A novel approach to boosting levels of nicotinamide adenine dinucleotide (NAD⁺) enhances mitochondrial function, increases the lifespan of worms, and provides protective health benefits in mice, according to a paper published online this week in Nature.

NAD⁺ is a key molecule in mitochondrial energy production, but its levels decline with age. Research suggests that increasing NAD⁺ could have many beneficial effects on metabolism and lifespan.

Johan Auwerx and colleagues report a novel method to increase synthesis of NAD⁺ by blocking the enzyme ACMSD, which reduces the availability of the molecule from which NAD⁺ is made. Increased levels of NAD⁺ enhanced mitochondrial function in Caenorhabditis elegans worms and mice. Genetic blocking of ACMSD production in worms increased their activity levels and lifespan, while in mice, genetic blocking of ACMSD protected liver cells from fatty acid-related cell death. Pharmacological blocking of ACMSD (using inhibitors TES-991 and TES-1025) increased NAD⁺ synthesis in the liver, kidney, and brain in mice. TES-991 protected mouse liver cells in a model of non-alcoholic fatty liver disease, and TES-1025 protected mouse kidney cells in a model of acute kidney injury.

Although these effects have not been tested in humans, the results warrant further research to investigate whether the findings could translate to a clinical setting, the authors conclude.