@article{6ff25b0d13f14df98da4006447e78808,
title = "CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD+ and NMN levels",
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+.",
author = "Chini, {Claudia C.S.} and Peclat, {Thais R.} and Warner, {Gina M.} and Sonu Kashyap and Espindola-Netto, {Jair Machado} and {de Oliveira}, {Guilherme C.} and Gomez, {Lilian S.} and Hogan, {Kelly A.} and Tarrag{\'o}, {Mariana G.} and Puranik, {Amrutesh S.} and Guillermo Agorrody and Thompson, {Katie L.} and Kevin Dang and Starlynn Clarke and Childs, {Bennett G.} and Kanamori, {Karina S.} and Witte, {Micaela A.} and Paola Vidal and Kirkland, {Anna L.} and {De Cecco}, Marco and Karthikeyani Chellappa and McReynolds, {Melanie R.} and Connor Jankowski and Tamara Tchkonia and Kirkland, {James L.} and Sedivy, {John M.} and {van Deursen}, {Jan M.} and Baker, {Darren J.} and {van Schooten}, Wim and Rabinowitz, {Joshua D.} and Baur, {Joseph A.} and Chini, {Eduardo N.}",
note = "Funding Information: This work was supported in part by grants from the Helen Diller Family Foundation, Ted Nash Long Life Foundation, the Glenn Foundation for Medical Research via the Paul F. Glenn Laboratories for the Biology of Aging at the Mayo Clinic (E.N.C, J.M.v.D. and D.B), sponsored research funding from Calico Life Sciences, the Mayo and Noaber Foundations, NIH National Institute of Aging (NIA) grants AG-26094 (to E.N.C.), AG58812 (to E.N.C.), CA233790 (to E.N.C.), AG13925 (to J.L.K.), AG057493 (to J.M.v.D.), AG016694 (to J.M.S.) and P01 AG051449 (to J.M.S). This work was also supported by grants from the National Institute of Diabetes, Digestive and Kidney disease (DK098656 to J.A.B.) R.J. Ryan and T.W. Ryan (to J.L.K.) and the Connor Group (to J.L.K.). A.S.P. thanks the Colton Center for Auto-Immunity at NYU Langone for funding support. Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2020",
month = nov,
doi = "10.1038/s42255-020-00298-z",
language = "English (US)",
volume = "2",
pages = "1284--1304",
journal = "Nature Metabolism",
issn = "2522-5812",
publisher = "Springer Berlin",
number = "11",
}