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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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SIRT1: roles in aging and cancer

  • Kim, Eun-Joo (Department of Molecular Biology, Dankook University) ;
  • Um, Soo-Jong (Department of Bioscience and Biotechnology/Institute of Bioscience, Sejong University,)
  • Published : 2008.11.30
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Abstract

Aging and cancer both occur as a result of accumulated cellular damage, and both are related to the regulation of specific genes in the damage response. Recent research has unveiled connections between the mechanisms of aging and cancer, but how to prevent the development of cancer and increase longevity remain unknown. SIRT1 (the mammalian Sir2), which has $NAD^+$-dependent class III histone deacetylase activity, may be a key gene linking the modulation of cancer and aging. SIRT1 has broad biological functions in growth regulation, stress response, tumorigenesis, endocrine signaling, and extended lifespan. Here, we focus on the current knowledge regarding the role of SIRT1 in aging and cancer, and discuss the implications of SIRT1 as a therapeutic target for the optimal balance between anti-aging and anti-cancer activities.

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References

  1. Yang, T., Fu, M., Pestell, R. and Sauve, A. A. (2006) SIRT1 and endocrine signaling.Trends Endocrinol. Metab. 17, 186-191 https://doi.org/10.1016/j.tem.2006.04.002
  2. Frye, R. A. (2000) Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem. Biophys. Res. Commun. 273, 793-798 https://doi.org/10.1006/bbrc.2000.3000
  3. Haigis, M. C. and Guarente, L. P. (2006) Mammalian sirtuins-- emerging roles in physiology, aging, and calorie restriction. Genes Dev. 20, 2913-2921 https://doi.org/10.1101/gad.1467506
  4. Michishita, E., Park, J. Y., Burneskis, J. M., Barrett, J. C. and Horikawa, I. (2005) Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol. Biol. Cell. 16, 4623-4635 https://doi.org/10.1091/mbc.E05-01-0033
  5. Dali-Youcef, N., Lagouge, M., Froelich, S., Koehl, C., Schoonjans, K. and Auwerx, J. (2007) Sirtuins: the 'magnificent seven', function, metabolism and longevity. Ann. Med. 39, 335-345 https://doi.org/10.1080/07853890701408194
  6. Sauve, A. A., Wolberger, C., Schramm, V. L. and Boeke, J. D. (2006) The biochemistry of sirtuins. Annu. Rev. Biochem. 75, 435-465 https://doi.org/10.1146/annurev.biochem.74.082803.133500
  7. North, B. J. and Verdin, E. (2004) Sirtuins: Sir2-related NADdependent protein deacetylases. Genome Biol. 5, 224 https://doi.org/10.1186/gb-2004-5-5-224
  8. Vaquero, A., Scher, M., Lee, D., Erdjument-Bromage, H., Tempst, P. and Reinberg, D. (2004) Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin. Mol. Cell 16, 93-105 https://doi.org/10.1016/j.molcel.2004.08.031
  9. Liszt, G., Ford, E., Kurtev, M. and Guarente, L. (2005) Mouse Sir2 homolog SIRT6 is a nuclear ADP- ribosyltransferase. J. Biol. Chem. 280, 21313-21320 https://doi.org/10.1074/jbc.M413296200
