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Nicotinamide Improves Aspects of Healthspan, but Not Lifespan, in Mice
Open accessAbstract
The role in longevity and healthspan of nicotinamide (NAM), the physiological precursor of NAD+, is elusive. Here, we report that chronic NAM supplementation improves healthspan measures in mice without extending lifespan. Untargeted metabolite profiling of the liver and metabolic flux analysis of liver-derived cells revealed NAM-mediated improvement in glucose homeostasis in mice on a high-fat diet (HFD) that was associated with reduced hepatic steatosis and inflammation concomitant with increased glycogen deposition and flux through the pentose phosphate and glycolytic pathways. Targeted NAD metabolome analysis in liver revealed depressed expression of NAM salvage in NAM-treated mice, an effect counteracted by higher expression of de novo NAD biosynthetic enzymes. Although neither hepatic NAD+ nor NADP+ was boosted by NAM, acetylation of some SIRT1 targets was enhanced by NAM supplementation in a diet- and NAM dose-dependent manner. Collectively, our results show health improvement in NAM-supplemented HFD-fed mice in the absence of survival effects.
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“restoration of NAD levels with the NAD precursor vitamins nicotinamide riboside (NR), nicotinamide (NAM) and nicotinic acid (NA), in addition to the biosynthetic NAD precursor nicotinamide mononucleotide (NMN), appears to mitigate several age-associated diseases2-4.”
From Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages (2020) · cites this paper as [3]
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“long-term administration of NAM prevented disease related to a high-fat diet, promoting healthspan, but it did not have significant effects on lifespan200.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [200]
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Cites
The Pathobiology of Diabetic Complications
Brownlee, M. (2005) · Diabetes · doi:10.2337/diabetes.54.6.1615 · Cited by 5,339
Lysine acetylation targets protein complexes and co-regulates major cellular functions
Choudhary, C., Kumar, C., Gnad, F., Nielsen, M. L., Rehman, M., Walther, T. C., Olsen, J. V., & Mann, M. (2009) · Science · doi:10.1126/science.1175371 · Cited by 4,040
Negative Control of p53 by Sir2α Promotes Cell Survival under Stress
Luo, J., Nikolaev, A. Y., Imai, S.-I., Chen, D., Su, F., Shiloh, A., Guarente, L., & Gu, W. (2001) · Cell · doi:10.1016/s0092-8674(01)00524-4 · Cited by 2,081
Regulation of cellular metabolism by protein lysine acetylation
Zhao, S., Xu, W., Jiang, W., Yu, W., Lin, Y., Zhang, T., Yao, J., Zhou, L., Zeng, Y., Li, H., et al. (2010) · Science · doi:10.1126/science.1179689 · Cited by 1,910
Cantó, C., Menzies, K. J., & Auwerx, J. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.023 · Cited by 1,648
High-Fat Diet Disrupts Behavioral and Molecular Circadian Rhythms in Mice
Kohsaka, A., Laposky, A. D., Ramsey, K. M., Estrada, C., Joshu, C., Kobayashi, Y., Turek, F. W., & Bass, J. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.09.006 · Cited by 1,528
Substrate and Functional Diversity of Lysine Acetylation Revealed by a Proteomics Survey
Kim, S. C., Sprung, R., Chen, Y., Xu, Y., Ball, H., Pei, J., Cheng, T., Kho, Y., Xiao, H., Xiao, L., et al. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.06.026 · Cited by 1,487
Gomes, A. P., Price, N. L., Ling, A. J. Y., Moslehi, J. J., Montgomery, M. K., Rajman, L., White, J. P., Teodoro, J. S., Wrann, C. D., Hubbard, B. P., et al. (2013) · Cell · doi:10.1016/j.cell.2013.11.037 · Cited by 1,482
Self-citationYoshino, 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
NAD + in aging, metabolism, and neurodegeneration
Verdin, E. (2015) · Science · doi:10.1126/science.aac4854 · Cited by 1,319
Cantó, 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
Self-citationThe interaction of hepatic lipid and glucose metabolism in liver diseases
