The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
NAD + repletion improves mitochondrial and stem cell function and enhances life span in mice
Open accessAbstract
A dietary supplement protects aging muscle: The oxidized form of cellular nicotinamide adenine dinucleotide (NAD + ) is critical for mitochondrial function, and its supplementation can lead to increased longevity. Zhang et al. found that feeding the NAD + precursor nicotinamide riboside (NR) to aging mice protected them from muscle degeneration (see the Perspective by Guarente). NR treatment enhanced muscle function and also protected mice from the loss of muscle stem cells. The treatment was similarly protective of neural and melanocyte stem cells, which may have contributed to the extended life span of the NR-treated animals. Science , this issue p. 1436 ; see also p. 1396
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“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 Zhang et al., 2016
In the citing paper
“Similarly, NR treatment of aged mice resulted in increased proliferation and increased neurogenesis in both the subventricular zone and the dentate gyrus of the hippocampus in aged mice (Zhang et al., 2016).”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Zhang et al., 2016
In the citing paper
“In primary cell culture, supplementation with NR delays cellular senescence (Wiley et al., 2016), and NR treatment also reduces the senescent state in both NSCs and other stem cell types (Zhang et al., 2016).”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Zhang et al., 2016
In the citing paper
“NR supplementation delayed senescence of adult NSCs in 2-year-old mice (Zhang et al., 2016), suggesting a role for a deficit in NAD+ or one or more of the enzymes it supports in neural-cell senescence.”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Zhang et al., 2016
In the citing paper
“NR administration in old mice showed a small but significant increase in lifespan (5%)198.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [198]
In the citing paper
“Treatment with NR also improved muscle stem cell functions by regulating mitochondrial metabolism in a mouse model of muscular dystrophy197,198.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [198]
In the citing paper
“In mice, NR causes a wide range of beneficial effects, including a moderate lifespan extension [202].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [202]
In the citing paper
“Additionally, nicotinamide riboside treatment in aging mice increased skeletal muscle function by preventing stem cell senescence, improved mitochondrial function, and a higher expression of genes involved in the TCA cycle and OXPHOS (266).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [266]
In the citing paper
“Reduced NAD+ levels in skeletal muscle of aged or Nampt deficient mice alter mitochondrial bioenergetics and impair muscle mass, strength and endurance49,50,52,53”
From Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities (2019) · cites this paper as [53]
In the citing paper
“the conversion of these precursors to NAD+ bypasses the rate limited enzyme NAMPT”
From Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities (2019) · cites this paper as [53]
In the citing paper
“new therapeutic strategies have emerged to restore NAD+ levels in muscle by administration of dietary NAD+ precursors such as NR or NMN46,53,54”
From Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities (2019) · cites this paper as [53]
In the citing paper
“For example, some old MuSCs become senescent, a state characterized by irreversible cell cycle arrest and secretion of cytokines and other proteins (senescence-associated secreted phenotype)39–43.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [39]
In the citing paper
“NAD precursors such as nicotinamide riboside can restore ageing defects in ISCs120, as well as in MuSCs, NSCs and melanocyte stem cells39.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [39]
In the citing paper
“The administration of NAD precursors, in particular nicotinamide riboside and nicotinamide mononucleotide, has shown benefits in terms of healthspan219 and lifespan39.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [39]
In the citing paper
“Nicotinamide riboside also has a beneficial effects on old MuSCs, NSCs and melanocyte stem cells, in part by rescuing mitochondrial function39.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [39]
Citations
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Ageing as a risk factor for neurodegenerative disease
Hou, Y., Dan, X., Babbar, M., Wei, Y., Hasselbalch, S. G., Croteau, D. L., & Bohr, V. A. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0244-7 · Cited by 3,310
NAD+ metabolism and its roles in cellular processes during ageing
Covarrubias, A. J., Perrone, R., Grozio, A., & Verdin, E. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00313-x · Cited by 1,617
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“Nevertheless, NAD boosting strategies seem to be successful in restoringmitochondrial and stem cell function (121) and in ameliorating diseases such as muscular dystrophy and diabetes (122, 123) or even prolonging life span (124).”
BackgroundAutophagy in healthy aging and disease
Aman, Y., Schmauck-Medina, T., Hansen, M., Morimoto, R. I., Simon, A. K., Bjedov, I., Palikaras, K., Simonsen, A., Johansen, T., Tavernarakis, N., et al. (2021) · Nature Aging · doi:10.1038/s43587-021-00098-4 · Cited by 1,313
Metadata
- Authors
- Zhang, H., Ryu, D., Wu, Y., Gariani, K., Wang, X., Luan, P., D’Amico, D., Ropelle, E. R., Lutolf, M. P., Aebersold, R., Schoonjans, K., Menzies, K. J., & Auwerx, J.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- ETH Zurich (CH)
- Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
- Universidade Estadual de Campinas (UNICAMP) (BR)
- Laboratory of Stem Cell Bioengineering, EPFL, 1015 Lausanne, Switzerland.
- University of Zurich (CH)
- University of Ottawa (CA)
- Corresponding author
- Menzies, Keir J.
- Auwerx, Johan
- ORCID
- Venue
- Science
- Published
- 2016-06-17
- Volume
- 352
- Issue
- 6292
- Pages
- 1436-1443
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2343193821
- Cited by
- 1,255
- References
- 54
- Citations by year
- 2026: 109 · 2025: 139 · 2024: 110 · 2023: 123 · 2022: 142 · 2021: 151 · 2020: 131 · 2019: 111 · 2018: 114 · 2017: 93 · 2016: 29
- FWCI
- 66.83
- Type
- journal article
- Language
- en
- Open access
- green
- infoscience.epfl.ch
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- University of Ottawa
- Heart and Stroke Foundation of Canada
- NIH (R01AG043930)
- Krebsforschung Schweiz/SwissCancerLeague (KFS-3082-02-2013)
- Systems X (SySX.ch 2013/153)
- Swiss National Science Foundation (31003A-140780)
- 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 › Cell Biology › Telomeres, Telomerase, and Senescence
- Keywords
- nicotinamide riboside, muscle stem cells, mitochondrial unfolded protein response, prohibitin, mitochondrial function, aging, lifespan extension, neural stem cells, melanocyte stem cells, mdx mice, muscular dystrophy, cellular reprogramming
- MeSH terms
- Prohibitins, Animals, Disease Models, Animal, Longevity, Melanocytes, Mice, Inbred C57BL, Mitochondria, Muscular Dystrophies, NAD, Niacinamide, Pyridinium Compounds, Repressor Proteins, Cellular Senescence, Mice, Inbred mdx, Oxidative Stress, Myoblasts, Skeletal, Mice, Unfolded Protein Response, Neural Stem Cells, Cellular Reprogramming
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