NAD + metabolism: A therapeutic target for age-related metabolic disease
Open accessAbstract
Nicotinamide adenine dinucleotide (NAD) is a central metabolic cofactor by virtue of its redox capacity, and as such regulates a wealth of metabolic transformations. However, the identification of the longevity protein silent regulator 2 (Sir2), the founding member of the sirtuin protein family, as being NAD⁺-dependent reignited interest in this metabolite. The sirtuins (SIRT1-7 in mammals) utilize NAD⁺ to deacetylate proteins in different subcellular compartments with a variety of functions, but with a strong convergence on optimizing mitochondrial function. Since cellular NAD⁺ levels are limiting for sirtuin activity, boosting its levels is a powerful means to activate sirtuins as a potential therapy for mitochondrial, often age-related, diseases. Indeed, supplying excess precursors, or blocking its utilization by poly(ADP-ribose) polymerase (PARP) enzymes or CD38/CD157, boosts NAD⁺ levels, activates sirtuins and promotes healthy aging. Here, we discuss the current state of knowledge of NAD⁺ metabolism, primarily in relation to sirtuin function. We highlight how NAD⁺ levels change in diverse physiological conditions, and how this can be employed as a pharmacological strategy.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Reduced NAD+ downregulates SIRT1, an NAD+-dependent deacetylase involved in mitochondrial homeostasis and XPA repair activity.
“They observed that the reduced level of NAD+ downregulated SIRT1, a NAD+- dependent deacetylase involved in regulating mitochondrial homeostasis and XPA repair activity 91–93.”
From Xeroderma Pigmentosa Group A (XPA), Nucleotide Excision Repair and Regulation by ATR in Response to Ultraviolet Irradiation (2017) · cites this paper as [93]
Nicotinamide riboside, nicotinamide mononucleotide, and nicotinic acid are pursued as strategies to boost metabolic flexibility through increased NAD+ and consequent activation of SIRTs.
“Nicotinamide riboside, nicotinamide mononucleotide, and nicotinic acid are pursued as strategies to boost metabolic flexibility through increased NAD+ and consequent activation of SIRTs (261, 262) (Fig. 5).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [262]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
3 retracted
Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in wistar rats
Braidy, N., Guillemin, G. J., Mansour, H., Chan-Ling, T., Poljak, A., & Grant, R. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019194 · Cited by 594 · cited 1× · see citing works
“Conversely, caloric excess by means of an HFD (Kim et al., 2011), but also aging (Braidy et al., 2011; Yoshino et al., 2011), lead to reduced NAD+ levels.”
BackgroundRetractedRETRACTED: SIRT1 Suppresses β-Amyloid Production by Activating the α-Secretase Gene ADAM10
Dönmez, G., Wang, D., Cohen, D. E., & Guarente, L. (2010) · Cell · doi:10.1016/j.cell.2010.06.020 · Cited by 433 · see citing works
RetractedThe NAD-dependent deacetylase SIRT2 is required for programmed necrosis
Narayan, N., Lee, I. H., Borenstein, R., Sun, J., Wong, R. P., Tong, G., Fergusson, M. M., Liu, J., Rovira, I. I., Cheng, H.-L., et al. (2012) · Nature · doi:10.1038/nature11700 · Cited by 136 · cited 2× · see citing works
“…phosphoenolpyruvate carboxykinase to control gluconeogenesis (Jiang et al., 2011) and was recently shown to deacetylate the receptor-interacting protein-1, and thereby serve as a critical component of the tumor necrosis factor a-mediated programmed necrosis pathway (Narayan et al., 2012).”
BackgroundRetractedCancer chemopreventive activity of resveratrol, a natural product derived from grapes
Jang, M., Cai, L., Udeani, G. O., Slowing, K. V., Thomas, C. F., Beecher, C. W. W., Fong, H. H. S., Farnsworth, N. R., Kinghorn, A. D., Mehta, R. G., et al. (1997) · Science · doi:10.1126/science.275.5297.218 · Cited by 4,935 · cited 2× · see citing works
“Since then resveratrol has been shown to be effective in preventing and delaying the progression of various diseases such as cancer (Jang et al., 1997), cardiovascular disease and glucose intolerance (Timmers et al.”
BackgroundResveratrol improves health and survival of mice on a high-calorie diet
Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., Prabhu, V. V., Allard, J. S., Lopez-Lluch, G., Lewis, K., et al. (2006) · Nature · doi:10.1038/nature05354 · Cited by 4,290 · cited 4× · see citing works
“…several hallmarks of aging, such as reduced inflammatory and apoptotic events in vascular endothelium, limiting the formation of cataracts, preservation of bone density and conservation of motor activity with age (Barger et al., 2008; Baur et al., 2006; Lagouge et al., 2006; Pearson et al., 2008).”
BackgroundInfluentialLagouge, M., Argmann, C., Gerhart-Hines, Z., Meziane, H., Lerin, C., Daussin, F., Messadeq, N., Milne, J., Lambert, P., Elliott, P., et al. (2006) · Cell · doi:10.1016/j.cell.2006.11.013 · Cited by 4,057 · cited 7× · see citing works
“In chow fed mice, resveratrol significantly attenuated several hallmarks of aging, such as reduced inflammatory and apoptotic events in vascular endothelium, limiting the formation of cataracts, preservation of bone density and conservation of motor activity with age (Barger et al., 2008; Baur et al., 2006; Lagouge et…”
BackgroundInfluentialSelf-citationTherapeutic potential of resveratrol: the in vivo evidence
Baur, J. A., & Sinclair, D. A. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2060 · Cited by 3,958 · cited 2× · see citing works
“A few decades later, in 1963, resveratrol was extracted from the roots of another plant, Japanese knotweed (Reynoutria japonica), commonly used in traditional Chinese and Japanese medicine (reviewed in Baur & Sinclair, 2006).”
BackgroundSmall molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan
Howitz, K. T., Bitterman, K. J., Cohen, H. Y., Lamming, D. W., Lavu, S., Wood, J. G., Zipkin, R. E., Chung, P., Kisielewski, A., Zhang, L.-L., et al. (2003) · Nature · doi:10.1038/nature01960 · Cited by 3,796 · cited 5× · see citing works
“The nuclear sirtuin SIRT1 is the best-known member of the family especially after it was described as the target of the polyphenol, resveratrol (Howitz et al., 2003), which is found in low quantities in red wine (see section ‘‘Pharmacological control of NAD+ levels’’).”
BackgroundInfluentialTranscriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
Imai, S.-I., Armstrong, C. M., Kaeberlein, M., & Guarente, L. (2000) · Nature · doi:10.1038/35001622 · Cited by 3,510 · cited 2× · see citing works
“, 1986; Rine & Herskowitz, 1987), which was originally described as a NAD-dependent class III histone deacetylases (Imai et al., 2000).”
BackgroundAMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity
Cantó, C., Gerhart-Hines, Z., Feige, J. N., Lagouge, M., Noriega, L., Milne, J. C., Elliott, P. J., Puigserver, P., & Auwerx, J. (2009) · Nature · doi:10.1038/nature07813 · Cited by 3,300 · cited 2× · see citing works
“During fasting and exercise, the level of NAD+ increases (Canto et al., 2009, 2010).”
BackgroundSelf-citationYang, Y., Li, S., Yang, Q., Shi, Y., Zheng, M., Liu, Y., Chen, F., Song, G., Xu, H., Wan, T., et al. (2014) · Cellular Physiology and Biochemistry · doi:10.1159/000358696 · Cited by 3,262 · see citing works
Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase
Brunet, A., Sweeney, L. B., Sturgill, J. F., Chua, K. F., Greer, P. L., Lin, Y., Tran, H., Ross, S. E., Mostoslavsky, R., Cohen, H. Y., et al. (2004) · Science · doi:10.1126/science.1094637 · Cited by 3,239 · cited 1× · see citing works
“SIRT1 deacetylates histones, but its key activity involves the regulation of mitochondrial biogenesis and stress response through the deacetylation of PGC-1a (Rodgers et al., 2005) and FOXO1 (Brunet et al., 2004; van der Horst et al., 2004).”
BackgroundNutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1
Rodgers, J. T., Lerin, C., Haas, W., Gygi, S. P., Spiegelman, B. M., & Puigserver, P. (2005) · Nature · doi:10.1038/nature03354 · Cited by 3,160 · see citing works
Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy
Egan, D. F., Shackelford, D. B., Mihaylova, M. M., Gelino, S., Kohnz, R. A., Mair, W., Vasquez, D. S., Joshi, A., Gwinn, D. M., Taylor, R., et al. (2011) · Science · doi:10.1126/science.1196371 · Cited by 2,600 · see citing works
Audeh, M. W., Carmichael, J., Penson, R. T., Friedlander, M., Powell, B., Bell-McGuinn, K. M., Scott, C., Weitzel, J. N., Oaknin, A., Loman, N., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60893-8 · Cited by 2,279 · see citing works
Caloric Restriction Delays Disease Onset and Mortality in Rhesus Monkeys
Colman, R. J., Anderson, R. M., Johnson, S. C., Kastman, E. K., Kosmatka, K. J., Beasley, T. M., Allison, D. B., Cruzen, C., Simmons, H. A., Kemnitz, J. W., et al. (2009) · Science · doi:10.1126/science.1173635 · Cited by 2,277 · cited 1× · see citing works
“These observations could explain the conflicting results obtained with CR in non-human primates, where two independent studies – both of which using a different control diet and feeding regimen – showed a different extent of CR health benefits (Colman et al., 2009; Mattison et al., 2012).”
ResultThe Effect of Retarded Growth Upon the Length of Life Span and Upon the Ultimate Body Size
McCay, C. M., Crowell, M. F., & Maynard, L. A. (1935) · The Journal of Nutrition · doi:10.1093/jn/10.1.63 · Cited by 2,264 · cited 1× · see citing works
“It was already known for ages that moderation and composition of diet can influence the aging process (Schafer, 2005), but the modern day founder was Clive McCay, who put its benefits in the scientific spotlight in 1935 (McCay et al., 1989).”
BackgroundKaeberlein, M., McVey, M., & Guarente, L. (1999) · Genes & Development · doi:10.1101/gad.13.19.2570 · Cited by 2,253 · cited 2× · see citing works
“Thus, the increased dosage of SIR2 in yeast prevents the formation of extrachromosomal ribosomal DNA circles and prolongs lifespan, whereas its inhibition has the opposite effect, reducing the replicative lifespan by 50% (Kaeberlein et al., 1999).”
BackgroundMammalian Sirtuins: Biological Insights and Disease Relevance
Haigis, M. C., & Sinclair, D. A. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathol.4.110807.092250 · Cited by 2,085 · cited 2× · see citing works
“Sirtuins are a class of metabolic regulators, of which seven orthologs exist in mammals (Blander & Guarente, 2004; Chalkiadaki & Guarente, 2012; Haigis & Sinclair, 2010; Houtkooper et al., 2012).”
BackgroundInfluentialSirtuins as regulators of metabolism and healthspan
Houtkooper, R. H., Pirinen, E., & Auwerx, J. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3293 · Cited by 2,008 · cited 3× · see citing works
“Sirtuins are a class of metabolic regulators, of which seven orthologs exist in mammals (Blander & Guarente, 2004; Chalkiadaki & Guarente, 2012; Haigis & Sinclair, 2010; Houtkooper et al., 2012).”
BackgroundSelf-citationIncreased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans
Tissenbaum, H. A., & Guarente, L. (2001) · Nature · doi:10.1038/35065638 · Cited by 1,918 · cited 1× · see citing works
“Initial work reported that increased expression of the yeast protein Sir2 and of related sirtuin proteins in Caenorhabditis elegans and D. melanogaster extends lifespan (Rogina & Helfand, 2004; Tissenbaum & Guarente, 2001).”
BackgroundPoly(ADP-ribose): novel functions for an old molecule
Schreiber, V., Dantzer, F., Amé, J., & de MURCIA, G. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1963 · Cited by 1,917 · cited 1× · see citing works
“The nuclear PARP1 accounts for most of the PARP activity in vivo and is the best-studied family member, but critical functions for other PARPs are emerging (Luo & Kraus, 2012; Schreiber et al., 2006).”
BackgroundSirtuin activators mimic caloric restriction and delay ageing in metazoans
Wood, J. G., Rogina, B., Lavu, S., Howitz, K., Helfand, S. L., Tatar, M., & Sinclair, D. (2004) · Nature · doi:10.1038/nature02789 · Cited by 1,868 · cited 2× · see citing works
“1 or Sir2p, respectively)dependent manner (Howitz et al., 2003; Wood et al., 2004), although this is controversial (Bass et al.”
