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Extracellular Vesicle-Contained eNAMPT Delays Aging and Extends Lifespan in Mice
Open accessAbstract
Aging is a significant risk factor for impaired tissue functions and chronic diseases. Age-associated decline in systemic NAD+ availability plays a critical role in regulating the aging process across many species. Here, we show that the circulating levels of extracellular nicotinamide phosphoribosyltransferase (eNAMPT) significantly decline with age in mice and humans. Increasing circulating eNAMPT levels in aged mice by adipose-tissue-specific overexpression of NAMPT increases NAD+ levels in multiple tissues, thereby enhancing their functions and extending healthspan in female mice. Interestingly, eNAMPT is carried in extracellular vesicles (EVs) through systemic circulation in mice and humans. EV-contained eNAMPT is internalized into cells and enhances NAD+ biosynthesis. Supplementing eNAMPT-containing EVs isolated from young mice significantly improves wheel-running activity and extends lifespan in aged mice. Our findings have revealed a novel EV-mediated delivery mechanism for eNAMPT, which promotes systemic NAD+ biosynthesis and counteracts aging, suggesting a potential avenue for anti-aging intervention in humans.
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“Furthermore, adding extracellular vesicles containing eNAMPT improved cognitive/neuronal function and extended lifespan in WT mice (Yoshida et al., 2019).”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Yoshida et al., 2019
In the citing paper
“Possible explanations for reduced cellular NAD+ during aging include increased NAD+ consumption by PARPs and CD38 (Camacho-Pereira et al., 2016; Fang et al., 2014) and reduced NAD+ production, such as that evidenced by reduced eNAMPT in the aged mice and humans (Yoshida et al., 2019).”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Yoshida et al., 2019
In the citing paper
“It has previously been reported that sEVs can have intrinsic metabolic activity (Iraci et al., 2017, Peruzzotti-Jametti et al., 2018, Yoshida et al., 2019).”
From Small Extracellular Vesicles Have GST Activity and Ameliorate Senescence-Related Tissue Damage (2020) · cites this paper as Yoshida et al., 2019
In the citing paper
“eNAMPT-EVs can induce NAD+ in recipient cells and counteract aging (Yoshida et al., 2019)”
From Small Extracellular Vesicles Have GST Activity and Ameliorate Senescence-Related Tissue Damage (2020) · cites this paper as Yoshida et al., 2019
In the citing paper
“nicotinamide phosphoribosyltransferase (eNAMPT) was shown to be present within EVs to ameliorate aging.”
From Small Extracellular Vesicles Have GST Activity and Ameliorate Senescence-Related Tissue Damage (2020) · cites this paper as Yoshida et al., 2019
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Metadata
- Authors
- Yoshida, M., Satoh, A., Lin, J. B., Mills, K. F., Sasaki, Y., Rensing, N., Wong, M., Apte, R. S., & Imai, S.-I.
- Affiliations
- Washington University in St. Louis (US)
- National Center for Geriatrics and Gerontology (JP)
- Corresponding author
- Imai, Shin-ichiro
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2019-08
- Volume
- 30
- Issue
- 2
- Pages
- 329-342.e5
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC6687560
- OpenAlex
- W2949166959
- Cited by
- 407
- References
- 34
- Citations by year
- 2026: 35 · 2025: 65 · 2024: 67 · 2023: 59 · 2022: 58 · 2021: 65 · 2020: 47 · 2019: 11
- FWCI
- 23.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Washington University in St. Louis (T32 GM007200)
- Takeda Science Foundation
- University of Washington
- VitreoRetinal Surgery Foundation
- American Federation for Aging Research
- Japan Society for the Promotion of Science (JP18H03186)
- Research to Prevent Blindness
- National Center for Geriatrics and Gerontology
- National Institutes of Health (P30 EY02687, R01 EY019287, U54 HD087011)
- Japan Agency for Medical Research and Development (JP18gm5010001h0001)
- National Institute on Aging (AG037457, AG047902)
- Nutrition Obesity Research Center, University of North Carolina (P30 DK56341)
- National Center for Research Resources (C06 RR015502)
- Diabetes Research Center (P30 DK020579)
- Institute of Clinical and Translational Sciences (TR002344, UL1 TR002345)
- Uehara Memorial Foundation
- 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 › Extracellular vesicles in disease
- Keywords
- extracellular vesicles, visfatin, aging, lifespan extension, NAD biosynthesis, healthspan, adipose tissue, anti-aging interventions, wheel running
- MeSH terms
- Extracellular Vesicles, Adult, Aged, Aged, 80 and over, Aging, Animals, Cells, Cultured, Humans, Longevity, Male, Mice, Inbred C57BL, Mice, Transgenic, Middle Aged, Cytokines, Mice, Nicotinamide Phosphoribosyltransferase, HEK293 Cells
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