  10. Mostoslavsky, R., Chua, K. F., Lombard, D. B., Pang, W. W., Fischer, M. R., Gellon, L., Liu, P., Mostoslavsky, G., Franco, S., Murphy, M. M., Mills, K. D., Patel, P., Hsu, J. T., Hong, A. L., Ford, E., Cheng, H. L., Kennedy, C., Nunez, N., Bronson, R., Frendewey, D., Auerbach, W., Valenzuela, D., Karow, M., Hottiger, M. O., Hursting, S., Barrett, J. C., Guarente, L., Mulligan, R., Demple, B., Yancopoulos, G. D. and Alt, F. W. (2006) Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell 124, 315-329 https://doi.org/10.1016/j.cell.2005.11.044
  11. Michishita, E., McCord, R. A., Berber, E., Kioi, M., Padilla-Nash, H., Damian, M., Cheung, P., Kusumoto, R., Kawahara, T. L., Barrett, J. C., Chang, H. Y., Bohr, V. A., Ried, T., Gozani, O. and Chua, K. F. (2008) SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Nature 452, 492-496 https://doi.org/10.1038/nature06736
  12. Ford, E., Voit, R., Liszt, G., Magin, C., Grummt, I. and Guarente, L. (2006) Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription. Genes. Dev. 20, 1075-1080 https://doi.org/10.1101/gad.1399706
  13. Vakhrusheva, O., Smolka, C., Gajawada, P., Kostin, S., Boettger, T., Kubin, T., Braun, T. and Bober, E. (2008) Sirt7 increases stress resistance of cardiomyocytes and prevents apoptosis and inflammatory cardiomyopathy in mice. Circ. Res. 102, 703-710 https://doi.org/10.1161/CIRCRESAHA.107.164558
  14. North, B. J., Marshall, B. L., Borra, M. T., Denu, J. M. and Verdin, E. (2003) The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase. Mol. Cell 11, 437-444 https://doi.org/10.1016/S1097-2765(03)00038-8
  15. Vaquero, A., Scher, M. B., Lee, D. H., Sutton, A., Cheng, H. L., Alt, F. W., Serrano, L., Sternglanz, R., Reinberg, D. and Vaquero, A. (2006) SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis. Genes. Dev. 20, 1256-1261 https://doi.org/10.1101/gad.1412706
  16. Outeiro, T. F., Kontopoulos, E., Altmann, S. M., Kufareva, I., Strathearn, K. E., Amore, A. M., Volk, C. B., Maxwell, M. M., Rochet, J. C., McLean, P. J., Young, A. B., Abagyan, R., Feany, M. B., Hyman, B. T. and Kazantsev, A. G. (2007) Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease. Science 317, 516-519 https://doi.org/10.1126/science.1143780
  17. Jing, E., Gesta, S. and Kahn, C. R. (2007) SIRT2 regulates adipocyte differentiation through FoxO1 acetylation/deacetylation. Cell Metab. 6, 105-114 https://doi.org/10.1016/j.cmet.2007.07.003
  18. Wallace, D. C. (2005) A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu. Rev. Genet. 39, 359-407 https://doi.org/10.1146/annurev.genet.39.110304.095751
  19. Shi, T., Wang, F., Stieren, E. and Tong, Q. (2005) SIRT3, a mitochondrial sirtuin deacetylase, regulates mitochondrial function and thermogenesis in brown adipocytes. J. Biol. Chem. 280, 13560-13567 https://doi.org/10.1074/jbc.M414670200
  20. Lombard, D. B., Alt ,F. W., Cheng, H. L., Bunkenborg, J., Streeper, R. S., Mostoslavsky, R., Kim, J., Yancopoulos, G., Valenzuela, D., Murphy, A., Yang, Y., Chen, Y., Hirschey, M. D., Bronson, R. T., Haigis, M,. Guarente, L. P., Farese, R. V. Jr., Weissman, S., Verdin, E. and Schwer, B. (2007) Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol. Cell. Biol. 27, 8807-8814 https://doi.org/10.1128/MCB.01636-07
  21. Yang, H., Yang, T., Baur, J. A., Perez, E., Matsui, T., Carmona, J. J , Lamming, DW., Souza-Pinto, N. C., Bohr, V. A., Rosenzweig, A., de Cabo, R., Sauve, A. A. and Sinclair, D. A. (2007) Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival. Cell 130, 1095-1107 https://doi.org/10.1016/j.cell.2007.07.035
