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

Yoshida, Mitsukuni; Satoh, Akira; Lin, Jonathan B.; Mills, Kathryn F.; Sasaki, Yo; Rensing, Nicholas; Wong, Michael; Apte, Rajendra S.; Imai, Shin‐ichiro

doi:10.1016/j.cmet.2019.05.015

Cited by 260 publications

(283 citation statements)

References 32 publications

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“…A recent paper showed that eNAMPT is carried in extracellular vesicles (EVs) through systemic circulation in mice and humans. EV-contained-eNAMPT is internalized into cells, enhancing NAD synthesis (120). The same conclusion was obtained by another group identifying that eNAMPT is actively secreted via exosomes from microglia during neuroinflammation due to ischemic injury (121).…”

Section: Namptsupporting

confidence: 59%

NAMPT and NAPRT: Two Metabolic Enzymes With Key Roles in Inflammation

2020

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Nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase (NAPRT) are two intracellular enzymes that catalyze the first step in the biosynthesis of NAD from nicotinamide and nicotinic acid, respectively. By fine tuning intracellular NAD levels, they are involved in the regulation/reprogramming of cellular metabolism and in the control of the activity of NAD-dependent enzymes, including sirtuins, PARPs, and NADases. However, during evolution they both acquired novel functions as extracellular endogenous mediators of inflammation. It is well-known that cellular stress and/or damage induce release in the extracellular milieu of endogenous molecules, called alarmins or damage-associated molecular patterns (DAMPs), which modulate immune functions through binding pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), and activate inflammatory responses. Increasing evidence suggests that extracellular (e)NAMPT and eNAPRT are novel soluble factors with cytokine/adipokine/DAMP-like actions. Elevated eNAMPT were reported in several metabolic and inflammatory disorders, including obesity, diabetes, and cancer, while eNAPRT is emerging as a biomarker of sepsis and septic shock. This review will discuss available data concerning the dual role of this unique family of enzymes.

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Section: Namptsupporting

confidence: 59%

NAMPT and NAPRT: Two Metabolic Enzymes With Key Roles in Inflammation

2020

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“…More interestingly, Yoshida et al found that EVs containing eNAMPT can delay aging and prolong life in mice. They also confirmed that eNAMPT in human plasma is mainly contained in EVs (26).…”

Section: Evaluation Of the Hypothesis Evs Participate In Interorgan Csupporting

confidence: 60%

Bone-Derived Extracellular Vesicles: Novel Players of Interorgan Crosstalk

Yin

Guo

et al. 2019

Front. Endocrinol.

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An increasing number of studies have shown that bone plays an active role in regulating glucose metabolism, affects renal, and cardiovascular diseases and even influences the development of offspring. These novel findings have indicated that bone plays a much more important role in the human body than only providing physical support. However, further investigations of the mechanisms underlying the effects of bone are needed. Recently, extracellular vesicles (EVs) have received increased attention because they can transfer functional proteins, mRNAs, and miRNAs between cells/organs. After reviewing the existing evidence, we hypothesized that bone may be involved in interorgan communication via EVs. Further research exploring bone-derived EVs may facilitate the understanding of bone as a multifunctional organ.

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“…CD38 inhibitors rescued NAD + decline and ameliorated a number of age-related metabolic outcomes in mice (Tarrago et al, 2018). A similar beneficial effect on mouse lifespan has been described also for the EV-mediated cell-to-cell transfer of the extracellular isoform of nicotinamide phosphoribosyltransferase (NAMPT), the ratelimiting enzyme of NAD + salvage pathway (Yoshida et al, 2019). EVs are membrane-coated nanoparticles actively released by almost all cell types, including ECs (Jansen et al, 2017).…”

Section: Me1mentioning

confidence: 57%

Where Metabolism Meets Senescence: Focus on Endothelial Cells

et al. 2019

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Despite the decline in their proliferative potential, senescent cells display a high metabolic activity. Senescent cells have been shown to acquire a more glycolytic state even in presence of high oxygen levels, in a way similar to cancer cells. The diversion of pyruvate, the final product of glycolysis, away from oxidative phosphorylation results in an altered bioenergetic state and may occur as a response to the enhanced oxidative stress caused by the accumulation of dysfunctional mitochondria. This metabolic shift leads to increased AMP/ATP and ADP/ATP ratios, to the subsequent AMPK activation, and ultimately to p53-mediated growth arrest. Mounting evidences suggest that metabolic reprogramming is critical to direct considerable amounts of energy toward specific activities related to the senescent state, including the senescence-associated secretory phenotype (SASP) and the modulation of immune responses within senescent cell tissue microenvironment. Interestingly, despite the relative abundance of oxygen in the vascular compartment, healthy endothelial cells (ECs) produce most of their ATP content from the anaerobic conversion of glucose to lactate. Their high glycolytic rate further increases during senescence. Alterations in EC metabolism have been identified in age-related diseases (ARDs) associated with a dysfunctional vasculature, including atherosclerosis, type 2 diabetes and cardiovascular diseases. In particular, higher production of reactive oxygen species deriving from a variety of enzymatic sources, including uncoupled endothelial nitric oxide synthase and the electron transport chain, causes DNA damage and activates the NAD +-consuming enzymes polyADP-ribose polymerase 1 (PARP1). These non-physiological mechanisms drive the impairment of the glycolytic flux and the diversion of glycolytic intermediates into many pathological pathways. Of note, accumulation of senescent ECs has been reported in the context of ARDs. Through their pro-oxidant, pro-inflammatory, vasoconstrictor, and prothrombotic activities, they negatively impact on vascular physiology, promoting both the onset and development of ARDs. Here, we review the current knowledge on the cellular senescence-related metabolic changes and their contribution to the mechanisms underlying the pathogenesis of ARDs, with a particular focus on ECs. Moreover, current and potential interventions aimed at modulating EC metabolism, in order to prevent or delay ARD onset, will be discussed.

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

Cited by 260 publications

References 32 publications

NAMPT and NAPRT: Two Metabolic Enzymes With Key Roles in Inflammation

NAMPT and NAPRT: Two Metabolic Enzymes With Key Roles in Inflammation

Bone-Derived Extracellular Vesicles: Novel Players of Interorgan Crosstalk

Where Metabolism Meets Senescence: Focus on Endothelial Cells

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