It takes two to tango: Nad+ and sirtuins in aging/longevity control

npj Aging and Mechanisms of Disease

Volumn 2, Issue 1, 2016, Pages

  Imai, Shin Ichiro ^a   Guarente, Leonard ^b  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 85014901935     PISSN: None     EISSN: 20563973     Source Type: Journal    
DOI: 10.1038/npjamd.2016.17     Document Type: Article

References (79)

1. Imai, S., Armstrong, C. M., Kaeberlein, M. & Guarente, L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 403, 795–800 (2000).
2. 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, 31–53 (2015).
3. Imai, S. & Guarente, L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 24, 464–471 (2014).
4. Choudhary, C., Weinert, B. T., Nishida, Y., Verdin, E. & Mann, M. The growing landscape of lysine acetylation links metabolism and cell signalling. Nat. Rev. Mol. Cell Biol. 15, 536–550 (2014).
5. Wagner, G. R. & Hirschey, M. D. Nonenzymatic protein acylation as a carbon stress regulated by sirtuin deacylases. Mol Cell. 54, 5–16 (2014).
6. Feldman, J. L., Dittenhafer-Reed, K. E. & Denu, J. M. Sirtuin catalysis and regulation. J. Biol. Chem. 287, 42419–42427 (2012).
7. Miller, E. S. et al. Complete genome sequence of the broad-host-range vibriophage KVP40: comparative genomics of a T4-related bacteriophage. J. Bacteriol. 185, 5220–5233 (2003).
8. Yoon, M. J. et al. SIRT1-Mediated eNAMPT secretion from adipose tissue regulates hypothalamic NAD(+) and function in mice. Cell Metab. 21, 706–717 (2015).
9. Imai, S. The NAD world: a new systemic regulatory network for metabolism and aging—Sirt1, systemic NAD biosynthesis, and their importance. Cell Biochem. Biophys. 53, 65–74 (2009).
10. Imai, S. ‘Clocks’ in the NAD World: NAD as a metabolic oscillator for the regulation of metabolism and aging. Biochim. Biophys. Acta. 1804, 1584–1590 (2010).
11. Imai, S. Dissecting systemic control of metabolism and aging in the NAD World: the importance of SIRT1 and NAMPT-mediated NAD biosynthesis. FEBS Lett. 585, 1657–1662 (2011).
12. Imai, S. & Yoshino, J. The importance of NAMPT/NAD/SIRT1 in the systemic regulation of metabolism and ageing. Diabetes Obes. Metab. 2013; 15: 26–33.
13. Gazzaniga, F., Stebbins, R., Chang, S. Z., McPeek, M. A. & Brenner, C. Microbial NAD metabolism: lessons from comparative genomics. Microbiol. Mol. Biol. Rev. 73, 529–541 (2009).
14. 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, 181–185 (2003).
15. Balan, V. et al. Life span extension and neuronal cell protection by Drosophila nicotinamidase. J. Biol. Chem. 283, 27810–27819 (2008).
16. 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, 346–349 (2007).
17. Feldman, J. L. et al. Kinetic and structural basis for acyl-group selectivity and NAD(+) dependence in sirtuin-catalyzed deacylation. Biochemistry 54, 3037–3050 (2015).
18. 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, 2570–2580 (1999).
19. Rogina, B. & Helfand, S. L. Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc. Natl. Acad. Sci. USA 101, 15998–16003 (2004).
20. Tissenbaum, H. A. & Guarente, L. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410, 227–230 (2001).
21. Burnett, C. et al. Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature 477, 482–485 (2011).
22. Herranz, D. et al. Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer. Nat. Commun. 1, 3 (2010).
23. Banerjee, K. K. et al. dSir2 in the adult fat body, but not in muscles, regulates life span in a diet-dependent manner. Cell Rep. 2, 1485–1491 (2012).
24. Kanfi, Y.et al. The sirtuin SIRT6 regulates lifespan in male mice. Nature 483, 218–221 (2012).
25. Mouchiroud, L. et al. The NAD(+)/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell 154, 430–441 (2013).
26. Rizki, G. et al. The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7, e1002235 (2011).
