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Nicotinamide Improves Aspects of Healthspan, but Not Lifespan, in Mice
Open accessAbstract
The role in longevity and healthspan of nicotinamide (NAM), the physiological precursor of NAD+, is elusive. Here, we report that chronic NAM supplementation improves healthspan measures in mice without extending lifespan. Untargeted metabolite profiling of the liver and metabolic flux analysis of liver-derived cells revealed NAM-mediated improvement in glucose homeostasis in mice on a high-fat diet (HFD) that was associated with reduced hepatic steatosis and inflammation concomitant with increased glycogen deposition and flux through the pentose phosphate and glycolytic pathways. Targeted NAD metabolome analysis in liver revealed depressed expression of NAM salvage in NAM-treated mice, an effect counteracted by higher expression of de novo NAD biosynthetic enzymes. Although neither hepatic NAD+ nor NADP+ was boosted by NAM, acetylation of some SIRT1 targets was enhanced by NAM supplementation in a diet- and NAM dose-dependent manner. Collectively, our results show health improvement in NAM-supplemented HFD-fed mice in the absence of survival effects.
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“restoration of NAD levels with the NAD precursor vitamins nicotinamide riboside (NR), nicotinamide (NAM) and nicotinic acid (NA), in addition to the biosynthetic NAD precursor nicotinamide mononucleotide (NMN), appears to mitigate several age-associated diseases2-4.”
From Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages (2020) · cites this paper as [3]
In the citing paper
“long-term administration of NAM prevented disease related to a high-fat diet, promoting healthspan, but it did not have significant effects on lifespan200.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [200]
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Lysine acetylation targets protein complexes and co-regulates major cellular functions
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High-Fat Diet Disrupts Behavioral and Molecular Circadian Rhythms in Mice
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Substrate and Functional Diversity of Lysine Acetylation Revealed by a Proteomics Survey
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Self-citationYoshino, J., Mills, K. F., Yoon, M. J., & Imai, S.-I. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.08.014 · Cited by 1,340
NAD + in aging, metabolism, and neurodegeneration
Verdin, E. (2015) · Science · doi:10.1126/science.aac4854 · Cited by 1,319
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Sodium rutin extends lifespan and health span in mice including positive impacts on liver health
Li, S., Li, J., Pan, R., Cheng, J., Cui, Q., Chen, J., & Yuan, Z. (2022) · British Journal of Pharmacology · doi:10.1111/bph.15410 · Cited by 36
Role and Potential Mechanisms of Nicotinamide Mononucleotide in Aging
Rahman, S. U., Qadeer, A., & Wu, Z. (2024) · Aging and disease · doi:10.14336/ad.2023.0519-1 · Cited by 34
Independent regulation of age associated fat accumulation and longevity
Beas, A. O., Gordon, P. B., Prentiss, C. L., Olsen, C. P., Kukurugya, M. A., Bennett, B. D., Parkhurst, S. M., & Gottschling, D. E. (2020) · Nature Communications · doi:10.1038/s41467-020-16358-7 · Cited by 33
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Hierarchical endpoints and win statistics for geromedicine trials
Abdellatif, M., Kim, Y., & Kroemer, G. (2026) · Nature Aging · doi:10.1038/s43587-026-01158-3
Metadata
- Authors
- Mitchell, S. J., Bernier, M., Aon, M. A., Cortassa, S., Kim, E. Y., Fang, E. F., Palacios, H. H., Ali, A., Navas-Enamorado, I., Di Francesco, A., Kaiser, T. A., Waltz, T. B., Zhang, N., Ellis, J. L., Elliott, P. J., Frederick, D. W., Bohr, V. A., Schmidt, M. S., Brenner, C., Sinclair, D. A., Sauve, A. A., Baur, J. A., & de Cabo, R.
- Affiliations
- National Institutes of Health (US)
- National Institute on Aging (US)
- Cornell University (US)
- University of Pennsylvania (US)
- University of Iowa (US)
- Harvard University (US)
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 27
- Issue
- 3
- Pages
- 667-676.e4
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC5854409
- OpenAlex
- W2789621916
- Cited by
- 338
- References
- 53
- Citations by year
- 2026: 25 · 2025: 26 · 2024: 44 · 2023: 40 · 2022: 52 · 2021: 53 · 2020: 40 · 2019: 42 · 2018: 16
- FWCI
- 20.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- KRIBB Repository (submittedVersion)
- Funders
- NIH (R01 AG028730)
- KRIBB Research Initiative Program
- Korea Research Institute of Bioscience and Biotechnology
- the Paul F. Glenn Foundation for Medical Research
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- nicotinamide, healthspan, lifespan, NAD+ metabolism, hepatic glucose homeostasis, high-fat diet, hepatic steatosis, glycogen accumulation, pentose phosphate pathway, glycolysis, metabolic flux analysis
- MeSH terms
- Healthy Aging, Animals, Disease Models, Animal, Fatty Liver, Inflammation, Liver, Longevity, Mice, Inbred C57BL, NAD, Niacinamide, Oxidative Stress, Dietary Supplements, Sirtuin 1, Diet, High-Fat
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