O-GlcNAcylation in Cancer Biology: Linking Metabolism and Signaling

Journal of Molecular Biology

Volumn 428, Issue 16, 2016, Pages 3282-3294

  Ferrer, Christina M ^a   Sodi, Valerie L ^a   Reginato, Mauricio J ^a  

^a DREXEL UNIVERSITY COLLEGE OF MEDICINE   (United States)

Author keywords

cancer; glycosylation; O GlcNAcylation; OGT; signaling

Indexed keywords

HEXOSAMINE; N ACETYLGLUCOSAMINE;

ACYLATION; CARBOHYDRATE SYNTHESIS; CARCINOGENESIS; EPIGENETICS; GLYCOLYSIS; HUMAN; MALIGNANT NEOPLASTIC DISEASE; METASTASIS; MOLECULAR BIOLOGY; MOLECULAR PATHOLOGY; NONHUMAN; NUCLEAR REPROGRAMMING; PRIORITY JOURNAL; PROTEIN TARGETING; REVIEW; SIGNAL TRANSDUCTION; TUMOR INVASION; TUMOR VASCULARIZATION; ANIMAL; BIOSYNTHESIS; GLYCOSYLATION; METABOLISM; NEOPLASM; PATHOLOGY; PHYSIOLOGY;

ANIMALS; BIOSYNTHETIC PATHWAYS; CARCINOGENESIS; GLYCOSYLATION; HUMANS; METABOLIC NETWORKS AND PATHWAYS; NEOPLASMS; SIGNAL TRANSDUCTION;

EID: 84982062721     PISSN: 00222836     EISSN: 10898638     Source Type: Journal    
DOI: 10.1016/j.jmb.2016.05.028     Document Type: Review

References (95)

