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Senescent cells promote tissue NAD + decline during ageing via the activation of CD38 + macrophages.
- Source :
-
Nature metabolism [Nat Metab] 2020 Nov; Vol. 2 (11), pp. 1265-1283. Date of Electronic Publication: 2020 Nov 16. - Publication Year :
- 2020
-
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.
- Subjects :
- ADP-ribosyl Cyclase metabolism
Adipose Tissue, White metabolism
Animals
Antigens, CD metabolism
Cytokines metabolism
Female
GPI-Linked Proteins metabolism
Gene Expression
Glycolysis genetics
Humans
Liver metabolism
Male
Metabolome
Mice
Mice, Inbred C57BL
Mice, Knockout
Mitochondria metabolism
NAD+ Nucleosidase metabolism
ADP-ribosyl Cyclase 1 genetics
Aging metabolism
Cellular Senescence
Macrophage Activation
Membrane Glycoproteins genetics
NAD metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2522-5812
- Volume :
- 2
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Nature metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 33199924
- Full Text :
- https://doi.org/10.1038/s42255-020-00305-3