The DOI matches its Crossref record; 456 of the 456 references it cites were found in a registry or an index.
NAD+ homeostasis in health and disease
Open accessAbstract
The conceptual evolution of nicotinamide adenine dinucleotide (NAD+) from being seen as a simple metabolic cofactor to a pivotal cosubstrate for proteins regulating metabolism and longevity, including the sirtuin family of protein deacylases, has led to a new wave of scientific interest in NAD+. NAD+ levels decline during ageing, and alterations in NAD+ homeostasis can be found in virtually all age-related diseases, including neurodegeneration, diabetes and cancer. In preclinical settings, various strategies to increase NAD+ levels have shown beneficial effects, thus starting a competitive race to discover marketable NAD+ boosters to improve healthspan and lifespan. Here, we review the basics of NAD+ biochemistry and metabolism, and its roles in health and disease, and we discuss current challenges and the future translational potential of NAD+ research.
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“Pharmacological agents that induce mitophagy and have a positive impact on murine healthspan include NAD + precursors (such as nicotinamide, nicotinamide mononucleotide and nicotinamide riboside) 124 and urolithin A 125 .”
From Hallmarks of aging: An expanding universe (2023) · cites this paper as [124]
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“Accordingly, NAD+ homeostasis is required for the proper function of various metabolic tissues, including fat, muscle, intestines, kidneys and liver (reviewed in72).”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [72]
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1 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
RetractedUniProt: a worldwide hub of protein knowledge
The UniProt Consortium (2019) · Nucleic Acids Research · doi:10.1093/nar/gky1049 · Cited by 7,698
Transcriptional 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
AMPK 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
Self-citationNutrient 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
Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy
The AIM-HIGH Investigators (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1107579 · Cited by 2,911
A subcellular map of the human proteome
Thul, P. J., Åkesson, L., Wiking, M., Mahdessian, D., Geladaki, A., Ait Blal, H., Alm, T., Asplund, A., Björk, L., Breckels, L. M., et al. (2017) · Science · doi:10.1126/science.aal3321 · Cited by 2,813
Kaeberlein, M., McVey, M., & Guarente, L. (1999) · Genes & Development · doi:10.1101/gad.13.19.2570 · Cited by 2,253
Brown, G., Albers, J. J., Fisher, L. D., Schaefer, S. M., Lin, J.-T., Kaplan, C., Zhao, X.-Q., Bisson, B. D., Fitzpatrick, V. F., & Dodge, H. T. (1990) · New England Journal of Medicine · doi:10.1056/nejm199011083231901 · Cited by 2,159
Mammalian 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
Research works printed but not linked: 2
- Allegri, G., Costa, C.V.L., Ragazzi, E., Steinhart, H. & Laresio, L. Developments in Tryptophan and Serotonin Metabolism (Springer, 2012).
- Choi, S. H. et al. Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer’s mouse model. Science 361, eaan8821 (2018). · DOI · Paper page
Cited by
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Hallmarks of aging: An expanding universe
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NAD+ metabolism and its roles in cellular processes during ageing
Covarrubias, A. J., Perrone, R., Grozio, A., & Verdin, E. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00313-x · Cited by 1,617
Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193
Mittelbrunn, M., & Kroemer, G. (2021) · Nature Immunology · doi:10.1038/s41590-021-00927-z · Cited by 702
Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women
Yoshino, M., Yoshino, J., Kayser, B. D., Patti, G. J., Franczyk, M. P., Mills, K. F., Sindelar, M., Pietka, T., Patterson, B. W., Imai, S.-I., et al. (2021) · Science · doi:10.1126/science.abe9985 · Cited by 439
CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD+ and NMN levels
Chini, C. C. S., Peclat, T. R., Warner, G. M., Kashyap, S., Espindola-Netto, J. M., de Oliveira, G. C., Gomez, L. S., Hogan, K. A., Tarragó, M. G., Puranik, A. S., et al. (2020) · Nature Metabolism · doi:10.1038/s42255-020-00298-z · Cited by 349
Making sense of the ageing methylome
Seale, K., Horvath, S., Teschendorff, A., Eynon, N., & Voisin, S. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-022-00477-6 · Cited by 274
Mithaiwala, M. N., Santana-Coelho, D., Porter, G. A., & O’Connor, J. C. (2021) · Cells · doi:10.3390/cells10061548 · Cited by 190
Luukkonen, P. K., Qadri, S., Ahlholm, N., Porthan, K., Männistö, V., Sammalkorpi, H., Penttilä, A. K., Hakkarainen, A., Lehtimäki, T. E., Gaggini, M., et al. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2021.10.013 · Cited by 170
Epistasis-driven identification of SLC25A51 as a regulator of human mitochondrial NAD import
Girardi, E., Agrimi, G., Goldmann, U., Fiume, G., Lindinger, S., Sedlyarov, V., Srndic, I., Gürtl, B., Agerer, B., Kartnig, F., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19871-x · Cited by 123
Caloric Restriction Mimetics in Nutrition and Clinical Trials
Hofer, S. J., Davinelli, S., Bergmann, M., Scapagnini, G., & Madeo, F. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2021.717343 · Cited by 109
Okabe, K., Yaku, K., Uchida, Y., Fukamizu, Y., Sato, T., Sakurai, T., Tobe, K., & Nakagawa, T. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.868640 · Cited by 105
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Yang, S., Park, J. H., & Lu, H.-C. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00634-3 · Cited by 94
Ren, Z., Xu, Y., Li, T., Sun, W., Tang, Z., Wang, Y., Zhou, K., Li, J., Ding, Q., Liang, K., et al. (2022) · Animal Nutrition · doi:10.1016/j.aninu.2022.06.009 · Cited by 44
Lai, X., Huang, S., Lin, S., Pu, L., Wang, Y., Lin, Y., Huang, W., & Wang, Z. (2022) · Stem Cell Research & Therapy · doi:10.1186/s13287-021-02688-w · Cited by 26
Importance of Adipose Tissue NAD+ Biology in Regulating Metabolic Flexibility
Franczyk, M. P., Qi, N., Stromsdorfer, K. L., Li, C., Yamaguchi, S., Itoh, H., Yoshino, M., Sasaki, Y., Brookheart, R. T., Finck, B. N., et al. (2021) · Endocrinology · doi:10.1210/endocr/bqab006 · Cited by 23
Metadata
- Authors
- Katsyuba, E., Romani, M., Hofer, D., & Auwerx, J.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Thermo Fisher Scientific (Switzerland) (CH)
- Corresponding author
- Auwerx, Johan
- Venue
- Nature Metabolism
- Published
- 2020-01-20
- Volume
- 2
- Issue
- 1
- Pages
- 9-31
- ISSN
- 2522-5812 (ISSN-L)
- OpenAlex
- W3000157665
- Cited by
- 627
- References
- 456
- Citations by year
- 2026: 102 · 2025: 101 · 2024: 92 · 2023: 110 · 2022: 110 · 2021: 77 · 2020: 34
- FWCI
- 10.28
- Type
- journal article
- Language
- en
- Open access
- green
- infoscience.epfl.ch
- Licence
- Locations
- Nature Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institute on Aging (R01AG043930)
- 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+ homeostasis, NAD+ metabolism, sirtuins, aging, age-related diseases, neurodegeneration, diabetes mellitus, cancer, healthspan, lifespan
- MeSH terms
- Animals, Disease, Glycolysis, Homeostasis, Humans, Longevity, Metabolism, NAD, NADP, Oxidation-Reduction, Phosphorylation, Subcellular Fractions, Sirtuins
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