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

Claudia C.S. Chini, Thais R. Peclat, Gina M. Warner, Sonu Kashyap, Jair Machado Espindola-Netto, Guilherme C. de Oliveira, Lilian S. Gomez, Kelly A. Hogan, Mariana G. Tarragó, Amrutesh S. Puranik, Guillermo Agorrody, Katie L. Thompson, Kevin Dang, Starlynn Clarke, Bennett G. Childs, Karina S. Kanamori, Micaela A. Witte, Paola Vidal, Anna L. Kirkland, Marco De CeccoKarthikeyani Chellappa, Melanie R. McReynolds, Connor Jankowski, Tamara Tchkonia, James L. Kirkland, John M. Sedivy, Jan M. van Deursen, Darren J. Baker, Wim van Schooten, Joshua D. Rabinowitz, Joseph A. Baur, Eduardo N. Chini

Research output: Contribution to journalArticlepeer-review

154 Scopus citations


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+.

Original languageEnglish (US)
Pages (from-to)1284-1304
Number of pages21
JournalNature Metabolism
Issue number11
StatePublished - Nov 2020

All Science Journal Classification (ASJC) codes

  • Physiology (medical)
  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Cell Biology


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