27. Satoh, A. et al. Sirt1 extends life span and delays aging in mice through the regulation of Nk2 homeobox 1 in the DMH and LH. Cell Metab. 18, 416–430 (2013).
28. Schmeisser, K. et al. Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide. Nat. Chem. Biol. 9, 693–700 (2013).
29. Stumpferl, S. W. et al. Natural genetic variation in yeast longevity. Genome Res. 22, 1963–1973 (2012).
30. Viswanathan, M. & Guarente, L. Regulation of Caenorhabditis elegans lifespan by sir-2.1 transgenes. Nature 477, E1–E2 (2011).
31. Satoh, A. & Imai, S. Systemic regulation of mammalian ageing and longevity by brain sirtuins. Nat. Commun. 5, 4211 (2014).
32. Giblin, W., Skinner, M. E. & Lombard, D. B. Sirtuins: guardians of mammalian healthspan. Trends Genet. 30, 271–286 (2014).
33. Longo, V. D. et al. Interventions to slow aging in humans: are we ready? Aging Cell 14, 497–510 (2015).
34. Sharples, A. P. et al. Longevity and skeletal muscle mass: the role of IGF signalling, the sirtuins, dietary restriction and protein intake. Aging Cell 14, 511–523 (2015).
35. Lin, S.-J., Defossez, P.-A. & Guarente, L. Life span extension by calorie restriction in S. cerevisiae requires NAD and SIR2. Science 289, 2126–2128 (2000).
36. Kaeberlein, M. et al. Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science 310, 1193–1196 (2005).
37. Bogan, K. L. et al. Identification of Isn1 and Sdt1 as glucose-and vitamin-regulated nicotinamide mononucleotide and nicotinic acid mononucleotide 5′-nucleotidases responsible for production of nicotinamide riboside and nicotinic acid riboside. J. Biol. Chem. 284, 34861–34869 (2009).
38. Lu, S. P., Kato, M. & Lin, S. J. Assimilation of endogenous nicotinamide riboside is essential for calorie restriction-mediated life span extension in Saccharomyces cerevisiae. J. Biol. Chem. 284, 17110–17119 (2009).
39. +. Cell 129, 473–484 (2007).
40. Moroz, N. et al. Dietary restriction involves NAD(+)-dependent mechanisms and a shift toward oxidative metabolism. Aging Cell 13, 1075–1085 (2014).
41. Garten, A., Petzold, S., Korner, A., Imai, S. & Kiess, W. Nampt: linking NAD biology, metabolism and cancer. Trends Endocrinol. Metab. 20, 130–138 (2009).
42. Imai, S. Nicotinamide phosphoribosyltransferase (Nampt): a link between NAD biology, metabolism, and diseases. Curr. Pharm. Des. 15, 20–28 (2009).
43. + salvage pathway by CLOCK-SIRT1. Science 324, 654–657 (2009).
44. Peek, C. B. et al. Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice. Science 342, 1243417 (2013).
45. + biosynthesis. Science 324, 651–654 (2009).
46. 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, 50754–50763 (2004).
47. Yang, H. et al. Nutrient-sensitive mitochondrial NAD(+) levels dictate cell survival. Cell 130, 1095–1107 (2007).
48. Costford, S. R. et al. Skeletal muscle NAMPT is induced by exercise in humans. Am. J. Physiol. Endocrinol. Metab. 298, E117–E126 (2010).
49. Fulco, M. et al. Glucose restriction inhibits skeletal myoblast differentiation by activating SIRT1 through AMPK-mediated regulation of Nampt. Dev. Cell. 14, 661–673 (2008).
50. Nakagawa, T., Lomb, D. J., Haigis, M. C. & Guarente, L. SIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle. Cell 137, 560–570 (2009).
51. Song, J. et al. Nicotinamide phosphoribosyltransferase is required for the calorie restriction-mediated improvements in oxidative stress, mitochondrial biogenesis, and metabolic adaptation. J. Gerontol. A Biol. Sci. Med. Sci. 69, 44–57 (2014).
52. Chang, H. C. & Guarente, L. SIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging. Cell 153, 1448–1460 (2013).
53. Masri, S. et al. Partitioning circadian transcription by SIRT6 leads to segregated control of cellular metabolism. Cell 158, 659–672 (2014).
54. Zhang, G. et al. Hypothalamic programming of systemic ageing involving IKK-beta, NF-kappaB and GnRH. Nature 497, 211–216 (2013).
