The NAD-booster nicotinamide riboside potently stimulates hematopoiesis through increased mitochondrial clearance
Open accessAbstract
It has been recently shown that increased oxidative phosphorylation, as reflected by increased mitochondrial activity, together with impairment of the mitochondrial stress response, can severely compromise hematopoietic stem cell (HSC) regeneration. Here we show that the NAD+-boosting agent nicotinamide riboside (NR) reduces mitochondrial activity within HSCs through increased mitochondrial clearance, leading to increased asymmetric HSC divisions. NR dietary supplementation results in a significantly enlarged pool of progenitors, without concurrent HSC exhaustion, improves survival by 80%, and accelerates blood recovery after murine lethal irradiation and limiting-HSC transplantation. In immune-deficient mice, NR increased the production of human leucocytes from hCD34+ progenitors. Our work demonstrates for the first time a positive effect of NAD+-boosting strategies on the most primitive blood stem cells, establishing a link between HSC mitochondrial stress, mitophagy, and stem-cell fate decision, and unveiling the potential of NR to improve recovery of patients suffering from hematological failure including post chemo- and radiotherapy.
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Mounting evidence supports a critical role for NAD+ in stem cell rejuvenation, including in hematopoietic stem cells, endothelial stem cells, muscle stem cells, and melanocyte stem cells.
“Mounting evidence supports a critical role for NAD+ in stem cell rejuvenation, including in HSCs, endothelial stem cells, muscle stem cells, and melanocyte stem cells (Das et al., 2018; Vannini et al., 2019; Zhang et al., 2016).”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Vannini et al., 2019
Nicotinamide riboside improves HSC function in young mice.
“Likewise, nicotinamide riboside improves HSC function in young mice221 and ameliorates the lymphoid potential of HSCs in old mice222.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [221]
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- Authors
- Vannini, N., Campos, V., Girotra, M., Trachsel, V., Rojas-Sutterlin, S., Tratwal, J., Ragusa, S., Stefanidis, E., Ryu, D., Rainer, P. Y., Nikitin, G., Giger, S., Li, T. Y., Semilietof, A., Oggier, A., Yersin, Y., Tauzin, L., Pirinen, E., Cheng, W.-C., Ratajczak, J., Canto, C., Ehrbar, M., Sizzano, F., Petrova, T. V., Vanhecke, D., Zhang, L., Romero, P., Nahimana, A., Cherix, S., Duchosal, M. A., Ho, P.-C., Deplancke, B., Coukos, G., Auwerx, J., Lutolf, M. P., & Naveiras, O.
- Affiliations
- Centre Hospitalier Universitaire Vaudois (CH)
- École Polytechnique Fédérale de Lausanne (CH)
- Democritus University of Thrace (GR)
- University of Zurich (CH)
- Corresponding author
- Vannini, Nicola
- Naveiras, Olaia
- ORCID
- Vannini, Nicola
- Girotra, Mukul
- Tratwal, Josefine
- Ragusa, Simone
- Stefanidis, Evangelos
- Ryu, Dongryeol
- Rainer, Pernille Y.
- Giger, Sonja
- Li, Terytty Y.
- Semilietof, Aikaterini
- Pirinen, Eija
- Ratajczak, Joanna
- Ehrbar, Martin
- Sizzano, Federico
- Petrova, Tatiana V.
- Vanhecke, Dominique
- Zhang, Lianjun
- Romero, Pedro
- Nahimana, Aimable
- Duchosal, Michel A.
- Ho, Ping-Chih
- Deplancke, Bart
- Coukos, George
- Auwerx, Johan
- Naveiras, Olaia
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2019-03
- Volume
- 24
- Issue
- 3
- Pages
- 405-418.e7
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2920849273
- Cited by
- 218
- References
- 71
- Citations by year
- 2026: 25 · 2025: 18 · 2024: 29 · 2023: 39 · 2022: 27 · 2021: 33 · 2020: 35 · 2019: 12
- FWCI
- 18.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- SERVAL (Université de Lausanne) (acceptedVersion, cc-by-nc-nd)
- Työväentutkimus Vuosikirja (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- IRIS (submittedVersion, cc-by-nc-nd)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- H2020 Marie Skłodowska-Curie Actions (CRSII3_147684)
- Swiss Cancer Foundation
- European Research Council (StG_311422)
- Fondation Pierre Mercier pour la Science
- École Polytechnique Fédérale de Lausanne
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A-140780, PP00P3_144857, PP00P3_176990)
- Swiss Cancer Research Foundation (KFS-3949-08-2016)
- F. Hoffmann-La Roche
- Fondation Dr Henri Dubois-Ferrière Dinu Lipatti
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
- Keywords
- nicotinamide riboside, NAD+ supplementation, hematopoiesis, hematopoietic stem cells, mitochondrial clearance, mitophagy, mitochondrial stress, asymmetric stem cell division, oxidative phosphorylation
- MeSH terms
- Animals, Cells, Cultured, Hematopoiesis, Hematopoietic Stem Cells, Humans, Mice, Inbred C57BL, Mitochondria, NAD, Niacinamide, Pyridinium Compounds, Mice, Knockout, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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