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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2017; 63(4): 105-113


M.S. Stupchuk, T.Yu. Voznesenskaja

    O.O.Bogomoletz Institute of physiology NAS of Ukraine, Kyiv, Ukraine


Current review summarizes and discusses the properties of specific proteins – sirtuins, that possess mono-ADPribosyltransferase and deacylase activities. The paper represents the latest idea regarding the classification and biological values of sirtuins: their role in the process of cellular aging, apoptosis, protecting against atherosclerosis and cardiovascular disease. We also consider the effect of sirtuins on the metabolism and a universal transcription factor NF-κB, which controls the expression of genes of the immune response, apoptosis and cell cycle. We describe a number of low molecular weight compounds that are able to activate and inhibit the activity of sirtuins and thus simulating their properties.

Keywords: sirtuins; histone deacetylase; mono-ADPribosyltransferase; aging; apoptosis; resveratrol; nicotinamide.


  1. Bitterman JL, Chung JH. Metabolic effects of resveratrol: addressing the controversies. Cell Mol Life Sci. 2015; (8):1473-88. CrossRef PubMed
  3. Kawahara TL, Michishita E, Adler AS, Damian M, Berber E, Lin M, McCord RA, Ongaigui KC, Boxer LD, Chang HY, Chua KF. SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span. Cell. 2009; 136(1): 62-74. CrossRef PubMed PubMedCentral
  5. Pan H, Finkel T. Key proteins and pathways that regulate lifespan. J Biol Chem. 2017;292(16): 6452-60. CrossRef PubMed
  7. Baur JA, Ungvari Z, Minor RK, Le Couteur DG, de Cabo R. Are sirtuins viable targets for improving healthspan and lifespan? Nat Rev Drug Discov 2012; 11: 443-61. CrossRef PubMed PubMedCentral
  9. van de Ven RA, Santos D, Haigis MC. Mitochondrial Sirtuins and Molecular Mechanisms of Aging.Trends Mol Med. 2017; 23(4): 320-31. CrossRef PubMed
  11. Haigis MC, Sinclair DA. Mammalian sirtuins: biological insights and disease relevance. Annu Rev Pathol. 2010; 5: 253-95. CrossRef PubMed PubMedCentral
  13. Orlandi I, Stamerra G, Strippoli M, Vai M. During yeast chronological aging resveratrol supplementation results in a short-lived phenotype Sir2-dependent. Redox Biol. 2017; 12: 745-54. CrossRef PubMed PubMedCentral
  15. Winnik S, Auwerx J, Sinclair DA, Matter CM. Protective effects of sirtuins in cardiovascular diseases from bench to bedside. Eur Heart J. 2015; 36(48): 3404-12. CrossRef PubMed PubMedCentral
  17. Carabetta VJ, Cristea IM. The regulation, function, and detection of protein acetylation in bacteria. J Bacteriol. 2017: 107-17. CrossRef  
  18. Haigis MC, Guarente LP. Mammalian sirtuins - emerging roles in physiology, aging, and calorierestriction. Genes Dev. 2006; 20: 2913-21. CrossRef PubMed
  20. Mouchiroud L, Houtkooper RH, Moullan N, Katsyuba E, Ryu D, Canto C, Mottis A,Jo YS, Viswanathan M, Schoonjans K, Guarente L, Auwerx J. The NAD(+)/Sirtuinpathway modulates longevity through activation of mitochondrial UPR and FOXOsignaling. Cell. 2013; 154: 430-41. CrossRef PubMed PubMedCentral
  22. Vaziri H, Dessain SK, Eaton EN, Imai SI, Frye RA. hSIR2(SIRT1) functions as an NADdependent p53 deacetylase. Cell. 2001; 107: 149-59. CrossRef  
  23. Brooks CL, Gu W. How does SIRT1 affect metabolism, senescence and cancer? Nat Rev Cancer. 2009; 9: 123-8. CrossRef PubMed PubMedCentral
  25. Kapahi P, Kaeberlein M, Hansen M. Dietary restriction and lifespan: Lessons from invertebrate models. Ageing Res Rev. 2016. pii: S1568-1637(16)30288-4.
