NAD metabolism: Implications in aging and longevity

Ageing Research Reviews

Volumn 47, Issue , 2018, Pages 1-17

  Yaku, Keisuke ^a,b   Okabe, Keisuke ^a,b   Nakagawa, Takashi ^a,b  

^a UNIVERSITY OF TOYAMA   (Japan)

^b UNIVERSITY OF TOYAMA   (Japan)

Author keywords

Aging; Aging associated disease; Longevity; NAD; Nampt; Nmnat

Indexed keywords

ADP RIBOSYL CYCLASE/CYCLIC ADP RIBOSE HYDROLASE 1; ENZYME; IDO ENZYME; MICRORNA; NAPRT ENZYME; NICOTINAMIDE ADENINE DINUCLEOTIDE; NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE; NMNAT1 ENZYME; NMNAT2 ENZYME; NMNAT3 ENZYME; QAPRT ENZYME; TDO ENZYME; UNCLASSIFIED DRUG;

AGING; BRAIN; CHRONIC INFLAMMATION; CIRCADIAN RHYTHM; DIPTERA; DNA DAMAGE; HEARING IMPAIRMENT; HUMAN; LONGEVITY; MOUSE; NONHUMAN; NUCLEOTIDE METABOLISM; REVIEW; SIGNAL TRANSDUCTION; SKELETAL MUSCLE; WORM; YEAST; ANIMAL; DEGENERATIVE DISEASE; GENETICS; METABOLISM; NEOPLASM; PATHOLOGY; PHYSIOLOGY;

AGING; ANIMALS; HUMANS; LONGEVITY; NAD; NEOPLASMS; NEURODEGENERATIVE DISEASES;

EID: 85048550197     PISSN: 15681637     EISSN: 18729649     Source Type: Journal    
DOI: 10.1016/j.arr.2018.05.006     Document Type: Review

References (243)

1. Adyshev, D.M., Elangovan, V.R., Moldobaeva, N., Mapes, B., Sun, X., Garcia, J.G., Mechanical stress induces pre-B-cell colony-enhancing factor/NAMPT expression via epigenetic regulation by miR-374a and miR-568 in human lung endothelium. Am. J. Respir. Cell Mol. Biol. 50 (2014), 409–418.
2. Airhart, S.E., Shireman, L.M., Risler, L.J., Anderson, G.D., Nagana Gowda, G.A., Raftery, D., Tian, R., Shen, D.D., O'Brien, K.D., An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR) and its effects on blood NAD+ levels in healthy volunteers. PLoS One, 12, 2017, e0186459.
3. Amici, A., Grolla, A.A., Del Grosso, E., Bellini, R., Bianchi, M., Travelli, C., Garavaglia, S., Sorci, L., Raffaelli, N., Ruggieri, S., Genazzani, A.A., Orsomando, G., Synthesis and degradation of adenosine 5’-tetraphosphate by nicotinamide and nicotinate phosphoribosyltransferases. Cell Chem. Biol. 24 (2017), 553–564 e554.
4. Anderson, R.M., Bitterman, K.J., Wood, J.G., Medvedik, O., Sinclair, D.A., Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae. Nature 423 (2003), 181–185.
5. Anderson, K.A., Madsen, A.S., Olsen, C.A., Hirschey, M.D., Metabolic control by sirtuins and other enzymes that sense NAD(+), NADH, or their ratio. Biochim. Biophys. Acta 1858 (2017), 991–998.
6. Asher, G., Gatfield, D., Stratmann, M., Reinke, H., Dibner, C., Kreppel, F., Mostoslavsky, R., Alt, F.W., Schibler, U., SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell 134 (2008), 317–328.
7. Auguet, T., Terra, X., Porras, J.A., Orellana-Gavalda, J.M., Martinez, S., Aguilar, C., Lucas, A., Pellitero, S., Hernandez, M., Del Castillo, D., Richart, C., Plasma visfatin levels and gene expression in morbidly obese women with associated fatty liver disease. Clin. Biochem. 46 (2013), 202–208.
8. Azhar, S., Ho, H.Y., Reaven, E., Reaven, G.M., Evidence for age-related changes in pyridine nucleotide content of isolated rat islets. Horm. Metab. Res. 20 (1988), 559–561.
9. Babcock, T.A., Carlin, J.M., Transcriptional activation of indoleamine dioxygenase by interleukin 1 and tumor necrosis factor alpha in interferon-treated epithelial cells. Cytokine 12 (2000), 588–594.
10. Baburski, A.Z., Sokanovic, S.J., Bjelic, M.M., Radovic, S.M., Andric, S.A., Kostic, T.S., Circadian rhythm of the Leydig cells endocrine function is attenuated during aging. Exp. Gerontol. 73 (2016), 5–13.
11. Badawy, A.A., Kynurenine pathway of tryptophan metabolism: regulatory and functional aspects. Int. J. Tryptophan. Res. 10 (2017), 1–10.
12. Bai, P., Canto, C., Oudart, H., Brunyanszki, A., Cen, Y., Thomas, C., Yamamoto, H., Huber, A., Kiss, B., Houtkooper, R.H., Schoonjans, K., Schreiber, V., Sauve, A.A., Menissier-de Murcia, J., Auwerx, J., PARP-1 inhibition increases mitochondrial metabolism through SIRT1 activation. Cell Metab. 13 (2011), 461–468.
13. Balan, V., Miller, G.S., Kaplun, L., Balan, K., Chong, Z.Z., Li, F., Kaplun, A., VanBerkum, M.F., Arking, R., Freeman, D.C., Maiese, K., Tzivion, G., Life span extension and neuronal cell protection by Drosophila nicotinamidase. J. Biol. Chem. 283 (2008), 27810–27819.
14. Banerjee, K.K., Ayyub, C., Ali, S.Z., Mandot, V., Prasad, N.G., Kolthur-Seetharam, U., dSir2 in the adult fat body, but not in muscles, regulates life span in a diet-dependent manner. Cell Rep. 2 (2012), 1485–1491.
15. Barata, H., Thompson, M., Zielinska, W., Han, Y.S., Mantilla, C.B., Prakash, Y.S., Feitoza, S., Sieck, G., Chini, E.N., The role of cyclic-ADP-ribose-signaling pathway in oxytocin-induced Ca2+ transients in human myometrium cells. Endocrinology 145 (2004), 881–889.
16. Barth, S., Klein, P., Horbach, T., Dotsch, J., Rauh, M., Rascher, W., Knerr, I., Expression of neuropeptide Y, omentin and visfatin in visceral and subcutaneous adipose tissues in humans: relation to endocrine and clinical parameters. Obes. Facts 3 (2010), 245–251.
17. Barzilai, N., Huffman, D.M., Muzumdar, R.H., Bartke, A., The critical role of metabolic pathways in aging. Diabetes 61 (2012), 1315–1322.
18. Beatty, W.L., Belanger, T.A., Desai, A.A., Morrison, R.P., Byrne, G.I., Tryptophan depletion as a mechanism of gamma interferon-mediated chlamydial persistence. Infect. Immun. 62 (1994), 3705–3711.
19. Behr, A., Taguchi, H., Gholson, R.K., Apparent pyridine nucleotide synthesis in mitochondria: an artifact of NMN and NAD glycohydrolase activity?. Biochem. Biophys. Res. Commun. 101 (1981), 767–774.
20. Beirowski, B., Babetto, E., Coleman, M.P., Martin, K.R., The WldS gene delays axonal but not somatic degeneration in a rat glaucoma model. Eur. J. Neurosci. 28 (2008), 1166–1179.
21. Belenky, P., Racette, F.G., Bogan, K.L., McClure, J.M., Smith, J.S., Brenner, C., Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+. Cell 129 (2007), 473–484.
22. Ben Abdallah, N.M., Slomianka, L., Vyssotski, A.L., Lipp, H.P., Early age-related changes in adult hippocampal neurogenesis in C57 mice. Neurobiol. Aging 31 (2010), 151–161.
23. Bender, D.A., Magboul, B.I., Wynick, D., Probable mechanisms of regulation of the utilization of dietary tryptophan, nicotinamide and nicotinic acid as precursors of nicotinamide nucleotides in the rat. Br. J. Nutr. 48 (1982), 119–127.
24. Berger, F., Lau, C., Dahlmann, M., Ziegler, M., Subcellular compartmentation and differential catalytic properties of the three human nicotinamide mononucleotide adenylyltransferase isoforms. J. Biol. Chem. 280 (2005), 36334–36341.
25. Berger, F., Lau, C., Ziegler, M., Regulation of poly(ADP-ribose) polymerase 1 activity by the phosphorylation state of the nuclear NAD biosynthetic enzyme NMN adenylyl transferase 1. Proc. Natl. Acad. Sci. U. S. A. 104 (2007), 3765–3770.
26. Bieganowski, P., Brenner, C., Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans. Cell 117 (2004), 495–502.
27. Bitterman, K.J., Anderson, R.M., Cohen, H.Y., Latorre-Esteves, M., Sinclair, D.A., Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1. J. Biol. Chem. 277 (2002), 45099–45107.
28. Braidy, N., Guillemin, G.J., Mansour, H., Chan-Ling, T., Poljak, A., Grant, R., Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in wistar rats. PLoS One, 6, 2011, e19194.