BackgroundLin, S.-J., Defossez, P.-A., & Guarente, L. (2000) · Science · doi:10.1126/science.289.5487.2126 · Cited by 1,775 · cited 4× · see citing works
“…concentration of the growth medium from 2% to 0.5% is sufficient to extend lifespan to a similar level as by overexpressing Sir2, and these effects were dependent on the Sir2 gene or the nicotinate phosphoribosyltransferase-1 gene, which is involved in the biosynthesis of NAD (Lin et al., 2000).”
BackgroundInfluentialPrevalence of impaired glucose tolerance among children and adolescents with marked obesity
Sinha, R., Fisch, G., Teague, B., Tamborlane, W. V., Banyas, B., Allen, K., Savoye, M., Rieger, V., Taksali, S., Barbetta, G., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa012578 · Cited by 1,709 · cited 1× · see citing works
“Since then resveratrol has been shown to be effective in preventing and delaying the progression of various diseases such as cancer (Jang et al., 1997), cardiovascular disease and glucose intolerance (Timmers et al., 2011) and ischemic stroke (Sinha et al., 2002; Wang et al., 2002).”
BackgroundSmall molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes
Milne, J. C., Lambert, P. D., Schenk, S., Carney, D. P., Smith, J. J., Gagne, D. J., Jin, L., Boss, O., Perni, R. B., Vu, C. B., et al. (2007) · Nature · doi:10.1038/nature06261 · Cited by 1,707 · cited 3× · see citing works
“metabolic abnormalities in mice models (Feige et al., 2008; Milne et al., 2007).”
BackgroundSIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation
Hirschey, M. D., Shimazu, T., Goetzman, E., Jing, E., Schwer, B., Lombard, D. B., Grueter, C. A., Harris, C., Biddinger, S., Ilkayeva, O. R., et al. (2010) · Nature · doi:10.1038/nature08778 · Cited by 1,687 · see citing works
Genomic Instability and Aging-like Phenotype in the Absence of Mammalian SIRT6
Mostoslavsky, R., Chua, K. F., Lombard, D. B., Pang, W. W., Fischer, M. R., Gellon, L., Liu, P., Mostoslavsky, G., Franco, S., Murphy, M. M., et al. (2006) · Cell · doi:10.1016/j.cell.2005.11.044 · Cited by 1,637 · cited 3× · see citing works
“Additionally, Sirt6 / mice have reduced insulinlike growth factor 1 levels and are severely hypoglycemic (Mostoslavsky et al., 2006), possibly mediated by the hypoxia-inducible factors-1a-dependent activation of glycolysis and subsequent decreases in glucose levels (Zhong et al.”
BackgroundThe Human Sir2 Ortholog, SIRT2, Is an NAD+-Dependent Tubulin Deacetylase
North, B. J., Marshall, B. L., Borra, M. T., Denu, J. M., & Verdin, E. M. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00038-8 · Cited by 1,542 · cited 1× · see citing works
“The cytosolic SIRT2 was shown to deacetylate tubulin (North et al., 2003), as well as the sterol regulatory element-binding protein-2 (LuthiCarter et al., 2010), although genetic evidence for this latter association is so far lacking.”
BackgroundThe Sir2 Family of Protein Deacetylases
Blander, G., & Guarente, L. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.011303.073651 · Cited by 1,496 · cited 1× · see citing works
“Sirtuins are a class of metabolic regulators, of which seven orthologs exist in mammals (Blander & Guarente, 2004; Chalkiadaki & Guarente, 2012; Haigis & Sinclair, 2010; Houtkooper et al., 2012).”
BackgroundSirt5 Is a NAD-Dependent Protein Lysine Demalonylase and Desuccinylase
Du, J., Zhou, Y., Su, X., Yu, J. J., Khan, S., Jiang, H., Kim, J., Woo, J., Kim, J. H., Choi, B. H., et al. (2011) · Science · doi:10.1126/science.1207861 · Cited by 1,429 · cited 1× · see citing works
“In addition, some of the sirtuins were reported to ADP-ribosylate proteins rather than deacetylate (Haigis et al., 2006), and SIRT5 was shown to act as a demalonylase and desuccinylase (Du et al., 2011; Peng et al., 2011; Wang et al., 2011).”
BackgroundSelf-citationPhylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins
Frye, R. A. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3000 · Cited by 1,409 · cited 3× · see citing works
“1 being the closest homolog of Sir2 (Frye, 2000), and sir-2.”
BackgroundSir2 mediates longevity in the fly through a pathway related to calorie restriction
Rogina, B., & Helfand, S. L. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404184101 · Cited by 1,361 · cited 2× · see citing works
“In the fruitfly Drosophila melanogaster, which expresses five homologs of Sir2 (Frye, 2000), CR extends lifespan and increases dSir2 mRNA expression, but was unable to mediate lifespan extension in flies where dSir2 had been deleted (Rogina & Helfand, 2004).”
BackgroundResveratrol Ameliorates Aging-Related Metabolic Phenotypes by Inhibiting cAMP Phosphodiesterases
Park, S. J., Ahmad, F., Philp, A., Baar, K., Williams, T., Luo, H., Ke, H., Rehmann, H., Taussig, R., Brown, A. L., et al. (2012) · Cell · doi:10.1016/j.cell.2012.01.017 · Cited by 1,352 · see citing works
Yoshino, J., Mills, K. F., Yoon, M. J., & Imai, S.-I. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.08.014 · Cited by 1,340 · cited 4× · see citing works
“Conversely, caloric excess by means of an HFD (Kim et al., 2011), but also aging (Braidy et al., 2011; Yoshino et al., 2011), lead to reduced NAD+ levels.”
BackgroundInfluentialTimmers, S., Konings, E., Bilet, L., Houtkooper, R. H., van de Weijer, T., Goossens, G. H., Hoeks, J., van der Krieken, S., Ryu, D., Kersten, S., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.10.002 · Cited by 1,320 · cited 3× · see citing works
“Importantly and reassuring from a clinical point of view, resveratrol supplementation in obese humans reached beneficial effects at a far lower dose (150 mg/day) (Timmers et al., 2011).”
BackgroundSelf-citationA role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis
Ahn, B.-H., Kim, H.-S., Song, S., Lee, I. H., Liu, J., Vassilopoulos, A., Deng, C.-X., & Finkel, T. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803790105 · Cited by 1,291 · cited 1× · see citing works
“The mitochondrial sirtuins – SIRT3, SIRT4 and SIRT5 – deacetylate protein targets involved in oxidative phosphorylation (Ahn et al., 2008), fatty acid oxidation (Hirschey et al., 2010), ketogenesis (Shimazu et al., 2010), oxidative stress (Someya et al., 2010), glutamate metabolism (Haigis et al.,…”
BackgroundCantó, 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., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.022 · Cited by 1,238 · cited 9× · see citing works
“Indeed, supplementation of NR to cells or mice increases the levels of NAD+ and results in the activation of its downstream signaling cascades (Canto et al., 2012), as will be discussed in more detail below.”
BackgroundInfluentialSelf-citationMammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation
Lombard, D. B., Alt, F. W., Cheng, H.-L., Bunkenborg, J., Streeper, R. S., Mostoslavsky, R., Kim, J., Yancopoulos, G., Valenzuela, D., Murphy, A., et al. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01636-07 · Cited by 1,216 · cited 1× · see citing works
“…do not develop an overt metabolic DOI: 10.3109/10409238.2013.789479 NAD+ in metabolic disease 399 phenotype under basal non-challenged conditions (FernandezMarcos et al., 2012; Haigis et al., 2006; Haigis & Sinclair, 2010; Hirschey et al., 2010; Lombard et al., 2007; Nakagawa et al., 2009).”
BackgroundInfluentialSchulz, T. J., Zarse, K., Voigt, A., Urban, N., Birringer, M., & Ristow, M. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.08.011 · Cited by 1,209 · cited 1× · see citing works
“…studies in worms added a new layer of complexity in this dynamic mechanism, by showing that an early burst of reactive oxygen species (ROS) is required for the induction of the ROS defense pathway and for the lifespan extension under CR conditions (Mouchiroud et al., 2011; Schulz et al., 2007).”
BackgroundHaigis, M. C., Mostoslavsky, R., Haigis, K. M., Fahie, K., Christodoulou, D. C., Murphy, A. J., Valenzuela, D. M., Yancopoulos, G. D., Karow, M., Blander, G., et al. (2006) · Cell · doi:10.1016/j.cell.2006.06.057 · Cited by 1,162 · cited 5× · see citing works
“than deacetylate (Haigis et al., 2006), and SIRT5 was shown to act as a demalonylase and desuccinylase (Du et al.”
BackgroundInfluentialPearson, K. J., Baur, J. A., Lewis, K. N., Peshkin, L., Price, N. L., Labinskyy, N., Swindell, W. R., Kamara, D., Minor, R. K., Perez, E., et al. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.06.011 · Cited by 1,162 · cited 3× · see citing works
“…several hallmarks of aging, such as reduced inflammatory and apoptotic events in vascular endothelium, limiting the formation of cataracts, preservation of bone density and conservation of motor activity with age (Barger et al., 2008; Baur et al., 2006; Lagouge et al., 2006; Pearson et al., 2008).”
BackgroundSomeya, S., Yu, W., Hallows, W. C., Xu, J., Vann, J. M., Leeuwenburgh, C., Tanokura, M., Denu, J. M., & Prolla, T. A. (2010) · Cell · doi:10.1016/j.cell.2010.10.002 · Cited by 1,150 · cited 2× · see citing works
“…in oxidative phosphorylation (Ahn et al., 2008), fatty acid oxidation (Hirschey et al., 2010), ketogenesis (Shimazu et al., 2010), oxidative stress (Someya et al., 2010), glutamate metabolism (Haigis et al., 2006), urea cycle (Nakagawa et al., 2009), as well as several other mitochondrial…”
BackgroundImpact of caloric restriction on health and survival in rhesus monkeys from the NIA study
Mattison, J. A., Roth, G. S., Beasley, T. M., Tilmont, E. M., Handy, A. M., Herbert, R. L., Longo, D. L., Allison, D. B., Young, J. E., Bryant, M., et al. (2012) · Nature · doi:10.1038/nature11432 · Cited by 1,145 · cited 1× · see citing works
“These observations could explain the conflicting results obtained with CR in non-human primates, where two independent studies – both of which using a different control diet and feeding regimen – showed a different extent of CR health benefits (Colman et al., 2009; Mattison et al., 2012).”
ResultGelmon, K. A., Tischkowitz, M. D., MacKay, H. J., Swenerton, K. D., Robidoux, A., Tonkin, K. S., Hirte, H. W., Huntsman, D. D., Clemons, M. J., Gilks, C. B., et al. (2011) · The Lancet Oncology · doi:10.1016/s1470-2045(11)70214-5 · Cited by 1,117 · cited 1× · see citing works
“While PARP inhibitors have not yet been tested for metabolic effects, their clinical development for cancer therapy could provide interesting opportunities in this direction (Audeh et al., 2010; Gelmon et al., 2011).”
BackgroundThe Cell Non-Autonomous Nature of Electron Transport Chain-Mediated Longevity
Durieux, J., Wolff, S., & Dillin, A. (2011) · Cell · doi:10.1016/j.cell.2010.12.016 · Cited by 1,059 · cited 2× · see citing works
“…new evidence suggest that other pro-longevity pathways, induced by CR and/or stress conditions, could also potentially involve SIRT1, such as mitophagy, mitochondrial dynamics (fission/fusion) and mitochondrial unfolded response (Durieux et al., 2011; Egan et al., 2011; Yang et al., 2011).”
BackgroundThe Histone Deacetylase Sirt6 Regulates Glucose Homeostasis via Hif1α
Zhong, L., D'Urso, A., Toiber, D., Sebastian, C., Henry, R. E., Vadysirisack, D. D., Guimaraes, A., Marinelli, B., Wikstrom, J. D., Nir, T., et al. (2010) · Cell · doi:10.1016/j.cell.2009.12.041 · Cited by 1,001 · cited 2× · see citing works
“Additionally, Sirt6 / mice have reduced insulinlike growth factor 1 levels and are severely hypoglycemic (Mostoslavsky et al., 2006), possibly mediated by the hypoxia-inducible factors-1a-dependent activation of glycolysis and subsequent decreases in glucose levels (Zhong et al., 2010).”
