Variability of the SIRT3 gene, human silent information regulator Sir2 homologue, and survivorship in the elderly. Experimental Gerontology 2003; 38 (Issue 10): 1065–70.
71. Bellizzi D, Rose G, Cavalcante P et al. A novel VNTR enhancer within the SIRT3 gene, a human homologue of SIR2, is associated with survival at oldest ges. Genomics 2005; 85: 258–63.
72. Huang C, Chen D, Xie Q et al. Nebivolol stimulates mitochondrial biogenesis in 3T3-L1 adipocytes. Biochem Biophys Res Commun 2013; 438 (1): 211–7.
73. Taddei S, Virdis A, Ghiadoni L et al. Age-related reduction of NO availability and oxidative stress in humans. Hypertension 2001; 38: 274–9.
74. Spier SA, Delp MD, Meininger CJ et al. Effects of ageing and exercise training on endothelium-dependent vasodilatation and structure of rat skeletal muscle arterioles. J Physiol 2004; 556: 947–58.
75. Brandes RP, Fleming I, Busse R. Endothelial aging. Cardiovasc Res 2005; 66: 286–94.
76. Агеев Ф.Т., Санкова А.В., Орлова Я.А. и др. Лечение стабильной стенокардии напряжения в амбулаторной практике: клинические и сосудистые эффекты перевода больных на небиволол. Сердце. 2006; 5 (5): 269–70. / Ageev F.T., Sankova A.V., Orlova Ia.A. i dr. Lechenie stabil'noi stenokardii napriazheniia v ambulatornoi praktike: klinicheskie i sosudistye effekty perevoda bol'nykh na nebivolol. Serdtse. 2006; 5 (5): 269–70. [in Russian]
77. Wick AN, Drury DR, Nakada HI, Wolfe JB. Localization of the primary metabolic block produced by 2-deoxyglucose. J Biol Chem 1957; 224: 963–9.
78. Lane MA, Ingram DK, Roth GS. 2-Deoxy-D-glucose feeding in rats mimics physiological effects of calorie restriction. J Anti Aging Med 1998; 1: 327–37.
79. Minor RK, Smith DL Jr., Sossong AM et al. Chronic ingestion of 2-deoxy-d-glucose induces cardiac vacuolization and increases mortality in rats. Toxicol Appl Pharmacol 2009; 22: 16–23.
80. Lane MA, Roth GS, Ingram DK. Caloric restriction mimetics: a novel approach for biogerontology. Methods Mol Biol 2007; 371: 143–9.
81. Smith DL Jr., Nagy TR, Allison DB. Calorie restriction: what recent results suggest for the future of ageing research. Eur J Clin Invest 2010; 40 (5): 440–50.
82. Anisimov VN. Effect of buformin and diphenylhydantoin on the life span, estrous function and spontaneous tumor incidence in rats. Vopr Onkol 1980; 26: 42–8.
83. Onken B, Driscoll M. Metformin induces a dietary restriction-like state and the oxidative stress response to extend C. elegans Healthspan via AMPK, LKB1, and SKN–1. PLoS One 2010; 5: e8758.
84. Анисимов В.Н., Михельсон В.М., Попович И.Г. и др. Метформин замедляет процессы старения на клеточном уровне у мышей линии SHR. Цитология. 2011; 2: 166–74. / Anisimov V.N., Mikhel'son V.M., Popovich I.G. i dr. Metformin zamedliaet protsessy stareniia na kletochnom urovne u myshei linii SHR. Tsitologiia. 2011; 2: 166–74. [in Russian]
85. Slack C, Foley A, Partridge L. Activation of AMPK by the putative dietary restriction mimetic metformin is insufficient to extend lifespan in Drosophila. PLoS One 2012; 7: e47699.
86. Greer EL, Dowlatshahi D, Banko MR et al. AMPK-FOXO pathway mediates the extension of lifespan induced by a novel method of dietary restriction in C. elegans. Curr Biol 2007; 17 (19): 1646–56.
87. Martin-Montalvo A, Mercken EM, Mitchell SJ et al. Metformin improves healthspan and lifespan in mice. Nat Commun 2013; 4: 2192.
88. 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.
