The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.
NAD+ and sirtuins in aging and disease
Open accessAbstract
Nicotinamide adenine dinucleotide (NAD(+)) is a classical coenzyme mediating many redox reactions. NAD(+) also plays an important role in the regulation of NAD(+)-consuming enzymes, including sirtuins, poly-ADP-ribose polymerases (PARPs), and CD38/157 ectoenzymes. NAD(+) biosynthesis, particularly mediated by nicotinamide phosphoribosyltransferase (NAMPT), and SIRT1 function together to regulate metabolism and circadian rhythm. NAD(+) levels decline during the aging process and may be an Achilles' heel, causing defects in nuclear and mitochondrial functions and resulting in many age-associated pathologies. Restoring NAD(+) by supplementing NAD(+) intermediates can dramatically ameliorate these age-associated functional defects, counteracting many diseases of aging, including neurodegenerative diseases. Thus, the combination of sirtuin activation and NAD(+) intermediate supplementation may be an effective antiaging intervention, providing hope to aging societies worldwide.
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In the citing paper
“The NAMPT (nicotinamide phosphoribosyltransferase) protein and NAD+ levels decreased significantly in organs, such as white adipose tissue and skeletal muscle in old mice [13] affecting the activity of NAD+ -dependent enzymes such as sirtuins [15, 98].”
From NAD+ Precursors Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR): Potential Dietary Contribution to Health (2023) · cites this paper as [15]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“During the aging process, DNA damage accumulates in the cell nucleus causing PARPs activation and reducing both NAD+ levels and SIRT1 activity [15].”
From NAD+ Precursors Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR): Potential Dietary Contribution to Health (2023) · cites this paper as [15]
Experimental — accuracy not yet measuredIn the citing paper
“several studies have proposed that PARP1 inhibition can be used to promote increases in cellular levels of NAD+ by decreasing its degradation”
From A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline (2018) · cites this paper as Imai and Guarente, 2014
In the citing paper
“PARP1 is the main PARP enzyme in mammalian tissues and utilize NAD+ during its catalysis”
From A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline (2018) · cites this paper as Imai and Guarente, 2014
In the citing paper
“have been implicated in the regulation of chromosomal integrity, DNA damage repair, metabolism, aging, health span, and longevity”
From A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline (2018) · cites this paper as Imai and Guarente, 2014
In the citing paper
“Sirtuins are enzymes that remove specific covalent modification in lysine residues, such as acetylation, malonylation, and succinylation, in several proteins”
From A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline (2018) · cites this paper as Imai and Guarente, 2014
In the citing paper
“Sirtuin activity and NAD levels both decline with age116,117.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [116]
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Citations
Cites
2 retracted
RETRACTED: 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
Self-citationRetractedSIRT1 Protects against α-Synuclein Aggregation by Activating Molecular Chaperones
Dönmez, G., Arun, A., Chung, C. Y., McLean, P. J., Lindquist, S. L., & Guarente, L. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.3442-11.2012 · Cited by 208
Self-citationRetractedTranscriptional 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
Self-citationStress-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
Nutrient 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
Kaeberlein, M., McVey, M., & Guarente, L. (1999) · Genes & Development · doi:10.1101/gad.13.19.2570 · Cited by 2,253
Self-citationMammalian 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
Lin, S.-J., Defossez, P.-A., & Guarente, L. (2000) · Science · doi:10.1126/science.289.5487.2126 · Cited by 1,775
Self-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 1,603
Self-citationGomes, 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
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Functions and mechanisms of non-histone protein acetylation
Narita, T., Weinert, B. T., & Choudhary, C. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0081-3 · Cited by 1,232
NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential
Xie, N., Zhang, L., Gao, W. Q., Huang, C., Huber, P., Zhou, X., Li, C. L., Shen, G., & Zou, B. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00311-7 · Cited by 1,147
NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR
Yoshino, J., Baur, J. A., & Imai, S.-I. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.11.002 · Cited by 1,061
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
Self-citationAcetyl-CoA and the regulation of metabolism: mechanisms and consequences
Shi, L., & Tu, B. P. (2015) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2015.02.003 · Cited by 903
“The dependency of sirtuins on NAD+ have led to the hypothesis that their activity could be regulated by fluctuations in NAD+ concentrations [63,64].”
Background
Metadata
- Authors
- Imai, S.-I., & Guarente, L.
- Affiliations
- Washington University in St. Louis (US)
- Koch Institute for Integrative Cancer Research At MIT (US)
- Corresponding author
- Imai, Shin-ichiro
- Guarente, Leonard
- Venue
- Trends in Cell Biology
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 24
- Issue
- 8
- Pages
- 464-471
- ISSN
- 0962-8924 (ISSN-L)
- PMC
- PMC4112140
- OpenAlex
- W1989674299
- Cited by
- 1,481
- References
- 71
- Citations by year
- 2026: 210 · 2025: 157 · 2024: 134 · 2023: 138 · 2022: 147 · 2021: 118 · 2020: 140 · 2019: 90 · 2018: 112 · 2017: 105 · 2016: 62 · 2015: 59 · 2014: 8
- FWCI
- 6.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- PMC
- Funders
- Glenn Foundation for Medical Research
- National Institutes of Health
- National Institute on Aging (R01AG024150, AG037457, R01AG037457, R01AG015339, AG024150, R01AG011119)
- 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 › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- NAD+, sirtuins, aging, NAD biosynthesis, visfatin, SIRT1, poly(ADP-ribose) polymerase, NAD+ precursors, anti-aging interventions, neurodegenerative diseases, mitochondrial function, circadian rhythm, metabolism
- MeSH terms
- Aging, Animals, Circadian Rhythm, Disease, Humans, Mitochondria, NAD, Sirtuins
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