Specific ablation of Nampt in adult neural stem cells recapitulates their functional defects during aging
Open accessAbstract
Neural stem/progenitor cell (NSPC) proliferation and self-renewal, as well as insult-induced differentiation, decrease markedly with age. The molecular mechanisms responsible for these declines remain unclear. Here, we show that levels of NAD(+) and nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme in mammalian NAD(+) biosynthesis, decrease with age in the hippocampus. Ablation of Nampt in adult NSPCs reduced their pool and proliferation in vivo. The decrease in the NSPC pool during aging can be rescued by enhancing hippocampal NAD(+) levels. Nampt is the main source of NSPC NAD(+) levels and required for G1/S progression of the NSPC cell cycle. Nampt is also critical in oligodendrocytic lineage fate decisions through a mechanism mediated redundantly by Sirt1 and Sirt2. Ablation of Nampt in the adult NSPCs in vivo reduced NSPC-mediated oligodendrogenesis upon insult. These phenotypes recapitulate defects in NSPCs during aging, giving rise to the possibility that Nampt-mediated NAD(+) biosynthesis is a mediator of age-associated functional declines in NSPCs.
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NAD+ declines with age in several tissues, linking NAD to both senescence and aging.
“Notably, NAD+ declines with age in several tissues”
From Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype (2016) · cites this paper as Stein and Imai, 2014
NMN has a significant effect on improving disease conditions and reducing age-related physiological decline.
“These studies also documented that NMN has a significant effect on improving disease conditions and reducing age-related physiological decline [203–206].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [206]
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Chen, X., Amorim, J. A., Moustafa, G. A., Lee, J., Yu, Z., Ishihara, K., Iesato, Y., Barbisan, P. R. T., Ueta, T., Togka, K. A., et al. (2020) · Aging · doi:10.18632/aging.202453 · Cited by 47 · see citing works
The crosstalk of NAD, ROS and autophagy in cellular health and ageing
Sedlackova, L., & Korolchuk, V. I. (2020) · Biogerontology · doi:10.1007/s10522-020-09864-0 · Cited by 47 · see citing works
Sirtuins and Their Implications in Neurodegenerative Diseases from a Drug Discovery Perspective
Yeong, K. Y., Berdigaliyev, N., & Chang, Y. (2020) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.0c00696 · Cited by 46 · see citing works
- Authors
- Stein, L. R., & Imai, S.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Imai, Shin‐ichiro
- ORCID
- Imai, Shin‐ichiro
- Venue
- The EMBO Journal
- Published
- 2014-05-08
- Volume
- 33
- Issue
- 12
- Pages
- 1321-1340
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC4194122
- OpenAlex
- W2003701712
- Cited by
- 265
- References
- 86
- Citations by year
- 2026: 3 · 2025: 18 · 2024: 15 · 2023: 31 · 2022: 24 · 2021: 32 · 2020: 35 · 2019: 25 · 2018: 21 · 2017: 28 · 2016: 17 · 2015: 12 · 2014: 4
- FWCI
- 7.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG024150, AG037457)
- Ellison Medical Foundation
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- visfatin, NAD biosynthesis, neural stem/progenitor cells, aging, hippocampus, cell proliferation, self-renewal, G1/S cell cycle progression, oligodendrogenesis, SIRT1, SIRT2, oligodendrocyte differentiation, NAD+ supplementation
- MeSH terms
- Aging, Animals, Bromodeoxyuridine, Cell Differentiation, Crosses, Genetic, Cuprizone, Fluorescent Antibody Technique, Mice, Transgenic, Nicotinamide Mononucleotide, Cytokines, Cell Culture Techniques, Cell Proliferation, Mice, Adult Stem Cells, Nicotinamide Phosphoribosyltransferase, Neural Stem Cells
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