29. Brown, K.D., Maqsood, S., Huang, J.Y., Pan, Y., Harkcom, W., Li, W., Sauve, A., Verdin, E., Jaffrey, S.R., Activation of SIRT3 by the NAD(+) precursor nicotinamide riboside protects from noise-induced hearing loss. Cell Metab. 20 (2014), 1059–1068.
30. Burnett, C., Valentini, S., Cabreiro, F., Goss, M., Somogyvari, M., Piper, M.D., Hoddinott, M., Sutphin, G.L., Leko, V., McElwee, J.J., Vazquez-Manrique, R.P., Orfila, A.M., Ackerman, D., Au, C., Vinti, G., Riesen, M., Howard, K., Neri, C., Bedalov, A., Kaeberlein, M., Soti, C., Partridge, L., Gems, D., Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature 477 (2011), 482–485.
31. Camacho-Pereira, J., Tarrago, M.G., Chini, C.C.S., Nin, V., Escande, C., Warner, G.M., Puranik, A.S., Schoon, R.A., Reid, J.M., Galina, A., Chini, E.N., CD38 dictates age-related NAD decline and mitochondrial dysfunction through an SIRT3-dependent mechanism. Cell Metab. 23 (2016), 1127–1139.
32. Cambronne, X.A., Stewart, M.L., Kim, D., Jones-Brunette, A.M., Morgan, R.K., Farrens, D.L., Cohen, M.S., Goodman, R.H., Biosensor reveals multiple sources for mitochondrial NAD(+). Science 352 (2016), 1474–1477.
33. Canto, C., Houtkooper, R.H., Pirinen, E., Youn, D.Y., Oosterveer, M.H., Cen, Y., Fernandez-Marcos, P.J., Yamamoto, H., Andreux, P.A., Cettour-Rose, P., Gademann, K., Rinsch, C., Schoonjans, K., Sauve, A.A., Auwerx, J., The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metab. 15 (2012), 838–847.
34. Canto, C., Menzies, K.J., Auwerx, J., NAD(+) metabolism and the control of energy homeostasis: a balancing act between mitochondria and the nucleus. Cell Metab. 22 (2015), 31–53.
35. Cavadini, G., Petrzilka, S., Kohler, P., Jud, C., Tobler, I., Birchler, T., Fontana, A., TNF-alpha suppresses the expression of clock genes by interfering with E-box-mediated transcription. Proc. Natl. Acad. Sci. U. S. A. 104 (2007), 12843–12848.
36. Ceni, C., Pochon, N., Brun, V., Muller-Steffner, H., Andrieux, A., Grunwald, D., Schuber, F., De Waard, M., Lund, F., Villaz, M., Moutin, M.J., CD38-dependent ADP-ribosyl cyclase activity in developing and adult mouse brain. Biochem. J. 370 (2003), 175–183.
37. Chaleckis, R., Murakami, I., Takada, J., Kondoh, H., Yanagida, M., Individual variability in human blood metabolites identifies age-related differences. Proc. Natl. Acad. Sci. U. S. A. 113 (2016), 4252–4259.
38. Chang, H.C., Guarente, L., SIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging. Cell 153 (2013), 1448–1460.
39. Chen, M.P., Chung, F.M., Chang, D.M., Tsai, J.C., Huang, H.F., Shin, S.J., Lee, Y.J., Elevated plasma level of visfatin/pre-B cell colony-enhancing factor in patients with type 2 diabetes mellitus. J. Clin. Endocrinol. Metab. 91 (2006), 295–299.
40. Cheng, X.S., Zhao, K.P., Jiang, X., Du, L.L., Li, X.H., Ma, Z.W., Yao, J., Luo, Y., Duan, D.X., Wang, J.Z., Zhou, X.W., Nmnat2 attenuates Tau phosphorylation through activation of PP2A. J. Alzheimers Dis. 36 (2013), 185–195.
41. Chew, E.Y., Nutrition effects on ocular diseases in the aging eye. Invest. Ophthalmol. Vis. Sci. 54 (2013), ORSF42–47.
42. Chiang, P.W., Wang, J., Chen, Y., Fu, Q., Zhong, J., Chen, Y., Yi, X., Wu, R., Gan, H., Shi, Y., Chen, Y., Barnett, C., Wheaton, D., Day, M., Sutherland, J., Heon, E., Weleber, R.G., Gabriel, L.A., Cong, P., Chuang, K., Ye, S., Sallum, J.M., Qi, M., Exome sequencing identifies NMNAT1 mutations as a cause of Leber congenital amaurosis. Nat. Genet. 44 (2012), 972–974.
43. Chiarugi, A., Dolle, C., Felici, R., Ziegler, M., The NAD metabolome–a key determinant of cancer cell biology. Nat. Rev. Cancer 12 (2012), 741–752.
44. Choi, S.E., Fu, T., Seok, S., Kim, D.H., Yu, E., Lee, K.W., Kang, Y., Li, X., Kemper, B., Kemper, J.K., Elevated microRNA-34a in obesity reduces NAD+ levels and SIRT1 activity by directly targeting NAMPT. Aging Cell 12 (2013), 1062–1072.
45. Chung, H.Y., Cesari, M., Anton, S., Marzetti, E., Giovannini, S., Seo, A.Y., Carter, C., Yu, B.P., Leeuwenburgh, C., Molecular inflammation: underpinnings of aging and age-related diseases. Ageing Res. Rev. 8 (2009), 18–30.
46. Conforti, L., Janeckova, L., Wagner, D., Mazzola, F., Cialabrini, L., Di Stefano, M., Orsomando, G., Magni, G., Bendotti, C., Smyth, N., Coleman, M., Reducing expression of NAD+ synthesizing enzyme NMNAT1 does not affect the rate of Wallerian degeneration. FEBS J. 278 (2011), 2666–2679.
47. Conforti, L., Gilley, J., Coleman, M.P., Wallerian degeneration: an emerging axon death pathway linking injury and disease. Nat. Rev. Neurosci. 15 (2014), 394–409.
48. Dahl, T.B., Haukeland, J.W., Yndestad, A., Ranheim, T., Gladhaug, I.P., Damas, J.K., Haaland, T., Loberg, E.M., Arntsen, B., Birkeland, K., Bjoro, K., Ulven, S.M., Konopski, Z., Nebb, H.I., Aukrust, P., Halvorsen, B., Intracellular nicotinamide phosphoribosyltransferase protects against hepatocyte apoptosis and is down-regulated in nonalcoholic fatty liver disease. J. Clin. Endocrinol. Metab. 95 (2010), 3039–3047.
49. de Figueiredo, L.F., Gossmann, T.I., Ziegler, M., Schuster, S., Pathway analysis of NAD+ metabolism. Biochem. J. 439 (2011), 341–348.
50. Del Nagro, C., Xiao, Y., Rangell, L., Reichelt, M., O'Brien, T., Depletion of the central metabolite NAD leads to oncosis-mediated cell death. J. Biol. Chem. 289 (2014), 35182–35192.
51. Di Stefano, M., Galassi, L., Magni, G., Unique expression pattern of human nicotinamide mononucleotide adenylyltransferase isozymes in red blood cells. Blood Cells. Mol. Dis. 45 (2010), 33–39.
52. Drew, J.E., Farquharson, A.J., Horgan, G.W., Williams, L.M., Tissue-specific regulation of sirtuin and nicotinamide adenine dinucleotide biosynthetic pathways identified in C57Bl/6 mice in response to high-fat feeding. J. Nutr. Biochem. 37 (2016), 20–29.
53. Ehrlich, R., Harris, A., Kheradiya, N.S., Winston, D.M., Ciulla, T.A., Wirostko, B., Age-related macular degeneration and the aging eye. Clin. Interv. Aging 3 (2008), 473–482.
54. Falk, M.J., Zhang, Q., Nakamaru-Ogiso, E., Kannabiran, C., Fonseca-Kelly, Z., Chakarova, C., Audo, I., Mackay, D.S., Zeitz, C., Borman, A.D., Staniszewska, M., Shukla, R., Palavalli, L., Mohand-Said, S., Waseem, N.H., Jalali, S., Perin, J.C., Place, E., Ostrovsky, J., Xiao, R., Bhattacharya, S.S., Consugar, M., Webster, A.R., Sahel, J.A., Moore, A.T., Berson, E.L., Liu, Q., Gai, X., Pierce, E.A., NMNAT1 mutations cause Leber congenital amaurosis. Nat. Genet. 44 (2012), 1040–1045.
55. Fang, E.F., Scheibye-Knudsen, M., Brace, L.E., Kassahun, H., SenGupta, T., Nilsen, H., Mitchell, J.R., Croteau, D.L., Bohr, V.A., Defective mitophagy in XPA via PARP-1 hyperactivation and NAD(+)/SIRT1 reduction. Cell 157 (2014), 882–896.
56. Fang, E.F., Kassahun, H., Croteau, D.L., Scheibye-Knudsen, M., Marosi, K., Lu, H., Shamanna, R.A., Kalyanasundaram, S., Bollineni, R.C., Wilson, M.A., Iser, W.B., Wollman, B.N., Morevati, M., Li, J., Kerr, J.S., Lu, Q., Waltz, T.B., Tian, J., Sinclair, D.A., Mattson, M.P., Nilsen, H., Bohr, V.A., NAD(+) replenishment improves lifespan and healthspan in ataxia telangiectasia models via mitophagy and DNA repair. Cell Metab. 24 (2016), 566–581.
