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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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“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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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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