89. Nunn AV, Bell JD, Guy GW. Lifestyle-induced metabolic inflexibility and accelerated ageing syndrome: insulin resistance, friend or foe? Nutr Metab (Lond) 2009; 6: 16; doi: 10.1186/1743-7075-6-16
90. De Haes W, Frooninckx L, van Assche R et al. Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2. Proc Natl Acad Sci USA 2014; 111 (24): E2501–E2509.
91. Bishop NA, Guarente L. Two neurons mediate diet-restriction-induced longevity in C. elegans. Nature 2007; 447: 545–9.
92. Panowski SH, Wolff S, Aguilaniu H et al. PHA-4/Foxa mediates diet-restriction-induced longevity of C. elegans. Nature 2007; 447: 550–5.
93. Siegfried Z, Berry EM, Hao S, Avraham Y. Animal models in the investigation of anorexia. Physiol Behav 2003; 79: 39–45.
94. Blagosklonny MV. Metformin and sex: Why suppression of aging may be harmful to young male mice. Aging (Albany NY) 2010; 2 (12): 897–9.
95. Anisimov VN. Metformin for aging and cancer prevention. Aging (Albany NY) 2010; 2 (11): 760–74.
96. Scarpello JH. Improving survival with metformin: the evidence base today. Diabetes Metab 2003; 29: 6S36–43.
97. Chlebowski RT, McTiernan A, Wactawski-Wende J et al. Diabetes, metformin, and breast cancer in postmenopausal women. J Clin Oncol 2012; 30 (23): 2844–52.
98. Vazquez-Martin A, Oliveras-Ferraros C, Menendez JA. The antidiabetic drug metformin suppresses HER2 (erbB-2) oncoprotein overexpression via inhibition of the mTOR effector p70S6K1 in human breast carcinoma cells. Cell Cycle 2009; 8 (1): 88–96.
99. Ng TP, Feng L, Yap KB et al. Long-term metformin usage and cognitive function among older adults with diabetes. J Alzheimers Dis 2014; 41 (1): 61–8.
100. Meaney E, Vela A, Samaniego V et al. Metformin, arterial function, intima-media thickness and nitroxidation in metabolic syndrome: the mefisto study. Clin Exp Pharmacol Physiol 2008; 35 (8): 895–903.
101. Sofer E, Boaz M, Matas Z et al. Treatment with insulin sensitizer metformin improves arterial properties, metabolic parameters, and liver function in patients with nonalcoholic fatty liver disease: a randomized, placebo-controlled trial. Metabolism 2011; 60 (9): 1278–84.
102. Bhalla RC, Toth KF, Tan E et al. Vascular effects of metformin. Possible mechanisms for its antihypertensive action in the spontaneously hypertensive rat. Am J Hypertens 1996; 9 (6): 570–6.
103. Wu S, Li X, Zhang H. Effects of metformin on endothelial function in type 2 diabetes. Exp Ther Med 2014; 7 (5): 1349–53.
104. Agarwal N, Rice SP, Bolusani H et al. Metformin reduces arterial stiffness and improves endothelial function in young women with polycystic ovary syndrome: a randomized, placebo-controlled, crossover trial. J Clin Endocrinol Metab 2010; 95 (2): 722–30.
105. Florez H, Temprosa MG, Orchard TJ et al. Diabetes Prevention Program Research Group. Metabolic syndrome components and their response to lifestyle and metformin interventions are associated with differences in diabetes risk in persons with impaired glucose tolerance. Diabetes Obes Metab 2014; 16 (4): 326–33.
106. Raub RM, Goldberg SJ. Assessment of metformin as an additional treatment to therapeutic lifestyle changes in pediatric patients with metabolic syndrome. Cholesterol 2012; 2012: 961410.
107. Li J, Xu JP, Zhao XZ et al. Protective effect of metformin on myocardial injury in metabolic syndrome patients following percutaneous coronary intervention. Cardiology 2014; 127 (2): 133–9.
108. Ladeiras-Lopes R, Fontes-Carvalho R, Bettencourt N et al. METformin in DIastolic Dysfunction of MEtabolic syndrome (MET-DIME) trial: rationale and study design : MET-DIME trial. Cardiovasc Drugs Ther 2014; 28 (2): 191–6.