57. Fang, E.F., Lautrup, S., Hou, Y., Demarest, T.G., Croteau, D.L., Mattson, M.P., Bohr, V.A., NAD(+) in aging: molecular mechanisms and translational implications. Trends Mol. Med. 23 (2017), 899–916.
58. Felici, R., Lapucci, A., Ramazzotti, M., Chiarugi, A., Insight into molecular and functional properties of NMNAT3 reveals new hints of NAD homeostasis within human mitochondria. PLoS One, 8, 2013, e76938.
59. Ferrero, E., Saccucci, F., Malavasi, F., The human CD38 gene: polymorphism, CpG island, and linkage to the CD157 (BST-1) gene. Immunogenetics 49 (1999), 597–604.
60. Flaxman, S.R., Bourne, R.R.A., Resnikoff, S., Ackland, P., Braithwaite, T., Cicinelli, M.V., Das, A., Jonas, J.B., Keeffe, J., Kempen, J.H., Leasher, J., Limburg, H., Naidoo, K., Pesudovs, K., Silvester, A., Stevens, G.A., Tahhan, N., Wong, T.Y., Taylor, H.R., Vision Loss Expert Group of the Global Burden of Disease, S., Global causes of blindness and distance vision impairment 1990–2020: a systematic review and meta-analysis. Lancet Glob. Health 5 (2017), e1221–e1234.
61. Fletcher, R.S., Ratajczak, J., Doig, C.L., Oakey, L.A., Callingham, R., Da Silva Xavier, G., Garten, A., Elhassan, Y.S., Redpath, P., Migaud, M.E., Philp, A., Brenner, C., Canto, C., Lavery, G.G., Nicotinamide riboside kinases display redundancy in mediating nicotinamide mononucleotide and nicotinamide riboside metabolism in skeletal muscle cells. Mol. Metab. 6 (2017), 819–832.
62. Franceschi, C., Campisi, J., Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J. Gerontol. A. Biol. Sci. Med. Sci. 69:Suppl. 1 (2014), S4–9.
63. Frederick, D.W., Davis, J.G., Davila, A. Jr., Agarwal, B., Michan, S., Puchowicz, M.A., Nakamaru-Ogiso, E., Baur, J.A., Increasing NAD synthesis in muscle via nicotinamide phosphoribosyltransferase is not sufficient to promote oxidative metabolism. J. Biol. Chem. 290 (2015), 1546–1558.
64. Frederick, D.W., Loro, E., Liu, L., Davila, A. Jr., Chellappa, K., Silverman, I.M., Quinn, W.J. 3rd, Gosai, S.J., Tichy, E.D., Davis, J.G., Mourkioti, F., Gregory, B.D., Dellinger, R.W., Redpath, P., Migaud, M.E., Nakamaru-Ogiso, E., Rabinowitz, J.D., Khurana, T.S., Baur, J.A., Loss of NAD homeostasis leads to progressive and reversible degeneration of skeletal muscle. Cell Metab. 24 (2016), 269–282.
65. Gaddipati, R., Sasikala, M., Padaki, N., Mukherjee, R.M., Sekaran, A., Jayaraj-Mansard, M., Rabella, P., Rao-Guduru, V., Reddy-Duvvuru, N., Visceral adipose tissue visfatin in nonalcoholic fatty liver disease. Ann. Hepatol. 9 (2010), 266–270.
66. Gallo, C.M., Smith, D.L. Jr., Smith, J.S., Nicotinamide clearance by Pnc1 directly regulates Sir2-mediated silencing and longevity. Mol. Cell. Biol. 24 (2004), 1301–1312.
67. Garten, A., Petzold, S., Barnikol-Oettler, A., Korner, A., Thasler, W.E., Kratzsch, J., Kiess, W., Gebhardt, R., Nicotinamide phosphoribosyltransferase (NAMPT/PBEF/visfatin) is constitutively released from human hepatocytes. Biochem. Biophys. Res. Commun. 391 (2010), 376–381.
68. Ghosh, D., Levault, K.R., Brewer, G.J., Relative importance of redox buffers GSH and NAD(P)H in age-related neurodegeneration and Alzheimer disease-like mouse neurons. Aging Cell 13 (2014), 631–640.
69. Gilley, J., Coleman, M.P., Endogenous Nmnat2 is an essential survival factor for maintenance of healthy axons. PLoS Biol., 8, 2010, e1000300.
70. Gilley, J., Adalbert, R., Yu, G., Coleman, M.P., Rescue of peripheral and CNS axon defects in mice lacking NMNAT2. J. Neurosci. 33 (2013), 13410–13424.
71. Gomes, A.P., Price, N.L., Ling, A.J., Moslehi, J.J., Montgomery, M.K., Rajman, L., White, J.P., Teodoro, J.S., Wrann, C.D., Hubbard, B.P., Mercken, E.M., Palmeira, C.M., de Cabo, R., Rolo, A.P., Turner, N., Bell, E.L., Sinclair, D.A., Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell 155 (2013), 1624–1638.
72. Gong, B., Pan, Y., Vempati, P., Zhao, W., Knable, L., Ho, L., Wang, J., Sastre, M., Ono, K., Sauve, A.A., Pasinetti, G.M., Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-gamma coactivator 1alpha regulated beta-secretase 1 degradation and mitochondrial gene expression in Alzheimer's mouse models. Neurobiol. Aging 34 (2013), 1581–1588.
73. Grunicke, H.K., Keller, H.J., Pushendorf, B., Benaguid, A., Biosynthesis of nicotinamide adenine dinucleotide in mitochondria. Eur. J. Biochem. 53 (1975), 41–45.
74. Guest, J., Grant, R., Mori, T.A., Croft, K.D., Changes in oxidative damage, inflammation and [NAD(H)] with age in cerebrospinal fluid. PLoS One, 9, 2014, e85335.
75. Hanus, J., Zhang, H., Wang, Z., Liu, Q., Zhou, Q., Wang, S., Induction of necrotic cell death by oxidative stress in retinal pigment epithelial cells. Cell. Death. Dis., 4, 2013, e965.
76. Hara, N., Yamada, K., Shibata, T., Osago, H., Hashimoto, T., Tsuchiya, M., Elevation of cellular NAD levels by nicotinic acid and involvement of nicotinic acid phosphoribosyltransferase in human cells. J. Biol. Chem. 282 (2007), 24574–24582.
77. Harden, A., Young, W.J., The alcoholic herment of yeast-juice. Proc. R. Soc. Lond. B 77 (1906), 405–420.
78. Harman, D., Alzheimer's disease pathogenesis: role of aging. Ann. N. Y. Acad. Sci. 1067 (2006), 454–460.
79. Harries, L.W., MicroRNAs as mediators of the ageing process. Genes (Basel) 5 (2014), 656–670.
80. Hashimoto, T., Horikawa, M., Nomura, T., Sakamoto, K., Nicotinamide adenine dinucleotide extends the lifespan of Caenorhabditis elegans mediated by sir-2.1 and daf-16. Biogerontology 11 (2010), 31–43.
81. Hasmann, M., Schemainda, I., FK866, a highly specific noncompetitive inhibitor of nicotinamide phosphoribosyltransferase, represents a novel mechanism for induction of tumor cell apoptosis. Cancer Res. 63 (2003), 7436–7442.
82. Heilbronn, L.K., Clinical trials corner. Nutr. Healthy Aging 4 (2017), 193–194.
83. Helzner, E.P., Cauley, J.A., Pratt, S.R., Wisniewski, S.R., Zmuda, J.M., Talbott, E.O., de Rekeneire, N., Harris, T.B., Rubin, S.M., Simonsick, E.M., Tylavsky, F.A., Newman, A.B., Race and sex differences in age-related hearing loss: the health, aging and body composition study. J. Am. Geriatr. Soc. 53 (2005), 2119–2127.
84. Herranz, D., Munoz-Martin, M., Canamero, M., Mulero, F., Martinez-Pastor, B., Fernandez-Capetillo, O., Serrano, M., Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer. Nat. Commun., 1, 2010, 3.
85. Hicks, A.N., Lorenzetti, D., Gilley, J., Lu, B., Andersson, K.E., Miligan, C., Overbeek, P.A., Oppenheim, R., Bishop, C.E., Nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2) regulates axon integrity in the mouse embryo. PLoS One, 7, 2012, e47869.
86. Hikosaka, K., Ikutani, M., Shito, M., Kazuma, K., Gulshan, M., Nagai, Y., Takatsu, K., Konno, K., Tobe, K., Kanno, H., Nakagawa, T., Deficiency of nicotinamide mononucleotide adenylyltransferase 3 (nmnat3) causes hemolytic anemia by altering the glycolytic flow in mature erythrocytes. J. Biol. Chem. 289 (2014), 14796–14811.
87. Hoffmann, J., Romey, R., Fink, C., Yong, L., Roeder, T., Overexpression of Sir2 in the adult fat body is sufficient to extend lifespan of male and female Drosophila. Aging (Albany NY) 5 (2013), 315–327.
