NAD+ centric mechanisms and molecular determinants of skeletal muscle disease and aging

• Published in: Molecular and cellular biochemistry 2022-06, Vol.477 (6), p.1829-1848
• Main Authors: Wagner, Sabrina, Manickam, Ravikumar, Brotto, Marco, Tipparaju, Srinivas M.
• Format: Article
• Language: English
• Subjects: Adenine; Adenosine diphosphate; Aging; Aging - metabolism; Animals; Antioxidants; Biochemistry; Biomedical and Life Sciences; Biosynthesis; Cardiology; CD38 antigen; Dietary supplements; Dystrophy; Energy metabolism; Epigenesis, Genetic; Epigenetics; Foreign bodies; Homeostasis; Life Sciences; Life span; Medical Biochemistry; Metabolic disorders; Mice; Mitochondria; Molecular modelling; Muscle, Skeletal - metabolism; Muscles; Muscular Diseases - metabolism; Muscular dystrophy; Musculoskeletal system; NAD; NAD - metabolism; Nicotinamide; Nicotinamide adenine dinucleotide; Nicotinamide phosphoribosyltransferase; Oncology; Oxidants; Oxidizing agents; Phosphoribosyltransferase; Poly(ADP-ribose) Polymerases - metabolism; Post-translation; Precursors; Ribose; Sirtuins; Skeletal muscle; Stem cells; Thermoregulation
• ISSN: 0300-8177; 1573-4919; 1573-4919
• DOI: 10.1007/s11010-022-04408-1

The nicotinamide adenine dinucleotide (NAD + ) is an essential redox cofactor, involved in various physiological and molecular processes, including energy metabolism, epigenetics, aging, and metabolic diseases. NAD + repletion ameliorates muscular dystrophy and improves the mitochondrial and muscle stem cell function and thereby increase lifespan in mice. Accordingly, NAD + is considered as an anti-oxidant and anti-aging molecule. NAD + plays a central role in energy metabolism and the energy produced is used for movements, thermoregulation, and defense against foreign bodies. The dietary precursors of NAD + synthesis is targeted to improve NAD + biosynthesis; however, studies have revealed conflicting results regarding skeletal muscle-specific effects. Recent advances in the activation of nicotinamide phosphoribosyltransferase in the NAD + salvage pathway and supplementation of NAD + precursors have led to beneficial effects in skeletal muscle pathophysiology and function during aging and associated metabolic diseases. NAD + is also involved in the epigenetic regulation and post-translational modifications of proteins that are involved in various cellular processes to maintain tissue homeostasis. This review provides detailed insights into the roles of NAD + along with molecular mechanisms during aging and disease conditions, such as the impacts of age-related NAD + deficiencies on NAD + -dependent enzymes, including poly (ADP-ribose) polymerase (PARPs), CD38, and sirtuins within skeletal muscle, and the most recent studies on the potential of nutritional supplementation and distinct modes of exercise to replenish the NAD + pool.