Ji Li Li
The Laboratory of Physiological Hygiene and Exercise Science, School of Kinesiology, University of Minnesota Twin Cities, Minneapolis, MN, USA.
Adv Exp Med Biol. 2025;1478:421-443. doi: 10.1007/978-3-031-88361-3_17.
Hyperacetylation of proteins represents a stress to aged organisms. Increased consumption and loss of NAD+ homeostasis underlie a major mechanism for the disturbed acetylation/deacetylation balance during aging. Nicotinamide adenine dinucleotide (NAD) is a versatile chemical compound serving as a coenzyme in metabolic pathways and as a substrate to support the enzymatic functions of sirtuins (SIRTs), poly (ADP-ribose) polymerase-1 (PARP-1), and cyclic ADP ribose hydrolase (CD38). Under normal physiological conditions, NAD+ consumption is matched by its synthesis primarily via the salvage pathway catalyzed by nicotinamide phosphoribosyltransferase (NAMPT). However, aging and muscular contraction enhance NAD+ utilization, whereas NAD+ replenishment is limited by cellular sources of NAD+ precursors and/or enzyme expression. This chapter will briefly review NAD+ metabolic functions, its roles in regulating cell signaling, mechanisms of its degradation and biosynthesis, and major challenges to maintain its cellular level in skeletal muscle. The effects of aging, physical exercise, and dietary supplementation on NAD+ homeostasis will be highlighted based on recent literature.
蛋白质的过度乙酰化对衰老生物体而言是一种应激。衰老过程中，NAD+内稳态的消耗增加及丧失是导致乙酰化/去乙酰化平衡紊乱的主要机制。烟酰胺腺嘌呤二核苷酸（NAD）是一种多功能化合物，在代谢途径中作为辅酶，并作为底物支持沉默调节蛋白（SIRTs）、聚（ADP-核糖）聚合酶-1（PARP-1）和环ADP核糖水解酶（CD38）的酶促功能。在正常生理条件下，NAD+的消耗主要通过烟酰胺磷酸核糖转移酶（NAMPT）催化的补救途径合成来匹配。然而，衰老和肌肉收缩会增强NAD+的利用，而NAD+的补充则受到NAD+前体的细胞来源和/或酶表达的限制。本章将简要回顾NAD+的代谢功能、其在调节细胞信号传导中的作用、其降解和生物合成机制，以及在骨骼肌中维持其细胞水平的主要挑战。基于近期文献，将重点介绍衰老、体育锻炼和膳食补充对NAD+内稳态的影响。