88. Hogeboom, G.H., Schneider, W.C., Cytochemical studies. VI. The synthesis of diphosphopyridine nucleotide by liver cell nuclei. J. Biol. Chem. 197 (1952), 611–620.
89. Hood, S., Amir, S., The aging clock: circadian rhythms and later life. J. Clin. Invest. 127 (2017), 437–446.
90. Hou, Y., Lautrup, S., Cordonnier, S., Wang, Y., Croteau, D.L., Zavala, E., Zhang, Y., Moritoh, K., O'Connell, J.F., Baptiste, B.A., Stevnsner, T.V., Mattson, M.P., Bohr, V.A., NAD(+) supplementation normalizes key Alzheimer's features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency. Proc. Natl. Acad. Sci. U. S. A. 115 (2018), E1876–E1885.
91. Houtkooper, R.H., Pirinen, E., Auwerx, J., Sirtuins as regulators of metabolism and healthspan. Nat. Rev. Mol. Cell Biol. 13 (2012), 225–238.
92. Howell, G.R., Libby, R.T., Jakobs, T.C., Smith, R.S., Phalan, F.C., Barter, J.W., Barbay, J.M., Marchant, J.K., Mahesh, N., Porciatti, V., Whitmore, A.V., Masland, R.H., John, S.W., Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma. J. Cell Biol. 179 (2007), 1523–1537.
93. Idelson, M., Alper, R., Obolensky, A., Ben-Shushan, E., Hemo, I., Yachimovich-Cohen, N., Khaner, H., Smith, Y., Wiser, O., Gropp, M., Cohen, M.A., Even-Ram, S., Berman-Zaken, Y., Matzrafi, L., Rechavi, G., Banin, E., Reubinoff, B., Directed differentiation of human embryonic stem cells into functional retinal pigment epithelium cells. Cell Stem Cell 5 (2009), 396–408.
94. Ingram, D.K., de Cabo, R., Calorie restriction in rodents: caveats to consider. Ageing Res. Rev. 39 (2017), 15–28.
95. Itoh, M., Ishihara, K., Hiroi, T., Lee, B.O., Maeda, H., Iijima, H., Yanagita, M., Kiyono, H., Hirano, T., Deletion of bone marrow stromal cell antigen-1 (CD157) gene impaired systemic thymus independent-2 antigen-induced IgG3 and mucosal TD antigen-elicited IgA responses. J. Immunol. 161 (1998), 3974–3983.
96. Ivanisevic, J., Stauch, K.L., Petrascheck, M., Benton, H.P., Epstein, A.A., Fang, M., Gorantla, S., Tran, M., Hoang, L., Kurczy, M.E., Boska, M.D., Gendelman, H.E., Fox, H.S., Siuzdak, G., Metabolic drift in the aging brain. Aging (Albany NY) 8 (2016), 1000–1020.
97. Jaleel, A., Aheed, B., Jaleel, S., Majeed, R., Zuberi, A., Khan, S., Ahmed, B., Shoukat, F., Hashim, H., Association of adipokines with obesity in children and adolescents. Biomark. Med. 7 (2013), 731–735.
98. Jiao, X., Doamekpor, S.K., Bird, J.G., Nickels, B.E., Tong, L., Hart, R.P., Kiledjian, M., 5’ end nicotinamide adenine dinucleotide cap in human cells promotes RNA decay through DXO-mediated deNADding. Cell 168 (2017), 1015–1027 e1010.
99. Jonas, J.B., Aung, T., Bourne, R.R., Bron, A.M., Ritch, R., Panda-Jonas, S., Glaucoma. Lancet 390 (2017), 2183–2193.
100. Kaeberlein, M., McVey, M., Guarente, L., The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev. 13 (1999), 2570–2580.
101. Kaminska, A., Kopczynska, E., Bronisz, A., Zmudzinska, M., Bielinski, M., Borkowska, A., Tyrakowski, T., Junik, R., An evaluation of visfatin levels in obese subjects. Endokrynol. Pol. 61 (2010), 169–173.
102. Kanai, M., Funakoshi, H., Takahashi, H., Hayakawa, T., Mizuno, S., Matsumoto, K., Nakamura, T., Tryptophan 2,3-dioxygenase is a key modulator of physiological neurogenesis and anxiety-related behavior in mice. Mol. Brain, 2, 2009, 8.
103. Kanfi, Y., Naiman, S., Amir, G., Peshti, V., Zinman, G., Nahum, L., Bar-Joseph, Z., Cohen, H.Y., The sirtuin SIRT6 regulates lifespan in male mice. Nature 483 (2012), 218–221.
104. Katsyuba, E., Auwerx, J., Modulating NAD(+) metabolism, from bench to bedside. EMBO J. 36 (2017), 2670–2683.
105. Kim, M.Y., Zhang, T., Kraus, W.L., Poly(ADP-ribosyl)ation by PARP-1: ‘PAR-laying’ NAD+ into a nuclear signal. Genes Dev. 19 (2005), 1951–1967.
106. Kitani, T., Okuno, S., Fujisawa, H., Growth phase-dependent changes in the subcellular localization of pre-B-cell colony-enhancing factor. FEBS Lett. 544 (2003), 74–78.
107. Kitaoka, Y., Munemasa, Y., Kojima, K., Hirano, A., Ueno, S., Takagi, H., Axonal protection by Nmnat3 overexpression with involvement of autophagy in optic nerve degeneration. Cell. Death. Dis., 4, 2013, e860.
108. Klempin, F., Kempermann, G., Adult hippocampal neurogenesis and aging. Eur. Arch. Psychiatry Clin. Neurosci. 257 (2007), 271–280.
109. Koenekoop, R.K., Wang, H., Majewski, J., Wang, X., Lopez, I., Ren, H., Chen, Y., Li, Y., Fishman, G.A., Genead, M., Schwartzentruber, J., Solanki, N., Traboulsi, E.I., Cheng, J., Logan, C.V., McKibbin, M., Hayward, B.E., Parry, D.A., Johnson, C.A., Nageeb, M., Finding of Rare Disease Genes Canada, C., Poulter, J.A., Mohamed, M.D., Jafri, H., Rashid, Y., Taylor, G.R., Keser, V., Mardon, G., Xu, H., Inglehearn, C.F., Fu, Q., Toomes, C., Chen, R., Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration. Nat. Genet. 44 (2012), 1035–1039.
110. Koltai, E., Szabo, Z., Atalay, M., Boldogh, I., Naito, H., Goto, S., Nyakas, C., Radak, Z., Exercise alters SIRT1, SIRT6, NAD and NAMPT levels in skeletal muscle of aged rats. Mech. Ageing Dev. 131 (2010), 21–28.
111. Kosaka, A., Spivey, H.O., Gholson, R.K., Nicotinate phosphoribosyltransferase of yeast: purification and properties. J. Biol. Chem. 246 (1971), 3277–3283.
112. Kourtis, N., Tavernarakis, N., Cellular stress response pathways and ageing: intricate molecular relationships. EMBO J. 30 (2011), 2520–2531.
113. Kover, K., Tong, P.Y., Watkins, D., Clements, M., Stehno-Bittel, L., Novikova, L., Bittel, D., Kibiryeva, N., Stuhlsatz, J., Yan, Y., Ye, S.Q., Moore, W.V., Expression and regulation of nampt in human islets. PLoS One, 8, 2013, e58767.
114. Kralisch, S., Klein, J., Lossner, U., Bluher, M., Paschke, R., Stumvoll, M., Fasshauer, M., Interleukin-6 is a negative regulator of visfatin gene expression in 3T3-L1 adipocytes. Am. J. Physiol. Endocrinol. Metab. 289 (2005), E586–590.
115. Krishnaswamy, K., Bapurao, S., Effect of leucine at different levels of pyridoxine on hepatic quinolinate phosphoribosyl transferase (EC 2.4.2.19) and leucine aminotransferase (EC 2.6.1.6) in rats. Br. J. Nutr. 39 (1978), 61–64.
116. Kumazawa, T., Nishimura, K., Kuroda, T., Ono, W., Yamaguchi, C., Katagiri, N., Tsuchiya, M., Masumoto, H., Nakajima, Y., Murayama, A., Kimura, K., Yanagisawa, J., Novel nucleolar pathway connecting intracellular energy status with p53 activation. J. Biol. Chem. 286 (2011), 20861–20869.
117. Lange, R.A., Jacobson, M.K., Synthesis of pyridine nucleotides by mitochondrial fractions of yeast. Biochem. Biophys. Res. Commun. 76 (1976), 424–428.
118. Lee, C.U., Song, E.K., Yoo, C.H., Kwak, Y.K., Han, M.K., Lipopolysaccharide induces CD38 expression and solubilization in J774 macrophage cells. Mol. Cells 34 (2012), 573–576.
119. Li, N., Muthusamy, S., Liang, R., Sarojini, H., Wang, E., Increased expression of miR-34a and miR-93 in rat liver during aging, and their impact on the expression of Mgst1 and Sirt1. Mech. Ageing Dev. 132 (2011), 75–85.
120. Li, J., Bonkowski, M.S., Moniot, S., Zhang, D., Hubbard, B.P., Ling, A.J., Rajman, L.A., Qin, B., Lou, Z., Gorbunova, V., Aravind, L., Steegborn, C., Sinclair, D.A., A conserved NAD(+) binding pocket that regulates protein-protein interactions during aging. Science 355 (2017), 1312–1317.
