Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages.
Nat Metab
; 2(11): 1265-1283, 2020 11.
Article
em En
| MEDLINE
| ID: mdl-33199924
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Envelhecimento
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Glicoproteínas de Membrana
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Senescência Celular
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ADP-Ribosil Ciclase 1
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Ativação de Macrófagos
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NAD
Limite:
Animals
/
Female
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Humans
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Male
Idioma:
En
Revista:
Nat Metab
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos