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Cerutti 2014: precursor supply versus consumption blockade
Cerutti and colleagues took a complementary two-pronged approach in the Sco2KO/KI mouse. They showed that either supplementing NR or inhibiting the NAD+-consuming PARPs improved the respiratory-chain defect and exercise intolerance, and they attributed the ben
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- Cerutti and colleagues took a complementary two-pronged approach in the Sco2KO/KI mouse. They showed that either supplementing NR or inhibiting the NAD+-consuming PARPs improved the respiratory-chain defect and exercise intolerance, and they attributed the benefit to NAD+-dependent activation of SIRT1 and downstream mitochondrial biogenesis.[4] The elegance of showing that two mechanistically opposite manipulations — adding substrate versus blocking its destruction — converge on the same functional improvement is what makes this study particularly persuasive about the causal role of NAD+ availability.