121. Liang, F.Q., Godley, B.F., Oxidative stress-induced mitochondrial DNA damage in human retinal pigment epithelial cells: a possible mechanism for RPE aging and age-related macular degeneration. Exp. Eye Res. 76 (2003), 397–403.
122. Lin, F.R., Yaffe, K., Xia, J., Xue, Q.L., Harris, T.B., Purchase-Helzner, E., Satterfield, S., Ayonayon, H.N., Ferrucci, L., Simonsick, E.M., Health, A.B.C.S.G., Hearing loss and cognitive decline in older adults. JAMA Intern. Med. 173 (2013), 293–299.
123. Lin, J.B., Kubota, S., Ban, N., Yoshida, M., Santeford, A., Sene, A., Nakamura, R., Zapata, N., Kubota, M., Tsubota, K., Yoshino, J., Imai, S.I., Apte, R.S., NAMPT-mediated NAD(+) biosynthesis is essential for vision in mice. Cell Rep. 17 (2016), 69–85.
124. Liu, F., Arias-Vasquez, A., Sleegers, K., Aulchenko, Y.S., Kayser, M., Sanchez-Juan, P., Feng, B.J., Bertoli-Avella, A.M., van Swieten, J., Axenovich, T.I., Heutink, P., van Broeckhoven, C., Oostra, B.A., van Duijn, C.M., A genomewide screen for late-onset Alzheimer disease in a genetically isolated Dutch population. Am. J. Hum. Genet. 81 (2007), 17–31.
125. Liu, L.Y., Wang, F., Zhang, X.Y., Huang, P., Lu, Y.B., Wei, E.Q., Zhang, W.P., Nicotinamide phosphoribosyltransferase may be involved in age-related brain diseases. PLoS One, 7, 2012, e44933.
126. Liu, L., Su, X., Quinn, W.J. 3rd, Hui, S., Krukenberg, K., Frederick, D.W., Redpath, P., Zhan, L., Chellappa, K., White, E., Migaud, M., Mitchison, T.J., Baur, J.A., Rabinowitz, J.D., Quantitative analysis of NAD synthesis-breakdown fluxes. Cell Metab. 27 (2018), 1067–1080.
127. Ljungberg, M.C., Ali, Y.O., Zhu, J., Wu, C.S., Oka, K., Zhai, R.G., Lu, H.C., CREB-activity and nmnat2 transcription are down-regulated prior to neurodegeneration, while NMNAT2 over-expression is neuroprotective, in a mouse model of human tauopathy. Hum. Mol. Genet. 21 (2012), 251–267.
128. Long, A.N., Owens, K., Schlappal, A.E., Kristian, T., Fishman, P.S., Schuh, R.A., Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits in an Alzheimer's disease-relevant murine model. BMC Neurol., 15, 2015, 19.
129. Lunn, E.R., Perry, V.H., Brown, M.C., Rosen, H., Gordon, S., Absence of wallerian degeneration does not hinder regeneration in peripheral nerve. Eur. J. Neurosci. 1 (1989), 27–33.
130. Lyon, M.F., Ogunkolade, B.W., Brown, M.C., Atherton, D.J., Perry, V.H., A gene affecting Wallerian nerve degeneration maps distally on mouse chromosome 4. Proc. Natl. Acad. Sci. U. S. A. 90 (1993), 9717–9720.
131. Mack, T.G., Reiner, M., Beirowski, B., Mi, W., Emanuelli, M., Wagner, D., Thomson, D., Gillingwater, T., Court, F., Conforti, L., Fernando, F.S., Tarlton, A., Andressen, C., Addicks, K., Magni, G., Ribchester, R.R., Perry, V.H., Coleman, M.P., Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene. Nat. Neurosci. 4 (2001), 1199–1206.
132. Magni, G., Amici, A., Emanuelli, M., Orsomando, G., Raffaelli, N., Ruggieri, S., Enzymology of NAD+ homeostasis in man. Cell. Mol. Life Sci. 61 (2004), 19–34.
133. Malavasi, F., Deaglio, S., Funaro, A., Ferrero, E., Horenstein, A.L., Ortolan, E., Vaisitti, T., Aydin, S., Evolution and function of the ADP ribosyl cyclase/CD38 gene family in physiology and pathology. Physiol. Rev. 88 (2008), 841–886.
134. Mandai, M., Watanabe, A., Kurimoto, Y., Hirami, Y., Morinaga, C., Daimon, T., Fujihara, M., Akimaru, H., Sakai, N., Shibata, Y., Terada, M., Nomiya, Y., Tanishima, S., Nakamura, M., Kamao, H., Sugita, S., Onishi, A., Ito, T., Fujita, K., Kawamata, S., Go, M.J., Shinohara, C., Hata, K.I., Sawada, M., Yamamoto, M., Ohta, S., Ohara, Y., Yoshida, K., Kuwahara, J., Kitano, Y., Amano, N., Umekage, M., Kitaoka, F., Tanaka, A., Okada, C., Takasu, N., Ogawa, S., Yamanaka, S., Takahashi, M., Autologous induced stem-cell-derived retinal cells for macular degeneration. N. Engl. J. Med. 376 (2017), 1038–1046.
135. Martens, C.R., Denman, B.A., Mazzo, M.R., Armstrong, M.L., Reisdorph, N., McQueen, M.B., Chonchol, M., Seals, D.R., Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD(+) in healthy middle-aged and older adults. Nat. Commun., 9, 2018, 1286.
136. Maruotti, J., Sripathi, S.R., Bharti, K., Fuller, J., Wahlin, K.J., Ranganathan, V., Sluch, V.M., Berlinicke, C.A., Davis, J., Kim, C., Zhao, L., Wan, J., Qian, J., Corneo, B., Temple, S., Dubey, R., Olenyuk, B.Z., Bhutto, I., Lutty, G.A., Zack, D.J., Small-molecule-directed, efficient generation of retinal pigment epithelium from human pluripotent stem cells. Proc. Natl. Acad. Sci. U. S. A. 112 (2015), 10950–10955.
137. Massudi, H., Grant, R., Braidy, N., Guest, J., Farnsworth, B., Guillemin, G.J., Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS One, 7, 2012, e42357.
138. Mayer, P.R., Huang, N., Dewey, C.M., Dries, D.R., Zhang, H., Yu, G., Expression, localization, and biochemical characterization of nicotinamide mononucleotide adenylyltransferase 2. J. Biol. Chem. 285 (2010), 40387–40396.
139. Mazucanti, C.H., Cabral-Costa, J.V., Vasconcelos, A.R., Andreotti, D.Z., Scavone, C., Kawamoto, E.M., Longevity pathways (mTOR, SIRT, insulin/IGF-1) as key modulatory targets on aging and neurodegeneration. Curr. Top. Med. Chem. 15 (2015), 2116–2138.
140. McClure, J.M., Wierman, M.B., Maqani, N., Smith, J.S., Isonicotinamide enhances Sir2 protein-mediated silencing and longevity in yeast by raising intracellular NAD+ concentration. J. Biol. Chem. 287 (2012), 20957–20966.
141. Metz, R., Duhadaway, J.B., Kamasani, U., Laury-Kleintop, L., Muller, A.J., Prendergast, G.C., Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical target of the antitumor indoleamine 2,3-dioxygenase inhibitory compound D-1-methyl-tryptophan. Cancer Res. 67 (2007), 7082–7087.
142. Milde, S., Coleman, M.P., Identification of palmitoyltransferase and thioesterase enzymes that control the subcellular localization of axon survival factor nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2). J. Biol. Chem. 289 (2014), 32858–32870.
143. Milde, S., Fox, A.N., Freeman, M.R., Coleman, M.P., Deletions within its subcellular targeting domain enhance the axon protective capacity of Nmnat2 in vivo. Sci. Rep., 3, 2013, 2567.
144. Milde, S., Gilley, J., Coleman, M.P., Subcellular localization determines the stability and axon protective capacity of axon survival factor Nmnat2. PLoS Biol., 11, 2013, e1001539.
145. Miller, K.N., Burhans, M.S., Clark, J.P., Howell, P.R., Polewski, M.A., DeMuth, T.M., Eliceiri, K.W., Lindstrom, M.J., Ntambi, J.M., Anderson, R.M., Aging and caloric restriction impact adipose tissue, adiponectin, and circulating lipids. Aging Cell 16 (2017), 497–507.
146. Mills, K.F., Yoshida, S., Stein, L.R., Grozio, A., Kubota, S., Sasaki, Y., Redpath, P., Migaud, M.E., Apte, R.S., Uchida, K., Yoshino, J., Imai, S.I., Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Cell Metab. 24 (2016), 795–806.
147. Mitchell, S.J., Bernier, M., Aon, M.A., Cortassa, S., Kim, E.Y., Fang, E.F., Palacios, H.H., Ali, A., Navas-Enamorado, I., Di Francesco, A., Kaiser, T.A., Waltz, T.B., Zhang, N., Ellis, J.L., Elliott, P.J., Frederick, D.W., Bohr, V.A., Schmidt, M.S., Brenner, C., Sinclair, D.A., Sauve, A.A., Baur, J.A., de Cabo, R., Nicotinamide improves aspects of healthspan, but not lifespan, in mice. Cell Metab. 27 (2018), 667–676 e664.
