Study summary · research use only
Senescent cells promote tissue NAD(+) decline during ageing via the activation of CD38(+) macrophages
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This study (species not specified) examined how tissue NAD levels decline during ageing, focusing on the role of CD38-expressing macrophages. The abstract reports that pro-inflammatory M1-like macrophages, but not naive or M2 macrophages, accumulated in metabolic tissues including visceral white adipose tissue and liver during ageing and acute inflammatory responses, and that these M1-like macrophages expressed high levels of the NAD-consuming enzyme CD38 with enhanced CD38-dependent NADase activity, reducing tissue NAD levels. It also reports that senescent cells progressively accumulated in visceral white adipose tissue and liver during ageing, and that cytokines secreted by senescent cells induced macrophage proliferation and CD38 expression.
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.
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