CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD+ and NMN levels.
Nat Metab
; 2(11): 1284-1304, 2020 11.
Article
in En
| MEDLINE
| ID: mdl-33199925
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+.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Aging
/
Membrane Glycoproteins
/
ADP-ribosyl Cyclase 1
/
NAD
Limits:
Animals
/
Humans
Language:
En
Journal:
Nat Metab
Year:
2020
Document type:
Article
Affiliation country:
United States