Department of Pharmaceutical Sciences, USF Health Taneja College of Pharmacy, University of South Florida, 12901 Bruce B. Downs Blvd, MDC 030, Tampa, FL, 33612, USA.
Bone-Muscle Research Center, College of Nursing & Health Innovation, University of Texas-Arlington (UTA), Arlington, TX, USA.
Mol Cell Biochem. 2022 Jun;477(6):1829-1848. doi: 10.1007/s11010-022-04408-1. Epub 2022 Mar 25.
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.
烟酰胺腺嘌呤二核苷酸（NAD）是一种必需的氧化还原辅助因子，参与各种生理和分子过程，包括能量代谢、表观遗传学、衰老和代谢疾病。NAD 的补充可以改善肌肉萎缩症，并改善线粒体和肌肉干细胞的功能，从而延长小鼠的寿命。因此，NAD 被认为是一种抗氧化剂和抗衰老分子。NAD 在能量代谢中起着核心作用，产生的能量用于运动、体温调节和抵御异物。NAD 合成的膳食前体被靶向用于改善 NAD 生物合成；然而，关于骨骼肌特异性影响的研究结果存在矛盾。最近在 NAD 补救途径中激活烟酰胺磷酸核糖转移酶和补充 NAD 前体方面的进展，导致在衰老和相关代谢疾病期间骨骼肌病理生理学和功能方面产生了有益的影响。NAD 还参与蛋白质的表观遗传调控和翻译后修饰，这些修饰参与各种细胞过程以维持组织内稳态。这篇综述详细介绍了 NAD 在衰老和疾病状态下的作用以及分子机制，例如年龄相关的 NAD 缺乏对骨骼肌中 NAD 依赖性酶（包括多聚（ADP-核糖）聚合酶（PARPs）、CD38 和沉默调节蛋白）的影响，以及关于营养补充和不同运动方式补充 NAD 池的最新研究。
