Cited by 417Sirtuins and Resveratrol in MedicineGenetics, Aging, and Longevity in Model OrganismsExtracellular vesicles in disease

Extracellular vesicle-contained eNAMPT delays aging and extends lifespan in mice

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Yoshida, Mitsukuni, Satoh, Akiko, Lin, Jonathan B., Mills, Kathryn F., Sasaki, Yo, Rensing, Nicholas, Wong, Michael, Apte, Rajendra S. +1 more·2019·Cell Metabolism

Abstract

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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Crossref · 10.1016/j.cmet.2019.05.015

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  • Extracellular vesicles containing eNAMPT improve cognitive/neuronal function and extend lifespan in wild-type mice.

    “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

  • Possible causes of reduced cellular NAD+ during aging include increased consumption by PARPs and CD38 and reduced production, as evidenced by reduced eNAMPT in aged mice and humans.

    “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

  • sEVs can have intrinsic metabolic activity.

    “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).”
  • eNAMPT-EVs can induce NAD+ in recipient cells and counteract aging.

    “eNAMPT-EVs can induce NAD+ in recipient cells and counteract aging (Yoshida et al., 2019)”
  • eNAMPT is present within EVs to ameliorate aging.

    “nicotinamide phosphoribosyltransferase (eNAMPT) was shown to be present within EVs to ameliorate aging.”

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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)
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
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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