| Literature DB >> 33199924 |
Abhijit Kale1, Rosalba Perrone1, Anthony J Covarrubias1,2, Jose Alberto Lopez-Dominguez1, Angela Oliveira Pisco3, Herbert G Kasler1, Mark S Schmidt4, Indra Heckenbach1,5, Ryan Kwok1, Christopher D Wiley1, Hoi-Shan Wong1, Eddy Gibbs1, Shankar S Iyer6, Nathan Basisty1, Qiuxia Wu1, Ik-Jung Kim1, Elena Silva1, Kaitlyn Vitangcol1, Kyong-Oh Shin7,8, Yong-Moon Lee7, Rebeccah Riley1, Issam Ben-Sahra9, Melanie Ott10, Birgit Schilling1, Morten Scheibye-Knudsen5, Katsuhiko Ishihara11, Stephen R Quake3,12, John Newman1,2, Charles Brenner4,13, Judith Campisi1, Eric Verdin14,15.
Abstract
Declining tissue nicotinamide adenine dinucleotide (NAD) levels are linked to ageing and its associated diseases. However, the mechanism for this decline is unclear. Here, we show that pro-inflammatory M1-like macrophages, but not naive or M2 macrophages, accumulate in metabolic tissues, including visceral white adipose tissue and liver, during ageing and acute responses to inflammation. These M1-like macrophages express high levels of the NAD-consuming enzyme CD38 and have enhanced CD38-dependent NADase activity, thereby reducing tissue NAD levels. We also find that senescent cells progressively accumulate in visceral white adipose tissue and liver during ageing and that inflammatory cytokines secreted by senescent cells (the senescence-associated secretory phenotype, SASP) induce macrophages to proliferate and express CD38. These results uncover a new causal link among resident tissue macrophages, cellular senescence and tissue NAD decline during ageing and offer novel therapeutic opportunities to maintain NAD levels during ageing.Entities:
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Year: 2020 PMID： 33199924 PMCID： PMC7908681 DOI： 10.1038/s42255-020-00305-3
Source DB: PubMed Journal: Nat Metab ISSN： 2522-5812