NAD depletion in skeletal muscle does not compromise muscle function or accelerate aging
Fecha
0022-06-25
Nota de Acceso
Fecha de embargo
Profe guía
Perfil ORCID
Título de la revista
ISSN de la revista
Título del volumen
Editor
Elsevier
ISBN
ISSN
1550-4131
ISSNe
1932-7420
Resumen
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.
Descripción
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Sponsorship
Citación
Cell Metabolism, Vol. 37, N° 7 (2025) p.1460 - 1481.
Palabras clave
NAD metabolism, Skeletal muscle, Mitochondrial, Supercomplexes
Licencia
Atribución-NoComercial-CompartirIgual 3.0 Chile (CC BY-NC-SA 3.0 CL)