148. Monteiro, R., Azevedo, I., Chronic inflammation in obesity and the metabolic syndrome. Mediators Inflamm., 2010, 2010.
149. Mori, V., Amici, A., Mazzola, F., Di Stefano, M., Conforti, L., Magni, G., Ruggieri, S., Raffaelli, N., Orsomando, G., Metabolic profiling of alternative NAD biosynthetic routes in mouse tissues. PLoS One, 9, 2014, e113939.
150. Mouchiroud, L., Houtkooper, R.H., Moullan, N., Katsyuba, E., Ryu, D., Canto, C., Mottis, A., Jo, Y.S., Viswanathan, M., Schoonjans, K., Guarente, L., Auwerx, J., The NAD(+)/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell 154 (2013), 430–441.
151. Murayama, A., Ohmori, K., Fujimura, A., Minami, H., Yasuzawa-Tanaka, K., Kuroda, T., Oie, S., Daitoku, H., Okuwaki, M., Nagata, K., Fukamizu, A., Kimura, K., Shimizu, T., Yanagisawa, J., Epigenetic control of rDNA loci in response to intracellular energy status. Cell 133 (2008), 627–639.
152. Musiek, E.S., Xiong, D.D., Patel, T., Sasaki, Y., Wang, Y., Bauer, A.Q., Singh, R., Finn, S.L., Culver, J.P., Milbrandt, J., Holtzman, D.M., Nmnat1 protects neuronal function without altering phospho-tau pathology in a mouse model of tauopathy. Ann. Clin. Transl. Neurol. 3 (2016), 434–442.
153. Musso, T., Deaglio, S., Franco, L., Calosso, L., Badolato, R., Garbarino, G., Dianzani, U., Malavasi, F., CD38 expression and functional activities are up-regulated by IFN-gamma on human monocytes and monocytic cell lines. J. Leukoc. Biol. 69 (2001), 605–612.
154. Nakahata, Y., Kaluzova, M., Grimaldi, B., Sahar, S., Hirayama, J., Chen, D., Guarente, L.P., Sassone-Corsi, P., The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell 134 (2008), 329–340.
155. Nakahata, Y., Sahar, S., Astarita, G., Kaluzova, M., Sassone-Corsi, P., Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1. Science 324 (2009), 654–657.
156. Nakajima, T.E., Yamada, Y., Hamano, T., Furuta, K., Gotoda, T., Katai, H., Kato, K., Hamaguchi, T., Shimada, Y., Adipocytokine levels in gastric cancer patients: resistin and visfatin as biomarkers of gastric cancer. J. Gastroenterol. 44 (2009), 685–690.
157. Nakamura, T., Niimi, S., Nawa, K., Noda, C., Ichihara, A., Takagi, Y., Anai, M., Sakaki, Y., Multihormonal regulation of transcription of the tryptophan 2,3-dioxygenase gene in primary cultures of adult rat hepatocytes with special reference to the presence of a transcriptional protein mediating the action of glucocorticoids. J. Biol. Chem. 262 (1987), 727–733.
158. Nash, B.M., Symes, R., Goel, H., Dinger, M.E., Bennetts, B., Grigg, J.R., Jamieson, R.V., NMNAT1 variants cause cone and cone-rod dystrophy. Eur. J. Hum. Genet., 2017.
159. Nickells, R.W., Howell, G.R., Soto, I., John, S.W., Under pressure: cellular and molecular responses during glaucoma, a common neurodegeneration with axonopathy. Annu. Rev. Neurosci. 35 (2012), 153–179.
160. Nikiforov, A., Dolle, C., Niere, M., Ziegler, M., Pathways and subcellular compartmentation of NAD biosynthesis in human cells: from entry of extracellular precursors to mitochondrial NAD generation. J. Biol. Chem. 286 (2011), 21767–21778.
161. Ohnishi, T., Matsuda, H., Tabira, T., Asada, T., Uno, M., Changes in brain morphology in Alzheimer disease and normal aging: is Alzheimer disease an exaggerated aging process?. AJNR Am. J. Neuroradiol. 22 (2001), 1680–1685.
162. Opitz, C.A., Litzenburger, U.M., Sahm, F., Ott, M., Tritschler, I., Trump, S., Schumacher, T., Jestaedt, L., Schrenk, D., Weller, M., Jugold, M., Guillemin, G.J., Miller, C.L., Lutz, C., Radlwimmer, B., Lehmann, I., von Deimling, A., Wick, W., Platten, M., An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature 478 (2011), 197–203.
163. Orsomando, G., Cialabrini, L., Amici, A., Mazzola, F., Ruggieri, S., Conforti, L., Janeckova, L., Coleman, M.P., Magni, G., Simultaneous single-sample determination of NMNAT isozyme activities in mouse tissues. PLoS One, 7, 2012, e53271.
164. Peek, C.B., Affinati, A.H., Ramsey, K.M., Kuo, H.Y., Yu, W., Sena, L.A., Ilkayeva, O., Marcheva, B., Kobayashi, Y., Omura, C., Levine, D.C., Bacsik, D.J., Gius, D., Newgard, C.B., Goetzman, E., Chandel, N.S., Denu, J.M., Mrksich, M., Bass, J., Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice. Science, 342, 2013, 1243417.
165. Perez, P., Bao, J., Why do hair cells and spiral ganglion neurons in the cochlea die during aging?. Aging Dis. 2 (2011), 231–241.
166. Perrault, I., Hanein, S., Zanlonghi, X., Serre, V., Nicouleau, M., Defoort-Delhemmes, S., Delphin, N., Fares-Taie, L., Gerber, S., Xerri, O., Edelson, C., Goldenberg, A., Duncombe, A., Le Meur, G., Hamel, C., Silva, E., Nitschke, P., Calvas, P., Munnich, A., Roche, O., Dollfus, H., Kaplan, J., Rozet, J.M., Mutations in NMNAT1 cause Leber congenital amaurosis with early-onset severe macular and optic atrophy. Nat. Genet. 44 (2012), 975–977.
167. Petrash, J.M., Aging and age-related diseases of the ocular lens and vitreous body. Invest. Ophthalmol. Vis. Sci. 54 (2013), ORSF54–59.
168. Petrzilka, S., Taraborrelli, C., Cavadini, G., Fontana, A., Birchler, T., Clock gene modulation by TNF-alpha depends on calcium and p38 MAP kinase signaling. J. Biol. Rhythms 24 (2009), 283–294.
169. Poulose, S.M., Miller, M.G., Scott, T., Shukitt-Hale, B., Nutritional factors affecting adult neurogenesis and cognitive function. Adv. Nutr. 8 (2017), 804–811.
170. Pugh, T.D., Conklin, M.W., Evans, T.D., Polewski, M.A., Barbian, H.J., Pass, R., Anderson, B.D., Colman, R.J., Eliceiri, K.W., Keely, P.J., Weindruch, R., Beasley, T.M., Anderson, R.M., A shift in energy metabolism anticipates the onset of sarcopenia in rhesus monkeys. Aging Cell 12 (2013), 672–681.
171. Quarona, V., Zaccarello, G., Chillemi, A., Brunetti, E., Singh, V.K., Ferrero, E., Funaro, A., Horenstein, A.L., Malavasi, F., CD38 and CD157: a long journey from activation markers to multifunctional molecules. Cytometry B Clin. Cytom. 84 (2013), 207–217.
172. Raffaelli, N., Sorci, L., Amici, A., Emanuelli, M., Mazzola, F., Magni, G., Identification of a novel human nicotinamide mononucleotide adenylyltransferase. Biochem. Biophys. Res. Commun. 297 (2002), 835–840.
173. Rajman, L., Chwalek, K., Sinclair, D.A., Therapeutic potential of NAD-boosting molecules: the in vivo evidence. Cell Metab. 27 (2018), 529–547.
174. Ramsey, K.M., Yoshino, J., Brace, C.S., Abrassart, D., Kobayashi, Y., Marcheva, B., Hong, H.K., Chong, J.L., Buhr, E.D., Lee, C., Takahashi, J.S., Imai, S., Bass, J., Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis. Science 324 (2009), 651–654.
175. Ratajczak, J., Joffraud, M., Trammell, S.A., Ras, R., Canela, N., Boutant, M., Kulkarni, S.S., Rodrigues, M., Redpath, P., Migaud, M.E., Auwerx, J., Yanes, O., Brenner, C., Canto, C., NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells. Nat. Commun., 7, 2016, 13103.
176. Revollo, J.R., Grimm, A.A., Imai, S., The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells. J. Biol. Chem. 279 (2004), 50754–50763.
177. Revollo, J.R., Korner, A., Mills, K.F., Satoh, A., Wang, T., Garten, A., Dasgupta, B., Sasaki, Y., Wolberger, C., Townsend, R.R., Milbrandt, J., Kiess, W., Imai, S., Nampt/PBEF/visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme. Cell Metab. 6 (2007), 363–375.
178. Rizki, G., Iwata, T.N., Li, J., Riedel, C.G., Picard, C.L., Jan, M., Murphy, C.T., Lee, S.S., The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet., 7, 2011, e1002235.