1. [1] Boroughs, L.K., DeBerardinis, R.J., Metabolic pathways promoting cancer cell survival and growth. Nat. Cell Biol. 17 (2015), 351–359.
2. [2] Vander Heiden, M.G., Cantley, L.C., Thompson, C.B., Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324 (2009), 1029–1033.
3. [3] Kaelin, W.G. Jr., Cancer and altered metabolism: potential importance of hypoxia-inducible factor and 2-oxoglutarate-dependent dioxygenases. Cold Spring Harb. Symp. Quant. Biol. 76 (2011), 335–345.
4. [4] Warburg, O., On the origin of cancer cells. Science. 123 (1956), 309–314.
5. [5] DeBerardinis, R.J., Lum, J.J., Hatzivassiliou, G., Thompson, C.B., The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab. 7 (2008), 11–20.
6. [6] Shaw, R.J., Cantley, L.C., Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature. 441 (2006), 424–430.
7. [7] Jones, R.G., Thompson, C.B., Tumor suppressors and cell metabolism: a recipe for cancer growth. Genes Dev. 23 (2009), 537–548.
8. [8] Dang, C.V., Semenza, G.L., Oncogenic alterations of metabolism. Trends Biochem. Sci. 24 (1999), 68–72.
9. [9] Zoncu, R., Efeyan, A., Sabatini, D.M., mTOR: from growth signal integration to cancer, diabetes and ageing. Nat. Rev. Mol. Cell Biol. 12 (2011), 21–35.
10. [10] DeBerardinis, R.J., Mancuso, A., Daikhin, E., Nissim, I., Yudkoff, M., Wehrli, S., Thompson, C.B., Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc. Natl. Acad. Sci. U. S. A. 104 (2007), 19,345–19,350.
11. [11] Flavin, R., Peluso, S., Nguyen, P.L., Loda, M., Fatty acid synthase as a potential therapeutic target in cancer. Future Oncol. 6 (2010), 551–562.
12. [12] Menendez, J.A., Lupu, R., Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat. Rev. Cancer 7 (2007), 763–777.
13. [13] Harris, A.L., Hypoxia—a key regulatory factor in tumour growth. Nat. Rev. Cancer 2 (2002), 38–47.
14. [14] Semenza, G.L., Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Oncogene. 29 (2010), 625–634.
15. [15] Guillaumond, F., Leca, J., Olivares, O., Lavaut, M.N., Vidal, N., Berthezene, P., et al. Strengthened glycolysis under hypoxia supports tumor symbiosis and hexosamine biosynthesis in pancreatic adenocarcinoma. Proc. Natl. Acad. Sci. U. S. A. 110 (2013), 3919–3924.
16. [16] Generali, D., Berruti, A., Brizzi, M.P., Campo, L., Bonardi, S., Wigfield, S., et al. Hypoxia-inducible factor-1alpha expression predicts a poor response to primary chemoendocrine therapy and disease-free survival in primary human breast cancer. Clin. Cancer Res. 12 (2006), 4562–4568.
17. [17] Palm, W., Park, Y., Wright, K., Pavlova, N.N., Tuveson, D.A., Thompson, C.B., The utilization of extracellular proteins as nutrients is suppressed by mTORC1. Cell 162 (2015), 259–270.
18. [18] Ying, H., Kimmelman, A.C., Lyssiotis, C.A., Hua, S., Chu, G.C., Fletcher-Sananikone, E., et al. Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell 149 (2012), 656–670.
19. [19] Shackelford, D.B., Shaw, R.J., The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat. Rev. Cancer 9 (2009), 563–575.
20. [20] Sengupta, S., Peterson, T.R., Sabatini, D.M., Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Mol. Cell 40 (2010), 310–322.
21. [21] Wellen, K.E., Lu, C., Mancuso, A., Lemons, J.M., Ryczko, M., Dennis, J., et al. The hexosamine biosynthetic pathway couples growth factor-induced glutamine uptake to glucose metabolism. Genes Dev. 24 (2010), 2784–2799.
22. [22] Gwinn, D.M., Shackelford, D.B., Egan, D.F., Mihaylova, M.M., Mery, A., Vasquez, D.S., et al. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol. Cell 30 (2008), 214–226.
