Uchida Hitoshi, Nakagawa Takashi
Department of Molecular and Medical Pharmacology, School of Medicine, University of Toyama.
Nihon Yakurigaku Zasshi. 2025;160(4):268-273. doi: 10.1254/fpj.24072.
Aging is a physiological process caused by various genetic and environmental factors. Recently, it has been proposed that the disturbance of the nutritional-metabolic sensing pathway is one of the aging characteristics. In particular, nicotinamide adenine dinucleotide (NAD) plays an important role in this pathway and is considered the regulator of aging. NAD regulates an energy metabolism as a co-factor and is also involved in various biological processes including transcription, stress responses, DNA repair, inflammatory responses as well as post-transcriptional modifications, as a substrate for sirtuins, poly ADP-ribose polymerase (PARP), and CD38. With age, DNA damage and chronic inflammation increase in organs, resulting in overconsumption of NAD via PARP and CD38. The reduced NAD levels decrease the activity of sirtuins and PARPs and impair energy metabolism, ultimately leading to aging and aging-related diseases. However, the precise metabolism of NAD in vivo and the mechanism of how NAD regulates aging remain elusive. Moreover, the clinical application of NAD supplementation therapy is still under development. In this review, we overview the NAD metabolism and its relation to aging. In addition, we describe the current issue and perspective of NAD supplementation therapy to promote a healthy lifespan.
衰老是一个由多种遗传和环境因素引起的生理过程。最近，有人提出营养代谢传感通路的紊乱是衰老的特征之一。特别是，烟酰胺腺嘌呤二核苷酸（NAD）在该通路中起重要作用，被认为是衰老的调节因子。NAD作为一种辅助因子调节能量代谢，同时作为沉默调节蛋白、聚ADP核糖聚合酶（PARP）和CD38的底物，还参与包括转录、应激反应、DNA修复、炎症反应以及转录后修饰在内的各种生物学过程。随着年龄的增长，器官中的DNA损伤和慢性炎症增加，导致通过PARP和CD38过度消耗NAD。NAD水平的降低会降低沉默调节蛋白和PARP的活性，并损害能量代谢，最终导致衰老和与衰老相关的疾病。然而，NAD在体内的确切代谢以及NAD调节衰老的机制仍然不清楚。此外，NAD补充疗法的临床应用仍在开发中。在这篇综述中，我们概述了NAD代谢及其与衰老的关系。此外，我们描述了NAD补充疗法促进健康寿命的当前问题和前景。
