1. CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD + and NMN levels.
- Author
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Chini CCS, Peclat TR, Warner GM, Kashyap S, Espindola-Netto JM, 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, and Chini EN
- Subjects
- ADP-ribosyl Cyclase 1 genetics, ADP-ribosyl Cyclase 1 immunology, Adipocytes, White metabolism, Adipose Tissue, White metabolism, Aging immunology, Animals, Bone Marrow Transplantation, Cellular Senescence, HEK293 Cells, Humans, Inflammation immunology, Liver growth & development, Liver metabolism, Membrane Glycoproteins genetics, Membrane Glycoproteins immunology, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Nicotinamide Mononucleotide metabolism, Phenotype, ADP-ribosyl Cyclase 1 metabolism, Aging metabolism, Membrane Glycoproteins metabolism, NAD biosynthesis
- Abstract
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+ .- Published
- 2020
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