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Skelet Muscle. 2018 Mar 7;8(1):9. doi: 10.1186/s13395-018-0154-1.

A need for NAD+ in muscle development, homeostasis, and aging.

Author information

1
School of Biology and Ecology, University of Maine, Orono, ME, 04469, USA.
2
School of Biology and Ecology, University of Maine, Orono, ME, 04469, USA. clarissa.henry@maine.edu.
3
Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME, 04469, USA. clarissa.henry@maine.edu.

Abstract

Skeletal muscle enables posture, breathing, and locomotion. Skeletal muscle also impacts systemic processes such as metabolism, thermoregulation, and immunity. Skeletal muscle is energetically expensive and is a major consumer of glucose and fatty acids. Metabolism of fatty acids and glucose requires NAD+ function as a hydrogen/electron transfer molecule. Therefore, NAD+ plays a vital role in energy production. In addition, NAD+ also functions as a cosubstrate for post-translational modifications such as deacetylation and ADP-ribosylation. Therefore, NAD+ levels influence a myriad of cellular processes including mitochondrial biogenesis, transcription, and organization of the extracellular matrix. Clearly, NAD+ is a major player in skeletal muscle development, regeneration, aging, and disease. The vast majority of studies indicate that lower NAD+ levels are deleterious for muscle health and higher NAD+ levels augment muscle health. However, the downstream mechanisms of NAD+ function throughout different cellular compartments are not well understood. The purpose of this review is to highlight recent studies investigating NAD+ function in muscle development, homeostasis, disease, and regeneration. Emerging research areas include elucidating roles for NAD+ in muscle lysosome function and calcium mobilization, mechanisms controlling fluctuations in NAD+ levels during muscle development and regeneration, and interactions between targets of NAD+ signaling (especially mitochondria and the extracellular matrix). This knowledge should facilitate identification of more precise pharmacological and activity-based interventions to raise NAD+ levels in skeletal muscle, thereby promoting human health and function in normal and disease states.

PMID:
29514713
PMCID:
PMC5840929
DOI:
10.1186/s13395-018-0154-1
[Indexed for MEDLINE]
Free PMC Article

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