NAD + metabolism governs the proinflammatory senescence-associated secretome.
Level 5 - mechanism / opinion, no new human data
Preclinical in vitro mechanistic study without human data.
PubMed 30778219 · doi:10.1038/s41556-019-0287-4
What was done
Investigated the molecular pathway linking NAD+ metabolism to the senescence-associated secretory phenotype (SASP). The authors evaluated the role of nicotinamide phosphoribosyltransferase (NAMPT), high mobility group A (HMGA) proteins, cellular glycolysis, mitochondrial respiration, and the AMPK, p53, p38 MAPK, and NF-kappaB signaling cascades during cellular senescence.
What was found
NAMPT-mediated NAD+ metabolism governs the proinflammatory SASP independent of senescence-associated growth arrest. HMGA proteins regulate NAMPT expression during senescence. The HMGA-NAMPT-NAD+ axis enhances glycolysis and mitochondrial respiration, suppresses AMPK kinase, relieves p53-mediated inhibition of p38 MAPK, and activates NF-kappaB to stimulate SASP. The abstract reports no numerical values.
Why it matters
Because the proinflammatory SASP can drive tumor progression, these findings suggest that indiscriminate anti-aging dietary NAD+ supplementation could carry cancer-promoting risks.
Limits
Preclinical bench research only, with no human clinical or in vivo confirmation reported in the abstract. Sample size and cell types are not specified, and no quantitative metrics or statistical ranges are provided.
Cited by
- supports A study in mice with pancreatic cancer found that NMN administration accelerated the growth of the pancreatic cancer cells.