BackgroundSirt1 protects against high-fat diet-induced metabolic damage
Pfluger, P. T., Herranz, D., Velasco-Miguel, S., Serrano, M., & Tschöp, M. H. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802917105 · Cited by 932 · cited 1× · see citing works
“…the Sirt1 gene, exhibit a range of features that are reminiscent of the phenotypes seen in CR mice, as they are lighter and metabolically more active, show improved glucose homeostasis and develop less cancer (Banks et al., 2008; Bordone et al., 2007; Herranz et al., 2010; Pfluger et al., 2008).”
BackgroundCantó, C., Jiang, L. Q., Deshmukh, A. S., Mataki, C., Coste, A., Lagouge, M., Zierath, J. R., & Auwerx, J. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.02.006 · Cited by 921 · cited 6× · see citing works
“…the ATP synthase complex in the oxidative phosphorylation (Zheng & Ramirez, 2000), it was hypothesized that the effects of resveratrol could be mediated by activation of the AMPK, rather than direct SIRT1 activation (Beher et al., 2009; Canto et al., 2010; Pacholec et al., 2010; Um et al., 2010).”
BackgroundInfluentialSelf-citationSRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1
Pacholec, M., Bleasdale, J. E., Chrunyk, B., Cunningham, D., Flynn, D., Garofalo, R. S., Griffith, D., Griffor, M., Loulakis, P., Pabst, B., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.088682 · Cited by 915 · cited 3× · see citing works
“…the ATP synthase complex in the oxidative phosphorylation (Zheng & Ramirez, 2000), it was hypothesized that the effects of resveratrol could be mediated by activation of the AMPK, rather than direct SIRT1 activation (Beher et al., 2009; Canto et al., 2010; Pacholec et al., 2010; Um et al., 2010).”
BackgroundNampt/PBEF/Visfatin Regulates Insulin Secretion in β Cells as a Systemic NAD Biosynthetic Enzyme
Revollo, J. R., Körner, A., Mills, K. F., Satoh, A., Wang, T., Garten, A., Dasgupta, B., Sasaki, Y., Wolberger, C., Townsend, R. R., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.09.003 · Cited by 911 · cited 4× · see citing works
“levels in brown adipose tissue, at least in female mice, was shown to impair glucose-stimulated insulin secretion (Revollo et al., 2007).”
BackgroundInfluentialThe secret life of NAD+: an old metabolite controlling new metabolic signaling pathways
Houtkooper, R. H., Cantó, C., Wanders, R. J., & Auwerx, J. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0026 · Cited by 899 · see citing works
Self-citationThe many faces of insulin-like peptide signalling in the brain
Fernandez, A. M., & Torres-Alemán, I. (2012) · Nature reviews. Neuroscience · doi:10.1038/nrn3209 · Cited by 872 · see citing works
Pace-Asciak, C. R., Hahn, S., Diamandis, E. P., Soleas, G. J., & Goldberg, D. M. (1995) · Clinica Chimica Acta · doi:10.1016/0009-8981(95)06045-1 · Cited by 871 · cited 1× · see citing works
“Resveratrol has attracted the attention of the scientific community when it was demonstrated that this molecule could be the origin cardioprotective effects specific to red wine which is commonly referred to as ‘‘the French paradox’’ (Kopp, 1998; Pace-Asciak et al., 1995).”
BackgroundResveratrol: A molecule whose time has come? And gone?
Soleas, G. J., Diamandis, E. P., & Goldberg, D. M. (1997) · Clinical Biochemistry · doi:10.1016/s0009-9120(96)00155-5 · Cited by 847 · cited 1× · see citing works
“It is also present in red wine at concentration ranging from 0.1 to 14.3 mg/l (Soleas et al., 1997).”
BackgroundInfluentialPARP-1 inhibition increases mitochondrial metabolism through SIRT1 activation
Bai, P., Cantó, C., Oudart, H., Brunyánszki, A., Cen, Y., Thomas, C., Yamamoto, H., Huber, A., Kiss, B., Houtkooper, R. H., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.03.004 · Cited by 837 · cited 14× · see citing works
“The effects of Parp1 deletion were due to elevation of NAD+ levels and subsequent SIRT1-dependent activation of mitochondrial metabolism in brown adipose tissue and muscle (Bai et al., 2011b).”
BackgroundInfluentialSelf-citationFulco, M., Cen, Y., Zhao, P., Hoffman, E. P., McBurney, M. W., Sauve, A. A., & Sartorelli, V. (2008) · Developmental Cell · doi:10.1016/j.devcel.2008.02.004 · Cited by 821 · cited 2× · see citing works
“Following AMPK activation, expression of NAMPT increased, leading to increased NAD levels and activation of SIRT1 (Canto et al., 2009, 2010; Fulco et al., 2008).”
BackgroundCalorie restriction–the SIR2 connection
Guarente, L., & Picard, F. (2005) · Cell · doi:10.1016/j.cell.2005.01.029 · Cited by 793 · cited 1× · see citing works
“…effects mediated by SIRT1 under CR conditions have been proposed to be due to an improvement of the mitochondrial function and biogenesis (Guarente & Picard, 2005), but also to a global increase in stress resistance and maintenance of the cellular and mitochondrial homeostasis (Figure 3).”
BackgroundCalorie Restriction Increases Muscle Mitochondrial Biogenesis in Healthy Humans
Civitarese, A. E., Carling, S., Heilbronn, L. K., Hulver, M. H., Ukropcova, B., Deutsch, W. A., Smith, S. R., & Ravussin, E. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040076 · Cited by 790 · see citing works
SIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle
Nakagawa, T., Lomb, D. J., Haigis, M. C., & Guarente, L. (2009) · Cell · doi:10.1016/j.cell.2009.02.026 · Cited by 787 · cited 2× · see citing works
“…do not develop an overt metabolic DOI: 10.3109/10409238.2013.789479 NAD+ in metabolic disease 399 phenotype under basal non-challenged conditions (FernandezMarcos et al., 2012; Haigis et al., 2006; Haigis & Sinclair, 2010; Hirschey et al., 2010; Lombard et al., 2007; Nakagawa et al., 2009).”
BackgroundInfluentialSpeakman, J. R., & Mitchell, S. E. (2011) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2011.07.001 · Cited by 769 · cited 1× · see citing works
“Indeed, CR permits to maintain neuronal plasticity with age (Adams et al., 2008; Halagappa et al., 2007; Patel et al., 2005) and reduces cancer risk (Kalaany & Sabatini, 2009), suggesting that increasing NAD+ levels could also be interesting within this context (Speakman & Mitchell, 2011).”
BackgroundmTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake
Yilmaz, Ö. H., Katajisto, P., Lamming, D. W., Gültekin, Y., Bauer-Rowe, K. E., Sengupta, S., Birsoy, K., Dursun, A., Yilmaz, V. O., Selig, M., et al. (2012) · Nature · doi:10.1038/nature11163 · Cited by 753 · cited 2× · see citing works
“It is interesting to note, however, that a recent study demonstrated a role for CD157 in the response of intestinal Paneth cells to caloric restriction (CR) (Yilmaz et al., 2012).”
BackgroundThe first identification of lysine malonylation substrates and its regulatory enzyme
Peng, C., Lu, Z., Xie, Z., Cheng, Z., Chen, Y., Tan, M., Luo, H., Zhang, Y., He, W., Yang, K., et al. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.012658 · Cited by 751 · cited 1× · see citing works
“In addition, some of the sirtuins were reported to ADP-ribosylate proteins rather than deacetylate (Haigis et al., 2006), and SIRT5 was shown to act as a demalonylase and desuccinylase (Du et al., 2011; Peng et al., 2011; Wang et al., 2011).”
BackgroundBieganowski, P., & Brenner, C. (2004) · Cell · doi:10.1016/s0092-8674(04)00416-7 · Cited by 750 · cited 2× · see citing works
“Even though this pathway for NAD biosynthesis was already known in bacteria, it was only recently demonstrated that NR – which is found in milk and yeast – could also be used to synthesize NAD+ in eukaryotes (Bieganowski & Brenner, 2004).”
BackgroundSubstrate-specific activation of sirtuins by resveratrol
Kaeberlein, M., McDonagh, T., Heltweg, B., Hixon, J., Westman, E. A., Caldwell, S. D., Napper, A., Curtis, R., DiStefano, P. S., Fields, S., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500655200 · Cited by 745 · cited 2× · see citing works
“, 2004), although this is controversial (Bass et al., 2007; Kaeberlein et al., 2005).”
BackgroundOn PAR with PARP: cellular stress signaling through poly(ADP-ribose) and PARP-1Preprint
Luo, X., & Kraus, W. L. (2012) · Genes & Development · doi:10.1101/gad.183509.111 · Cited by 725 · cited 2× · see citing works
“The nuclear PARP1 accounts for most of the PARP activity in vivo and is the best-studied family member, but critical functions for other PARPs are emerging (Luo & Kraus, 2012; Schreiber et al., 2006).”
BackgroundSIRT1 transgenic mice show phenotypes resembling calorie restriction
Bordone, L., Cohen, D., Robinson, A., Motta, M. C., Van Veen, E., Czopik, A., Steele, A. D., Crowe, H., Marmor, S., Luo, J., et al. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00335.x · Cited by 722 · cited 1× · see citing works
“…the Sirt1 gene, exhibit a range of features that are reminiscent of the phenotypes seen in CR mice, as they are lighter and metabolically more active, show improved glucose homeostasis and develop less cancer (Banks et al., 2008; Bordone et al., 2007; Herranz et al., 2010; Pfluger et al., 2008).”
BackgroundFeige, J. N., Lagouge, M., Canto, C., Strehle, A., Houten, S. M., Milne, J. C., Lambert, P. D., Mataki, C., Elliott, P. J., & Auwerx, J. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.08.017 · Cited by 719 · cited 3× · see citing works
“metabolic abnormalities in mice models (Feige et al., 2008; Milne et al., 2007).”
BackgroundSelf-citationRine, J., & Herskowitz, I. (1987) · Genetics · doi:10.1093/genetics/116.1.9 · Cited by 711 · cited 2× · see citing works
“After a period of relative anonymity, NAD+ became again in the spotlight because it was identified as a substrate for a major class of deacetylase proteins, the sirtuins, named after the founding member of the family yeast Sir2p (Ivy et al., 1986; Rine & Herskowitz, 1987).”
BackgroundThe effect of retarded growth upon the length of life span and upon the ultimate body size. 1935.
Cm, M., Crowell, M. F., & MAYNARD, L. A. (1989) · PubMed · Cited by 670 · see citing works
Sirtuin regulation of mitochondria: energy production, apoptosis, and signaling
Verdin, E., Hirschey, M. D., Finley, L. W. S., & Haigis, M. C. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.07.003 · Cited by 661 · cited 1× · see citing works
“…metabolism (Haigis et al., 2006), urea cycle (Nakagawa et al., 2009), as well as several other mitochondrial pathways (Hebert et al., 2013), and thereby regulate multiple facets of mitochondrial metabolism (reviewed in Houtkooper et al., 2012; Pirinen et al., 2012 and Verdin et al., 2010).”
BackgroundAMP-activated protein kinase-deficient mice are resistant to the metabolic effects of resveratrol
Um, J.-H., Park, S.-J., Kang, H., Yang, S., Foretz, M., McBurney, M. W., Kim, M. K., Viollet, B., & Chung, J. H. (2010) · Diabetes · doi:10.2337/db09-0482 · Cited by 647 · cited 10× · see citing works
“Resveratrol promotes mitochondrial biogenesis and functions through indirect AMPK and SIRT1 activation.”
BackgroundInfluentialSirT1 Gain of Function Increases Energy Efficiency and Prevents Diabetes in Mice
Banks, A. S., Kon, N., Knight, C. M., Matsumoto, M., Juárez, R. G., Rossetti, L., Gu, W. J., & Accili, D. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.08.014 · Cited by 639 · cited 1× · see citing works
“…the Sirt1 gene, exhibit a range of features that are reminiscent of the phenotypes seen in CR mice, as they are lighter and metabolically more active, show improved glucose homeostasis and develop less cancer (Banks et al., 2008; Bordone et al., 2007; Herranz et al., 2010; Pfluger et al., 2008).”
BackgroundVakhrusheva, O., Smolka, C., Gajawada, P., Sawa Kostin, D., Boettger, T., Kubin, T., Braun, T. W., & Bober, E. (2008) · Circulation Research · doi:10.1161/circresaha.107.164558 · Cited by 639 · cited 1× · see citing works
“A thorough characterization of Sirt7 / mice has not been performed but mice deficient for SIRT7 display hyperacetylation of p53, develop cardiomyopathy and die young (Vakhrusheva et al., 2008).”
BackgroundCalorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome
Hebert, A. S., Dittenhafer-Reed, K. E., Yu, W., Bailey, D. J., Selen, E. S., Boersma, M. D., Carson, J. J., Tonelli, M., Balloon, A. J., Higbee, A. J., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2012.10.024 · Cited by 636 · cited 2× · see citing works
“…(Someya et al., 2010), glutamate metabolism (Haigis et al., 2006), urea cycle (Nakagawa et al., 2009), as well as several other mitochondrial pathways (Hebert et al., 2013), and thereby regulate multiple facets of mitochondrial metabolism (reviewed in Houtkooper et al., 2012; Pirinen et al., 2012…”
BackgroundMammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription
Ford, E., Voit, R., Liszt, G., Magin, C., Grummt, I., & Guarente, L. (2006) · Genes & Development · doi:10.1101/gad.1399706 · Cited by 629 · cited 1× · see citing works
“No in vivo molecular deacetylation targets have been described for the nucleolar SIRT7, but knockdown or overexpression of SIRT7 resulted in decreased or increased RNA polymerase I-mediated transcription, respectively (Ford et al., 2006).”
BackgroundAbsence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila
Burnett, C., Valentini, S., Cabreiro, F., Goss, M., Somogyvári, M., Piper, M. D., Hoddinott, M., Sutphin, G. L., Leko, V., McElwee, J. J., et al. (2011) · Nature · doi:10.1038/nature10296 · Cited by 624 · cited 1× · see citing works
“1 and fly SIR2 on lifespan is, at best, limited or even absent (Burnett et al., 2011; Viswanathan & Guarente, 2011).”
BackgroundEvidence for a Common Mechanism of SIRT1 Regulation by Allosteric Activators
Hubbard, B. P., Gomes, A. P., Dai, H., Li, J., Case, A. W., Considine, T., Riera, T. V., Lee, J. E., Yen, E. S., Lamming, D. W., et al. (2013) · Science · doi:10.1126/science.1231097 · Cited by 618 · cited 4× · see citing works
“, 2010), although recent evidence suggests that this may be dictated by specific hydrophobic residues in SIRT1 substrates (Hubbard et al., 2013).”
BackgroundInfluentialSirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer
Herranz, D., Muñoz-Martin, M., Cañamero, M., Mulero, F., Martinez-Pastor, B., Fernandez-Capetillo, O., & Serrano, M. (2010) · Nature Communications · doi:10.1038/ncomms1001 · Cited by 612 · cited 3× · see citing works
“In line with these beneficial effects of CR on age-associated pathologies, transgenic mice with SIRT1 overexpression are not only protected against HFD-induced metabolic pathology, but also show protection against tumor development (Herranz et al., 2010) and progression of neurodegenerative disease (Donmez et al.”
BackgroundHalagappa, V. K. M., Guo, Z., Pearson, M., Matsuoka, Y., Cutler, R. G., LaFerla, F. M., & Mattson, M. P. (2007) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.12.019 · Cited by 580 · cited 2× · see citing works
“Indeed, CR permits to maintain neuronal plasticity with age (Adams et al., 2008; Halagappa et al., 2007; Patel et al., 2005) and reduces cancer risk (Kalaany & Sabatini, 2009), suggesting that increasing NAD+ levels could also be interesting within this context (Speakman & Mitchell, 2011).”
BackgroundBarger, J. L., Kayo, T., Vann, J. M., Arias, E. B., Wang, J., Hacker, T. A., Wang, Y., Raederstorff, D., Morrow, J. D., Leeuwenburgh, C., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002264 · Cited by 580 · cited 2× · see citing works
“…several hallmarks of aging, such as reduced inflammatory and apoptotic events in vascular endothelium, limiting the formation of cataracts, preservation of bone density and conservation of motor activity with age (Barger et al., 2008; Baur et al., 2006; Lagouge et al., 2006; Pearson et al., 2008).”
BackgroundEvolutionary medicine: from dwarf model systems to healthy centenarians?
Longo, V. D., & Finch, C. E. (2003) · Science · doi:10.1126/science.1077991 · Cited by 575 · see citing works
Tissue-specific regulation of SIRT1 by calorie restriction
Chen, D., Bruno, J., Easlon, E., Lin, S.-J., Cheng, H.-L., Alt, F. W., & Guarente, L. (2008) · Genes & Development · doi:10.1101/gad.1650608 · Cited by 567 · cited 2× · see citing works
“In a similar way, CR in mouse models leads to an increase in the level of NAD in different tissues, such as muscle, liver and white adipose tissue (Canto et al., 2010; Chen et al., 2008).”
BackgroundFOXO4 Is Acetylated upon Peroxide Stress and Deacetylated by the Longevity Protein hSir2
van der Horst, A., Tertoolen, L. G. J., Smits, L. M. M., Frye, R. A., Medema, R. H., & Burgering, B. M. T. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m401138200 · Cited by 545 · cited 1× · see citing works
“SIRT1 deacetylates histones, but its key activity involves the regulation of mitochondrial biogenesis and stress response through the deacetylation of PGC-1a (Rodgers et al., 2005) and FOXO1 (Brunet et al., 2004; van der Horst et al., 2004).”
BackgroundResveratrol protects against global cerebral ischemic injury in gerbils
Wang, Q., Xu, J., Rottinghaus, G. E., Simonyi, Á., Lubahn, D. E., Sun, G. Y., & Sun, A. Y. (2002) · Brain Research · doi:10.1016/s0006-8993(02)03543-6 · Cited by 528 · cited 1× · see citing works
“Since then resveratrol has been shown to be effective in preventing and delaying the progression of various diseases such as cancer (Jang et al., 1997), cardiovascular disease and glucose intolerance (Timmers et al., 2011) and ischemic stroke (Sinha et al., 2002; Wang et al., 2002).”
BackgroundThe new life of a centenarian: signalling functions of NAD(P)
Berger, F. (2004) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2004.01.007 · Cited by 489 · cited 1× · see citing works
“Its function as a cofactor for a multitude of enzymatic reactions has been appreciated since the early 1900s, when NAD+ was described as a ‘‘cozymase’’ in fermentation and its characteristics were elucidated, not in the last place by several Nobel prize winners (Berger et al., 2004).”
BackgroundShimazu, T., Hirschey, M. D., Hua, L., Dittenhafer-Reed, K. E., Schwer, B., Lombard, D. B., Li, Y., Bunkenborg, J., Alt, F. W., Denu, J. M., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.11.003 · Cited by 484 · cited 2× · see citing works
“…SIRT5 – deacetylate protein targets involved in oxidative phosphorylation (Ahn et al., 2008), fatty acid oxidation (Hirschey et al., 2010), ketogenesis (Shimazu et al., 2010), oxidative stress (Someya et al., 2010), glutamate metabolism (Haigis et al., 2006), urea cycle (Nakagawa et al., 2009), as…”
BackgroundTumours with PI3K activation are resistant to dietary restriction
Kalaany, N. Y., & Sabatini, D. M. (2009) · Nature · doi:10.1038/nature07782 · Cited by 468 · cited 1× · see citing works
“Indeed, CR permits to maintain neuronal plasticity with age (Adams et al., 2008; Halagappa et al., 2007; Patel et al., 2005) and reduces cancer risk (Kalaany & Sabatini, 2009), suggesting that increasing NAD+ levels could also be interesting within this context (Speakman & Mitchell, 2011).”
BackgroundHow does calorie restriction work?Preprint
Koubova, J., & Guarente, L. (2003) · Genes & Development · doi:10.1101/gad.1052903 · Cited by 457 · cited 1× · see citing works
“CR remains the most effective and reproducible intervention to extend lifespan and delay the development of ageassociated diseases in divergent species, from yeast to monkeys (Houtkooper et al., 2010b; Koubova & Guarente, 2003).”
BackgroundInhibition of mitochondrial proton F0F1‐ATPase/ATP synthase by polyphenolic phytochemicals
Zheng, J., & Ramirez, V. D. (2000) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0703397 · Cited by 453 · cited 1× · see citing works
“Since it was known that resveratrol acts as an inhibitor of the ATP synthase complex in the oxidative phosphorylation (Zheng & Ramirez, 2000), it was hypothesized that the effects of resveratrol could be mediated by activation of the AMPK, rather than direct SIRT1 activation (Beher et al., 2009;…”
BackgroundSirT1 Regulates Energy Metabolism and Response to Caloric Restriction in Mice
Boily, G., Seifert, E. L., Bevilacqua, L., He, X. H., Sabourin, G., Estey, C., Moffat, C., Crawford, S., Saliba, S., Jardine, K., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001759 · Cited by 444 · cited 1× · see citing works
“In fact, in Sirt1 / mice the beneficial effects on metabolism and longevity induced by a CR diet are attenuated, although it should be noted that these mice are very sick to start with (Boily et al., 2008; Chen et al., 2005).”
BackgroundEffects of resveratrol on lifespan in Drosophila melanogaster and Caenorhabditis elegans
Bass, T. M., Weinkove, D., Houthoofd, K., Gems, D., & Partridge, L. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2007.07.007 · Cited by 435 · cited 1× · see citing works
“1 or Sir2p, respectively)dependent manner (Howitz et al., 2003; Wood et al., 2004), although this is controversial (Bass et al., 2007; Kaeberlein et al., 2005).”
BackgroundTargeting Sirtuin 1 to Improve Metabolism: All You Need Is NAD+?
Cantó, C., & Auwerx, J. (2012) · Pharmacological Reviews · doi:10.1124/pr.110.003905 · Cited by 433 · cited 2× · see citing works
“Its role in stress response is further confirmed by the identification of p53, hypoxiainducible factor-1a, and NF- B as SIRT1 targets (reviewed in Canto & Auwerx, 2012; Houtkooper et al., 2012).”
BackgroundSelf-citationPoly(ADP-Ribose) Regulates Stress Responses and MicroRNA Activity in the Cytoplasm
Leung, A. K. L., Vyas, S., Rood, J., Bhutkar, A. J., Sharp, P. A., & Chang, P. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.04.015 · Cited by 430 · cited 1× · see citing works
“For example, when protein translation is stalled, PARP13 localizes to cytosolic stress granules and regulates microRNA expression and activity, alleviating the protein stress (Leung et al., 2011).”
BackgroundResveratrol is not a direct activator of SIRT1 enzyme activity
Beher, D., Wu, J., Cumine, S., Kim, K. W., Lu, S., Atangan, L., & Wang, M. (2009) · Chemical Biology & Drug Design · doi:10.1111/j.1747-0285.2009.00901.x · Cited by 426 · cited 2× · see citing works
“…the ATP synthase complex in the oxidative phosphorylation (Zheng & Ramirez, 2000), it was hypothesized that the effects of resveratrol could be mediated by activation of the AMPK, rather than direct SIRT1 activation (Beher et al., 2009; Canto et al., 2010; Pacholec et al., 2010; Um et al., 2010).”
BackgroundIncrease in Activity During Calorie Restriction Requires Sirt1
Chen, D., Steele, A. D., Lindquist, S., & Guarente, L. (2005) · Science · doi:10.1126/science.1118357 · Cited by 419 · cited 1× · see citing works
“In fact, in Sirt1 / mice the beneficial effects on metabolism and longevity induced by a CR diet are attenuated, although it should be noted that these mice are very sick to start with (Boily et al., 2008; Chen et al., 2005).”
BackgroundJiang, W., Wang, S., Xiao, M., Lin, Y., Zhou, L., Lei, Q., Xiong, Y., Guan, K., & Zhao, S. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.04.028 · Cited by 415 · cited 2× · see citing works
“phosphoenolpyruvate carboxykinase to control gluconeogenesis (Jiang et al., 2011) and was recently shown to deacetylate the receptor-interacting protein-1, and thereby serve as a critical component of the tumor necrosis factor a-mediated programmed necrosis pathway (Narayan et al.”
BackgroundKopp, P. A. (1998) · European Journal of Endocrinology · doi:10.1530/eje.0.1380619 · Cited by 392 · cited 1× · see citing works
“Resveratrol has attracted the attention of the scientific community when it was demonstrated that this molecule could be the origin cardioprotective effects specific to red wine which is commonly referred to as ‘‘the French paradox’’ (Kopp, 1998; Pace-Asciak et al., 1995).”
