CD38 Inhibition Reverses Age-Related Cognitive Decline via Brain-Fluid Pathway

Researchers led by Eric Verdin have identified a promising mechanism for reversing age-related cognitive decline. The study focused on CD38, an enzyme that consumes NAD+, a critical cellular energy molecule that declines with age. By inhibiting CD38 in aging mice, the team observed improvements in cognitive function—but the mechanism was unexpected. Rather than acting directly on neurons, CD38 inhibition appears to work through the choroid plexus, a tissue that produces cerebrospinal fluid, which then positively affects the hippocampus, a brain region critical for memory. This "choroid plexus-cerebrospinal fluid-hippocampus axis" represents a novel pathway for cognitive interventions. The findings build on growing evidence that NAD+ boosting strategies may combat aging, but this work specifically implicates the brain's fluid systems as key mediators. While this is still preclinical research in rodents, CD38 inhibitors are already in human trials for other conditions, potentially accelerating translation to human cognitive aging studies.