  27. Winnik S, Stein S, Matter CM. SIRT1 – an antiinflammatory pathway at the crossroads between metabolic disease and atherosclerosis. Curr Vasc Pharmacol 2012; 10: 1-3. CrossRef  
  28. Smith DL Jr,McClure JM, Matecic M, Smith JS. Calorie restriction extends the chronological lifespan of Saccharomyces cerevisiae independently of the Sirtuins. Aging Cell. 2007; 6(5): 649-62. CrossRef PubMed
  30. Mahajan SS, Leko V, Simon JA, Bedalov A. Sirtuin modulators. Handb Exp Pharmacol. 2011; 206: 241-55. CrossRef PubMed PubMedCentral
  32. Carnevale I, Pellegrini L, D'Aquila P, Saladini S, Lococo E, Polletta L, Vernucci E, Foglio E, Coppola S, Sansone L, Passarino G, Bellizzi D, Russo MA, Fini M, Tafani M. SIRT1-SIRT3 Axis Regulates Cellular Response to Oxidative Stress and Etoposide.J Cell Physiol. 2017; 232(7): 1835-44. CrossRef PubMed
  34. Bellizzi D, Dato S, Cavalcante P, Covello G, Di Cianni F. Characterization of a bidirectional promoter shared between two human genes related to aging: SIRT3 and PSMD13. Genomics. 2007; 89: 143-50. CrossRef PubMed
  36. Lee IH, Cao L, Mostoslavsky R, Lombard DB, Liu J. A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc Natl Acad Sci USA. 2008; 105: 3374-9. CrossRef PubMed PubMedCentral
  38. Rane S, He M, Sayed D, Vashistha H, Malhotra A. Downregulation of miR-199a derepresses hypoxia-inducible factor-1a and sirtuin 1 and recapitulates hypoxia preconditioning in cardiacmyocytes. Circ Res. 2009; 104: 879-86. CrossRef PubMed PubMedCentral
  40. Mei Z, Zhang X, Yi J, Huang J, He J, Tao Y. Sirtuins in metabolism, DNA repair and cancerJ Exp Clin Cancer Res. 2016; 35(1): 182-96. CrossRef PubMed PubMedCentral
  42. Zhao W, Kruse JP, Tang Y, Jung SY, Qin J, Gu W. Negative regulation of the deacetylase SIRT1 by DBC1. Nature. 2008; 451: 587-90. CrossRef PubMed PubMedCentral
  44. Purushotham A, Schug TT, Xu Q, Surapureddi S, Guo X, Li X. Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. Cell Metab. 2009; 9: 327-8. CrossRef PubMed PubMedCentral
  46. You M, Liang X, Ajmo JM, Ness GC. Involvement of mammalian sirtuin 1 in the action of ethanol in the liver. Am J Physiol Gastrointest Liver Physiol. 2008; 294: G892-8. CrossRef PubMed
  48. Moynihan KA, Grimm AA, Plueger MM, Bernal-Mizrachi E, Ford E. Increased dosage of mammalian Sir2 in pancreatic ß cells enhances glucose-stimulated insulin secretion in mice. Cell Metab. 2005; 2: 105-17. CrossRef PubMed
  50. Lappas M. Anti-inflammatory properties of sirtuin 6 in human umbilical vein endothelial cells. Mediators Inflamm 2012; 2012: 597514. CrossRef PubMed PubMedCentral
  52. Deng CX. SIRT1, is it a tumor promoter or tumor suppressor? Int J Biol Sci. 2009; 5: 147-52. CrossRef PubMed PubMedCentral