109. Barger JL, Walford RL, Weindruch R. The retardation of aging by caloric restriction: its significance in the transgenic era. Exp Gerontol 2003; 38: 1343–51.

________________________________________________

1. World Population Prospects: The 2008 Revision Population Division of the Department of Economic and Social Affairs of the United Nations Secretariat. June 2009.
2. Федеральная служба государственной статистики (Росстат). Численность населения Российской Федерации по полу и возрасту на 1 января 2013 года. Статистический бюллетень. М., 2013.
3. http://www.gks.ru/bgd/regl/b13_13/IssWWW.exe/Stg/d4/26-03.htm
4. Butler RN, Miller RA, Perry D et al. New model of health promotion and disease prevention for the 21st century. BMJ 2008; 337: a399.
5. Goldman DP, Cutler D, Rowe JW et al. Substantial Health And Economic Returns From Delayed Aging May Warrant A New Focus For Medical Research. Health Affairs 2013; 32 (10): 1698–705.
6. Dirks AJ, Hofer T, Marzetti E et al. Mitochondrial DNA mutations, energy metabolism and apoptosis in aging muscle. Ageing Res Rev 2006; 5: 179–95.
7. Kritchevsky D. Diet, lipid metabolism, and aging. Fed Proc 1979; 38: 2001–6.
8. Roberts-Thomson IC, Whittingham S, Youngchaiyud U, Mackay IR. Ageing, immune response, and mortality. Lancet 1974; 2: 368–70.
9. Koga H, Kaushik S, Cuervo AM. Protein homeostasis and aging: The importance of exquisite quality control. Ageing Res Rev 2011; 10: 205–15.
10. Wei M, Fabrizio P, Hu J et al. Life span extension by calorie restriction depends on Rim15 and transcription factors downstream of Ras/PKA, Tor, and Sch9. PLoS Genet 2008; 4: e13. [PMC free article] [PubMed].
11. McCay CM, Crowell MF, Maynard LA. The effect of retarded growth upon the length of life span and upon the ultimate body size. J Nutr 1935; 10: 63–79.
12. Lee CK, Klopp RG, Weindruch R, Prolla TA. Gene expression profile of aging and its retardation by caloric restriction. Science 1999; 285: 1390–3.
13. Bordone L, Guarente L. Calorie restriction, SIRT1 and metabolism: understanding longevity. Nat Rev Mol Cell Biol 2005; 6: 298–305.
14. Fontana L, Partridge L, Longo VD. Extending healthy life span – from yeast to humans. Science 2010; 328: 321–6.
15. McCay CM, Crowell MF, Maynard LA. The effect of retarded growth upon the length of life span and upon the ultimate body size. 1935. Nutrition 1989; 5: 155–171, discussion 172.
16. Colman RJ, Anderson RM, Johnson SC et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 2009; 325: 201–4.
17. Lin SJ, Kaeberlein M, Andalis AA et al. Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration. Nature 2002; 418: 344–8.
18. Nisoli E, Tonello C, Cardile A et al. Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science 2005; 310: 314–7.
19. Powers RW, Kaeberlein M, Caldwell SD et al. Extension of chronological life span in yeast by decreased TOR pathway signaling. Genes Dev 2006; 20: 174.
20. Qin W, Chachich M, Lane M et al. Calorie restriction attenuates Alzheimer's disease type brain amyloidosis in Squirrel monkeys (Saimiri sciureus). J Alzheimers Dis 2006; 10: 417–22.
21. Lane MA, Tilmont EM, de Angelis H et al. Short-term calorie restriction improves disease-related markers in older male rhesus monkeys (Macaca mulatta). Mech Ageing Dev 2000; 112: 185–96.
22. Hansen BC, Bodkin NL. Primary prevention of diabetes mellitus by prevention of obesity in monkeys. Diabetes 1993; 42: 1809–14.
23. Kemnitz JW. Calorie Restriction and Aging in Nonhuman Primates. ILAR Journal 2011; 52: 66–77.
24. Edwards AG, Donato AJ, Lesniewski LA et al. Life-long caloric restriction elicits pronounced protection of the aged myocardium: a role for AMPK. Mech Ageing Dev 2010; 131: 739–42.