BackgroundYoshino, J., Conte, C., Fontana, L., Mittendorfer, B., Imai, S., Schechtman, K. B., Gu, C. C., Kunz, I., Fanelli, F. R., Patterson, B. W., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.09.015 · Cited by 381 · cited 1× · see citing works
“It should be noted, however, that resveratrol failed to exert beneficial effects in non-obese female subjects (Yoshino et al., 2012), in line with mouse data where resveratrol is particularly effective in HFD fed mice (Baur et al., 2006; Lagouge et al., 2006).”
BackgroundMetabolomic Analysis of Livers and Serum from High-Fat Diet Induced Obese Mice
Kim, H.-J., Kim, J. H., Noh, S., Hur, H. J., Sung, M. J., Hwang, J.-T., Park, J. H., Yang, H. J., Kim, M.-S., Kwon, D. Y., et al. (2011) · Journal of Proteome Research · doi:10.1021/pr100892r · Cited by 376 · cited 11× · see citing works
“This effect on longevity is, however, only observed when mice are fed with an HFD.”
BackgroundInfluentialCui, L., Supinski, A., Savas, J. N., Yates, J. R., Bordone, L., Guarente, L., Cohen, D. E., Mazzulli, J. R., Krainc, D., & Jeong, H. (2011) · PubMed Central · doi:10.1038/nm.2559 · Cited by 367 · cited 2× · see citing works
“, 2010) and progression of neurodegenerative disease (Donmez et al., 2010; Jeong et al., 2012; Wareski et al., 2009).”
Background“Control” laboratory rodents are metabolically morbid: Why it matters
Martin, B., Ji, S., Maudsley, S., & Mattson, M. P. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912955107 · Cited by 354 · cited 2× · see citing works
“…questioned whether the beneficial effects observed under CR were not due to a simple ‘‘rescue’’ of the deleterious effects brought by the state of overnutrition specific of the artificial diets prepared in laboratories (Harper et al., 2006; Longo & Finch, 2003; Martin et al., 2010; Prentice, 2005).”
BackgroundSirtuins mediate mammalian metabolic responses to nutrient availability
Chalkiadaki, A., & Guarente, L. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.225 · Cited by 342 · cited 1× · see citing works
“Sirtuins are a class of metabolic regulators, of which seven orthologs exist in mammals (Blander & Guarente, 2004; Chalkiadaki & Guarente, 2012; Haigis & Sinclair, 2010; Houtkooper et al., 2012).”
BackgroundSIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis
Luthi‐Carter, R., Taylor, D. M., Pallos, J., Lambert, E., Amore, A. M., Parker, J. A., Moffitt, H., Smith, D. L., Runne, H., Gökçe, Ö., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002924107 · Cited by 338 · see citing works
Caloric restriction attenuates Aβ-deposition in Alzheimer transgenic models
Patel, N. V., Gordon, M. N., Connor, K. E., Good, R. A., Engelman, R. W., Mason, J., Morgan, D. G., Morgan, T. E., & Finch, C. E. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.09.014 · Cited by 329 · cited 2× · see citing works
“Indeed, CR permits to maintain neuronal plasticity with age (Adams et al., 2008; Halagappa et al., 2007; Patel et al., 2005) and reduces cancer risk (Kalaany & Sabatini, 2009), suggesting that increasing NAD+ levels could also be interesting within this context (Speakman & Mitchell, 2011).”
BackgroundPathways and Subcellular Compartmentation of NAD Biosynthesis in Human Cells
Nikiforov, A., Dölle, C., Niere, M., & Ziegler, M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.213298 · Cited by 326 · cited 1× · see citing works
“Still, even if most CD38 activity occurs outside the cell, the resultant metabolites can be transported inside, most likely in the form of NR (Nikiforov et al., 2011).”
BackgroundHolloszy, J. O., & Fontana, L. (2007) · Experimental Gerontology · doi:10.1016/j.exger.2007.03.009 · Cited by 304 · cited 1× · see citing works
“The concept that enhanced mitochondrial function upon CR contributes to its beneficial effects on lifespan was extended to humans, in which a general improvement in metabolic health occurs during CR (Civitarese et al., 2007 and reviewed in Holloszy & Fontana, 2007).”
BackgroundNAD+ and Vitamin B3: From Metabolism to Therapies
Sauve, A. A. (2007) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.107.120758 · Cited by 303 · cited 1× · see citing works
“NA, also called niacin, has been used to treat dietary tryptophan deficits (pellagra) and hyperlipidemia (Elvehjem et al., 1937; Karpe & Frayn, 2004; Sauve, 2008).”
BackgroundSRT1720 improves survival and healthspan of obese mice
Minor, R. K., Baur, J. A., Gomes, A. P., Ward, T. M., Csiszár, A., Mercken, E. M., Abdelmohsen, K., Shin, Y., Cantó, C., Scheibye‐Knudsen, M., et al. (2011) · Scientific Reports · doi:10.1038/srep00070 · Cited by 297 · see citing works
Self-citationPGC-1α and PGC-1Β Regulate Mitochondrial Density in Neurons
Warȩski, P., Vaarmann, A., Choubey, V., Safiulina, D., Liiv, J., Kuum, M., & Kaasik, A. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.018911 · Cited by 294 · see citing works
Cloning and characterization of four SIR genes of Saccharomyces cerevisiae.
Ivy, J. M., Klar, A. J. S., & Hicks, J. B. (1986) · Molecular and Cellular Biology · doi:10.1128/mcb.6.2.688 · Cited by 294 · see citing works
Enzymology of NAD+ homeostasis in man
Magni, G., Amici, A., Emanuelli, M., Orsomando, G., Raffaelli, N., & Ruggieri, S. (2004) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-003-3161-1 · Cited by 289 · see citing works
Overlapping and distinct functions for a Caenorhabditis elegans SIR2 and DAF-16/FOXO
Wang, Y., & Tissenbaum, H. A. (2005) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2005.09.005 · Cited by 263 · cited 1× · see citing works
“1 is required for the lifespan extension in response to the CR-mutation eat-2 (Wang & Tissenbaum, 2006).”
BackgroundPARP-2 Regulates SIRT1 Expression and Whole-Body Energy Expenditure
Bai, P., Cantó, C., Brunyánszki, A., Huber, A., Szántó, M., Cen, Y., Yamamoto, H., Houten, S. M., Kiss, B., Oudart, H., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.03.013 · Cited by 250 · cited 14× · see citing works
“The effects of Parp1 deletion were due to elevation of NAD+ levels and subsequent SIRT1-dependent activation of mitochondrial metabolism in brown adipose tissue and muscle (Bai et al., 2011b).”
BackgroundInfluentialSelf-citationBarbosa, M. T., Soares, S. M., Novak, C. M., Sinclair, D. A., Levine, J. A., Aksoy, P., & Chini, E. N. (2007) · The FASEB Journal · doi:10.1096/fj.07-8290com · Cited by 249 · cited 13× · see citing works
“While PARPs are stress response proteins, the NAD+-consuming CD38 is an ubiquitous, but still quite enigmatic enzyme, involved in maintaining calcium homeostasis (Lee, 2012).”
BackgroundInfluentialRELATION OF NICOTINIC ACID AND NICOTINIC ACID AMIDE TO CANINE BLACK TONGUE
Elvehjem, C. A., Madden, R. J., Strong, F. M., & Woolley, D. W. (1937) · Journal of the American Chemical Society · doi:10.1021/ja01288a509 · Cited by 244 · cited 4× · see citing works
“Pellagra, in dogs prevalent as black tongue disease, is caused by deficiency of NAD+ (precursors) and can be easily treated by providing the vitamin in the diet (Elvehjem et al., 1937).”
BackgroundInfluentialMetabolic networks of longevity
Houtkooper, R. H., Williams, R. W., & Auwerx, J. (2010) · Cell · doi:10.1016/j.cell.2010.06.029 · Cited by 217 · cited 4× · see citing works
“De novo biosynthesis, which starts from the amino acid tryptophan, occurs primarily in the liver and kidney but is considered a minor contributor to the total pool of NAD+ (reviewed in detail in Houtkooper et al., 2010a).”
BackgroundInfluentialDoes caloric restriction extend life in wild mice?
Harper, J. M., Leathers, C. W., & Austad, S. N. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00236.x · Cited by 212 · cited 1× · see citing works
“…questioned whether the beneficial effects observed under CR were not due to a simple ‘‘rescue’’ of the deleterious effects brought by the state of overnutrition specific of the artificial diets prepared in laboratories (Harper et al., 2006; Longo & Finch, 2003; Martin et al., 2010; Prentice, 2005).”
BackgroundSIRT1 Activation by Small Molecules
Dai, H., Kustigian, L. M., Carney, D. P., Case, A. W., Considine, T., Hubbard, B. P., Perni, R. B., Riera, T. V., Szczepankiewicz, B. G., Vlasuk, G. P., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.133892 · Cited by 211 · see citing works
Lee, H. C. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.r112.349464 · Cited by 197 · cited 2× · see citing works
“While PARPs are stress response proteins, the NAD+-consuming CD38 is an ubiquitous, but still quite enigmatic enzyme, involved in maintaining calcium homeostasis (Lee, 2012).”
BackgroundRegulation of Caenorhabditis elegans lifespan by sir-2.1 transgenes
Viswanathan, M., & Guarente, L. (2011) · Nature · doi:10.1038/nature10440 · Cited by 191 · cited 1× · see citing works
“1 and fly SIR2 on lifespan is, at best, limited or even absent (Burnett et al., 2011; Viswanathan & Guarente, 2011).”
BackgroundThe nicotinic acid receptor–a new mechanism for an old drug
Karpe, F., & Frayn, K. N. (2004) · The Lancet · doi:10.1016/s0140-6736(04)16359-9 · Cited by 186 · cited 1× · see citing works
“NA, also called niacin, has been used to treat dietary tryptophan deficits (pellagra) and hyperlipidemia (Elvehjem et al., 1937; Karpe & Frayn, 2004; Sauve, 2008).”
BackgroundBeirowski, B., Gustin, J. A., Armour, S., Yamamoto, H., Viader, A., North, B., Michán, S., Baloh, R., Golden, J., Schmidt, R., et al. (2011) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1104969108 · Cited by 175 · cited 1× · see citing works
“Finally, SIRT2 controls myelin formation in vivo through the atypical protein kinase C regulator PAR3 (Beirowski et al., 2011).”
BackgroundSelf-citationCaloric restriction and age affect synaptic proteins in hippocampal CA3 and spatial learning ability
Adams, M. M., Shi, L., Linville, M. C., Forbes, M. E., Long, A. B., Bennett, C., Newton, I. G., Carter, C. S., Sonntag, W. E., Riddle, D. R., et al. (2008) · Experimental Neurology · doi:10.1016/j.expneurol.2008.01.016 · Cited by 170 · cited 1× · see citing works
“Indeed, CR permits to maintain neuronal plasticity with age (Adams et al., 2008; Halagappa et al., 2007; Patel et al., 2005) and reduces cancer risk (Kalaany & Sabatini, 2009), suggesting that increasing NAD+ levels could also be interesting within this context (Speakman & Mitchell, 2011).”
BackgroundFernandez-Marcos, P. J., Jeninga, E. H., Canto, C., Harach, T., de Boer, V. C. J., Andreux, P., Moullan, N., Pirinen, E., Yamamoto, H., Houten, S. M., et al. (2012) · Scientific Reports · doi:10.1038/srep00425 · Cited by 137 · see citing works
Self-citationSauve, A. A., Munshi, C. B., Lee, H. C., & Schramm, V. L. (1998) · Biochemistry · doi:10.1021/bi981248s · Cited by 120 · cited 1× · see citing works
“Small molecule CD38 inhibitors (or CD157 inhibitors if identified) may circumvent this problem, but further insights in the NAD+ accumulation and trafficking are required (Sauve et al., 1998; Sauve & Schramm, 2002).”
BackgroundExploring the therapeutic space around NAD+
Houtkooper, R. H., & Auwerx, J. H. (2012) · The Journal of Cell Biology · doi:10.1083/jcb.201207019 · Cited by 109 · cited 2× · see citing works
“…development, it has become apparent that pathways involved in synthesis or consumption of NAD+ are attractive targets for the management of conditions with dysfunctional metabolism, including not only obesity and diabetes, but also cancer and neurodegenerative diseases (Houtkooper & Auwerx, 2012).”
