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CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD+ and NMN levels.

Claudia C S ChiniEduardo Nunes ChiniGina M WarnerSonu KashyapJair Machado Espindola-NettoGuilherme C de OliveiraLilian Sales GomezKelly A HoganMariana G TarragóAmrutesh S PuranikGuillermo AgorrodyKatie L ThompsonKevin DangStarlynn ClarkeBennett G ChildsKarina S KanamoriMicaela A WittePaola VidalAnna L KirklandMarco De CeccoKarthikeyani ChellappaMelanie R McReynoldsConnor S R JankowskiTamara TchkoniaJames L KirklandJohn M SedivyJan M van DeursenDarren J BakerWim van SchootenJoshua D RabinowitzJoseph A BaurEduardo Nunes Chini
Published in: Nature metabolism (2020)
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+.
Keyphrases
  • adipose tissue
  • nk cells
  • induced apoptosis
  • type diabetes
  • cell cycle arrest
  • nitric oxide
  • hydrogen peroxide
  • skeletal muscle
  • metabolic syndrome
  • high fat diet
  • signaling pathway
  • cell proliferation
  • high glucose