179. Rogina, B., Helfand, S.L., Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc. Natl. Acad. Sci. U. S. A. 101 (2004), 15998–16003.
180. Rossi, F., Geiszler, P.C., Meng, W., Barron, M.R., Prior, M., Herd-Smith, A., Loreto, A., Lopez, M.Y., Faas, H., Pardon, M.C., Conforti, L., NAD-biosynthetic enzyme NMNAT1 reduces early behavioral impairment in the htau mouse model of tauopathy. Behav. Brain Res. 339 (2018), 140–152.
181. Saini, J.S., Corneo, B., Miller, J.D., Kiehl, T.R., Wang, Q., Boles, N.C., Blenkinsop, T.A., Stern, J.H., Temple, S., Nicotinamide ameliorates disease phenotypes in a human iPSC model of age-related macular degeneration. Cell Stem Cell 20 (2017), 635–647 e637.
182. Samal, B., Sun, Y., Stearns, G., Xie, C., Suggs, S., McNiece, I., Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor. Mol. Cell. Biol. 14 (1994), 1431–1437.
183. Sasaki, Y., Vohra, B.P., Baloh, R.H., Milbrandt, J., Transgenic mice expressing the Nmnat1 protein manifest robust delay in axonal degeneration in vivo. J. Neurosci. 29 (2009), 6526–6534.
184. Sasaki, T., Kikuchi, O., Shimpuku, M., Susanti, V.Y., Yokota-Hashimoto, H., Taguchi, R., Shibusawa, N., Sato, T., Tang, L., Amano, K., Kitazumi, T., Kuroko, M., Fujita, Y., Maruyama, J., Lee, Y.S., Kobayashi, M., Nakagawa, T., Minokoshi, Y., Harada, A., Yamada, M., Kitamura, T., Hypothalamic SIRT1 prevents age-associated weight gain by improving leptin sensitivity in mice. Diabetologia 57 (2014), 819–831.
185. Sasaki, Y., Margolin, Z., Borgo, B., Havranek, J.J., Milbrandt, J., Characterization of leber congenital amaurosis-associated NMNAT1 mutants. J. Biol. Chem. 290 (2015), 17228–17238.
186. Satoh, A., Brace, C.S., Rensing, N., Cliften, P., Wozniak, D.F., Herzog, E.D., Yamada, K.A., Imai, S., Sirt1 extends life span and delays aging in mice through the regulation of Nk2 homeobox 1 in the DMH and LH. Cell Metab. 18 (2013), 416–430.
187. Scheen, A.J., Diabetes mellitus in the elderly: insulin resistance and/or impaired insulin secretion?. Diabetes Metab., 2005 31 Spec No 2, 5S27-25S34.
188. Schmeisser, K., Mansfeld, J., Kuhlow, D., Weimer, S., Priebe, S., Heiland, I., Birringer, M., Groth, M., Segref, A., Kanfi, Y., Price, N.L., Schmeisser, S., Schuster, S., Pfeiffer, A.F., Guthke, R., Platzer, M., Hoppe, T., Cohen, H.Y., Zarse, K., Sinclair, D.A., Ristow, M., Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide. Nat. Chem. Biol. 9 (2013), 693–700.
189. Smith-Vikos, T., Slack, F.J., MicroRNAs and their roles in aging. J. Cell Sci. 125 (2012), 7–17.
190. Someya, S., Yamasoba, T., Weindruch, R., Prolla, T.A., Tanokura, M., Caloric restriction suppresses apoptotic cell death in the mammalian cochlea and leads to prevention of presbycusis. Neurobiol. Aging 28 (2007), 1613–1622.
191. Someya, S., Yu, W., Hallows, W.C., Xu, J., Vann, J.M., Leeuwenburgh, C., Tanokura, M., Denu, J.M., Prolla, T.A., Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell 143 (2010), 802–812.
192. Son, N., Hur, H.J., Sung, M.J., Kim, M.S., Hwang, J.T., Park, J.H., Yang, H.J., Kwon, D.Y., Yoon, S.H., Chung, H.Y., Kim, H.J., Liquid chromatography-mass spectrometry-based metabolomic analysis of livers from aged rats. J. Proteome Res. 11 (2012), 2551–2558.
193. Song, T., Yang, L., Kabra, N., Chen, L., Koomen, J., Haura, E.B., Chen, J., The NAD+ synthesis enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT1) regulates ribosomal RNA transcription. J. Biol. Chem. 288 (2013), 20908–20917.
194. Sorrentino, V., Romani, M., Mouchiroud, L., Beck, J.S., Zhang, H., D'Amico, D., Moullan, N., Potenza, F., Schmid, A.W., Rietsch, S., Counts, S.E., Auwerx, J., Enhancing mitochondrial proteostasis reduces amyloid-beta proteotoxicity. Nature 552 (2017), 187–193.
195. Stein, L.R., Imai, S., Specific ablation of Nampt in adult neural stem cells recapitulates their functional defects during aging. EMBO J. 33 (2014), 1321–1340.
196. Stein, L.R., Wozniak, D.F., Dearborn, J.T., Kubota, S., Apte, R.S., Izumi, Y., Zorumski, C.F., Imai, S., Expression of Nampt in hippocampal and cortical excitatory neurons is critical for cognitive function. J. Neurosci. 34 (2014), 5800–5815.
197. Stromsdorfer, K.L., Yamaguchi, S., Yoon, M.J., Moseley, A.C., Franczyk, M.P., Kelly, S.C., Qi, N., Imai, S., Yoshino, J., NAMPT-mediated NAD(+) biosynthesis in adipocytes regulates adipose tissue function and multi-organ insulin sensitivity in mice. Cell Rep. 16 (2016), 1851–1860.
198. Stumpferl, S.W., Brand, S.E., Jiang, J.C., Korona, B., Tiwari, A., Dai, J., Seo, J.G., Jazwinski, S.M., Natural genetic variation in yeast longevity. Genome Res. 22 (2012), 1963–1973.
199. Sun, Y., Zhu, S., Wu, Z., Huang, Y., Liu, C., Tang, S., Wei, L., Elevated serum visfatin levels are associated with poor prognosis of hepatocellular carcinoma. Oncotarget 8 (2017), 23427–23435.
200. Tan, B., Young, D.A., Lu, Z.H., Wang, T., Meier, T.I., Shepard, R.L., Roth, K., Zhai, Y., Huss, K., Kuo, M.S., Gillig, J., Parthasarathy, S., Burkholder, T.P., Smith, M.C., Geeganage, S., Zhao, G., Pharmacological inhibition of nicotinamide phosphoribosyltransferase (NAMPT), an enzyme essential for NAD+ biosynthesis, in human cancer cells: metabolic basis and potential clinical implications. J. Biol. Chem. 288 (2013), 3500–3511.
201. Tavanai, E., Mohammadkhani, G., Role of antioxidants in prevention of age-related hearing loss: a review of literature. Eur. Arch. Otorhinolaryngol. 274 (2017), 1821–1834.
202. Terakata, M., Fukuwatari, T., Sano, M., Nakao, N., Sasaki, R., Fukuoka, S., Shibata, K., Establishment of true niacin deficiency in quinolinic acid phosphoribosyltransferase knockout mice. J. Nutr. 142 (2012), 2148–2153.
203. Terakata, M., Fukuwatari, T., Kadota, E., Sano, M., Kanai, M., Nakamura, T., Funakoshi, H., Shibata, K., The niacin required for optimum growth can be synthesized from L-tryptophan in growing mice lacking tryptophan-2,3-dioxygenase. J. Nutr. 143 (2013), 1046–1051.
204. Terra, X., Auguet, T., Quesada, I., Aguilar, C., Luna, A.M., Hernandez, M., Sabench, F., Porras, J.A., Martinez, S., Lucas, A., Pellitero, S., Llutart, J., del Castillo, D., Richart, C., Increased levels and adipose tissue expression of visfatin in morbidly obese women: the relationship with pro-inflammatory cytokines. Clin. Endocrinol. (Oxf.) 77 (2012), 691–698.
205. Tischler, M.E., Friedrichs, D., Coll, K., Williamson, J.R., Pyridine nucleotide distributions and enzyme mass action ratios in hepatocytes from fed and starved rats. Arch. Biochem. Biophys. 184 (1977), 222–236.
206. Tissenbaum, H.A., Guarente, L., Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410 (2001), 227–230.
207. Trammell, S.A., Schmidt, M.S., Weidemann, B.J., Redpath, P., Jaksch, F., Dellinger, R.W., Li, Z., Abel, E.D., Migaud, M.E., Brenner, C., Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat. Commun., 7, 2016, 12948.
208. Trammell, S.A., Weidemann, B.J., Chadda, A., Yorek, M.S., Holmes, A., Coppey, L.J., Obrosov, A., Kardon, R.H., Yorek, M.A., Brenner, C., Nicotinamide riboside opposes type 2 diabetes and neuropathy in mice. Sci. Rep., 6, 2016, 26933.
209. Trammell, S.A., Yu, L., Redpath, P., Migaud, M.E., Brenner, C., Nicotinamide riboside is a major NAD+ precursor vitamin in cow milk. J. Nutr. 146 (2016), 957–963.
210. Tsubota, K., The first human clinical study for NMN has started in Japan. Npj Aging and Mechanisms of Disease, Vol. 2, 2016.