  54. Vazquez BN, Thackray JK, Serrano L. Sirtuins and DNA damage repair: SIRT7 comes to play. Nucleus. 2017; 8(2): 107-15. CrossRef PubMed PubMedCentral
  56. Bai P, Canto C, Oudart H. PARP-1 inhibition increases mitochondrial metabolism through SIRT1 activation. Cell Metab. 2011; 13: 461-8. CrossRef PubMed PubMedCentral
  58. Pogribny IP, Muskhelishvili L, Tryndyak VP The tumor-promoting activity of 2-acetyl-aminofluorene is associated with disruption of the p53 signaling pathway and the balance between apoptosis and cell proliferation. Toxicol Appl Pharmacol. 2009; 235: 305-11. CrossRef PubMed
  60. Yamakuchi M, Lowenstein CJ. MiR-34, SIRT1 and p53: the feedback loop. Cell Cycle. 2009; 8: 712-5. CrossRef PubMed
  62. You W, Rotili D, Li TM, Kambach C, Meleshin M, Schutkowski M, Chua KF, Mai A, Steegborn C. Structural Basis of Sirtuin 6 Activation by Synthetic Small Molecules. Angew Chem Int Ed Engl. 2017 Jan 19; 56(4): 1007-11. CrossRef PubMed
  64. Zhang QJ, Wang Z, Chen HZ, Zhou S, Zheng W, et al. Endothelium-specific overexpression of class III deacetylase SIRT1 decreases atherosclerosis in apolipoprotein E-deficient mice. Cardiovasc Res. 2008; 80: 191-9. CrossRef PubMed PubMedCentral
  66. Canto C, Auwerx J. PGC-1a, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Curr Opin Lipidol. 2009; 20: 98-105. CrossRef PubMed PubMedCentral
  68. Firestein R, Blander G, Michan S, Oberdoerffer P, Ogino S. The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth. PLoS ONE. 2008; 3: e2020. CrossRef PubMed PubMedCentral
  70. Yue L, Zhao L, Liu H, Li X, Wang B, Guo H, Gao L, Feng D, Qu Y. Adiponectin Protects against Glutamate-Induced Excitotoxicity via Activating SIRT1-Dependent PGC-1a Expression in HT22 Hippocampal Neurons. Oxid Med Cell Longev. 2016; 1: 1-12. CrossRef PubMed PubMedCentral
  72. Lin Q, Geng Y, Lin S, Tian Z.Sirtuin1 (SIRT1) Regulates Tumor Necrosis Factor-alpha (TNF-a-Induced) Aquaporin-2 (AQP2) Expression in Renal Medullary Collecting Duct Cells Through Inhibiting the NF-?B Pathway. Med Sci Monit Basic Res. 2016; 22: 165-74. CrossRef PubMed PubMedCentral
  74. Rajendrasozhan S, Yang SR, Kinnula VL, Rahman I. SIRT1, an antiinflammatory and antiaging protein, is decreased in lungs of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008; 177: 861-70. CrossRef PubMed PubMedCentral
  76. Anderson G. Linking the biological underpinnings of depression: Role of mitochondria interactions with melatonin, inflammation, sirtuins, tryptophan catabolites, DNA repair and oxidative and nitrosative stress, with consequences for classification and cognition.Prog Neuropsychopharmacol Biol Psychiatry. 2017; (16): 30383-9.