  22. Scher, M. B., Vaquero, A. and Reinberg, D. (2007) SirT3 is a nuclear NAD+-dependent histone deacetylase that translocates to the mitochondria upon cellular stress. Genes. Dev. 21, 920-928 https://doi.org/10.1101/gad.1527307
  23. Haigis, M. C., Mostoslavsky, R., Haigis, K. M., Fahie, K., Christodoulou, D. C., Murphy, A. J., Valenzuela, D. M., Yancopoulos, G. D., Karow, M., Blander, G., Wolberger, C., Prolla, T. A., Weindruch, R., Alt, F. W. and Guarente, L. (2006) SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell 126, 941-954 https://doi.org/10.1016/j.cell.2006.06.057
  24. Guarente, L. and Picard, F. (2005) Calorie restriction-the SIR2 connection. Cell 120, 473-482 https://doi.org/10.1016/j.cell.2005.01.029
  25. Lin, S. J., Defossez, P. A. and Guarente, L. (2000) Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science 289, 2126-2128 https://doi.org/10.1126/science.289.5487.2126
  26. Sinclair, D. A. and Guarente, L. (1997) Extrachromosomal rDNA circles-a cause of aging in yeast. Cell 91, 1033-1042 https://doi.org/10.1016/S0092-8674(00)80493-6
  27. Tissenbaum, H. A. and Guarente, L. (2001) Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410, 227-230 https://doi.org/10.1038/35065638
  28. Berdichevsky, A., Viswanathan, M., Horvitz, H. R. and Guarente, L. (2006) C. elegans SIR-2.1 interacts with 14-3-3 proteins to activate DAF-16 and extend life span. Cell 125, 1165-1177 https://doi.org/10.1016/j.cell.2006.04.036
  29. Wood, J. G., Rogina, B., Lavu, S., Howitz, K., Helfand, S. L., Tatar, M. and Sinclair, D. (2004) Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 430, 686-689 https://doi.org/10.1038/nature02789
  30. Cohen, H. Y., Miller, C., Bitterman, K. J., Wall, N. R., Hekking, B., Kessler, B., Howitz, K. T., Gorospe, M., de Cabo, R. and Sinclair, D. A. (2004) Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science 305, 390-392 https://doi.org/10.1126/science.1099196
  31. Nisoli, E., Tonello, C., Cardile, A., Cozzi, V., Bracale, R., Tedesco, L., Falcone, S., Valerio, A., Cantoni, O., Clementi, E., Moncada, S. and Carruba, M. O. (2005) Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science 310, 314-317 https://doi.org/10.1126/science.1117728
  32. Civitarese, A. E., Carling, S., Heilbronn, L. K., Hulver, M. H., Ukropcova, B., Deutsch, W. A., Smith, S. R. and Ravussin, E. (2007) Calorie restriction increases muscle mitochondrial biogenesis in healthy humans. PLoS Med. 4, e76 https://doi.org/10.1371/journal.pmed.0040076
  33. Bordone, L. and Guarente, L. (2005) Calorie restriction, SIRT1 and metabolism: understanding longevity. Nat. Rev. Mol. Cell. Biol. 6, 298-305 https://doi.org/10.1038/nrm1616
  34. Moynihan, K. A., Grimm, A. A., Plueger, M. M., Bernal- Mizrachi, E., Ford, E., Cras-Meneur, C., Permutt, M.A. and Imai, S. (2005) Increased dosage of mammalian Sir2 in pancreatic beta cells enhances glucose-stimulated insulin secretion in mice. Cell Metab. 2, 105-117 https://doi.org/10.1016/j.cmet.2005.07.001
