Circadian Clock Feedback Cycle Through NAMPT-Mediated NAD + Biosynthesis
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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NAD+ levels fluctuate with the circadian cycle, instructing nuclear sirtuins to control chromatin epigenetic state.
“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 Ramsey et al., 2009
In wild-type mouse liver, NAD+ abundance shows two ultradian peaks and troughs per 24 hr cycle, with peak-to-trough fluctuation of 20-30%.
“When NAD+ levels were measured in liver tissue of wild-type mice, two ultradian sets of peaks and troughs of NAD+ abundance were observed per 24 hr cycle (Ramsey et al., 2009). The peak-to-trough fluctuation in NAD+ abundance varied by 20%–30%, as reported in the latter study.”
From Influence of Metabolism on Epigenetics and Disease (2013) · cites this paper as Ramsey et al., 2009
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- Authors
- Ramsey, K. M., Yoshino, J., Brace, C. S., Abrassart, D., Kobayashi, Y., Marcheva, B., Hong, H.-K., Chong, J. L., Buhr, E. D., Lee, C., Takahashi, J. S., Imai, S.-I., & Bass, J.
- Affiliations
- Northwestern University (US)
- Washington University in St. Louis (US)
- Florida State University (US)
- Corresponding author
- Ramsey, Kathryn Moynihan
- Yoshino, Jun
- Brace, Cynthia S.
- Imai, Shin-ichiro
- Bass, Joseph
- ORCID
- Venue
- Science
- Published
- 2009-05
- Volume
- 324
- Issue
- 5927
- Pages
- 651-654
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2738420
- OpenAlex
- W2160700740
- Cited by
- 1,126
- References
- 25
- Citations by year
- 2026: 43 · 2025: 45 · 2024: 43 · 2023: 59 · 2022: 63 · 2021: 68 · 2020: 76 · 2019: 63 · 2018: 70 · 2017: 62 · 2016: 68 · 2015: 81 · 2014: 71 · 2013: 81 · 2012: 65
- FWCI
- 33.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (5p50mh074924-05)
- National Institute on Aging (R01AG024150, P01AG011412, AG02150)
- National Institute of Mental Health (P50 MH-074924)
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007169)
- 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 › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- circadian clock, visfatin, NAD biosynthesis, SIRT1, NAD+ salvage pathway, circadian oscillations, metabolic rhythms, protein deacetylase
- MeSH terms
- Acrylamides, Animals, Biological Clocks, Cell Line, Circadian Rhythm, Enzyme Inhibitors, Gene Expression Regulation, Humans, Liver, NAD, Nuclear Proteins, Piperidines, Protein Binding, Transcription Factors, Transcription, Genetic, Trans-Activators, Cytokines, Cell Cycle Proteins, Hepatocytes, Feedback, Physiological, Sirtuins, Cell Line, Tumor, Mice, Basic Helix-Loop-Helix Proteins, Adipose Tissue, White, Nicotinamide Phosphoribosyltransferase, Sirtuin 1, CLOCK Proteins, ARNTL Transcription Factors, Period Circadian Proteins
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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.
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