23. [23] Hanover, J.A., Krause, M.W., Love, D.C., The hexosamine signaling pathway: O-GlcNAc cycling in feast or famine. Biochim. Biophys. Acta 1800 (2010), 80–95.
24. [24] Bond, M.R., Hanover, J.A., A little sugar goes a long way: the cell biology of O-GlcNAc. J. Cell Biol. 208 (2015), 869–880.
25. [25] Hardiville, S., Hart, G.W., Nutrient regulation of signaling, transcription, and cell physiology by O-GlcNAcylation. Cell Metab. 20 (2014), 208–213.
26. [26] Marshall, S., Bacote, V., Traxinger, R.R., Discovery of a metabolic pathway mediating glucose-induced desensitization of the glucose transport system. Role of hexosamine biosynthesis in the induction of insulin resistance. J. Biol. Chem. 266 (1991), 4706–4712.
27. [27] Dennis, J.W., Lau, K.S., Demetriou, M., Nabi, I.R., Adaptive regulation at the cell surface by N-glycosylation. Traffic 10 (2009), 1569–1578.
28. [28] Love, D.C., Hanover, J.A., The hexosamine signaling pathway: deciphering the “O-GlcNAc code”. Sci. STKE., 2005, 2005, re13.
29. [29] Gloster, T.M., Zandberg, W.F., Heinonen, J.E., Shen, D.L., Deng, L., Vocadlo, D.J., Hijacking a biosynthetic pathway yields a glycosyltransferase inhibitor within cells. Nat. Chem. Biol. 7 (2011), 174–181.
30. [30] Gao, Y., Wells, L., Comer, F.I., Parker, G.J., Hart, G.W., Dynamic O-glycosylation of nuclear and cytosolic proteins: cloning and characterization of a neutral, cytosolic beta-N-acetylglucosaminidase from human brain. J. Biol. Chem. 276 (2001), 9838–9845.
31. [31] Vincenz, L., Hartl, F.U., Sugarcoating ER stress. Cell 156 (2014), 1125–1127.
32. [32] Lynch, T.P., Reginato, M.J., O-GlcNAc transferase: a sweet new cancer target. Cell Cycle 10 (2011), 1712–1713.
33. [33] Slawson, C., Hart, G.W., O-GlcNAc signalling: implications for cancer cell biology. Nat. Rev. Cancer 11 (2011), 678–684.
34. [34] Caldwell, S.A., Jackson, S.R., Shahriari, K.S., Lynch, T.P., Sethi, G., Walker, S., et al. Nutrient sensor O-GlcNAc transferase regulates breast cancer tumorigenesis through targeting of the oncogenic transcription factor FoxM1. Oncogene 29 (2010), 2831–2842.
35. [35] Gu, Y., Mi, W., Ge, Y., Liu, H., Fan, Q., Han, C., et al. GlcNAcylation plays an essential role in breast cancer metastasis. Cancer Res. 70 (2010), 6344–6351.
36. [36] Gu, Y., Ande, S.R., Mishra, S., Altered O-GlcNAc modification and phosphorylation of mitochondrial proteins in myoblast cells exposed to high glucose. Arch. Biochem. Biophys. 505 (2011), 98–104.
37. [37] Krzeslak, A., Forma, E., Bernaciak, M., Romanowicz, H., Brys, M., Gene expression of O-GlcNAc cycling enzymes in human breast cancers. Clin. Exp. Med. 12 (2012), 61–65.
38. [38] Champattanachai, V., Netsirisawan, P., Chaiyawat, P., Phueaouan, T., Charoenwattanasatien, R., Chokchaichamnankit, D., et al. Proteomic analysis and abrogated expression of O-GlcNAcylated proteins associated with primary breast cancer. Proteomics 13 (2013), 2088–2099.
39. [39] Ferrer, C.M., Lynch, T.P., Sodi, V.L., Falcone, J.N., Schwab, L.P., Peacock, D.L., et al. O-GlcNAcylation regulates cancer metabolism and survival stress signaling via regulation of the HIF-1 pathway. Mol. Cell 54 (2014), 820–831.
40. [40] Lynch, T.P., Ferrer, C.M., Jackson, S.R., Shahriari, K.S., Vosseller, K., Reginato, M.J., Critical role of O-linked beta-N-acetylglucosamine transferase in prostate cancer invasion, angiogenesis, and metastasis. J. Biol. Chem. 287 (2012), 11,070–11,081.
41. [41] Itkonen, H.M., Minner, S., Guldvik, I.J., Sandmann, M.J., Tsourlakis, M.C., Berge, V., et al. O-GlcNAc transferase integrates metabolic pathways to regulate the stability of c-MYC in human prostate cancer cells. Cancer Res. 73 (2013), 5277–5287.
