Cited by 112Sirtuins and Resveratrol in MedicineBiochemical and Molecular ResearchGenetics, Aging, and Longevity in Model Organisms

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NAD+ flux is maintained in aged mice despite lower tissue concentrations

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McReynolds, Melanie R., Chellappa, Karthikeyani, Chiles, Eric, Jankowski, Connor, Shen, Yihui, Chen, Li, Descamps, Hélène C., Mukherjee, Sarmistha, Bhat, Yashaswini R., Lingala, Siddharth R., Chu, Qingwei, Botolin, Paul, Hayat, Faisal, Doke, Tomohito, Susztak, Katalin, Thaiss, Christoph A., Lu, Wenyun, Migaud, Marie E., Su, Xiaoyang, Rabinowitz, Joshua D., Baur, Joseph A.·2021·Cell Systems

DOI 10.1016/j.cels.2021.09.001PMC PMC8678178

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Abstract

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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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: McReynolds, Melanie R.
Chellappa, Karthikeyani
Chiles, Eric
Jankowski, Connor
Shen, Yihui
Chen, Li
Descamps, Hélène C.
Mukherjee, Sarmistha
Bhat, Yashaswini R.
Botolin, Paul
Hayat, Faisal
Doke, Tomohito
Thaiss, Christoph A.
Lu, Wenyun
Migaud, Marie E.
Su, Xiaoyang
Rabinowitz, Joshua D.
Baur, Joseph A.
Venue: Cell Systems
Publisher: Elsevier BV
Published: 2021-12
Volume: 12
Issue: 12
Pages: 1160-1172.e4
ISSN: 2405-4712 (ISSN-L)
DOI: 10.1016/j.cels.2021.09.001
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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NAD+ flux is maintained in aged mice despite lower tissue concentrations

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