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

TitleCD38 ecto-enzyme in immune cells is induced during aging and regulates NAD and NMN levels.
Publication TypeJournal Article
Year of Publication2020
AuthorsChini, CCS, Peclat, TR, Warner, GM, Kashyap, S, Espindola-Netto, JMachado, de Oliveira, GC, Gomez, LS, Hogan, KA, Tarragó, MG, Puranik, AS, Agorrody, G, Thompson, KL, Dang, K, Clarke, S, Childs, BG, Kanamori, KS, Witte, MA, Vidal, P, Kirkland, AL, De Cecco, M, Chellappa, K, McReynolds, MR, Jankowski, C, Tchkonia, T, Kirkland, JL, Sedivy, JM, van Deursen, JM, Baker, DJ, van Schooten, W, Rabinowitz, JD, Baur, JA, Chini, EN
JournalNat Metab
Volume2
Issue11
Pagination1284-1304
Date Published2020 11
ISSN2522-5812
KeywordsAdipocytes, White, Adipose Tissue, White, ADP-ribosyl Cyclase 1, Aging, Animals, Bone Marrow Transplantation, Cellular Senescence, HEK293 Cells, Humans, Inflammation, Liver, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, NAD, Nicotinamide Mononucleotide, Phenotype
Abstract

<p>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.</p>

DOI10.1038/s42255-020-00298-z
Alternate JournalNat Metab
PubMed ID33199925
Grant ListP01 AG051449 / AG / NIA NIH HHS / United States
R01 AG016694 / AG / NIA NIH HHS / United States