@article{93f31f14464249c89276966c6f227f00,
title = "Loss of NAD Homeostasis Leads to Progressive and Reversible Degeneration of Skeletal Muscle",
abstract = "NAD is an obligate co-factor for the catabolism of metabolic fuels in all cell types. However, the availability of NAD in several tissues can become limited during genotoxic stress and the course of natural aging. The point at which NAD restriction imposes functional limitations on tissue physiology remains unknown. We examined this question in murine skeletal muscle by specifically depleting Nampt, an essential enzyme in the NAD salvage pathway. Knockout mice exhibited a dramatic 85% decline in intramuscular NAD content, accompanied by fiber degeneration and progressive loss of both muscle strength and treadmill endurance. Administration of the NAD precursor nicotinamide riboside rapidly ameliorated functional deficits and restored muscle mass despite having only a modest effect on the intramuscular NAD pool. Additionally, lifelong overexpression of Nampt preserved muscle NAD levels and exercise capacity in aged mice, supporting a critical role for tissue-autonomous NAD homeostasis in maintaining muscle mass and function.",
author = "Frederick, {David W.} and Emanuele Loro and Ling Liu and Antonio Davila and Karthikeyani Chellappa and Silverman, {Ian M.} and Quinn, {William J.} and Gosai, {Sager J.} and Tichy, {Elisia D.} and Davis, {James G.} and Foteini Mourkioti and Gregory, {Brian D.} and Dellinger, {Ryan W.} and Philip Redpath and Migaud, {Marie E.} and Eiko Nakamaru-Ogiso and Rabinowitz, {Joshua D.} and Khurana, {Tejvir S.} and Baur, {Joseph A.}",
note = "Funding Information: We wish to thank M. Neinast and J. Gong for technical assistance, C. Franzini-Armstrong and K.-J. Won for expert advice, and all members of the J.A.B. lab for feedback and suggestions. This work was supported by grants from the National Institutes of Health (R01 AG043483 and R01 DK098656 to J.A.B.). We thank the University of Pennsylvania Diabetes Research Center (DRC) for the use of the Biomarkers, Next-Generation Sequencing, Mouse Metabolic Phenotyping, and Metabolism Cores (P30-DK19525), W.-J. Tseng and the Penn Center for Musculoskeletal Disorders (P30-AR050950), J. Tobias and the Genomic Analysis Core, and R. Meade of the Electron Microscopy Core. R.W.D. is an employee and stockholder of Chromadex Inc., which manufactures and distributes NR. M.E.M. is a consultant for Chromadex Inc. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = aug,
day = "9",
doi = "10.1016/j.cmet.2016.07.005",
language = "English (US)",
volume = "24",
pages = "269--282",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "2",
}