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mixed-mode lc-ms-based method nature portfolio journals permissions reprints nature portfolio privacy policy interest policies genotoxic/senescence-induced nad+ decline advertising age-related nad+ decline humanized cd38-targeting antibody multi-faceted ecto-enzyme cd38 therapeutic tools dromedary heavy-chain antibodies cd38/cyclic adp-ribose system colorado research partners sponsored research funding discover anti-cd38 uniabs chief scientific officer marco de cecco cd38/adp-ribosyl cyclase mouse anti-cd38 antibodies cyclase/nad glycohydrolase ratio cd38-mediated pathway correlates high-performance liquid chromatography sequence-based discovery demonstrates nad synthesis-breakdown fluxes jair machado espindola-netto remodeling tumor–host interactions scientific advisory board respective lineweaver-burk plots nature+ nature 530 nature 479 nature 566 nature 499 nature 363 nature cyclic adp-ribose production ectocellular cd38-catalyzed synthesis medical research n-ribosyl hydrolase activity intracellular ca2+-signalling activity nad-hydrolyzing enzyme cd38 regulates protein–protein interactions fk866-treated tumor cells real-time qpcr assays research cd38+cd31+ cell population anti-cd38 antibodies permissions

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         headline:CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD+ and NMN levels
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      headline:CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD+ and NMN levels
      description:Decreased NAD+ levels have been shown to contribute to metabolic dysfunction during aging. NAD+ decline can be partially prevented by knockout of the enzyme CD38. However, it is not known how CD38 is regulated during aging, and how its ecto-enzymatic activity impacts NAD+ homeostasis. Here we show that an increase in CD38 in white adipose tissue (WAT) and the liver during aging is mediated by accumulation of CD38+ immune cells. Inflammation increases CD38 and decreases NAD+. In addition, senescent cells and their secreted signals promote accumulation of CD38+ cells in WAT, and ablation of senescent cells or their secretory phenotype decreases CD38, partially reversing NAD+ decline. Finally, blocking the ecto-enzymatic activity of CD38 can increase NAD+ through a nicotinamide mononucleotide (NMN)-dependent process. Our findings demonstrate that senescence-induced inflammation promotes accumulation of CD38 in immune cells that, through its ecto-enzymatic activity, decreases levels of NMN and NAD+. Chini et al. demonstrate that CD38+ expression in immune cells increases during aging, owing to the senescence-associated secretory phenotype of senescent cells, and the ecto-enzymatic activity of CD38+ affects intracellular NAD+ levels in vivo by hydrolyzing the NAD+ intermediate nicotinamide mononucleotide extracellularly.
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         Metabolomics
         Senescence
         Life Sciences
         general
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               type:PostalAddress
            type:Organization
      name:Eduardo N. Chini
      url:http://orcid.org/0000-0003-1555-4834
      affiliation:
            name:Mayo Clinic College of Medicine
            address:
               name:Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, USA
      name:Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, USA
      name:Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, USA
      name:Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, USA
      name:Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, USA
      name:Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, USA
      name:Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, USA
      name:Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, USA
      name:Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, USA
      name:Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, USA
      name:Division of Rheumatology, Department of Medicine, NYU Langone Health, New York, USA
      name:Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, USA
      name:Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, USA
      name:Teneobio, Newark, USA
      name:Teneobio, Newark, USA
      name:Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, USA
      name:Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, USA
      name:Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, USA
      name:Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, USA
      name:Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, USA
      name:Center on the Biology of Aging and Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, USA
      name:Astellas Institute for Regenerative Medicine, Marlborough, USA
      name:Department of Physiology and Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
      name:Lewis-Sigler Institute for Integrative Genomics, Department of Chemistry, Princeton University, Princeton, USA
      name:Lewis-Sigler Institute for Integrative Genomics, Department of Chemistry, Princeton University, Princeton, USA
      name:Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, USA
      name:Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, USA
      name:Center on the Biology of Aging and Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, USA
      name:Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, USA
      name:Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, USA
      name:Teneobio, Newark, USA
      name:Lewis-Sigler Institute for Integrative Genomics, Department of Chemistry, Princeton University, Princeton, USA
      name:Department of Physiology and Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
      name:Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, USA
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