25. Csiszar A, Labinskyy N, Jimenez R et al. Anti-oxidative and anti-inflammatory vasoprotective effects of caloric restriction in aging: role of circulating factors and SIRT1. Mech Ageing Dev 2009; 130: 518–27.
26. Guodong Zhao,Song Guo, Mehmet Somel, Philipp Khaitovich. Evolution of Human Longevity Uncoupled from Caloric Restriction Mechanisms. PLoS One 2014; 9 (1): e84117; doi: 10.1371/journal.pone.0084117
27. Strom A, Jensen RA. Mortality from circulatory diseases in Norway 1940–1945. Lancet 1951; 258: 126–9.
28. Hindhede M. The effects of food restriction duringwar on mortality in Copenhagen. JAMA 1921; 74: 381–2.
29. Kagawa Y. Impact of Westernization on the nutrition of Japanese: changes in physique, cancer, longevity and centenarians. Prev Med 1978; 7: 205–17.
30. Lefevre M, Redman LM, Heilbronn LK et al. Caloric restriction alone and with exercise improves CVD risk in healthy non-obese individuals. Atherosclerosis 2009; 203: 206–13.
31. Heilbronn LK, de Jonge L, Frisard MI et al. Pennington CALERIE Team. Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: a randomized controlled trial. JAMA 2006; 295: 1539–48.
32. Larson-Meyer DE, Heilbronn LK, Redman LM et al. Effect of calorie restriction with or without exercise on insulin sensitivity, beta-cell function, fat cell size, and ectopic lipid in overweight subjects. Diabetes Care 2006; 29: 1337–44.
33. Redman LM, Heilbronn LK, Martin CK et al. Effect of calorie restriction with or without exercise on body composition and fat distribution [published online ahead of print January 2, 2007]. J Clin Endocrinol Metab 2007; doi:10.1210/jc.2006-2184.
34. Racette SB, Weiss EP, Villareal DT et al. Washington University School of Medicine CALERIE Group. One year of caloric restriction in humans: feasibility and effects on body composition and abdominal adipose tissue. J Gerontol A Biol Sci Med Sci 2006; 61: 943–50.
35. Weiss EP, Racette SB, Villareal DT et al. Improvements in glucose tolerance and insulin action induced by increasing energy expenditure or decreasing energy intake: a randomized controlled trial. Am J Clin Nutr 2006; 84: 1033–42.
36. Villareal DT, Fontana L,Weiss EP et al. Bone mineral density response to caloric restriction-induced weight loss or exercise-induced weight loss: a randomized controlled trial. Arch Intern Med 2006; 166: 2502–10.
37. Weiss EP, Racette SB, Villareal DT et al. Lower extremity muscle size and strength and aerobic capacity decrease with caloric restriction but not with exercise-induced weight loss [published online ahead of print 2006]. J Appl Physiol 2006; doi:10.1152/ japplphysiol.00853.2006
38. Person S.A. Osnovopolozhnik klinicheskoi meditsiny Tomas Sidenkhem. Klin. meditsina. 1965; 43 (11). [in Russian]
39. Lakatta E, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part I: aging arteries: a «set up» for vascular disease. Circulation 2003; 107: 139–46.
40. Tanaka H, Dinenno FA, Monahan KD et al. Aging, habitual exercise, and dynamic arterial compliance. Circulation 2000; 102: 1270–5.
41. Blacher J, Guerin AP, Pannier B et al. Impact of aortic stiffness on survival in end-stage renal disease. Circulation 1999; 99: 2434–9.
42. Laurent S, Boutouyrie P, Asmar R et al. Aortic Stiffness Is an Independent Predictor of All-Cause and Cardiovascular Mortality in Hypertensive Patients. Hypertension 2001; 37: 1236–41.
43. Cruickshank K, Riste L, Anderson SG et al. Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function? Circulation 2002; 106: 2085–90.
44. Orlova Ia.A. Nuraliev E.Iu. Baldina O.N. i dr. Skorost' pul'sovoi volny – prediktor razvitiia serdechno-sosudistykh oslozhnenii u muzhchin s IBS. Kardiologich. vestn. 2007; 2 (1): 17–22. [in Russian]
45. Singer J, Trollor JN, Crawford J et al The association between pulse wave velocity and cognitive function: the Sydney Memory and Ageing Study. PLoS One 2013; 8 (4): e61855; doi: 10.1371/journal.pone.0061855
46. Donato AJ, Walker AE, Magerko KA et al. Life-long caloric restriction reduces oxidative stress and preserves nitric oxide bioavailability and function in arteries of old mice. Aging Cell 2013; 12 (Issue 5): 772–83.
