Nicotinamide Riboside Reverses Age-Related Fatty Liver Disease: Preclinical Findings

Synopsis

Aging is a major risk factor for non-alcoholic fatty liver disease (NAFLD), but the biological link between the two has remained unclear. This study shows that declining levels of nicotinamide adenine dinucleotide (NAD+), a key molecule for energy metabolism and cellular repair, contribute to the development of fatty liver in aging. Researchers found that both aged mice and humans have reduced liver NAD+ levels due to lower activity of NAMPT, an enzyme that recycles NAD+ in cells. Mice with reduced NAMPT activity developed typical features of NAFLD—fat buildup in the liver, inflammation, oxidative stress, and insulin resistance—which worsened with a high-fat diet. Remarkably, oral supplementation with nicotinamide riboside (NR), a natural NAD+ precursor, completely reversed these liver abnormalities, while increasing SIRT1, a longevity-related enzyme, only partially improved them. These findings identify NAD+ deficiency as a key driver of age-related fatty liver and suggest that boosting NAD+ levels with NR could be an effective therapy for NAFLD in older adults.

Journal

British Journal of Pharmacology