The DOI matches its Crossref record; 136 of the 137 references it cites were found in a registry or an index.
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.
Overview
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
Verification
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?
In the citing paper
“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]
In the citing paper
“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.
Citations
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×
“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 443
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×
“…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×
“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×
“…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×
“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×
“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×
“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×
“, 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×
“During fasting and exercise, the level of NAD+ increases (Canto et al., 2009, 2010).”
BackgroundSelf-citation
Research works printed but not linked: 2
- McCay CM, 1989, 1935. Nutrition, 5, 155
- Takaoka MJ, 1939, J Chem Soc Jpn, 60, 1090
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
“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
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
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
Jones, D. P., & Sies, H. (2015) · Antioxidants & Redox Signaling · doi:10.1089/ars.2015.6247 · Cited by 647
“The NAD system is increasingly recognized as an attractive target for intervention in age-associated disorders (72).”
Background
Metadata
- 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
