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Because SAM is also required for many other methylation reactions, including gene-expression regulation, high NNMT activity draws heavily on SAM and is associated in studies with reduced NAD, a coenzyme central to cellular energy production
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Eric Verdin, in a review published in Science (2015), documented NAD+ depletion across aging tissues and its downstream effects on sirtuin enzyme activity, PARP-mediated DNA repair, and mitochondrial function