Evandro Fei Fang, Henok Kassahun,
Deborah L. Croteau,
Mark P. Mattson, Hilde Nilsen,
Vilhelm A. Bohr
Mitochondrial damage and NAD+ depletion are key features in ataxia telangiectasia. Fang et al. show that mitochondrial dysfunction in ATM deficiency is caused by compromised mitophagy due to NAD+ /SIRT1 inhibition. NAD+ replenishment significantly extends lifespan and improves healthspan in both ATM worms and mice through mitophagy and DNA repair.