The DOI matches its Crossref record; 78 of the 79 references it cites were found in a registry or an index.
NAD+ flux is maintained in aged mice despite lower tissue concentrations
Open accessAbstract
NAD+ is an essential coenzyme for all living cells. NAD+ concentrations decline with age, but whether this reflects impaired production or accelerated consumption remains unclear. We employed isotope tracing and mass spectrometry to probe age-related changes in NAD+ metabolism across tissues. In aged mice, we observed modest tissue NAD+ depletion (median decrease ∼30%). Circulating NAD+ precursors were not significantly changed, and isotope tracing showed the unimpaired synthesis of nicotinamide from tryptophan. In most tissues of aged mice, turnover of the smaller tissue NAD+ pool was modestly faster such that absolute NAD+ biosynthetic flux was maintained, consistent with more active NAD+-consuming enzymes. Calorie restriction partially mitigated age-associated NAD+ decline by decreasing consumption. Acute inflammatory stress induced by LPS decreased NAD+ by impairing synthesis in both young and aged mice. Thus, the decline in NAD+ with normal aging is relatively subtle and occurs despite maintained NAD+ production, likely due to increased consumption.
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“It is recognized the decrease of NAD+ levels in various tissues during aging [11, 13, 96, 97], playing a critical role in the pathophysiology of several diseases, including age-associated metabolic disorders, neurodegenerative diseases, and mental disorders [14].”
From NAD+ Precursors Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR): Potential Dietary Contribution to Health (2023) · cites this paper as [96]
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1 retracted
Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in wistar rats
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Self-citationNampt/PBEF/Visfatin Regulates Insulin Secretion in β Cells as a Systemic NAD Biosynthetic Enzyme
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Metadata
- Authors
- McReynolds, M. R., Chellappa, K., Chiles, E., Jankowski, C., Shen, Y., Chen, L., Descamps, H. C., Mukherjee, S., Bhat, Y. R., Lingala, S. R., Chu, Q., Botolin, P., Hayat, F., Doke, T., Susztak, K., Thaiss, C. A., Lu, W., Migaud, M. E., Su, X., Rabinowitz, J. D., & Baur, J. A.
- Affiliations
- Princeton University (US)
- University of Pennsylvania (US)
- Rutgers, The State University of New Jersey (US)
- USA Mitchell Cancer Institute (US)
- Corresponding author
- Rabinowitz, Joshua D.
- Baur, Joseph A.
- ORCID
- Venue
- Cell Systems
- Publisher
- Elsevier BV
- Published
- 2021-12
- Volume
- 12
- Issue
- 12
- Pages
- 1160-1172.e4
- ISSN
- 2405-4712 (ISSN-L)
- PMC
- PMC8678178
- OpenAlex
- W3199408799
- Cited by
- 112
- References
- 79
- Citations by year
- 2026: 19 · 2025: 21 · 2024: 25 · 2023: 28 · 2022: 17 · 2021: 2
- FWCI
- 9.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 379 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell Systems (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIDDK (R01DK098656, DP1DK113643)
- Crohn's and Colitis Foundation of America
- National Institutes of Health
- Princeton University
- Children's Hospital of Philadelphia
- Rutgers Cancer Institute of New Jersey
- Diabetes Research Center (P30-DK19525)
- Burroughs Wellcome Fund
- NIA (R01AG043483)
- Howard Hughes Medical Institute
- NCI (CA211437, -CCSG P30CA072720-5923)
- 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+ metabolism, aging, NAD biosynthesis, NAD+ consumption, tryptophan, NAD+ precursors, caloric restriction, lipopolysaccharide, inflammation, aged mice
- MeSH terms
- Aging, Animals, NAD, Niacinamide, Caloric Restriction, Mice
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