  35. Bordone, L., Motta, M. C., Picard, F., Robinson, A., Jhala, U. S., Apfeld, J., McDonagh, T., Lemieux, M., McBurney, M., Szilvasi, A., Easlon, E. J., Lin, S. J. and Guarente, L. (2006) Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic beta cells. PLoS Biol. 4, e31 https://doi.org/10.1371/journal.pbio.0040031
  36. Rodgers, J. T., Lerin, C., Haas, W., Gygi, S. P., Spiegelman, B. M. and Puigserver, P. (2005) Nutrient control of glucose homeostasis through a complex of PGC-1$\alpha$ and SIRT1. Nature 434, 113-118 https://doi.org/10.1038/nature03354
  37. Lagouge, M., Argmann, C., Gerhart-Hines, Z., Meziane, H., Lerin, C., Daussin, F., Messadeq, N., Milne, J., Lambert, P., Elliott, P., Geny, B., Laakso, M., Puigserver, P. and Auwerx, J. (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1$\alpha$. Cell 127, 1109-1122 https://doi.org/10.1016/j.cell.2006.11.013
  38. Picard, F., Kurtev, M., Chung, N., Topark-Ngarm, A., Senawong, T., Machado De Oliveira, R., Leid, M., McBurney, M. W. and Guarente, L. (2004) Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature 429, 771-776 https://doi.org/10.1038/nature02583
  39. Pillai, J. B., Isbatan, A., Imai, S., Gupta, M. P. (2005) Poly (ADP-ribose) polymerase-1-dependent cardiac myocyte cell death during heart failure is mediated by NAD+ depletion and reduced Sir2alpha deacetylase activity. J. Biol. Chem. 280, 43121-43130
  40. Alcendor, R. R., Kirshenbaum, L. A., Imai, S., Vatner, S. F. and Sadoshima, J. (2004) Silent information regulator 2alpha, a longevity factor and class III histone deacetylase, is an essential endogenous apoptosis inhibitor in cardiac myocytes. Circ. Res. 95, 971-980 https://doi.org/10.1161/01.RES.0000147557.75257.ff
  41. Araki, T., Sasaki, Y. and Milbrandt, J. (2004) Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration. Science 305, 1010-1013 https://doi.org/10.1126/science.1098014
  42. Anekonda, T. S and Reddy, P. H. (2006) Neuronal protection by sirtuins in Alzheimer's disease. J. Neurochem. 96, 305-313 https://doi.org/10.1111/j.1471-4159.2005.03492.x
  43. Tang, B. L. and Chua, C. E. (2008) SIRT1 and neuronal diseases. Mol. Aspects Med. 29, 187-200 https://doi.org/10.1016/j.mam.2007.02.001
  44. Prozorovski, T., Schulze-Topphoff, U., Glumm, R., Baumgart, J., Schroter, F., Ninnemann, O., Siegert, E., Bendix, I., Brustle, O., Nitsch, R., Zipp, F. and Aktas, O. (2008) Sirt1 contributes critically to the redox-dependent fate of neural progenitors. Nat. Cell. Biol. 10, 385-394 https://doi.org/10.1038/ncb1700
  45. Han, M. K., Song, E. K., Guo, Y., Ou, X., Mantel, C. and Broxmeyer, H. E. (2008) SIRT1 regulates apoptosis and Nanog expression in mouse embryonic stem cells by controlling p53 subcellular localization. Cell Stem Cell 2, 241-251 https://doi.org/10.1016/j.stem.2008.01.002
  46. Chen, D., Steele, A. D., Lindquist, S. and Guarente, L. (2005) Increase in activity during calorie restriction requires Sirt1. Science 310, 1641 https://doi.org/10.1126/science.1118357
  47. Bordone, L., Cohen, D., Robinson, A., Motta, M. C., van Veen, E., Czopik, A., Steele, A. D., Crowe, H., Marmor, S., Luo, J., Gu, W. and Guarente, L. (2007) SIRT1 transgenic mice show phenotypes resembling calorie restriction. Aging Cell 6, 759-767 https://doi.org/10.1111/j.1474-9726.2007.00335.x