42. [42] Kamigaito, T., Okaneya, T., Kawakubo, M., Shimojo, H., Nishizawa, O., Nakayama, J., Overexpression of O-GlcNAc by prostate cancer cells is significantly associated with poor prognosis of patients. Prostate Cancer Prostatic Dis. 17 (2014), 18–22.
43. [43] Gu, Y., Gao, J., Han, C., Zhang, X., Liu, H., Ma, L., et al. O-GlcNAcylation is increased in prostate cancer tissues and enhances malignancy of prostate cancer cells. Mol. Med. Rep. 10 (2014), 897–904.
44. [44] Mi, W., Gu, Y., Han, C., Liu, H., Fan, Q., Zhang, X., et al. O-GlcNAcylation is a novel regulator of lung and colon cancer malignancy. Biochim. Biophys. Acta 1812 (2011), 514–519.
45. [45] Yehezkel, G., Cohen, L., Kliger, A., Manor, E., Khalaila, I., O-linked beta-N-acetylglucosaminylation (O-GlcNAcylation) in primary and metastatic colorectal cancer clones and effect of N-acetyl-beta-D-glucosaminidase silencing on cell phenotype and transcriptome. J. Biol. Chem. 287 (2012), 28,755–28,769.
46. [46] Yang, Y.R., Jang, H.J., Yoon, S., Lee, Y.H., Nam, D., Kim, I.S., et al. OGA heterozygosity suppresses intestinal tumorigenesis in Apc(min/+) mice. Oncogenesis, 3, 2014, 1–6.
47. [47] Yang, Y.R., Kim, D.H., Seo, Y.K., Park, D., Jang, H.J., Choi, S.Y., et al. Elevated O-GlcNAcylation promotes colonic inflammation and tumorigenesis by modulating NF-kappaB signaling. Oncotarget 6 (2015), 12,529–12,542.
48. [48] Phueaouan, T., Chaiyawat, P., Netsirisawan, P., Chokchaichamnankit, D., Punyarit, P., Srisomsap, C., Svasti, J., Champattanachai, V., Aberrant O-GlcNAc-modified proteins expressed in primary colorectal cancer. Oncol. Rep. 30 (2013), 2929–2936.
49. [49] Rozanski, W., Krzeslak, A., Forma, E., Brys, M., Blewniewski, M., Wozniak, P., Lipinski, M., Prediction of bladder cancer based on urinary content of MGEA5 and OGT mRNA level. Clin. Lab. 58 (2012), 579–583.
50. [50] Zhu, Q., Zhou, L., Yang, Z., Lai, M., Xie, H., Wu, L., et al. O-GlcNAcylation plays a role in tumor recurrence of hepatocellular carcinoma following liver transplantation. Med. Oncol. 29 (2012), 985–993.
51. [51] Shi, Y., Tomic, J., Wen, F., Shaha, S., Bahlo, A., Harrison, R., et al. Aberrant O-GlcNAcylation characterizes chronic lymphocytic leukemia. Leukemia 24 (2010), 1588–1598.
52. [52] Swamy, M., Pathak, S., Grzes, K.M., Damerow, S., Sinclair, L.V., van Aalten, D.M., Cantrell, D.A., Glucose and glutamine fuel protein O-GlcNAcylation to control T cell self-renewal and malignancy. Nat. Immunol. 17 (2016), 712–720.
53. [53] Yi, W., Clark, P.M., Mason, D.E., Keenan, M.C., Hill, C., Goddard, W.A. III, et al. Phosphofructokinase 1 glycosylation regulates cell growth and metabolism. Science 337 (2012), 975–980.
54. [54] Ma, Z., Vocadlo, D.J., Vosseller, K., Hyper-O-GlcNAcylation is anti-apoptotic and maintains constitutive NF-kappaB activity in pancreatic cancer cells. J. Biol. Chem. 288 (2013), 15,121–15,130.
55. [55] Sodi, V.L., Khaku, S., Krutilina, R., Schwab, L.P., Vocadlo, D.J., Seagroves, T.N., Reginato, M.J., mTOR/MYC axis regulates O-GlcNAc transferase expression and O-GlcNAcylation in breast cancer. Mol. Cancer Res. 13 (2015), 923–933.
56. [56] Zhang, X., Ma, L., Qi, J., Shan, H., Yu, W., Gu, Y., MAPK/ERK signaling pathway-induced hyper-O-GlcNAcylation enhances cancer malignancy. Mol. Cell. Biochem. 410 (2015), 101–110.
57. [57] Yang, Y., Yin, X., Yang, H., Xu, Y., Histone demethylase LSD2 acts as an E3 ubiquitin ligase and inhibits cancer cell growth through promoting proteasomal degradation of OGT. Mol. Cell 58 (2015), 47–59.
58. [58] Hanahan, D., Weinberg, R.A., Hallmarks of cancer: the next generation. Cell 144 (2011), 646–674.
