David W. Frederick, Emanuele Loro,
Ling Liu, …, Joshua D. Rabinowitz,
Tejvir S. Khurana, Joseph A. Baur
NAD levels decline in multiple tissues with age or in disease. Frederick et al. show that impaired intramuscular NAD synthesis compromises skeletal muscle mass and strength over time but can be quickly restored with an oral NAD precursor. Upregulation of the NAD salvage pathway preserves exercise performance in aged mice.