55. Benedict, C. et al. Diurnal rhythm of circulating nicotinamide phosphoribosyltransferase (Nampt/visfatin/PBEF): impact of sleep loss and relation to glucose metabolism. J. Clin. Endocrinol. Metab. 97, E218–E222 (2012).
56. 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, 528–536 (2011).
57. Gomes, A. P. et al. Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell 155, 1624–1638 (2013).
58. Stein, L. R. & Imai, S. Specific ablation of Nampt in adult neural stem cells recapitulates their functional defects during aging. EMBO J. 33, 1321–1340 (2014).
59. Dahl, T. B. et al. Intracellular nicotinamide phosphoribosyltransferase protects against hepatocyte apoptosis and is down-regulated in nonalcoholic fatty liver disease. J. Clin. Endocrinol. Metab. 95, 3039–3047 (2010).
60. 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, 631–640 (2014).
61. Hsu, C. P., Oka, S., Shao, D., Hariharan, N. & Sadoshima, J. Nicotinamide phosphoribosyltransferase regulates cell survival through NAD+ synthesis in cardiac myocytes. Circ. Res. 105, 481–491 (2009).
62. Jukarainen, S. et al. Obesity is associated with low NAD/SIRT pathway expression in adipose tissue of BMI-discordant monozygotic twins. J. Clin. Endocrinol. Metab. 101, 275–283 (2015).
63. 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, 45099–45107 (2002).
64. Bernofsky, C. Physiology aspects of pyridine nucleotide regulation in mammals. Mol. Cell. Biochem. 33, 135–143 (1980).
65. Catz, P. et al. Simultaneous determination of myristyl nicotinate, nicotinic acid, and nicotinamide in rabbit plasma by liquid chromatography-tandem mass spectrometry using methyl ethyl ketone as a deproteinization solvent. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 829, 123–135 (2005).
66. Jacobson, E. L., Dame, A. J., Pyrek, J. S. & Jacobson, M. K. Evaluating the role of niacin in human carcinogenesis. Biochimie 77, 394–398 (1995).
67. Lin, S.-J., Ford, E., Haigis, M., Liszt, G. & Guarente, L. Calorie restriction extends yeast life span by lowering the level of NADH. Genes Dev. 18, 12–16 (2004).
68. Madsen, A. S. et al. Investigating the sensitivity of NAD+-dependent sirtuin deacylation activities to NADH. J. Biol. Chem. 291, 7128–7141 (2016).
69. Schmidt, M. T., Smith, B. C., Jackson, M. D. & Denu, J. M. Co-enzyme specificity of Sir2 protein deacetylases: Implications for physiological regulation. J. Biol. Chem. 279, 40122–40129 (2004).
70. Feldman, J. L., Baeza, J. & Denu, J. M. Activation of the protein deacetylase SIRT6 by long-chain fatty acids and widespread deacylation by mammalian sirtuins. J. Biol. Chem. 288, 31350–31356 (2013).
71. Bai, P. et al. PARP-1 inhibition increases mitochondrial metabolism through SIRT1 activation. Cell Metab. 13, 461–468 (2011).
72. Barbosa, M. T. et al. The enzyme CD38 (a NAD glycohydrolase, EC 3.2.2.5) is necessary for the development of diet-induced obesity. Faseb J. 21, 3629–3639 (2007).
73. Escande, C. et al. Flavonoid apigenin is an inhibitor of the NAD+ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome. Diabetes 62, 1084–1093 (2013).
74. Brunet, A. et al. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science 303, 2011–2015 (2004).
75. Rodgers, J. T. et al. Nutrient control of glucose homeostasis through a complex of PGC-1a and SIRT1. Nature 434, 113–118 (2005).
76. Papa, L. & Germain, D. SirT3 regulates the mitochondrial unfolded protein response. Mol. Cell. Biol. 34, 699–710 (2014).
77. Zhang, H. et al. NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science, pii: aaf2693; doi:10.1126/science.aaf2693 (28 April 2016).
78. Houtkooper, R. H. et al. Mitonuclear protein imbalance as a conserved longevity mechanism. Nature 497, 451–457 (2013).
79. Satoh, A., Brace, C. S., Rensing, N. & Imai, S. Deficiency of Prdm13, a dorsomedial hypothalamus-enriched gene, mimics age-associated changes in sleep quality and adiposity. Aging Cell 14, 209–218 (2015).