Nicotinamide Riboside Restores NAD+ and Prevents Age-Related Bone Loss: Preclinical Findings

Synopsis

Age-related osteoporosis happens because of a decline in osteoblasts—the cells that build bone—and fewer osteoblast progenitor cells, which show signs of aging called senescence. FoxO transcription factors reduce bone formation by lowering Wnt/β-catenin signaling and slowing progenitor cell growth. The enzyme Sirtuin1 (Sirt1), which depends on NAD+, can remove acetyl groups from FoxOs and β-catenin in these progenitors, boosting bone mass. This study found that older mice have lower NAD+ levels in osteoblast progenitors, leading to more acetylation of FoxO1 and increased cell aging markers. Giving nicotinamide riboside (NR), a NAD+ precursor, reversed these effects—reducing acetylation, lowering senescence markers, and improving the bone-forming ability of old cells. NR treatment in mice also prevented age-related bone loss. Reducing NAD+ in young osteoprogenitors decreased bone formation via FoxO, and mice with low NAD+ in bone cells lost bone mass early. These results suggest that age-related bone loss is partly caused by lower NAD+ and disruption of the Sirt1/FoxO/β-catenin pathway, making NAD+ restoration a promising therapy for bone health.

Journal

npj Aging and Mechanisms of Disease