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

Nature Metabolism
Claudia C S ChiniEduardo N Chini

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+.

References

Jun 3, 1993·Nature·C Hamers-CastermanR Hamers
Jan 23, 1998·The International Journal of Biochemistry & Cell Biology·A De FloraE Zocchi
Jul 3, 1998·The EMBO Journal·M LauwereysS Muyldermans
Nov 5, 1999·Archives of Biochemistry and Biophysics·M LiangT P Dousa
Mar 5, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Li SunMone Zaidi
Feb 12, 2004·Genes & Development·Bernhard MaierHeidi Scrable
Sep 10, 2005·Nature Biotechnology·Philipp Holliger, Peter J Hudson
May 30, 2006·Biochemical and Biophysical Research Communications·Pinar AksoyEduardo N Chini
Aug 29, 2006·Biochemical and Biophysical Research Communications·Pinar AksoyEduardo N Chini
Mar 24, 2007·Molecular Medicine·Richard A BillingtonElena Zocchi
Apr 9, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Pallavi SinghGretchen Darlington
Jun 17, 2009·Medical Microbiology and Immunology·Janusz WesolowskiFriedrich Koch-Nolte
Aug 28, 2009·Current Opinion in Biotechnology·Carrie EneverArmin Sepp
Jan 29, 2010·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Mark J CartwrightJames L Kirkland
Nov 15, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Carey N LumengRaymond L Yung
Nov 28, 2012·Molecules and Cells·Cha-Uk LeeMyung-Kwan Han
Jan 11, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael J OsbornMarianne Brüggemann
Jul 23, 2013·Methods : a Companion to Methods in Enzymology·Omid VafaWilliam R Strohl
Jul 25, 2013·The Journal of Biological Chemistry·Alessia GrozioSantina Bruzzone
May 17, 2014·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Claudio Franceschi, Judith Campisi
May 23, 2014·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Sangeeta GhoshNicolas Musi
Jul 6, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jutta DeckertVéronique Blanc
Sep 25, 2014·Archives of Biochemistry and Biophysics·Frank PreugschatLisa M Shewchuk
Dec 3, 2014·Cell Metabolism·Morten Scheibye-KnudsenVilhelm A Bohr
Aug 13, 2015·Journal of Medicinal Chemistry·J David BechererJohn C Ulrich
Nov 19, 2015·Proceedings of the National Academy of Sciences of the United States of America·Ming XuJames L Kirkland
Dec 22, 2015·Cell Metabolism·Christopher D WileyJudith Campisi
Dec 25, 2015·PloS One·Kyle A JablonskiMireia Guerau-de-Arellano
Jan 17, 2016·BMC Microbiology·Kyung-Ah KimDong-Hyun Kim
Feb 4, 2016·Nature·Darren J BakerJan M van Deursen
Oct 13, 2016·Scientific Reports·Grasiella Angelina AndrianiCristina Montagna

❮ Previous
Next ❯

Citations

Nov 18, 2020·Nature Metabolism·Shuai Wu, Rugang Zhang
Jan 30, 2021·Science·Friedrich Becker, K Lenhard Rudolph
Dec 24, 2020·Nature Reviews. Molecular Cell Biology·Anthony J CovarrubiasEric Verdin
Apr 1, 2021·Physiological Reviews·Alberto L HorensteinFabio Malavasi
May 1, 2021·Cell Metabolism·Claudia C S ChiniEduardo Nunes Chini
May 4, 2021·Frontiers in Immunology·Fabio MorandiFabio Malavasi
Apr 6, 2021·British Journal of Pharmacology·Maria N NavarroMaria Mittelbrunn
Jun 8, 2021·Frontiers in Molecular Biosciences·Benjamin GrothSu-Ju Lin
Jul 20, 2021·Aging Cell·Michela PalmieriElena Ambrogini
Jul 27, 2021·Frontiers in Molecular Biosciences·Eleanor L HopkinsMichael P Coleman
Aug 8, 2021·Endocrinology·Akilavalli NarasimhanLaura J Niedernhofer

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
transgenic
X-ray
PCR
transfections
transfection
Assay
FCS
enzyme-linked
ELISA

Software Mentioned

ZEN
UniRats
GraphPad Prism
Excel
ImageJ

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.