BackgroundSelf-citationBai, P., Houten, S. M., Huber, A., Schreiber, V., 渡辺, 光., Kiss, B., de MURCIA, G., Auwerx, J. H., & Murcia, J. M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m701021200 · Cited by 105 · cited 1× · see citing works
“More recently, however, the role of the different PARPs in metabolism has become more apparent, as Parp1 and Parp2 knockout mice are protected against high-fat diet (HFD)induced obesity (Bai et al., 2007, 2011a,b).”
BackgroundSelf-citationProtein 8‐class secondary structure prediction using conditional neural fields
Wang, Z., Zhao, F., Peng, J., & Xu, J. (2011) · PROTEOMICS · doi:10.1002/pmic.201100196 · Cited by 102 · cited 1× · see citing works
“In addition, some of the sirtuins were reported to ADP-ribosylate proteins rather than deacetylate (Haigis et al., 2006), and SIRT5 was shown to act as a demalonylase and desuccinylase (Du et al., 2011; Peng et al., 2011; Wang et al., 2011).”
BackgroundStarvation in humans: Evolutionary background and contemporary implications
Prentice, A. M. (2005) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2005.03.018 · Cited by 92 · cited 1× · see citing works
“…questioned whether the beneficial effects observed under CR were not due to a simple ‘‘rescue’’ of the deleterious effects brought by the state of overnutrition specific of the artificial diets prepared in laboratories (Harper et al., 2006; Longo & Finch, 2003; Martin et al., 2010; Prentice, 2005).”
BackgroundMouchiroud, L., Molin, L., Kasturi, P., Triba, M. N., Dumas, M., Wilson, M. C., Halestrap, A. P., Roussel, D., Masse, I., Dallière, N., et al. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00640.x · Cited by 90 · cited 1× · see citing works
“…studies in worms added a new layer of complexity in this dynamic mechanism, by showing that an early burst of reactive oxygen species (ROS) is required for the induction of the ROS defense pathway and for the lifespan extension under CR conditions (Mouchiroud et al., 2011; Schulz et al., 2007).”
BackgroundSelf-citationCloning and Characterization of Four SIR Genes of Saccharomyces cerevisiae
Ivy, J. M., Klar, A. J. S., & Hicks, J. B. (1986) · Molecular and Cellular Biology · doi:10.1128/mcb.6.2.688-702.1986 · Cited by 90 · cited 4× · see citing works
“After a period of relative anonymity, NAD+ became again in the spotlight because it was identified as a substrate for a major class of deacetylase proteins, the sirtuins, named after the founding member of the family yeast Sir2p (Ivy et al., 1986; Rine & Herskowitz, 1987).”
BackgroundInfluentialYang, C. C., Chen, D., Lee, S. S., & Walter, L. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2011.00711.x · Cited by 61 · cited 2× · see citing works
“…new evidence suggest that other pro-longevity pathways, induced by CR and/or stress conditions, could also potentially involve SIRT1, such as mitophagy, mitochondrial dynamics (fission/fusion) and mitochondrial unfolded response (Durieux et al., 2011; Egan et al., 2011; Yang et al., 2011).”
BackgroundMitochondrial sirtuins and metabolic homeostasis
Pirinen, E., Sasso, G. L., & Auwerx, J. H. (2012) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2012.05.001 · Cited by 56 · cited 2× · see citing works
“SIRT1, SIRT6 and SIRT7 are mainly found in the nucleus, SIRT2 is predominantly in the cytoplasm, while SIRT3, SIRT4 and SIRT5 are localized in mitochondria (Pirinen et al., 2012).”
BackgroundSelf-citationDesign, synthesis and biological characterization of novel inhibitors of CD38
Dong, M., Si, Y.-Q., Sun, S.-Y., Pu, X., Yang, Z.-J., Zhang, L., Zhang, L., Leung, F. P., Lam, C. M. C., Kwong, A. K., et al. (2011) · Organic & Biomolecular Chemistry · doi:10.1039/c0ob00768d · Cited by 37 · cited 14× · see citing works
“While PARPs are stress response proteins, the NAD+-consuming CD38 is an ubiquitous, but still quite enigmatic enzyme, involved in maintaining calcium homeostasis (Lee, 2012).”
BackgroundInfluentialMechanism-Based Inhibitors of CD38: A Mammalian Cyclic ADP-Ribose Synthetase
Sauve, A. A., & Schramm, V. L. (2002) · Biochemistry · doi:10.1021/bi0258795 · Cited by 30 · cited 1× · see citing works
“Small molecule CD38 inhibitors (or CD157 inhibitors if identified) may circumvent this problem, but further insights in the NAD+ accumulation and trafficking are required (Sauve et al., 1998; Sauve & Schramm, 2002).”
BackgroundAging, Longevity, and Diet: Historical Remarks on Calorie Intake Reduction
Schäfer, D. (2005) · Gerontology · doi:10.1159/000082198 · Cited by 23 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Takaoka MJ Resveratrol, a new phenolic compound, from Veratrum grandiflorum Journal of the Chemical Society of Japan 1939 60 1090 1100
Cited by
Sorted by citations
Promoting Health and Longevity through Diet: From Model Organisms to Humans
Fontana, L., & Partridge, L. (2015) · Cell · doi:10.1016/j.cell.2015.02.020 · Cited by 1,245 · see citing works
“2014), TOR (Kapahi et al., 2010; Johnson et al., 2013), AMPK (Geer et al., 2007; Burkewitz et al. 2014), sirtuins (Mouchiroud et al., 2013; Guarente.”
InfluentialSlowing ageing by design: the rise of NAD+ and sirtuin-activating compounds
Bonkowski, M. S., & Sinclair, D. A. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.93 · Cited by 834 · see citing works
Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease
Smith, R. L., Soeters, M. R., Wüst, R. C. I., & Houtkooper, R. H. (2018) · Endocrine Reviews · doi:10.1210/er.2017-00211 · Cited by 787 · see citing works
Self-citationPhysiological and pathophysiological roles of NAMPT and NAD metabolism.
Garten, A., Schuster, S., Penke, M., Gorski, T., de Giorgis, T., & Kiess, W. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.117 · Cited by 708 · see citing works
Jones, D. P., & Sies, H. (2015) · Antioxidants & Redox Signaling · doi:10.1089/ars.2015.6247 · Cited by 647 · see citing works
“The NAD system is increasingly recognized as an attractive target for intervention in age-associated disorders (72).”
BackgroundMartens, C. R., Denman, B. A., Mazzo, M. R., Armstrong, M. L., Reisdorph, N., McQueen, M. B., Chonchol, M., & Seals, D. R. (2018) · Nature Communications · doi:10.1038/s41467-018-03421-7 · Cited by 588 · see citing works
NAD+ metabolism, stemness, the immune response, and cancer
Navas, L. E., & Carnero, A. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00354-w · Cited by 529 · see citing works
“Therefore, there is an increase in PARP activity and the amount of NAD used as a substrate.(119,120) Genetic or pharmacological inhibition of PARP1 prevents NAD decline during aging.”
BackgroundImpairment of an endothelial NAD(+)-H2S signaling network is a reversible cause of vascular aging
Das, A., Huang, G. X., Bonkowski, M. S., Longchamp, A., Li, C., Schultz, M. B., Kim, L.-J., Osborne, B., Joshi, S., Lu, Y., et al. (2018) · Cell · doi:10.1016/j.cell.2018.02.008 · Cited by 496 · see citing works
“During aging, the level of NAD+ declines in many tissues, in part, due to increased activity of the NAD-consuming enzymes CD38 and PARP1 (Bai et al., 2011b; Camacho-Pereira et al., 2016; Li et al., 2017; Mouchiroud et al., 2013).”
Zhu, X.-H., Lu, M., Lee, B.-Y., Ugurbil, K., & Chen, W. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1417921112 · Cited by 468 · see citing works
Role of NAD+ in regulating cellular and metabolic signaling pathways
Amjad, S., Nisar, S., Bhat, A. A., Shah, A. R., Frenneaux, M. P., Fakhro, K. A., Haris, M., Reddy, R. D., Patay, Z. J., Baur, J. A., et al. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101195 · Cited by 394 · see citing works
Eight Kinetically Stable but Thermodynamically Activated Molecules that Power Cell Metabolism
Walsh, C. T., Tu, B. P., & Tang, Y. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00510 · Cited by 302 · see citing works
NAD+ homeostasis in human health and disease
Perez, R. Z., Wanders, R. J. A., van Karnebeek, C., & Houtkooper, R. H. (2021) · EMBO Molecular Medicine · doi:10.15252/emmm.202113943 · Cited by 240 · see citing works
“…case of NAM, or through the equilibrative nucleoside transporters (ENTs) SLC29A1-4 in the case of NR, both molecules are directly converted into nicotinamide mononucleotide (NMN) by the enzyme NAM phosphoribosyltransferase (NAMPT) or the NR kinases (NRKs), respectively (Mouchiroud et al, 2013a).”
BackgroundInfluentialSelf-citationSources and implications of NADH/NAD+ redox imbalance in diabetes and its complications
Yan, L.-J., Wu, J., Jin, Z., & Zheng, H. (2016) · Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy · doi:10.2147/dmso.s106087 · Cited by 198 · see citing works
Emerging therapeutic roles for NAD+ metabolism in mitochondrial and age‐related disorders
Srivastava, S. (2016) · Clinical and Translational Medicine · doi:10.1186/s40169-016-0104-7 · Cited by 193 · see citing works
“Reduced NAD+ levels have been reported in mitochondrial and age-related disorders, and NAD+ levels also decline with age [17, 26, 45, 53, 60, 67, 71].”
BackgroundDellinger, R. W., Santos, S. R., Morris, M., Evans, M., Alminana, D., Guarente, L., & Marcotulli, E. (2017) · npj Aging and Mechanisms of Disease · doi:10.1038/s41514-017-0016-9 · Cited by 181 · see citing works
Pizzorno, L. (2015) · PubMed Central · Cited by 183 · see citing works
Unravelling the mechanisms regulating muscle mitochondrial biogenesis
Hood, D. A., Tryon, L. D., Carter, H. N., Kim, Y., & Chen, C. C. W. (2016) · Biochemical Journal · doi:10.1042/bcj20160009 · Cited by 159 · see citing works
Calorie restriction mimetics: Can you have your cake and eat it, too?
Ingram, D. K., & Roth, G. S. (2014) · Ageing Research Reviews · doi:10.1016/j.arr.2014.11.005 · Cited by 162 · see citing works
Haffner, C. D., Becherer, J. D., Boros, E. E., Cadilla, R., Carpenter, T., Cowan, D., Deaton, D. N., Guo, Y., Harrington, W., Henke, B. R., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/jm502009h · Cited by 137 · see citing works
Sirtuin and metabolic kidney disease
Wakino, S., Hasegawa, K., & Itoh, H. (2015) · Kidney International · doi:10.1038/ki.2015.157 · Cited by 136 · see citing works
Preclinical and clinical evidence of NAD+ precursors in health, disease, and ageing
Reiten, O. K., Wilvang, M. A., Mitchell, S. J., Hu, Z., & Fang, E. F. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111567 · Cited by 133 · see citing works
Hyperglycemic Stress and Carbon Stress in Diabetic Glucotoxicity
Luo, X., Wu, J., Jing, S., & Yan, L. (2016) · Aging and Disease · doi:10.14336/ad.2015.0702 · Cited by 136 · see citing works
Chandrasekaran, K., Anjaneyulu, M., Choi, J., Kumar, P., Salimian, M., Ho, C.-Y., & Russell, J. W. (2019) · International review of neurobiology · doi:10.1016/bs.irn.2019.04.002 · Cited by 131 · see citing works
Wang, L.-F., Wang, X., Huang, C., Hu, L. H., Xiao, Y., Guan, X., Qian, Y., Deng, K., & Xin, H. (2017) · Lipids in Health and Disease · doi:10.1186/s12944-017-0464-z · Cited by 124 · see citing works
“NAD, served as substrate in various signaling conduction pathways, plays an important role in age and metabolism-associated diseases [30, 31].”