  48. Jones, P. A. and Baylin, S. B. (2002) The fundamental role of epigenetic events in cancer. Nat. Rev. Genet. 3, 415-428 https://doi.org/10.1038/nrg816
  49. Pruitt, K., Zinn, R. L., Ohm, J. E., McGarvey, K. M., Kang, S. H., Watkins, D. N., Herman, J. G. and Baylin, S. B. (2006) Inhibition of SIRT1 reactivates silenced cancer genes without loss of promoter DNA hypermethylation. PLoS Genet. 2, e40 https://doi.org/10.1371/journal.pgen.0020040
  50. Vaquero, A., Scher, M., Erdjument-Bromage, H., Tempst, P., Serrano, L. and Reinberg, D. (2007) SIRT1 regulates the histone methyl-transferase SUV39H1 during heterochromatin formation. Nature 450, 440-444 https://doi.org/10.1038/nature06268
  51. Luo, J., Nikolaev, A. Y., Imai, S., Chen, D., Su, F., Shiloh, A., Guarente, L. and Gu, W. (2001) Negative control of p53 by Sir2alpha promotes cell survival under stress. Cell 107, 137-148 https://doi.org/10.1016/S0092-8674(01)00524-4
  52. Vaziri, H., Dessain, S. K., Eaton, E. N., Imai, S.I., Frye, R. A., Pandita, T. K., Guarente, L. and Weinberg, R. A. (2001) hSIR2 (SIRT1) functions as an NAD-dependent p53 deacetylase. Cell 107,149-159 https://doi.org/10.1016/S0092-8674(01)00527-X
  53. Langley, E., Pearson, M., Faretta, M., Bauer, U. M., Frye, R. A., Minucci, S., Pelicci, P. G. and Kouzarides, T. (2002) Human SIR2 deacetylates p53 and antagonizes PML/p53- induced cellular senescence. EMBO J. 21, 2383- 2396 https://doi.org/10.1093/emboj/21.10.2383
  54. Brunet, A., Sweeney, L. B., Sturgill, J. F., Chua, K. F., Greer, P. L., Lin, Y., Tran, H., Ross, S. E., Mostoslavsky, R., Cohen, H. Y., Hu, L. S., Cheng, H. L., Jedrychowski, M. P., Gygi, S. P., Sinclair, D. A., Alt, F. W. and Greenberg, M. E. (2004) Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science 303, 2011-2015 https://doi.org/10.1126/science.1094637
  55. Motta, M. C., Divecha, N., Lemieux, M., Kamel, C., Chen, D., Gu, W., Bultsma, Y., McBurney, M. and Guarente, L. (2004) Mammalian SIRT1 represses forkhead transcription factors. Cell 116, 551-563 https://doi.org/10.1016/S0092-8674(04)00126-6
  56. Yeung, F., Hoberg, J. E., Ramsey, C. S., Keller, M. D., Jones, D. R., Frye, R. A. and Mayo, M. W. (2004) Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J. 23, 2369-2380 https://doi.org/10.1038/sj.emboj.7600244
  57. Chen, W. Y., Wang, D. W., Yen, R. C., Luo, J., Gu, W. and Baylin, S. B. (2005) Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses. Cell 123, 437-448 https://doi.org/10.1016/j.cell.2005.08.011
  58. Fu, M., Liu, M., Sauve, A. A., Jiao, X., Zhang, X., Powell, M., Yang, T., Gu, W., Avantaggiati, M. L., Pattabiraman, N., Pestell, T. G., Wang, F., Quong, A., Wang, C. and Pestell R. G. (2006) Hormonal control of androgen receptor function through SIRT1. Mol. Cell. Biol. 26, 8122-8135 https://doi.org/10.1128/MCB.00289-06
  59. Ford, J., Jiang, M. and Milner, J. (2005) Cancer-specific functions of SIRT1 enable human epithelial cancer cell growth and survival. Cancer Res. 65, 10457-10463 https://doi.org/10.1158/0008-5472.CAN-05-1923
  60. Firestein, R., Blander, G., Michan, S., Oberdoerffer, P., Ogino, S., Campbell, J., Bhimavarapu, A., Luikenhuis, S., de Cabo, R., Fuchs, C., Hahn, W. C., Guarente, L. P. and Sinclair, D. A. (2008) The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth. PLoS ONE 3, e2020 https://doi.org/10.1371/journal.pone.0002020
