NAD(+) metabolism governs the proinflammatory senescence-associated secretome

Nacarelli T, Lau L, Fukumoto T, Zundell J, Fatkhutdinov N, Wu S · Nature Cell Biology

Raising NAD+ through NAMPT amplified the pro-inflammatory senescence-associated secretory phenotype rather than suppressing it, independently of the senescence growth arrest. In a Kras-driven mouse model of pancreatic pre-cancer, NMN at 500 mg/kg by daily intraperitoneal injection for 13 days cut the proportion of normal acinar tissue and raised desmoplasia, IL1-beta, IL-6, IL-8 and immune-cell infiltration, while leaving the senescence markers themselves unchanged. The authors concluded that anti-ageing dietary NAD+ augmentation 'should be administered with precision'.

Population

Senescent human and mouse cells; mouse tumour models

Intervention

Manipulation of NAMPT and NAD+ levels in senescent cells

Comparator

Unmanipulated senescent cells

Limitations

Cell work and a cancer-prone mouse model. The in vivo dose was 500 mg/kg given intraperitoneally to mice already carrying an activated oncogene, and whether an oral precursor dose reaches those concentrations in human tissue is unknown. The finding is about senescent and pre-malignant tissue rather than healthy tissue.