211. Uddin, G.M., Youngson, N.A., Sinclair, D.A., Morris, M.J., Head to head comparison of short-term treatment with the NAD(+) precursor nicotinamide mononucleotide (NMN) and 6 weeks of exercise in obese female mice. Front. Pharmacol., 7, 2016, 258.
212. van der Horst, A., Schavemaker, J.M., Pellis-van Berkel, W., Burgering, B.M., The Caenorhabditis elegans nicotinamidase PNC-1 enhances survival. Mech. Ageing Dev. 128 (2007), 346–349.
213. VanLinden, M.R., Dolle, C., Pettersen, I.K., Kulikova, V.A., Niere, M., Agrimi, G., Dyrstad, S.E., Palmieri, F., Nikiforov, A.A., Tronstad, K.J., Ziegler, M., Subcellular distribution of NAD+ between cytosol and mitochondria determines the metabolic profile of human cells. J. Biol. Chem. 290 (2015), 27644–27659.
214. Viswanathan, M., Guarente, L., Regulation of Caenorhabditis elegans lifespan by sir-2.1 transgenes. Nature 477 (2011), E1–2.
215. Wang, G., Han, T., Nijhawan, D., Theodoropoulos, P., Naidoo, J., Yadavalli, S., Mirzaei, H., Pieper, A.A., Ready, J.M., McKnight, S.L., P7C3 neuroprotective chemicals function by activating the rate-limiting enzyme in NAD salvage. Cell 158 (2014), 1324–1334.
216. Wang, X., Hu, X., Yang, Y., Takata, T., Sakurai, T., Nicotinamide mononucleotide protects against beta-amyloid oligomer-induced cognitive impairment and neuronal death. Brain Res. 1643 (2016), 1–9.
217. Wasko, B.M., Kaeberlein, M., Yeast replicative aging: a paradigm for defining conserved longevity interventions. FEMS Yeast Res. 14 (2014), 148–159.
218. Williams, P.A., Harder, J.M., Foxworth, N.E., Cardozo, B.H., Cochran, K.E., John, S.W.M., Nicotinamide and WLD(S) act together to prevent neurodegeneration in glaucoma. Front. Neurosci., 11, 2017, 232.
219. Williams, P.A., Harder, J.M., Foxworth, N.E., Cochran, K.E., Philip, V.M., Porciatti, V., Smithies, O., John, S.W., Vitamin B3 modulates mitochondrial vulnerability and prevents glaucoma in aged mice. Science 355 (2017), 756–760.
220. Yaku, K., Okabe, K., Nakagawa, T., Simultaneous measurement of NAD metabolome in aged mice tissue using liquid chromatography tandem–mass spectrometry (LC/MS/MS). Biomed. Chromatogr., 32, 2018, e4205.
221. Yamada, M., Mizuguchi, M., Otsuka, N., Ikeda, K., Takahashi, H., Ultrastructural localization of CD38 immunoreactivity in rat brain. Brain Res. 756 (1997), 52–60.
222. Yamada, Y., Arai, T., Sugawara, S., Okato, A., Kato, M., Kojima, S., Yamazaki, K., Naya, Y., Ichikawa, T., Seki, N., Impact of novel oncogenic pathways regulated by antitumor miR-451a in renal cell carcinoma. Cancer Sci. 109 (2018), 1239–1253.
223. Yamakuchi, M., Ferlito, M., Lowenstein, C.J., miR-34a repression of SIRT1 regulates apoptosis. Proc. Natl. Acad. Sci. U. S. A. 105 (2008), 13421–13426.
224. Yamamoto, M., Hikosaka, K., Mahmood, A., Tobe, K., Shojaku, H., Inohara, H., Nakagawa, T., Nmnat3 is dispensable in mitochondrial NAD level maintenance in vivo. PLoS One, 11, 2016, e0147037.
225. Yamamoto, M., Inohara, H., Nakagawa, T., Targeting metabolic pathways for head and neck cancers therapeutics. Cancer Metastasis Rev. 36 (2017), 503–514.
226. Yan, T., Feng, Y., Zheng, J., Ge, X., Zhang, Y., Wu, D., Zhao, J., Zhai, Q., Nmnat2 delays axon degeneration in superior cervical ganglia dependent on its NAD synthesis activity. Neurochem. Int. 56 (2010), 101–106.
227. Yang, H., Yang, T., Baur, J.A., Perez, E., Matsui, T., Carmona, J.J., Lamming, D.W., Souza-Pinto, N.C., Bohr, V.A., Rosenzweig, A., de Cabo, R., Sauve, A.A., Sinclair, D.A., Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival. Cell 130 (2007), 1095–1107.
228. Yao, Z., Yang, W., Gao, Z., Jia, P., Nicotinamide mononucleotide inhibits JNK activation to reverse Alzheimer disease. Neurosci. Lett. 647 (2017), 133–140.
229. Yoon, M.J., Yoshida, M., Johnson, S., Takikawa, A., Usui, I., Tobe, K., Nakagawa, T., Yoshino, J., Imai, S., SIRT1-mediated eNAMPT secretion from adipose tissue regulates hypothalamic NAD+ and function in mice. Cell Metab. 21 (2015), 706–717.
230. Yoshino, J., Mills, K.F., Yoon, M.J., Imai, S., Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 14 (2011), 528–536.
231. Yoshino, J., Baur, J.A., Imai, S.I., NAD(+) intermediates: the biology and therapeutic potential of NMN and NR. Cell Metab. 27 (2017), 513–528.
232. Zalkin, H., NAD synthetase. Methods Enzymol. 113 (1985), 297–302.
233. Zamporlini, F., Ruggieri, S., Mazzola, F., Amici, A., Orsomando, G., Raffaelli, N., Novel assay for simultaneous measurement of pyridine mononucleotides synthesizing activities allows dissection of the NAD(+) biosynthetic machinery in mammalian cells. FEBS J. 281 (2014), 5104–5119.
234. Zhang, X., Kurnasov, O.V., Karthikeyan, S., Grishin, N.V., Osterman, A.L., Zhang, H., Structural characterization of a human cytosolic NMN/NaMN adenylyltransferase and implication in human NAD biosynthesis. J. Biol. Chem. 278 (2003), 13503–13511.
235. Zhang, T., Berrocal, J.G., Frizzell, K.M., Gamble, M.J., DuMond, M.E., Krishnakumar, R., Yang, T., Sauve, A.A., Kraus, W.L., Enzymes in the NAD+ salvage pathway regulate SIRT1 activity at target gene promoters. J. Biol. Chem. 284 (2009), 20408–20417.
236. Zhang, T., Berrocal, J.G., Yao, J., DuMond, M.E., Krishnakumar, R., Ruhl, D.D., Ryu, K.W., Gamble, M.J., Kraus, W.L., Regulation of poly(ADP-ribose) polymerase-1-dependent gene expression through promoter-directed recruitment of a nuclear NAD+ synthase. J. Biol. Chem. 287 (2012), 12405–12416.
237. Zhang, C., Tong, J., Huang, G., Nicotinamide phosphoribosyl transferase (Nampt) is a target of microRNA-26b in colorectal cancer cells. PLoS One, 8, 2013, e69963.
238. Zhang, H., Ryu, D., Wu, Y., Gariani, K., Wang, X., Luan, P., D'Amico, D., Ropelle, E.R., Lutolf, M.P., Aebersold, R., Schoonjans, K., Menzies, K.J., Auwerx, J., NAD(+) repletion improves mitochondrial and stem cell function and enhances life span in mice. Science 352 (2016), 1436–1443.
239. Zhang, L.Q., Van Haandel, L., Xiong, M., Huang, P., Heruth, D.P., Bi, C., Gaedigk, R., Jiang, X., Li, D.Y., Wyckoff, G., Grigoryev, D.N., Gao, L., Li, L., Wu, M., Leeder, J.S., Ye, S.Q., Metabolic and molecular insights into an essential role of nicotinamide phosphoribosyltransferase. Cell. Death. Dis., 8, 2017, e2705.
240. Zhou, C.C., Yang, X., Hua, X., Liu, J., Fan, M.B., Li, G.Q., Song, J., Xu, T.Y., Li, Z.Y., Guan, Y.F., Wang, P., Miao, C.Y., Hepatic NAD(+) deficiency as a therapeutic target for non-alcoholic fatty liver disease in ageing. Br. J. Pharmacol. 173 (2016), 2352–2368.
241. Zhu, Y., Zhang, L., Sasaki, Y., Milbrandt, J., Gidday, J.M., Protection of mouse retinal ganglion cell axons and soma from glaucomatous and ischemic injury by cytoplasmic overexpression of Nmnat1. Invest. Ophthalmol. Vis. Sci. 54 (2013), 25–36.
242. Zhu, X.H., Lu, M., Lee, B.Y., Ugurbil, K., Chen, W., In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences. Proc. Natl. Acad. Sci. U. S. A. 112 (2015), 2876–2881.
243. Zhu, Y., Zhao, K.K., Tong, Y., Zhou, Y.L., Wang, Y.X., Zhao, P.Q., Wang, Z.Y., Exogenous NAD(+) decreases oxidative stress and protects H2O2-treated RPE cells against necrotic death through the up-regulation of autophagy. Sci. Rep., 6, 2016, 26322.