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

Chubanava, S, Karavaeva, I, Ehrlich, AM, Justicia, RM, Basse, AL, Kulik, I, Dalbram, E, Ahwazi, D, Heaselgrave, SR, Trošt, K, Stocks, B, Hodek, O, Rodrigues, RN, Havelund, JF, Schlabs, FL, Larsen, S, Yonamine, CY, Henriquez-Olguín, C, Ludwig, C, Giustarini, D, Rossi, R, Gerhart-Hines, Z, Moritz, T, Zierath, JR, Sakamoto, K, Jensen, TE, Færgeman, NJ, Lavery, GG ORCID: https://orcid.org/0000-0001-5794-748X, Deshmukh, AS and Treebak, JT, 2025. NAD depletion in skeletal muscle does not compromise muscle function or accelerate aging. Cell Metabolism, 37 (7), 1460-1481.e17. ISSN 1550-4131

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Abstract

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.

Item Type:	Journal article
Publication Title:	Cell Metabolism
Creators:	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-Olguín, C., Ludwig, 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. and Treebak, J.T.
Publisher:	Elsevier BV
Date:	1 July 2025
Volume:	37
Number:	7
ISSN:	1550-4131
Identifiers:	Number Type 10.1016/j.cmet.2025.04.002 DOI 2554193 Other
Rights:	© 2025 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Divisions:	Schools > School of Science and Technology
Record created by:	Laura Borcherds
Date Added:	08 Jan 2026 17:28
Last Modified:	08 Jan 2026 17:28
URI:	https://irep.ntu.ac.uk/id/eprint/54992

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