| First Author | Chini CCS | Year | 2020 |
| Journal | Nat Metab | Volume | 2 |
| Issue | 11 | Pages | 1284-1304 |
| PubMed ID | 33199925 | Mgi Jnum | J:301123 |
| Mgi Id | MGI:6502883 | Doi | 10.1038/s42255-020-00298-z |
| Citation | Chini CCS, et al. (2020) CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD(+) and NMN levels. Nat Metab 2(11):1284-1304 |
| abstractText | 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(+). |
