NAD+ combination treatment restores muscle and bone in old mice
Topping up a single supplement helps a little. But what if you also stopped the leaking? Researchers tested that dual strategy for NAD+, and the results in aged mice are striking.
NAD+ (nicotinamide adenine dinucleotide) is a molecule found in every cell of the body, central to energy metabolism, DNA repair, and the activation of sirtuins, proteins that regulate stress responses and are closely linked to longevity. The problem: NAD+ levels decline sharply in most tissues with age, and that decline is associated with muscle weakness, bone loss, and impaired metabolic function.
Researchers gave aged mice a combination of NMN (nicotinamide mononucleotide), a precursor compound the body converts into NAD+, and apigenin, a plant-derived compound that inhibits the enzyme CD38. CD38 is one of the body’s main NAD+ consumers, and its activity increases with age. By boosting supply and reducing consumption simultaneously, NAD+ levels rose significantly more than with either compound alone, reports Lifespan.io.
Measurable gains in muscle and bone
The effects showed up in two systems that typically deteriorate with aging: muscle and bone. Mice receiving the combination treatment showed improved muscle function, measured via grip strength and treadmill performance, as well as improved bone density and structure. Both effects were larger than in groups receiving NMN or apigenin alone.
That sounds promising, but a note of caution is warranted. Mouse studies don’t reliably translate to humans. NAD+ precursor supplementation using compounds like NMN or NR (nicotinamide riboside) has already been studied in humans, with results that are encouraging but modest, measurable increases in NAD+ levels, but more limited clinical effects than seen in rodents. Whether the combination strategy tested here produces the same results in people remains unknown.
Why the dual-target approach makes sense
What makes this research conceptually interesting is the logic behind it. Most supplementation strategies address one side of the equation: increase supply. But if the primary ‘drain’ in the system, here, CD38, remains active, the net effect is limited. By targeting both sides simultaneously, essentially putting the NAD+ metabolism in a vice, the net increase is substantially larger. That principle is broadly applicable and could inform future combination therapies for age-related conditions.