Bechmann, L. P., Hannivoort, R. A., Gerken, G., Hotamışlıgil, G. S., Trauner, M., & Canbay, A. E. (2011) · Journal of Hepatology · doi:10.1016/j.jhep.2011.08.025 · Cited by 1,033
Acetylation of Metabolic Enzymes Coordinates Carbon Source Utilization and Metabolic Flux
Wang, Q., Zhang, Y., Yang, C., Xiong, H., Lin, Y., Yao, J., Li, H., Xie, L., Zhao, W., Yao, Y., et al. (2010) · Science · doi:10.1126/science.1179687 · Cited by 1,008
NAD+ metabolism in health and disease
Belenky, P. A., Bogan, K. L., & Brenner, C. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2006.11.006 · Cited by 1,006
Self-citationBitterman, K. J., Anderson, R. M., Cohen, H. Y., Latorre-Esteves, M., & Sinclair, D. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205670200 · Cited by 1,002
Self-citationMills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., Redpath, P., Migaud, M. E., Apte, R. S., Uchida, K., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.09.013 · Cited by 930
Camacho-Pereira, J., Tarragó, M. G., Chini, C. C. S., Nin, V., Escande, C., Warner, G. M., Puranik, A. S., Schoon, R. A., Reid, J. M., Galina, A., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.006 · Cited by 901
Bieganowski, P., & Brenner, C. (2004) · Cell · doi:10.1016/s0092-8674(04)00416-7 · Cited by 750
Self-citationThe randle cycle revisited: a new head for an old hat.
Hue, L., & Taegtmeyer, H. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00093.2009 · Cited by 743
Therapeutic application of histone deacetylase inhibitors for central nervous system disorders
Kazantsev, A. G., & Thompson, L. M. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2681 · Cited by 727
Bogan, K. L., & Brenner, C. (2008) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.28.061807.155443 · Cited by 707
Self-citationNicotinamide riboside is uniquely and orally bioavailable in mice and humans
Trammell, S. A. J., Schmidt, M. S., Weidemann, B. J., Redpath, P., Jaksch, F., Dellinger, R. W., Li, Z., Abel, E. D., Migaud, M. E., & Brenner, C. (2016) · Nature Communications · doi:10.1038/ncomms12948 · Cited by 697
Self-citationQuality control for plant metabolomics: reporting MSI‐compliant studies
Fiehn, O., Wohlgemuth, G., Scholz, M., Kind, T., Lee, D. Y., Lü, Y., Moon, S. M., & Nikolau, B. J. (2008) · The Plant Journal · doi:10.1111/j.1365-313x.2007.03387.x · Cited by 677
Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice
Mitchell, S. J., Madrigal-Matute, J., Scheibye-Knudsen, M., Fang, E., Aon, M., González-Reyes, J. A., Cortassa, S., Kaushik, S., Gonzalez-Freire, M., Patel, B., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.027 · Cited by 451 · cited 2×
“Metabolomic analysis was performed by the West Coast Metabolomics Center at UC Davis (Davis, CA) in livers and serum of nonfasted animals as previously described (Mitchell et al., 2016).”
MethodSelf-citationBelenky, P., Racette, F. G., Bogan, K. L., McClure, J. M., Smith, J. S., & Brenner, C. (2007) · Cell · doi:10.1016/j.cell.2007.03.024 · Cited by 411
Self-citationPicciotto, N. E., Gano, L. B., Johnson, L. C., Martens, C. R., Sindler, A. L., Mills, K. F., Imai, S., & Seals, D. R. (2016) · Aging Cell · doi:10.1111/acel.12461 · Cited by 396
Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3
Khan, N. A., Auranen, M., Paetau, I., Pirinen, E., Euro, L., Forsström, S., Pasila, L., Velagapudi, V., Carroll, C. J., Auwerx, J., et al. (2014) · EMBO Molecular Medicine · doi:10.1002/emmm.201403943 · Cited by 385
NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells
Ratajczak, J., Joffraud, M., Trammell, S. A. J., Ras, R., Canela, N., Boutant, M., Kulkarni, S. S., Rodrigues, M., Redpath, P., Migaud, M. E., et al. (2016) · Nature Communications · doi:10.1038/ncomms13103 · Cited by 378 · cited 3×
“Quantitative metabolomic analysis has made it clear that oral NR boosts hepatic NAD metabolism and sirtuin activity independently of NAMPT (Ratajczak et al., 2016; Fletcher et al., 2017), thereby leading to a wave of hepatic NAM production (Trammell et al.”