  78. Zhang F, Zhang M, Wang A, Xu M, Wang C, Xu G, Zhang B, Zou X, Zhuge Y. TWEAK increases SIRT1 expression and promotes p53 deacetylation affecting human hepatic stellate cell senescence.Cell Biol Int. 2017; 41(2): 147-54. CrossRef PubMed
  80. Erdogan CS, Mørup-Lendal M, Dalgaard LT, Vang O. Sirtuin 1 independent effects of resveratrol in INS-1E ß-cells.Chem Biol Interact. 2017; 264: 52-60. CrossRef PubMed
  82. Bordone L, Motta MC, Picard F, Robinson A, Jhala US, et al. Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic ß cells. PLoS Biol. 2006; 4: e31. CrossRef PubMed PubMedCentral
  84. Frye RA. Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem Biophys Res Commun. 2000; 273: 793-98. CrossRef PubMed
  86. Nassir F, Ibdah JA. Sirtuins and nonalcoholic fatty liver disease. World J Gastroenterol. 2016; 22(46): 10084-92. CrossRef PubMed PubMedCentral
  88. Zhao D., Yang J., Yang L. Insights for Oxidative Stress and mTOR Signaling in Myocardial Ischemia/Reperfusion Injury under Diabetes. Oxid Med Cell Longev. 2017; 1: 1-12. CrossRef  
  89. Salminen A, Huuskonen J, Ojala J, Kauppinen A, Kaarniranta K, Suuronen T. Activation of innate immunity system during aging: NF-?B signaling is the molecular culprit of inflamm-aging. Ageing Res Rev. 2008; 7: 83-105. CrossRef PubMed
  91. Ajmo JM, Liang X, Rogers CQ, Pennock B, You M. Resveratrol alleviates alcoholic fatty liver in mice. Am J Physiol Gastrointest Liver Physiol. 2008; 295: G833-42. CrossRef PubMed PubMedCentral
  93. Feige JN, Lagouge M, Canto C, Strehle A, Houten SM, et al. Specific SIRT1 activation mimics low energy levels and protects against diet-induced metabolic disorders by enhancing fat oxidation. Cell Metab. 2008; 8: 347–358. CrossRef PubMed
  95. Winnik S, Stein S, Matter CM. SIRT1 – an antiinflammatory pathway at the crossroads between metabolic disease and atherosclerosis. Curr Vasc Pharmacol. 2012; 10: 1-3. CrossRef  
  96. Chen GD, Yu WD, Chen XP. SirT1 activator represses the transcription of TNF-a in THP-1 cells of a sepsis model via deacetylation of H4K16. Mol Med Rep. 2016; 14(6): 5544-50. CrossRef PubMed PubMedCentral
  98. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006; 444: 337-42. CrossRef PubMed PubMedCentral
  100. Paik JH. FOXOs in the maintenance of vascular homoeostasis. Biochem Soc Trans. 2006; 34: 731-34. CrossRef PubMed
  102. Chen Y, Liu H, Zhang H, Liu E, Xu CB, Su X. The sirt1/ NF-kB signaling pathway is involved in regulation of endothelin type B receptors mediated by homocysteine in vascular smooth muscle cells. Biomed Pharmacother. 2016; 84:1979-85. CrossRef PubMed
  104. Lin QQ, Geng YW, Jiang ZW, Tian ZJ. SIRT1 regulates lipopolysaccharide-induced CD40 expression in renal medullary collecting duct cells by suppressing the TLR4- NF-?B signaling pathway. Life Sci. 2017; 170: 100-7. CrossRef PubMed
  106. Kelly G. A review of the sirtuin system, its clinical implications, and the potential role of dietary activators like resveratrol: part 1. Altern Med Rev. 2010; 15(3): 245-63. PubMed
  108. Gertz M, Nguyen GTT, Fischer F, Suenkel B, Schlicker C. A Molecular Mechanism for Direct Sirtuin Activation by Resveratrol. 2012. PLoS ONE 7(11): e49761. doi:10.1371/journal.pone.0049761. CrossRef  
  109. Farghali H, Kutinová Canová N, Lekic N. SResveratrol and related compounds as antioxidants with an allosteric mechanism of action in epigenetic drug targets. Physiol Res. 2013; 62(1): 1-13. PubMed
  111. Zhang M, Pan Y, Dorfman RG, Yin Y, Zhou Q, Huang S, Liu J, Zhao S. Sirtinol promotes PEPCK1 degradation and inhibits gluconeogenesis by inhibiting deacetylase SIRT2.Sci Rep. 2017; 7(1): 7-17. CrossRef PubMed PubMedCentral
  113. Hwang ES, Song SB. Nicotinamide is an inhibitor of SIRT1 in vitro, but can be a stimulator in cells.Cell Mol Life Sci. 2017; 1: 2527-38. CrossRef  

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