BackgroundNAD+ flux is maintained in aged mice despite lower tissue concentrations
McReynolds, M. R., Chellappa, K., Chiles, E., Jankowski, C., Shen, Y., Chen, L., Descamps, H. C., Mukherjee, S., Bhat, Y. R., Lingala, S. R., et al. (2021) · Cell Systems · doi:10.1016/j.cels.2021.09.001 · Cited by 112 · see citing works
Dihydronicotinamide riboside is a potent NAD+ concentration enhancer in vitro and in vivo
Yang, Y. J., Mohammed, N. A. K., Zhang, N., & Sauve, A. A. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.005772 · Cited by 111 · see citing works
PARP1 Inhibitors: Antitumor Drug Design
Maluchenko, N. V., Kotova, E. Y., Kulaeva, O. I., Kirpichnikov, M. P., & Studitskiy, V. M. (2015) · Acta Naturae · doi:10.32607/20758251-2015-7-3-27-37 · Cited by 111 · see citing works
The chemistry of the vitamin B3 metabolome
Makarov, M. V., Trammell, S. A. J., & Migaud, M. E. (2018) · Biochemical Society Transactions · doi:10.1042/bst20180420 · Cited by 110 · see citing works
Caloric restriction mimetics: natural/physiological pharmacological autophagy inducers
Mariño, G., Pietrocola, F., Madeo, F., & Kroemer, G. (2014) · Autophagy · doi:10.4161/auto.36413 · Cited by 107 · see citing works
Lopatina, O. L., Yoshihara, T., Nishimura, T., Zhong, J., Akther, S., Fakhrul, A. A. K. M., Liang, M., Higashida, C., Sumi, K., Furuhara, K., et al. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00133 · Cited by 106 · see citing works
“CD157 plays a variety of roles in humoral immune responses, neutrophil transmigration and haematopoietic stem cell support (Ishihara and Hirano, 2000; Funaro et al., 2004; Podestà et al., 2005; Malavasi et al., 2006; Mouchiroud et al., 2013).”
BackgroundDolopikou, C. F., Kourtzidis, I. A., Margaritelis, N. V., Vrabas, I. S., Koidou, E., Kyparos, A., Theodorou, A. A., Paschalis, V., & Nikolaidis, M. G. (2019) · European Journal of Nutrition · doi:10.1007/s00394-019-01919-4 · Cited by 105 · see citing works
Jokinen, R., Pirnes-Karhu, S., Pietiläinen, K. H., & Pirinen, E. (2017) · Redox Biology · doi:10.1016/j.redox.2017.02.011 · Cited by 103 · see citing works
“The intracellular NAD+ levels are also influenced via the action of several NAD+ consumer families such as SIRTs, PARPs and the NAD+ glycohydrolases CD38 and CD157 [77].”
Dietary restriction involves NAD +‐dependent mechanisms and a shift toward oxidative metabolism
Moroz, N., Carmona, J. J., Anderson, E. N., Hart, A. C., Sinclair, D. A., & Blackwell, T. K. (2014) · Aging Cell · doi:10.1111/acel.12273 · Cited by 90 · see citing works
“We circumvented this issue by measuring oxygen consumption rate (OCR) using the Seahorse XF24 Analyzer, which can precisely examine tens of animals per replicate.”
BackgroundResultInfluentialNicotinamide ribose ameliorates cognitive impairment of aged and Alzheimer’s disease model mice
Xie, X. M., Gao, Y., Zeng, M., Wang, Y., Wei, T.-F., Lu, Y., & Zhang, W. (2018) · Metabolic Brain Disease · doi:10.1007/s11011-018-0346-8 · Cited by 88 · see citing works
The CD38 glycohydrolase and the NAD sink: implications for pathological conditions
Zeidler, J. D., Hogan, K. A., Agorrody, G., Peclat, T., Kashyap, S., Kanamori, K. S., Gomez, L. S., Mazdeh, D. Z., Warner, G. M., Thompson, K. L., et al. (2022) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00451.2021 · Cited by 90 · see citing works
Redox imbalance and mitochondrial abnormalities in the diabetic lung
Wu, J., Jin, Z. H., & Yan, L. (2016) · Redox Biology · doi:10.1016/j.redox.2016.11.003 · Cited by 88 · see citing works
Uddin, G. M., Youngson, N. A., Doyle, B. M., Sinclair, D. A., & Morris, M. J. (2017) · Scientific Reports · doi:10.1038/s41598-017-14866-z · Cited by 82 · see citing works
Chandrasekaran, K., Choi, J., Arvas, M. I., Salimian, M., Singh, S., Xu, S., Gullapalli, R. P., Kristián, T., & Russell, J. W. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21113756 · Cited by 82 · see citing works
“NAD+ levels decline with age, in neurodegenerative conditions, after acute brain injury, and in obesity or in diabetes [18,19].”
BackgroundPoljšak, B., & Milisav, I. (2016) · Rejuvenation Research · doi:10.1089/rej.2015.1767 · Cited by 86 · see citing works
Age-dependent remodeling of gut microbiome and host serum metabolome in mice
Wu, C., Muthyala, S. D. V., Klemashevich, C. L., Ufondu, A., Menon, R., Chen, Z., Devaraj, S., Jayaraman, A., & Sun, Y. (2021) · Aging · doi:10.18632/aging.202525 · Cited by 80 · see citing works
“Emerging evidence suggests that NAD is a critical signaling molecule and essential substrate for sirtuins, a class of enzymes that mediate several of the beneficial effects of calorie restriction in model organisms, including the maintenance of cardiovascular function [38].”
Background才原一浩, Kamikubo, R., Ikemoto, K., Uchida, K., & Akagawa, M. (2017) · Biochemistry · doi:10.1021/acs.biochem.7b01185 · Cited by 78 · see citing works
Antiaging effects of bioactive molecules isolated from plants and fungi
Martel, J., Ojcius, D. M., Ko, Y., Chang, C., & Young, J. D. (2019) · Medicinal Research Reviews · doi:10.1002/med.21559 · Cited by 79 · see citing works
Luo, X., Li, R., & Yan, L. (2015) · Journal of Diabetes Research · doi:10.1155/2015/512618 · Cited by 77 · see citing works
Zhang, Z.-F., Fan, S., Zheng, Y., Lu, J. L., Wu, D., Shan, Q., & Hu, B. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.07.002 · Cited by 75 · see citing works
“Substantial evidence shows that increasing cellular NAD level exhibits beneficial effects on obesity and age-related diseases including metabolic syndrome [7,10,11,31].”
BackgroundReduced nicotinamide mononucleotide is a new and potent NAD + precursor in mammalian cells and mice
Perez, R. Z., Tammaro, A., Schomakers, B. V., Scantlebery, A. M. L., Denis, S. W., Elfrink, H. L., Giroud‐Gerbetant, J., Cantó, C., López‐Leonardo, C., McIntyre, R. L., et al. (2021) · The FASEB Journal · doi:10.1096/fj.202001826r · Cited by 75 · see citing works
Self-citationPositive effects of intermittent fasting in ischemic stroke
Fann, D., Ng, G., Poh, L., & Arumugam, T. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2017.01.014 · Cited by 66 · see citing works
Caloric restriction and exercise “mimetics”: ready for prime time
Handschin, C. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2015.11.009 · Cited by 72 · see citing works
Diverse therapeutic efficacies and more diverse mechanisms of nicotinamide
Song, S. B., Park, J., Chung, G. J., Lee, I. H., & Hwang, E. S. (2019) · Metabolomics · doi:10.1007/s11306-019-1604-4 · Cited by 72 · see citing works
Ruggieri, S., Orsomando, G., Sorci, L., & Raffaelli, N. (2015) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2015.02.021 · Cited by 71 · see citing works
“Accordingly, manipulation of NADbiosynthesis appears very promising for therapeutic benefits and, indeed, accumulating data point to enhancement of NAD synthesis as having protective effects in metabolic and neurodegenerative diseases [14].”
BackgroundChandrasekaran, K., Salimian, M., Konduru, S. R., Choi, J., Kumar, P., Long, A. N., Klimova, N., Ho, C.-Y., Kristián, T., & Russell, J. W. (2019) · Brain · doi:10.1093/brain/awz324 · Cited by 71 · see citing works
“Results from other laboratories are consistent with the observation that deletion (knockout) or inhibition of axonal degenerating pathways involving SARM1, PARP1, CD38 and DBC1 preserve NAD + for SIRT1 to mediate axonal regeneration (Barbosa et al., 2007; Obrosova et al., 2008; Osterloh et al., 2012; Chiang et al., 20…”
BackgroundInfluentialLehmann, S., Costa, A. C., Celardo, I., Loh, S. H. Y., & Martins, L. M. (2016) · Cell Death & Disease · doi:10.1038/cddis.2016.72 · Cited by 69 · see citing works
Kato, M., & Lin, S.-J. (2014) · DNA repair · doi:10.1016/j.dnarep.2014.07.009 · Cited by 68 · see citing works
The mitochondrial unfolded protein response in mammalian physiology
Mottis, A., Jovaisaite, V., & Auwerx, J. H. (2014) · Mammalian Genome · doi:10.1007/s00335-014-9525-z · Cited by 68 · see citing works
“1 overexpression, also trigger the UPRmt (Mouchiroud et al. 2013b).”
BackgroundSelf-citationZhang, Z.-F., Zhang, Y., Fan, S., Zhuang, J., Zheng, Y., Lu, J. L., Wu, D., Shan, Q., & Hu, B. (2014) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2014.09.012 · Cited by 68 · see citing works
Jadeja, R. N., Powell, F. L., Jones, M. A., Fuller, J., Joseph, E., Thounaojam, M. C., Bartoli, M., & Martin, P. M. (2018) · Aging · doi:10.18632/aging.101469 · Cited by 69 · see citing works
Sims, C. A., Guan, Y., Mukherjee, S., Singh, K., Botolin, P., Dávila, A., & Baur, J. A. (2018) · JCI Insight · doi:10.1172/jci.insight.120182 · Cited by 64 · see citing works
A systems genetics resource and analysis of sleep regulation in the mouse
Diessler, S., Jan, M., Emmenegger, Y., Guex, N., Middleton, B., Skene, D. J., Ibberson, M. R., Burdet, F., Götz, L., Pagni, M., et al. (2018) · PLoS Biology · doi:10.1371/journal.pbio.2005750 · Cited by 61 · see citing works
The role of the ribosome in the regulation of longevity and lifespan extension
MacInnes, A. W. (2016) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1325 · Cited by 61 · see citing works
Zhang, J., Zhang, W., Gao, X., Zhao, Y., Chen, D., Xu, N., Pu, H., Stetler, R. A., & Gao, Y. (2018) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x18785480 · Cited by 61 · see citing works
Clock genes-dependent acetylation of complex I sets rhythmic activity of mitochondrial OxPhos
Cela, O., Scrima, R., Pazienza, V., Merla, G., Benegiamo, G., Augello, B., Fugetto, S., Menga, M., Rubino, R., Fuhr, L., et al. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2015.12.018 · Cited by 60 · see citing works
NAD+ metabolism as a target for metabolic health: have we found the silver bullet?
Connell, N. J., Houtkooper, R. H., & Schrauwen, P. (2019) · Diabetologia · doi:10.1007/s00125-019-4831-3 · Cited by 60 · see citing works
Self-citationResveratrol attenuates oxidative stress in mitochondrial Complex I deficiency: Involvement of SIRT3
Mathieu, L., Costa, A. L., Bachelier, C. L., Slama, A., Lèbre, A.-S., Taylor, R. W., Bastin, J., & Djouadi, F. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.04.027 · Cited by 59 · see citing works
“12 acid (NA), or nicotinamide (NAM), or were based on treatment with pharmacological inhibitors of Poly(ADP ribose) polymerases (PARPs) [31].”
BackgroundPoly(ADP-Ribose) Polymerases in Host-Pathogen Interactions, Inflammation, and Immunity
Brady, P. N., Goel, A., & Johnson, M. A. (2019) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00038-18 · Cited by 58 · see citing works
Li, B. S., Zhu, R. Z., Lim, S.-H., Seo, J. H., & Choi, B.-M. (2021) · The American Journal of Chinese Medicine · doi:10.1142/s0192415x21500592 · Cited by 54 · see citing works
Pancreatic mitochondrial complex I exhibits aberrant hyperactivity in diabetes
Wu, J., Luo, X., Thangthaeng, N., Sumien, N., Chen, Z., Rutledge, M. A., Jing, S., Forster, M. J., & Yan, L. (2017) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2017.07.007 · Cited by 52 · see citing works
Epigenetic Regulation of Metabolism and Inflammation by Calorie Restriction
Hernández‐Saavedra, D., Moody, L., Xu, G. B., Chen, H., & Pan, Y. (2018) · Advances in Nutrition · doi:10.1093/advances/nmy129 · Cited by 51 · see citing works
Zheng, D., Zhang, Y., Zheng, M., Cao, T., Wang, G., Zhang, L., Ni, R., Brockman, J., Zhong, H., Fan, G., et al. (2019) · Clinical Science · doi:10.1042/cs20181022 · Cited by 51 · see citing works
Kasai, S., Yoshihara, T., Lopatina, O. L., Ishihara, K., & Higashida, H. (2017) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2017.00075 · Cited by 49 · see citing works
“CD157/BST-1 has a variety of roles in the humoral immune response, neutrophil transmigration and hematopoietic stem cell support (Ishihara and Hirano, 2000; Funaro et al., 2004; Podestà et al., 2005; Malavasi et al., 2006; Mouchiroud et al., 2013).”
