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Circadian Control of the NAD + Salvage Pathway by CLOCK-SIRT1
Open accessAbstract
Circadian Oscillations: The 24-hour day-night cycle plays an important role in mammalian physiology and behavior and, as most travelers are well aware, there is an intimate link between our in-built circadian clocks and metabolic rhythms. This link is in part forged by the protein deacetylase SIRT1, which regulates the clock's molecular circuitry. SIRT1 uses as a cofactor the cellular metabolite NAD + , which is synthesized through a salvage pathway that includes the enzyme nicotinamide phosphoribosyltransferase (NAMPT) (see the Perspective by Wijnen ). Ramsey et al. (p. 651 ; published online 19 March) and Nakahata et al. (p. 654 , published online 12 March) now show that NAMPT and NAD + levels oscillate during the daily 24-hour cycle and that this oscillation is regulated by the circadian clock. Furthermore, the oscillations in NAD + modulate the activity of SIRT1 feeding back into the circadian clock.
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“Mouse embryo fibroblast (MEF) cells deficient in the CLOCK transcription factor were reported to contain only 4%–5% as much NAD+ as wild-type MEF cells”
From Influence of Metabolism on Epigenetics and Disease (2013) · cites this paper as Nakahata et al., 2009
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“NAD+ levels fluctuate as a function of the circadian cycle, thereby instructing nuclear sirtuin enzymes to control the epigenetic state of chromatin in an NAD+-regulated manner.”
From Influence of Metabolism on Epigenetics and Disease (2013) · cites this paper as Nakahata et al., 2009
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Metadata
- Authors
- Nakahata, Y., Sahar, S., Astarita, G., Kaluzova, M., & Sassone-Corsi, P.
- Affiliations
- University of California, Irvine (US)
- Department of Pharmacology, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.
- Venue
- Science
- Published
- 2009-05
- Volume
- 324
- Issue
- 5927
- Pages
- 654-657
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC6501775
- OpenAlex
- W1968890500
- Cited by
- 1,198
- References
- 27
- Citations by year
- 2026: 49 · 2025: 60 · 2024: 47 · 2023: 58 · 2022: 71 · 2021: 70 · 2020: 83 · 2019: 67 · 2018: 63 · 2017: 68 · 2016: 75 · 2015: 86 · 2014: 75 · 2013: 80 · 2012: 69
- FWCI
- 35.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM081634)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Keywords
- circadian clock, NAD+ salvage pathway, SIRT1, visfatin, Clock/BMAL1, histone deacetylase, histone acetyltransferase, NAD levels, circadian gene expression, FK866, cellular metabolism
- MeSH terms
- Acrylamides, Animals, Biological Clocks, Cell Line, Circadian Rhythm, Enzyme Inhibitors, Gene Expression Regulation, Male, Mice, Inbred BALB C, NAD, Niacinamide, Piperidines, Promoter Regions, Genetic, Transcription, Genetic, Trans-Activators, Cytokines, Mice, Knockout, Feedback, Physiological, Sirtuins, Chromatin Assembly and Disassembly, Mice, Basic Helix-Loop-Helix Proteins, Nicotinamide Phosphoribosyltransferase, Sirtuin 1, CLOCK Proteins, ARNTL Transcription Factors
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