  61. Anastasiou, D. and Krek, W. (2006) SIRT1: linking adaptive cellular responses to aging-associated changes in organismal physiology. Physiology (Bethesda) 21, 404-410 https://doi.org/10.1152/physiol.00031.2006
  62. Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., Prabhu, V. V., Allard, J.S., Lopez-Lluch, G., Lewis, K., Pistell, P.J., Poosala, S., Becker, K. G., Boss, O., Gwinn, D., Wang, M., Ramaswamy, S., Fishbein, K. W., Spencer, R. G., Lakatta, E. G., Le Couteur, D., Shaw, R. J., Navas, P., Puigserver, P., Ingram, D. K., de Cabo, R., Sinclair, D. A. (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444, 337-342 https://doi.org/10.1038/nature05354
  63. Milne, J. C., Lambert, P. D., Schenk, S., Carney, D. P., Smith, J. J., Gagne, D. J., Jin, L., Boss, O., Perni, R. B., Vu, C. B. Bemis, J. E., Xie, R., Disch, J. S., Ng, P. Y., Nunes, J. J., Lynch, A. V., Yang, H., Galonek, H., Israelian, K., Choy, W., Iffland, A., Lavu, S., Medvedik, O., Sinclair, D. A., Olefsky, J. M., Jirousek, M. R., Elliott, P. J. and Westphal, C. H. (2007) Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature 450, 712-716 https://doi.org/10.1038/nature06261
  64. Yang, Y., Fu, W., Chen, J., Olashaw, N., Zhang, X., Nicosia, S. V., Bhalla, K. and Bai, W. (2007) SIRT1 sumoylation regulates its deacetylase activity and cellular response to genotoxic stress. Nat. Cell. Biol. 9, 1253-1262 https://doi.org/10.1038/ncb1645
  65. Kim, E. J., Kho, J. H., Kang, M. R. and Um, S. J. (2007) Active regulator of SIRT1 cooperates with SIRT1 and facilitates suppression of p53 activity. Mol. Cell 28, 277-290 https://doi.org/10.1016/j.molcel.2007.08.030
  66. Westphal, C. H., Dipp, M. A. and Guarente, L. (2007) A therapeutic role for sirtuins in diseases of aging? Trends Biochem. Sci. 32, 555-560 https://doi.org/10.1016/j.tibs.2007.09.008
  67. Lain, S., Hollick, J. J., Campbell, J., Staples, O. D., Higgins, M., Aoubala, M., McCarthy, A., Appleyard, V., Murray, K. E., Baker, L., Thompson, A., Mathers, J., Holland, S. J., Stark, M. J., Pass, G., Woods, J., Lane, D. P. and Westwood, N. J. (2008) Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator. Cancer Cell 13, 454-463 https://doi.org/10.1016/j.ccr.2008.03.004
  68. Brooks, C. L. and Gu, W. (2008) p53 Activation: a case against Sir. Cancer Cell 13, 377-378 https://doi.org/10.1016/j.ccr.2008.04.009
  69. Kim, J. E., Chen, J and Lou, Z. (2008) DBC1 is a negative regulator of SIRT1. Nature 451, 583-586 https://doi.org/10.1038/nature06500
  70. Zhao, W., Kruse, J. P., Tang, Y., Jung, S. Y., Qin, J. and Gu, W. (2008) Negative regulation of the deacetylase SIRT1 by DBC1. Nature 451, 587-590 https://doi.org/10.1038/nature06515

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  14. Autophagy counteracts apoptosis in human multiple myeloma cells exposed to oridonin in vitro via regulating intracellular ROS and SIRT1 vol.33, pp.1, 2012, https://doi.org/10.1038/aps.2011.143
  15. HIF-1α and rapamycin act as gerosuppressant in multiple myeloma cells upon genotoxic stress vol.15, pp.16, 2016, https://doi.org/10.1080/15384101.2016.1196302
  16. SirT1 knockdown potentiates radiation-induced bystander effect through promoting c-Myc activity and thus facilitating ROS accumulation vol.772, 2015, https://doi.org/10.1016/j.mrfmmm.2014.12.010