BackgroundNew Therapeutic Concept of NAD Redox Balance for Cisplatin Nephrotoxicity
Oh, G., Kim, H., Shen, A., Lee, S., Yang, S., Shim, H., Cho, E. Y., Kwon, K., Kwak, T. H., & So, H. (2016) · BioMed Research International · doi:10.1155/2016/4048390 · Cited by 48 · see citing works
NutrimiRAging: Micromanaging Nutrient Sensing Pathways through Nutrition to Promote Healthy Aging
Micó, V., Berninches, L., Tapia, J., & Daimiel, L. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18050915 · Cited by 48 · see citing works
“For that reason, before these activators could be implemented, the precise role of SIRT1 in lifespan extension needs to be further clarified [85].”
BackgroundInnate Immune Cells and Their Contribution to T-Cell-Based Immunotherapy
Ginefra, P., Lorusso, G., & Vannini, N. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124441 · Cited by 47 · see citing works
Zamporlini, F., Ruggieri, S., Mazzola, F., Amici, A., Orsomando, G., & Raffaelli, N. (2014) · FEBS Journal · doi:10.1111/febs.13050 · Cited by 48 · see citing works
Ruan, Q., Ruan, J., Zhang, W., Qian, F., & Yu, Z. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.08.010 · Cited by 44 · see citing works
Lippi, L., Uberti, F., Folli, A., Turco, A., Curci, C., D’Abrosca, F., Alessandro de, S. I. R. E., & Invernizzi, M. (2022) · Aging Clinical and Experimental Research · doi:10.1007/s40520-022-02203-y · Cited by 43 · see citing works
“L-Trp, NA, and NAM are involved in the NAD+ metabolisms pathway, functioning as precursors in the biosynthesis process and enhancing NAD+ formation [47].”
BackgroundNAD+ in Cancer Prevention and Treatment: Pros and Cons
Poljšak, B. (2016) · Journal of Clinical & Experimental Oncology · doi:10.4172/2324-9110.1000165 · Cited by 44 · see citing works
“Additionally, it was reported that SIRT3 can repress the Warburg effect by regulating HIF - 1α and reprogramming cancer cell metabolism; from highly glycolytic to a shift toward oxidative phosphorylation [117,118,130,131].”
BackgroundPodocytopathy: The role of actin cytoskeleton
Ahmadian, E., Eftekhari, A., Atakishizada, S., Valiyeva, M. N., Ardalan, M., Khalilov, R. I., & Kavetskyy, T. S. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113920 · Cited by 43 · see citing works
Preyat, N., Rossi, M., Kers, J., Chen, L., Bertin, J., Gough, P. J., Moine, A. L., Rongvaux, A., Gool, F. V., & Léo, O. (2015) · Cell Death and Differentiation · doi:10.1038/cdd.2015.60 · Cited by 42 · see citing works
Implications of NAD+ Metabolism in the Aging Retina and Retinal Degeneration
Jadeja, R. N., Thounaojam, M. C., Bartoli, M., & Martin, P. M. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/2692794 · Cited by 43 · see citing works
Zhang, H., Li, J., Cao, C., Zhang, B., Yang, W., Shi, B., & Shan, A. (2020) · Food & Function · doi:10.1039/c9fo02609f · Cited by 39 · see citing works
Liu, Y., Luo, C., Li, T., Zhang, W., Zong, Z., Liu, X., & Deng, H. (2021) · Journal of Proteome Research · doi:10.1021/acs.jproteome.0c01037 · Cited by 40 · see citing works
Drugs in Development for Acute Kidney Injury
Hulse, M., & Rosner, M. H. (2019) · Drugs · doi:10.1007/s40265-019-01119-8 · Cited by 39 · see citing works
van der Velpen, V., Rosenberg, N., Maillard, V., Teav, T., Chatton, J., Gallart‐Ayala, H., & Ivanišević, J. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15362 · Cited by 38 · see citing works
“…the NAD+ production (Katsyuba et al., 2018; Rajman et al., 2018; Shi et al., 2017), considered as essential for the mitochondrial function and to improve the health outcome of age- associated metabolic diseases, such as AD (Hikosaka et al., 2021; Mitchell et al., 2018; Mouchiroud et al., 2013).”
BackgroundThe metabolite alpha-ketobutyrate extends lifespan by promoting peroxisomal function in C. elegans
Wu, N., Ma, Y., Gong, X.-Q., Zhao, P., Jia, Y.-J., Zhao, Q., Duan, J.-H., & Zou, C. (2023) · Nature Communications · doi:10.1038/s41467-023-35899-1 · Cited by 40 · see citing works
Vidugirienė, J., Leippe, D. M., Sobol, M., Vidugiris, G. J. A., Zhou, W., Meisenheimer, P. L., Gautam, P., Wennerberg, K., & Cali, J. J. (2014) · Assay and Drug Development Technologies · doi:10.1089/adt.2014.605 · Cited by 38 · see citing works
“Given the important role of nicotinamide adenine dinucleotides as redox factors in cellular metabolism and substrates in various signaling pathways, NAD(P)/NAD(P)H metabolism is a therapeutic target for novel drug development.(14,15) However, the lack of widely accepted high-throughput screening (HTS) assays for monit…”
Endothelial SIRT1 as a Target for the Prevention of Arterial Aging: Promises and Challenges
Begum, M. K., Konja, D., Singh, S., Chłopicki, S., & Wang, Y. (2021) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000001154 · Cited by 38 · see citing works
Nie, H., Zhang, Y., Yu, H., Xiao, H., Li, T., & Yang, Q. (2021) · Drug Delivery · doi:10.1080/10717544.2021.1886198 · Cited by 37 · see citing works
“More importantly, it has been reported to increase NMNAT activity and enhance NADþ biosynthesis (Grant, 2010; Mouchiroud et al., 2013; Mathieu et al., 2016).”
BackgroundChandrasekaran, K., Najimi, N., Sagi, A. R., Yarlagadda, S., Salimian, M., Arvas, M. I., Hedayat, A. F., Kevas, Y., Kadakia, A., & Russell, J. W. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094887 · Cited by 37 · see citing works
“The maintenance of NAD+ levels is central to axonal degeneration and regeneration pathways and to Mt homeostasis, including Mt oxidative phosphorylation, Mt biogenesis, and nuclear–mitochondrial communication [34,35].”
BackgroundOxidative Status Predicts Quality in Human Mesenchymal Stem Cells
Bertolo, A., Capossela, S., Fränkl, G., Baur, M., Pötzel, T., & Stoyanov, J. (2017) · Stem Cell Research & Therapy · doi:10.1186/s13287-016-0452-7 · Cited by 36 · see citing works
Nicotinamide mononucleotide as a therapeutic agent to alleviate multi-organ failure in sepsis
Cao, T., Ni, R., Ding, W., Ji, X., Fan, G., Zhang, Z., & Peng, T. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04767-3 · Cited by 36 · see citing works
“NAD + is generated through three pathways in mammals: the de novo pathway from the L-tryptophan amino acid precursor; the salvage pathway; and the Priess-Handler pathway from precursors such as nicotinamide, niacin, nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN) [2].”
Mahon, R. N., & Hafner, R. (2015) · Clinical Infectious Diseases · doi:10.1093/cid/civ621 · Cited by 36 · see citing works
Jia, Q., Cui, C., Deng, Q., Wang, L., Chen, R., Zhai, D., Xie, L., & Yu, J. (2018) · Oncology Letters · doi:10.3892/ol.2018.9400 · Cited by 37 · see citing works
“NMNAT2 is a sensitive enzyme marker for NAD levels that reflects the intracellular redox equilibrium and cellular energy state, acting as a sensor for cells with a high energy demand, including cancer cells (20,21).”
Mitochondrial Genetic Disorders: Cell Signaling and Pharmacological Therapies
Djouadi, F., & Bastin, J. (2019) · Cells · doi:10.3390/cells8040289 · Cited by 36 · see citing works
Reductive stress: The key pathway in metabolic disorders induced by overnutrition
Zhang, S., Wang, N., Gao, Z., Gao, Z., Wang, X., Xie, H., Wang, C.-Y., & Zhang, S. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2025.01.012 · Cited by 34 · see citing works
“Therefore, upregulation of sirtuins may lead to competition for NAD + with other NAD + -consuming enzymes, leading to more severe NAD + depletion, and thus aggravating reductive stress [94,95].”
Recent Advances in Inhibitors of Sirtuin1/2: An Update and Perspective
Zhou, Z., Ma, T., Zhu, Q., Xu, Y., & Zha, X. (2018) · Future Medicinal Chemistry · doi:10.4155/fmc-2017-0207 · Cited by 34 · see citing works
Connell, N., Grevendonk, L., Fealy, C., Moonen-Kornips, E., Bruls, Y., Schrauwen-Hinderling, V., de Vogel, J., Hageman, R., Geurts, J., Zapata-Perez, R., et al. (2021) · The Journal of Nutrition · doi:10.1093/jn/nxab193 · Cited by 33 · see citing works
Self-citationNeutrophil Maturation and Survival Is Controlled by IFN-Dependent Regulation of NAMPT Signaling
Siakaeva, E., Pylaeva, E., Spyra, I., Bordbari, S., Höing, B., Kürten, C. H. L., Lang, S., & Jabłońska, J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20225584 · Cited by 32 · see citing works
“As NAD+ is needed in many critical cellular processes, such as transcription, cell-cycle progression, DNA repair, and regulation of apoptosis [31,32], maintaining NAD+ content in cells prevents their death [33].”
BackgroundNovel role of PKR in palmitate-induced Sirt1 inactivation and endothelial cell senescence
Li, Y., Peng, Z., Wang, C., Li, L., Leng, Y., Chen, R., Yuan, H., Zhou, S., Zhang, Z., & Chen, A. F. (2018) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00038.2018 · Cited by 32 · see citing works
Nutritional Epigenetic Regulators in the Field of Cancer
Schnekenburger, M., & Diederich, M. F. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-800206-3.00018-5 · Cited by 32 · see citing works
Schiffers, C., Reynaert, N. L., Wouters, E. F. �., & van der Vliet, A. (2021) · Antioxidants · doi:10.3390/antiox10111799 · Cited by 31 · see citing works
“Furthermore, nicotinamide adenine dinucleotide (NAD+) is a hydrogen carrier for redox enzymes with important roles in redox homeostasis and has emerged as a critical signaling molecule and essential substrate for sirtuins (SIRT), a class of enzymes that mediate several beneficial effects related to ageing [246], inclu…”
BackgroundTherapeutic potential of nicotinamide adenine dinucleotide (NAD)
Arenas‐Jal, M., Suñé-Negre, J. M., & García‐Montoya, E. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173158 · Cited by 30 · see citing works
- Authors
- Mouchiroud, L., Houtkooper, R. H., & Auwerx, J.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Amsterdam UMC Location University of Amsterdam (NL)
- Corresponding author
- Auwerx, Johan
- Venue
- Critical Reviews in Biochemistry and Molecular Biology
- Publisher
- Informa UK Limited
- Published
- 2013-06-06
- Volume
- 48
- Issue
- 4
- Pages
- 397-408
- ISSN
- 0045-6411 (ISSN-L)
- 1040-9238
- 1549-7798
- PMC
- PMC3858599
- OpenAlex
- W2089838011
- Cited by
- 193
- References
- 137
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 11 · 2023: 8 · 2022: 9 · 2021: 25 · 2020: 16 · 2019: 18 · 2018: 18 · 2017: 19 · 2016: 15 · 2015: 22 · 2014: 14 · 2013: 2
- FWCI
- 1.71
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Critical Reviews in Biochemistry and Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (136201, 124713)
- ZonMw (91613050)
- National Heart, Lung, and Blood Institute (R01HL106511)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- NAD+ metabolism, sirtuins, Sir2, NAD+ precursors, PARP inhibition, mitochondrial function, aging, healthy aging, NAD+ supplementation, protein deacetylation
- MeSH terms
- Animals, Humans, Metabolic Diseases, NAD, Sirtuins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
