"The metabolic molecule nicotinamide adenine dinucleotide (NAD+) is emerging as a fundamental regulator of mitochondrial homeostasis, genome stability, neuroprotection, healthy aging and longevity.
Interestingly, genetic and/or pharmacological upregulation of intracellular NAD+ levels protects against obesity and type 2 diabetes in rodents, and against age-related diseases and neurodegenerative diseases such as Alzheimer’s disease.
We therefore examined whether mitochondrial dysfunction and NAD+ depletion occur in WS, and if so, how it contributes to the molecular pathology in WS.
We report that NAD+ depletion is a major driver of the severe metabolic dysfunction in WS through dysregulation of mitochondrial homeostasis.
NAD+ augmentation extends lifespan and healthspan in both C. elegans and Drosophila models of WS. Understanding how WRN affects metabolism has important implications for elucidating the mechanism of accelerated aging in WS and for therapeutic strategies for this currently incurable disease and possibly other age-related diseases."