• Kenneth Ladd Seldeen, Aref Shahini, Ramkumar Thiyagarajan, Yonas Redae, Merced Leiker, Nika Rajabian, Andrew Dynka, Stelios T Andreadis, and Bruce Robert Troen.
• Division of Geriatrics and Palliative Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo and Research Service, Veterans Affairs Western New York Healthcare System, Buffalo, NY, United States.
• Nutrition. 2021 Jul 1; 87-88: 111189.

ObjectivesNicotinamide adenine dinucleotide (NAD+), an essential cofactor for mitochondrial function, declines with aging, which may lead to impaired physical performance. Nicotinamide riboside (NR), a NAD+ precursor, restores cellular NAD+ levels. The aim of this study was to examine the effects of short-term NR supplementation on physical performance in middle-aged mice and the effects on mouse and human muscle stem cells.MethodsWe treated 15-mo-old male C57BL/6J mice with NR at 300 mg·kg·d-1 (NR3), 600 mg·kg·d-1 (NR6), or placebo (PLB), n = 8 per group, and assessed changes in physical performance, muscle histology, and NAD+ content after 4 wk of treatment.ResultsNR increased total NAD+ in muscle tissue (NR3 P = 0.01; NR6 P = 0.004, both versus PLB), enhanced treadmill endurance and open-field activity, and prevented decline in grip strength. Histologic analysis revealed NR-treated mice exhibited enlarged slow-twitch fibers (NR6 versus PLB P = 0.014; NR3 P = 0.16) and a trend toward more slow fibers (NR3 P = 0.14; NR6 P = 0.22). We next carried out experiments to characterize NR effects on mitochondrial activity and cellular energetics in vitro. We observed that NR boosted basal and maximal cellular aerobic and anaerobic respiration in both mouse and human myoblasts and human myotubes. Additionally, NR treatment improved the differentiating capacity of myoblasts and increased myotube size and fusion index upon stimulation of these progenitors to form multinucleated myotubes.ConclusionThese findings support a role for NR in improving cellular energetics and functional capacity in mice, which support the translation of this work into clinical settings as a strategy for improving and/or maintaining health span during aging.Published by Elsevier Inc.

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