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Cell Metab. 2019 Jun 7. pii: S1550-4131(19)30255-4. doi: 10.1016/j.cmet.2019.05.015. [Epub ahead of print]

Extracellular Vesicle-Contained eNAMPT Delays Aging and Extends Lifespan in Mice.

Author information

1
Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA; MD-PhD Program, Washington University School of Medicine, St. Louis, MO 63110, USA.
2
Sleep and Aging Research Regulation Project Team, National Center for Geriatrics and Gerontology, Aichi, Japan.
3
Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA; MD-PhD Program, Washington University School of Medicine, St. Louis, MO 63110, USA.
4
Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.
5
Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.
6
Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
7
Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
8
Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Gerontology, Laboratory of Molecular Life Science, Institute of Biomedical Research and Innovation, Kobe, Japan. Electronic address: imaishin@wustl.edu.

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.

KEYWORDS:

EV; NAD+; adipose tissue; aging; eNAMPT; exosome; extracellular vesicle; hypothalamus; longevity; metabolism

PMID:
31204283
DOI:
10.1016/j.cmet.2019.05.015

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