59. [59] Zeidan, Q., Hart, G.W., The intersections between O-GlcNAcylation and phosphorylation: implications for multiple signaling pathways. J. Cell Sci. 123 (2010), 13–22.
60. [60] O'Donnell, N., Zachara, N.E., Hart, G.W., Marth, J.D., Ogt-dependent X-chromosome-linked protein glycosylation is a requisite modification in somatic cell function and embryo viability. Mol. Cell. Biol. 24 (2004), 1680–1690.
61. [61] Jang, H., Kim, T.W., Yoon, S., Choi, S.Y., Kang, T.W., Kim, S.Y., et al. O-GlcNAc regulates pluripotency and reprogramming by directly acting on core components of the pluripotency network. Cell Stem Cell. 11 (2012), 62–74.
62. [62] Onodera, Y., Nam, J.M., Bissell, M.J., Increased sugar uptake promotes oncogenesis via EPAC/RAP1 and O-GlcNAc pathways. J. Clin. Invest. 124 (2014), 367–384.
63. [63] Dang, C.V., O'Donnell, K.A., Juopperi, T., The great MYC escape in tumorigenesis. Cancer Cell 8 (2005), 177–178.
64. [64] Ramakrishnan, P., Clark, P.M., Mason, D.E., Peters, E.C., Hsieh-Wilson, L.C., Baltimore, D., Activation of the transcriptional function of the NF-kappaB protein c-Rel by O-GlcNAc glycosylation. Sci. Signal., 6, 2013, ra75.
65. [65] El Mjiyad, N., Caro-Maldonado, A., Ramirez-Peinado, S., Munoz-Pinedo, C., Sugar-free approaches to cancer cell killing. Oncogene 30 (2011), 253–264.
66. [66] Thiery, J.P., Sleeman, J.P., Complex networks orchestrate epithelial-mesenchymal transitions. Nat. Rev. Mol. Cell Biol. 7 (2006), 131–142.
67. [67] Park, S.Y., Kim, H.S., Kim, N.H., Ji, S., Cha, S.Y., Kang, J.G., et al. Snail1 is stabilized by O-GlcNAc modification in hyperglycaemic condition. EMBO J. 29 (2010), 3787–3796.
68. [68] Huang, X., Pan, Q., Sun, D., Chen, W., Shen, A., Huang, M., et al. O-GlcNAcylation of cofilin promotes breast cancer cell invasion. J. Biol. Chem. 288 (2013), 36,418–36,425.
69. [69] Lucena, M.C., Carvalho-Cruz, P., Donadio, J.L., Oliveira, I.A., de Queiroz, R.M., Marinho-Carvalho, M.M., et al. Epithelial mesenchymal transition induces aberrant glycosylation through hexosamine biosynthetic pathway activation. J. Biol. Chem. 291:25 (2016), 12917–12929.
70. [70] Ferrer, C.M., Lu, T., Bacigalupa, Z.A., Katsetos, C.D., Sinclair, D.A., Reginato, M.J., O-GlcNAcylation regulates breast cancer metastasis via SIRT1 modulation of FoxM1 pathway. Oncogene, 2016 (in press, Epub ahead of print).
71. [71] Hida, K., Maishi, N., Torii, C., Hida, Y., Tumor angiogenesis—characteristics of tumor endothelial cells. Int. J. Clin. Oncol. 21 (2016), 206–212.
72. [72] Cai, Y., Balli, D., Ustiyan, V., Fulford, L., Hiller, A., Misetic, V., et al. Foxm1 expression in prostate epithelial cells is essential for prostate carcinogenesis. J. Biol. Chem. 288 (2013), 22,527–22,541.
73. [73] Rao, X., Duan, X., Mao, W., Li, X., Li, Z., Li, Q., et al. O-GlcNAcylation of G6PD promotes the pentose phosphate pathway and tumor growth. Nat. Commun., 6, 2015, 8468.
74. [74] Chaiyawat, P., Chokchaichamnankit, D., Lirdprapamongkol, K., Srisomsap, C., Svasti, J., Champattanachai, V., Alteration of O-GlcNAcylation affects serine phosphorylation and regulates gene expression and activity of pyruvate kinase M2 in colorectal cancer cells. Oncol. Rep. 34 (2015), 1933–1942.
75. [75] Bullen, J.W., Balsbaugh, J.L., Chanda, D., Shabanowitz, J., Hunt, D.F., Neumann, D., Hart, G.W., Cross-talk between two essential nutrient-sensitive enzymes: O-GlcNAc transferase (OGT) and AMP-activated protein kinase (AMPK). J. Biol. Chem. 289 (2014), 10,592–10,606.
76. [76] Vella, P., Scelfo, A., Jammula, S., Chiacchiera, F., Williams, K., Cuomo, A., et al. Tet proteins connect the O-linked N-acetylglucosamine transferase Ogt to chromatin in embryonic stem cells. Mol. Cell 49 (2013), 645–656.
