A metabolic molecule promotes memory in innate immune cells
Experiments found that a molecule inside innate immune-cell nuclei preserved chemical marks on DNA-packaging proteins, strengthening responses to repeat stimulation.
Limit: The abstract does not give the dose
Edited by Boris Djordjevic · AgingResearch.News
In innate immune cells, experiments identified a role for nicotinamide adenine dinucleotide (NAD), a metabolic molecule, in trained immunity—a lasting change that strengthens responses to later stimulation. Inducing this memory raised NAD levels inside nuclei, where cells house their DNA. NAD bound to and inhibited KDM5A, an enzyme that removes chemical marks from DNA-packaging proteins. This sustained those marks and kept inflammatory genes accessible, enhancing responses to repeat stimulation.
Deleting or inhibiting NAMPT, an enzyme needed to make NAD, impaired trained immunity and its associated antitumor activity. Nicotinamide mononucleotide supplementation rescued defective immune-memory-related antitumor activity in aged mice and mice lacking NAMPT. In human cancer, NAMPT levels in myeloid cells, a group of immune cells, correlated with an inflammatory environment around tumors.
Why it matters
Trained immunity contributes to immune activity against tumors. The aged-mouse experiments bear on whether this function can be supported as bodies grow older.
Caveats
These were mechanistic experiments, not a clinical trial; the supplement rescue was reported in mice. The abstract does not identify the cells or species used for the molecular experiments or report mouse sample sizes, supplement dose or duration.
The paper
Nuclear NAD ⁺ promotes innate immune memory by inhibiting KDM5A-dependent histone demethylation
Sun Yat-sen University Cancer Center
Science Immunology, Oct 30, 2026
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