47. Tipping the Scales: How obesity and unhealthy lifestyles have become a weighty problem for the North Carolina economy. Be Active North Carolina, 2008; p. 12 (Chenoweth & Associates).
48. Calle EE, Thun MJ, Petrelli JM et al. Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med 1999; 341: 1097–105.
49. Stevens J, Cai J, Pamuk ER et al. The effect of age on the association between body-mass index and mortality. N Engl J Med 1998; 338: 1–7.
50. Hoffmann J, Romey R, Fink C et al. Overexpression of Sir2 in the adult fat body is sufficient to extend lifespan of male and female Drosophila. Aging (Albany NY) 2013; 5 (4): 315–27.
51. Burnett C, Valentini S, Cabreiro F et al. Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature 2011; 477: 482–5.
52. Ludewig AH, Izrayelit Y, Park D et al. Pheromone sensing regulates Caenorhabditis elegans lifespan and stress resistance via the deacetylase SIR-2.1. Proc Natl Acad Sci 2013; 110: 5522–7.
53. Guarente L. Calorie restriction and sirtuins revisited. Genes Dev 2013; 27 (19): 2072–85.
54. Mouchiroud L, Houtkooper RH, Moullan N et al. The NAD(+)/Sirtuin Pathway Modulates Longevity through Activation of Mitochondrial UPR and FOXO Signaling. Cell 2013; 154 (2): 430–41.
55. Banerjee KK, Ayyub C, Ali SZ et al. dSir2 in the adult fat body, but not in muscles, regulates life span in a diet-dependent manner. Cell Rep 2012; 2: 1485–91.
56. Kim E-J, Um S-J. SIRT1: roles in aging and cancer. BMB Reports 2008; 41 (11): 751–6.
57. Stumpferl SW, Brand SE, Jiang JC et al. Natural genetic variation in yeast longevity. Genome Res 2012; 22: 1963–73.
58. Frye RA. Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem Biophys Res Commun 2000; 273793–8; doi: 10.1006/bbrc.2000.3000
59. Oberdoerffer P, Michan S, McVay et al. SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging. Cell 2008; 135 (5): 907–18.
60. Jarolim S, Millen J, Heeren G et al. A novel assay for replicative lifespan in Saccharomyces cerevisiae. FEMS Yeast Res 2004; 5: 169–77.
61. Viswanathan M, Kim SK, Berdichevsky A, Guarente L. A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span. Dev Cell 2005; 9: 605–15.
62. Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 2006; 5: 493–506.
63. Bass TM, Weinkove D, Houthoofd K et al. Effects of resveratrol on lifespan in Drosophila melanogaster and Caenorhabditis elegans. Mech Ageing Dev 2007; 128: 546–52.
64. Valenzano DR, Terzibasi E, Genade T et al. Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Curr Biol 2006; 16: 296–300.
65. Miller RA, Harrison DE, Astle CM et al. An Aging Interventions Testing Program: study design and interim report. Aging Cell 2013; 6: 565–75.
66. Kincaid B, Bossy-Wetzel E. Forever young: SIRT3 a shield against mitochondrial meltdown, aging, and neurodegeneration. Front Aging Neurosci 2013; 5: 48; doi: 10.3389/fnagi.2013.00048.
67. Palacios OM, Carmona JJ, Michan S et al. Diet and exercise signals regulate SIRT3 and activate AMPK and PGC-1alpha in skeletal muscle. Aging (Albany NY) 2009; 1771–83.
68. Tauriainen E, Luostarinen M, Martonen E et al. Distinct effects of calorie restriction and resveratrol on diet-induced obesity and fatty liver formation. J Nutr Metab 2011; doi: 525094.10.1155/2011/525094.
69. Hirschey MD, Shimazu T, Jing E et al. SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndrome. Mol Cell 2011; 44177–90.
