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Chubanava, S.* ; Karavaeva, I.* ; Ehrlich, A.M.* ; Justicia, R.M.* ; Basse, A.L.* ; Kulik, I. ; Dalbram, E.* ; Ahwazi, D.* ; Heaselgrave, S.R.* ; Trošt, K.* ; Stocks, B.* ; Hodek, O.* ; Rodrigues, R.N.* ; Havelund, J.F.* ; Schlabs, F.L.* ; Larsen, S.* ; Yonamine, C.Y.* ; Henriquez-Olguin, C.* ; Giustarini, D.* ; Rossi, R.* ; Gerhart-Hines, Z.* ; Moritz, T.* ; Zierath, J.R.* ; Sakamoto, K.* ; Jensen, T.E.* ; Færgeman, N.J.* ; Lavery, G.G.* ; Deshmukh, A.S.* ; Treebak, J.T.*

NAD depletion in skeletal muscle does not compromise muscle function or accelerate aging.

Cell Metab., DOI: 10.1016/j.cmet.2025.04.002 (2025)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Nicotinamide adenine dinucleotide (NAD) is a ubiquitous electron carrier essential for energy metabolism and post-translational modification of numerous regulatory proteins. Dysregulations of NAD metabolism are widely regarded as detrimental to health, with NAD depletion commonly implicated in aging. However, the extent to which cellular NAD concentration can decline without adverse consequences remains unclear. To investigate this, we generated a mouse model in which nicotinamide phosphoribosyltransferase (NAMPT)-mediated NAD+ biosynthesis was disrupted in adult skeletal muscle. The intervention resulted in an 85% reduction in muscle NAD+ abundance while maintaining tissue integrity and functionality, as demonstrated by preserved muscle morphology, contractility, and exercise tolerance. This absence of functional impairments was further supported by intact mitochondrial respiratory capacity and unaltered muscle transcriptomic and proteomic profiles. Furthermore, lifelong NAD depletion did not accelerate muscle aging or impair whole-body metabolism. Collectively, these findings suggest that NAD depletion does not contribute to age-related decline in skeletal muscle function.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Nad Metabolism ; Nad(+) Biosynthesis ; Nampt ; Aging ; Epigenetic Clock ; Exercise ; Mitochondrial Supercomplexes ; Nicotinamide ; Reactive Oxygen Species ; Skeletal Muscle
ISSN (print) / ISBN 1550-4131
e-ISSN 1932-7420
Zeitschrift Cell Metabolism
Verlag Elsevier
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Transl. Stem Cell Research (ITS)