  17. Antiaging, longevity and calorie restriction vol.13, pp.1, 2010, https://doi.org/10.1097/MCO.0b013e3283331384
  18. Identification and characterization of novel sirtuin inhibitor scaffolds vol.17, pp.19, 2009, https://doi.org/10.1016/j.bmc.2009.07.073
  19. Metformin is not just an antihyperglycaemic drug but also has protective effects on the vascular endothelium vol.219, pp.1, 2017, https://doi.org/10.1111/apha.12644
  20. AROS Is a Significant Biomarker for Tumor Aggressiveness in Non-cirrhotic Hepatocellular Carcinoma vol.30, pp.9, 2015, https://doi.org/10.3346/jkms.2015.30.9.1253
  21. Healthy clocks, healthy body, healthy mind vol.20, pp.1, 2010, https://doi.org/10.1016/j.tcb.2009.10.005
  22. Sumoylation of Sir2 differentially regulates transcriptional silencing in yeast 2015, https://doi.org/10.1093/nar/gkv842
  23. The protective effects of Resveratrol against radiation-induced intestinal injury vol.17, pp.1, 2017, https://doi.org/10.1186/s12906-017-1915-9
  24. When less is more: the PI3K pathway as a determinant of tumor response to dietary restriction vol.19, pp.7, 2009, https://doi.org/10.1038/cr.2009.81
  25. Structural basis for sirtuin function: What we know and what we don't vol.1804, pp.8, 2010, https://doi.org/10.1016/j.bbapap.2009.09.009
  26. Zebrafish as a Model Organism to Evaluate Drugs Potentially Able to Modulate Sirtuin Expression vol.8, pp.1, 2011, https://doi.org/10.1089/zeb.2010.0677
  27. Sirtuins inhibitors: The approach to affinity and selectivity vol.1804, pp.8, 2010, https://doi.org/10.1016/j.bbapap.2009.11.010
  28. SIRT1 induces EMT by cooperating with EMT transcription factors and enhances prostate cancer cell migration and metastasis vol.31, pp.43, 2012, https://doi.org/10.1038/onc.2011.612
  29. Impact of Maternal Diet on the Epigenome during In Utero Life and the Developmental Programming of Diseases in Childhood and Adulthood vol.7, pp.12, 2015, https://doi.org/10.3390/nu7115467
  30. CBX8 suppresses Sirtinol-induced premature senescence in human breast cancer cells via cooperation with SIRT1 vol.335, pp.2, 2013, https://doi.org/10.1016/j.canlet.2013.02.051
  31. The time-dependent autophagy protects against apoptosis with possible involvement of Sirt1 protein in multiple myeloma under nutrient depletion vol.91, pp.3, 2012, https://doi.org/10.1007/s00277-011-1315-z
  32. Expression of silent mating type information regulator 2 homolog 1 and its role in human intervertebral disc cell homeostasis vol.13, pp.6, 2011, https://doi.org/10.1186/ar3533
  33. Resveratrol delays Wallerian degeneration in a NAD+ and DBC1 dependent manner vol.251, 2014, https://doi.org/10.1016/j.expneurol.2013.11.013
  34. NAD-dependent histone deacetylase, SIRT1, plays essential roles in the maintenance of hematopoietic stem cells vol.418, pp.4, 2012, https://doi.org/10.1016/j.bbrc.2012.01.109
  35. Aging and exercise affect the level of protein acetylation and SIRT1 activity in cerebellum of male rats vol.11, pp.6, 2010, https://doi.org/10.1007/s10522-010-9279-2
  36. Mechanisms Underlying Tumor Suppressive Properties of Melatonin vol.19, pp.8, 2018, https://doi.org/10.3390/ijms19082205