70. Rose G, Dato S, Altomare K et al. Variability of the SIRT3 gene, human silent information regulator Sir2 homologue, and survivorship in the elderly. Experimental Gerontology 2003; 38 (Issue 10): 1065–70.
71. Bellizzi D, Rose G, Cavalcante P et al. A novel VNTR enhancer within the SIRT3 gene, a human homologue of SIR2, is associated with survival at oldest ges. Genomics 2005; 85: 258–63.
72. Huang C, Chen D, Xie Q et al. Nebivolol stimulates mitochondrial biogenesis in 3T3-L1 adipocytes. Biochem Biophys Res Commun 2013; 438 (1): 211–7.
73. Taddei S, Virdis A, Ghiadoni L et al. Age-related reduction of NO availability and oxidative stress in humans. Hypertension 2001; 38: 274–9.
74. Spier SA, Delp MD, Meininger CJ et al. Effects of ageing and exercise training on endothelium-dependent vasodilatation and structure of rat skeletal muscle arterioles. J Physiol 2004; 556: 947–58.
75. Brandes RP, Fleming I, Busse R. Endothelial aging. Cardiovasc Res 2005; 66: 286–94.
76. Ageev F.T., Sankova A.V., Orlova Ia.A. i dr. Lechenie stabil'noi stenokardii napriazheniia v ambulatornoi praktike: klinicheskie i sosudistye effekty perevoda bol'nykh na nebivolol. Serdtse. 2006; 5 (5): 269–70. [in Russian]
77. Wick AN, Drury DR, Nakada HI, Wolfe JB. Localization of the primary metabolic block produced by 2-deoxyglucose. J Biol Chem 1957; 224: 963–9.
78. Lane MA, Ingram DK, Roth GS. 2-Deoxy-D-glucose feeding in rats mimics physiological effects of calorie restriction. J Anti Aging Med 1998; 1: 327–37.
79. Minor RK, Smith DL Jr., Sossong AM et al. Chronic ingestion of 2-deoxy-d-glucose induces cardiac vacuolization and increases mortality in rats. Toxicol Appl Pharmacol 2009; 22: 16–23.
80. Lane MA, Roth GS, Ingram DK. Caloric restriction mimetics: a novel approach for biogerontology. Methods Mol Biol 2007; 371: 143–9.
81. Smith DL Jr., Nagy TR, Allison DB. Calorie restriction: what recent results suggest for the future of ageing research. Eur J Clin Invest 2010; 40 (5): 440–50.
82. Anisimov VN. Effect of buformin and diphenylhydantoin on the life span, estrous function and spontaneous tumor incidence in rats. Vopr Onkol 1980; 26: 42–8.
83. Onken B, Driscoll M. Metformin induces a dietary restriction-like state and the oxidative stress response to extend C. elegans Healthspan via AMPK, LKB1, and SKN–1. PLoS One 2010; 5: e8758.
84. Anisimov V.N., Mikhel'son V.M., Popovich I.G. i dr. Metformin zamedliaet protsessy stareniia na kletochnom urovne u myshei linii SHR. Tsitologiia. 2011; 2: 166–74. [in Russian]
85. Slack C, Foley A, Partridge L. Activation of AMPK by the putative dietary restriction mimetic metformin is insufficient to extend lifespan in Drosophila. PLoS One 2012; 7: e47699.
86. Greer EL, Dowlatshahi D, Banko MR et al. AMPK-FOXO pathway mediates the extension of lifespan induced by a novel method of dietary restriction in C. elegans. Curr Biol 2007; 17 (19): 1646–56.
87. Martin-Montalvo A, Mercken EM, Mitchell SJ et al. Metformin improves healthspan and lifespan in mice. Nat Commun 2013; 4: 2192.
88. 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.
89. Nunn AV, Bell JD, Guy GW. Lifestyle-induced metabolic inflexibility and accelerated ageing syndrome: insulin resistance, friend or foe? Nutr Metab (Lond) 2009; 6: 16; doi: 10.1186/1743-7075-6-16
90. De Haes W, Frooninckx L, van Assche R et al. Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2. Proc Natl Acad Sci USA 2014; 111 (24): E2501–E2509.
91. Bishop NA, Guarente L. Two neurons mediate diet-restriction-induced longevity in C. elegans. Nature 2007; 447: 545–9.