BackgroundSelf-citationA high-fat diet and NAD(+) activate Sirt1 to rescue premature aging in Cockayne syndrome
Scheibye-Knudsen, M., Mitchell, S. J., Fang, E. F., Iyama, T., Ward, T., Wang, J., Dunn, C. A., Singh, N., Veith, S., Hasan-Olive, M. M., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.10.005 · Cited by 352
Self-citationNormalization of NAD + Redox Balance as a Therapy for Heart Failure
Lee, C. F., Chavez, J. D., Garcia‐Menendez, L., Choi, Y. S., Roe, N. D., Chiao, Y. A., Edgar, J. S., Goo, Y. A., Goodlett, D. R., Bruce, J. E., et al. (2016) · Circulation · doi:10.1161/circulationaha.116.022495 · Cited by 342
SRT1720 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 306
Self-citationNicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice
Trammell, S. A. J., Weidemann, B. J., Chadda, A., Yorek, M. S., Holmes, A., Coppey, L. J., Obrosov, A., Kardon, R. H., Yorek, M. A., & Brenner, C. (2016) · Scientific Reports · doi:10.1038/srep26933 · Cited by 301 · cited 7×
“Quantitative metabolomic analysis has made it clear that oral NR boosts hepatic NAD metabolism and sirtuin activity independently of NAMPT (Ratajczak et al., 2016; Fletcher et al., 2017), thereby leading to a wave of hepatic NAM production (Trammell et al., 2016a).”
BackgroundMethodInfluentialSelf-citationAnderson, R. M., Bitterman, K. J., Wood, J. G., Medvedik, O., Cohen, H. Y., Lin, S., Manchester, J. K., Gordon, J. I., & Sinclair, D. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111773200 · Cited by 295
Self-citationThe clinical development of histone deacetylase inhibitors as targeted anticancer drugs
Marks, P. (2010) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2010.510514 · Cited by 285
Oxenkrug, G. F. (2013) · Molecular Neurobiology · doi:10.1007/s12035-013-8497-4 · Cited by 264
Hong, S., Moreno‐Navarrete, J. M., Wei, X., Kikukawa, Y., Tzameli, I., Prasad, D., Lee, Y., Asara, J. M., Fernández‐Real, J. M., Maratos–Flier, E., et al. (2015) · Nature Medicine · doi:10.1038/nm.3882 · Cited by 260
NAD + repletion improves muscle function in muscular dystrophy and counters global PARylation
Ryu, D., Zhang, H., Ropelle, E. R., Sorrentino, V., Mázala, D. A. G., Mouchiroud, L., Marshall, P. L., Campbell, M. D., Ali, A. S., Knowels, G. M., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf5504 · Cited by 256
Self-citationMitochondrially targeted compounds and their impact on cellular bioenergetics
Reily, C., Mitchell, T., Chacko, B. K., Benavides, G. A., Murphy, M. P., & Darley-Usmar, V. M. (2013) · Redox Biology · doi:10.1016/j.redox.2012.11.009 · Cited by 227
Hepatic NAD+ deficiency as a therapeutic target for non‐alcoholic fatty liver disease in ageing
Zhou, C., Yang, X., Hua, X., Liu, J., Fan, M.-B., Li, G., Song, J., Xu, T., Li, Z., Guan, Y., et al. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13513 · Cited by 202
Kaneko, S., Wang, J., Kaneko, M., Yiu, G. C., Hurrell, J., Chitnis, T., Khoury, S. J., & He, Z. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.2116-06.2006 · Cited by 161
Yang, S. J., Choi, J. M., Kim, L., Park, S. E., Rhee, E., Lee, W., Oh, K. W., Park, S. W., & Park, C.-Y. (2013) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2013.09.004 · Cited by 135
Lysine acetylation in obesity, diabetes and metabolic disease
Iyer, A., Fairlie, D. P., & Brown, L. (2011) · Immunology and Cell Biology · doi:10.1038/icb.2011.99 · Cited by 127
