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?
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.