Nicotinamide Riboside Rejuvenates Aged Muscle Stem Cell Function: Preclinical Findings

Synopsis

Aging reduces the regenerative capacity of tissues by driving senescence in adult stem cells (SCs), including those that repair muscle, brain, and skin. This study identifies declining levels of NAD+, a key metabolic coenzyme, as a central trigger of stem cell aging. In aged mice, supplementation with the NAD+ precursor nicotinamide riboside (NR) restored mitochondrial function by activating the mitochondrial unfolded protein response and increasing levels of prohibitin proteins, which protect mitochondrial integrity. NR treatment rejuvenated muscle stem cells (MuSCs) in old mice, prevented premature stem cell aging in a muscular dystrophy (mdx) model, and delayed senescence in both neural and melanocyte stem cells. Importantly, NR supplementation also extended lifespan in mice. These results highlight NAD+ restoration as a powerful strategy to counter stem cell aging and enhance tissue regeneration, offering promise for treating muscle wasting and age-related degenerative diseases.

Journal

Science