Fletcher, R. S., Ratajczak, J., Doig, C. L., Oakey, L. A., Callingham, R., Xavier, G. D. S., Garten, A., Elhassan, Y., Redpath, P., Migaud, M. E., et al. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.05.011 · Cited by 125
Self-citationIntegrating Mitochondrial Energetics, Redox and ROS Metabolic Networks: A Two-Compartment Model
Kembro, J. M., Aon, M. A., Winslow, R. L., O'Rourke, B. P., & Cortassa, S. C. (2013) · Biophysical Journal · doi:10.1016/j.bpj.2012.11.3808 · Cited by 105
Self-citationImai, S. (2010) · Pharmacological Research · doi:10.1016/j.phrs.2010.01.006 · Cited by 92
Cortassa, S. C., Aon, J. C., & Aon, M. A. (1995) · Biotechnology and Bioengineering · doi:10.1002/bit.260470211 · Cited by 90
Self-citationGuan, X., Lin, P. C., Knoll, E., & Chakrabarti, R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0107729 · Cited by 87
Savinell, J. M., & Palsson, B. Ø. (1992) · Journal of Theoretical Biology · doi:10.1016/s0022-5193(05)80595-8 · Cited by 81
NNMT: A Bad Actor in Fat Makes Good in Liver
Trammell, S. A. J., & Brenner, C. H. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.07.017 · Cited by 50
Self-citationQi, Z., Xia, J., Xue, X., He, Q., Ji, L., & Ding, S. (2016) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2016.07.005 · Cited by 37
Is NADH Effective in the Treatment of Parkinson??s Disease?
Swerdlow, R. H. (1998) · Drugs & Aging · doi:10.2165/00002512-199813040-00002 · Cited by 24
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Aitken, M., Broadhurst, B., & Hladky, S. (2009) · Garland Science eBooks · doi:10.4324/9780203833520 · Cited by 15
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Doube, M. (2010) · Journal of Anatomy · doi:10.1111/j.1469-7580.2009.01195.x · Cited by 5
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Metadata
- Authors
- Mitchell, S. J., Bernier, M., Aon, M. A., Cortassa, S., Kim, E. Y., Fang, E. F., Palacios, H. H., Ali, A., Navas-Enamorado, I., Di Francesco, A., Kaiser, T. A., Waltz, T. B., Zhang, N., Ellis, J. L., Elliott, P. J., Frederick, D. W., Bohr, V. A., Schmidt, M. S., Brenner, C., Sinclair, D. A., Sauve, A. A., Baur, J. A., & de Cabo, R.
- Affiliations
- National Institutes of Health (US)
- National Institute on Aging (US)
- Cornell University (US)
- University of Pennsylvania (US)
- University of Iowa (US)
- Harvard University (US)
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 27
- Issue
- 3
- Pages
- 667-676.e4
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC5854409
- OpenAlex
- W2789621916
- Cited by
- 338
- References
- 53
- Citations by year
- 2026: 25 · 2025: 26 · 2024: 44 · 2023: 40 · 2022: 52 · 2021: 53 · 2020: 40 · 2019: 42 · 2018: 16
- FWCI
- 20.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- KRIBB Repository (submittedVersion)
- Funders
- NIH (R01 AG028730)
- KRIBB Research Initiative Program
- Korea Research Institute of Bioscience and Biotechnology
- the Paul F. Glenn Foundation for Medical Research
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- nicotinamide, healthspan, lifespan, NAD+ metabolism, hepatic glucose homeostasis, high-fat diet, hepatic steatosis, glycogen accumulation, pentose phosphate pathway, glycolysis, metabolic flux analysis
- MeSH terms
- Healthy Aging, Animals, Disease Models, Animal, Fatty Liver, Inflammation, Liver, Longevity, Mice, Inbred C57BL, NAD, Niacinamide, Oxidative Stress, Dietary Supplements, Sirtuin 1, Diet, High-Fat
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