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NAD and the aging process: Role in life, death and everything in between
Open accessAbstract
Life as we know it cannot exist without the nucleotide nicotinamide adenine dinucleotide (NAD). From the simplest organism, such as bacteria, to the most complex multicellular organisms, NAD is a key cellular component. NAD is extremely abundant in most living cells and has traditionally been described to be a cofactor in electron transfer during oxidation-reduction reactions. In addition to participating in these reactions, NAD has also been shown to play a key role in cell signaling, regulating several pathways from intracellular calcium transients to the epigenetic status of chromatin. Thus, NAD is a molecule that provides an important link between signaling and metabolism, and serves as a key molecule in cellular metabolic sensoring pathways. Importantly, it has now been clearly demonstrated that cellular NAD levels decline during chronological aging. This decline appears to play a crucial role in the development of metabolic dysfunction and age-related diseases. In this review we will discuss the molecular mechanisms responsible for the decrease in NAD levels during aging. Since other reviews on this subject have been recently published, we will concentrate on presenting a critical appraisal of the current status of the literature and will highlight some controversial topics in the field. In particular, we will discuss the potential role of the NADase CD38 as a driver of age-related NAD decline.
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“This decline in NAD+ levels is implicated in the development of age-related muscle dysfunction, glucose intolerance, and stem cell senescence”
From A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline (2018) · cites this paper as Chini et al., 2016
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Metadata
- Authors
- Chini, C. C. S., Tarragó, M. G., & Chini, E. N.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Chini, Eduardo N.
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 2017-11
- Volume
- 455
- Pages
- 62-74
- ISSN
- 0303-7207 (ISSN-L)
- PMC
- PMC5419884
- OpenAlex
- W2548864808
- Cited by
- 208
- References
- 155
- Citations by year
- 2026: 14 · 2025: 22 · 2024: 24 · 2023: 24 · 2022: 25 · 2021: 36 · 2020: 23 · 2019: 21 · 2018: 12 · 2017: 7
- FWCI
- 7.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG026094)
- National Cancer Institute (P50CA102701)
- 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+, aging, CD38, NADase, age-related diseases, metabolic dysfunction, NAD+ signaling, NAD+ cofactor, electron transfer, signal transduction, epigenetic regulation, calcium transients, NAD+ metabolism
- MeSH terms
- Aging, Animals, Cytoskeletal Proteins, Humans, Membrane Glycoproteins, Mitochondria, NAD, NADP, Oxidation-Reduction, Poly(ADP-ribose) Polymerases, Protein Processing, Post-Translational, Signal Transduction, Caloric Restriction, Cyclic ADP-Ribose, Sirtuins, Armadillo Domain Proteins, ADP-ribosyl Cyclase 1
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