Topping up a key energy molecule isn’t enough — you have to stop it breaking down too
A molecule central to how cells make energy drops sharply as we age. Scientists have known for years that supplements can partially restore it.
NAD+ — nicotinamide adenine dinucleotide — is present in virtually every cell in the body and is essential for energy metabolism, DNA repair, and the regulation of proteins linked to ageing. Its levels decline substantially with age in both humans and animals, and that decline is associated with muscle loss, metabolic dysfunction, and a broader vulnerability to age-related disease.
Supplements like NMN (nicotinamide mononucleotide) and NR (nicotinamide riboside) act as raw materials the body can use to manufacture NAD+, and have been shown in multiple studies to raise tissue levels. But NAD+ is also constantly being broken down — notably by an enzyme called CD38, whose activity increases with age. A new study reported by Lifespan.io tested a dual approach: NMN to boost production, combined with apigenin — a plant compound found in parsley, chamomile, and celery — to inhibit CD38 and slow the rate of degradation.
Muscle function and bone structure both improved
In aged mice, the combination treatment restored muscle function to a degree that neither NMN alone nor apigenin alone achieved. Bone structure also improved — a finding with clinical relevance, since age-related muscle loss (sarcopenia) and bone loss (osteoporosis) typically progress together and together determine fracture risk and physical frailty.
The results point to a broader principle: replenishing a depleted resource is less effective when the destruction of that resource is simultaneously accelerating. It’s the equivalent of filling a bath with the drain open — you can raise the water level by pouring faster, but the more efficient solution is to also reduce the outflow. The NMN-apigenin combination attempts exactly that for NAD+ metabolism.
The usual caveats about mouse research apply
Translating findings from mouse models to humans is never straightforward. Dosing, bioavailability, and long-term safety in clinical populations remain uninvestigated. Apigenin is available as a supplement and is generally considered safe at low doses, but that says nothing about the efficacy of the combination at concentrations used in animal experiments. Human metabolism of these compounds differs from mouse metabolism in ways that matter.
What the study does add is a mechanistic argument for treating NAD+ biology as a system with multiple leverage points, rather than a simple deficit to fill. Whether that argument holds in humans — and at what doses — is the question that human trials will need to answer. Several NMN trials in people are already underway; whether they will incorporate CD38 inhibition alongside supplementation remains to be seen.