77. [77] Balasubramani, A., Rao, A., O-GlcNAcylation and 5-methylcytosine oxidation: an unexpected association between OGT and TETs. Mol. Cell 49 (2013), 618–619.
78. [78] Myers, S.A., Panning, B., Burlingame, A.L., Polycomb repressive complex 2 is necessary for the normal site-specific O-GlcNAc distribution in mouse embryonic stem cells. Proc. Natl. Acad. Sci. U. S. A. 108 (2011), 9490–9495.
79. [79] Huang, Y., Rao, A., Connections between TET proteins and aberrant DNA modification in cancer. Trends Genet. 30 (2014), 464–474.
80. [80] Itkonen, H.M., Gorad, S.S., Duveau, D.Y., Martin, S.E., Barkovskaya, A., Bathen, T.F., et al. Inhibition of O-GlcNAc transferase activity reprograms prostate cancer cell metabolism. Oncotarget, 2016.
81. [81] Ortiz -Meoz, R.F., Jiang, J., Lazarus, M.B., Orman, M., Janetzko, J., Fan, C., et al. A small molecule that inhibits OGT activity in cells. ACS Chem. Biol. 10 (2015), 1392–1397.
82. [82] Gross, B.J., Kraybill, B.C., Walker, S., Discovery of O-GlcNAc transferase inhibitors. J. Am. Chem. Soc. 127 (2005), 14,588–14,589.
83. [83] Kwei, K.A., Baker, J.B., Pelham, R.J., Modulators of sensitivity and resistance to inhibition of PI3K identified in a pharmacogenomic screen of the NCI-60 human tumor cell line collection. PLoS One, 7, 2012, e46518.
84. [84] Kanwal, S., Fardini, Y., Pagesy, P., N'Tumba-Byn, T., Pierre-Eugene, C., Masson, E., et al. O-GlcNAcylation-inducing treatments inhibit estrogen receptor alpha expression and confer resistance to 4-OH-tamoxifen in human breast cancer-derived MCF-7 cells. PLoS One, 8, 2013, e69150.
85. [85] Alejandro, E.U., Bozadjieva, N., Kumusoglu, D., Abdulhamid, S., Levine, H., Haataja, L., et al. Disruption of O-linked N-acetylglucosamine signaling induces ER stress and beta cell failure. Cell Rep. 13 (2015), 2527–2538.
86. [86] Yuzwa, S.A., Vocadlo, D.J., O-GlcNAc and neurodegeneration: biochemical mechanisms and potential roles in Alzheimer's disease and beyond. Chem. Soc. Rev. 43 (2014), 6839–6858.
87. [87] Ruan, H.B., Dietrich, M.O., Liu, Z.W., Zimmer, M.R., Li, M.D., Singh, J.P., et al. O-GlcNAc transferase enables AgRP neurons to suppress browning of white fat. Cell 159 (2014), 306–317.
88. [88] Tomic, J., McCaw, L., Li, Y., Hough, M.R., Ben-David, Y., Moffat, J., Spaner, D.E., Resveratrol has anti-leukemic activity associated with decreased O-GlcNAcylated proteins. Exp. Hematol. 41 (2013), 675–686.
89. [89] Wu, L.E., Gomes, A.P., Sinclair, D.A., Geroncogenesis: metabolic changes during aging as a driver of tumorigenesis. Cancer Cell 25 (2014), 12–19.
90. [90] Yang, Y.R., Song, M., Lee, H., Jeon, Y., Choi, E.J., Jang, H.J., et al. O-GlcNAcase is essential for embryonic development and maintenance of genomic stability. Aging Cell 11 (2012), 439–448.
91. [91] Rubinsztein, D.C., Marino, G., Kroemer, G., Autophagy and aging. Cell 146 (2011), 682–695.
92. [92] Hursting, S.D., Lavigne, J.A., Berrigan, D., Perkins, S.N., Barrett, J.C., Calorie restriction, aging, and cancer prevention: mechanisms of action and applicability to humans. Annu. Rev. Med. 54 (2003), 131–152.
93. [93] Wang, P., Hanover, J.A., Nutrient-driven O-GlcNAc cycling influences autophagic flux and neurodegenerative proteotoxicity. Autophagy 9 (2013), 604–606.
94. [94] Haigis, M.C., Guarente, L.P., Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction. Genes Dev. 20 (2006), 2913–2921.
95. [95] Mercken, E.M., Hu, J., Krzysik-Walker, S., Wei, M., Li, Y., McBurney, M.W., et al. SIRT1 but not its increased expression is essential for lifespan extension in caloric-restricted mice. Aging Cell 13 (2014), 193–196.