92. Panowski SH, Wolff S, Aguilaniu H et al. PHA-4/Foxa mediates diet-restriction-induced longevity of C. elegans. Nature 2007; 447: 550–5.
93. Siegfried Z, Berry EM, Hao S, Avraham Y. Animal models in the investigation of anorexia. Physiol Behav 2003; 79: 39–45.
94. Blagosklonny MV. Metformin and sex: Why suppression of aging may be harmful to young male mice. Aging (Albany NY) 2010; 2 (12): 897–9.
95. Anisimov VN. Metformin for aging and cancer prevention. Aging (Albany NY) 2010; 2 (11): 760–74.
96. Scarpello JH. Improving survival with metformin: the evidence base today. Diabetes Metab 2003; 29: 6S36–43.
97. Chlebowski RT, McTiernan A, Wactawski-Wende J et al. Diabetes, metformin, and breast cancer in postmenopausal women. J Clin Oncol 2012; 30 (23): 2844–52.
98. Vazquez-Martin A, Oliveras-Ferraros C, Menendez JA. The antidiabetic drug metformin suppresses HER2 (erbB-2) oncoprotein overexpression via inhibition of the mTOR effector p70S6K1 in human breast carcinoma cells. Cell Cycle 2009; 8 (1): 88–96.
99. Ng TP, Feng L, Yap KB et al. Long-term metformin usage and cognitive function among older adults with diabetes. J Alzheimers Dis 2014; 41 (1): 61–8.
100. Meaney E, Vela A, Samaniego V et al. Metformin, arterial function, intima-media thickness and nitroxidation in metabolic syndrome: the mefisto study. Clin Exp Pharmacol Physiol 2008; 35 (8): 895–903.
101. Sofer E, Boaz M, Matas Z et al. Treatment with insulin sensitizer metformin improves arterial properties, metabolic parameters, and liver function in patients with nonalcoholic fatty liver disease: a randomized, placebo-controlled trial. Metabolism 2011; 60 (9): 1278–84.
102. Bhalla RC, Toth KF, Tan E et al. Vascular effects of metformin. Possible mechanisms for its antihypertensive action in the spontaneously hypertensive rat. Am J Hypertens 1996; 9 (6): 570–6.
103. Wu S, Li X, Zhang H. Effects of metformin on endothelial function in type 2 diabetes. Exp Ther Med 2014; 7 (5): 1349–53.
104. Agarwal N, Rice SP, Bolusani H et al. Metformin reduces arterial stiffness and improves endothelial function in young women with polycystic ovary syndrome: a randomized, placebo-controlled, crossover trial. J Clin Endocrinol Metab 2010; 95 (2): 722–30.
105. Florez H, Temprosa MG, Orchard TJ et al. Diabetes Prevention Program Research Group. Metabolic syndrome components and their response to lifestyle and metformin interventions are associated with differences in diabetes risk in persons with impaired glucose tolerance. Diabetes Obes Metab 2014; 16 (4): 326–33.
106. Raub RM, Goldberg SJ. Assessment of metformin as an additional treatment to therapeutic lifestyle changes in pediatric patients with metabolic syndrome. Cholesterol 2012; 2012: 961410.
107. Li J, Xu JP, Zhao XZ et al. Protective effect of metformin on myocardial injury in metabolic syndrome patients following percutaneous coronary intervention. Cardiology 2014; 127 (2): 133–9.
108. Ladeiras-Lopes R, Fontes-Carvalho R, Bettencourt N et al. METformin in DIastolic Dysfunction of MEtabolic syndrome (MET-DIME) trial: rationale and study design : MET-DIME trial. Cardiovasc Drugs Ther 2014; 28 (2): 191–6.
109. Barger JL, Walford RL, Weindruch R. The retardation of aging by caloric restriction: its significance in the transgenic era. Exp Gerontol 2003; 38: 1343–51.

Я.А.Орлова

ФГБОУ ВПО Московский государственный университет им. М.В.Ломоносова. 119991, Россия, Москва, Ленинские горы, д. 1
*orlova@cardio.ru

________________________________________________

Ya.A.Orlova

M.V.Lomonosov Moscow State University. 119991, Russian Federation, Moscow, Leninskie gory, d. 1
*orlova@cardio.ru