Hong Weiqi, Mo Fei, Zhang Ziqi, Huang Mengyuan, Wei Xiawei
Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, Department of Biotherapy, Chengdu, China.
Front Cell Dev Biol. 2020 Apr 28;8:246. doi: 10.3389/fcell.2020.00246. eCollection 2020.
NAD+, a co-enzyme involved in a great deal of biochemical reactions, has been found to be a network node of diverse biological processes. In mammalian cells, NAD+ is synthetized, predominantly through NMN, to replenish the consumption by NADase participating in physiologic processes including DNA repair, metabolism, and cell death. Correspondingly, aberrant NAD+ metabolism is observed in many diseases. In this review, we discuss how the homeostasis of NAD+ is maintained in healthy condition and provide several age-related pathological examples related with NAD+ unbalance. The sirtuins family, whose functions are NAD-dependent, is also reviewed. Administration of NMN surprisingly demonstrated amelioration of the pathological conditions in some age-related disease mouse models. Further clinical trials have been launched to investigate the safety and benefits of NMN. The NAD+ production and consumption pathways including NMN are essential for more precise understanding and therapy of age-related pathological processes such as diabetes, ischemia-reperfusion injury, heart failure, Alzheimer's disease, and retinal degeneration.
烟酰胺腺嘌呤二核苷酸（NAD+）是一种参与大量生化反应的辅酶，已被发现是多种生物过程的网络节点。在哺乳动物细胞中，NAD+主要通过烟酰胺单核苷酸（NMN）合成，以补充参与包括DNA修复、代谢和细胞死亡等生理过程的NAD酶的消耗。相应地，在许多疾病中都观察到NAD+代谢异常。在本综述中，我们讨论了在健康状态下NAD+的稳态是如何维持的，并提供了几个与NAD+失衡相关的年龄相关病理实例。还对其功能依赖于NAD的沉默调节蛋白家族进行了综述。令人惊讶的是，在一些与年龄相关的疾病小鼠模型中，施用NMN显示出病理状况有所改善。进一步的临床试验已经启动，以研究NMN的安全性和益处。包括NMN在内的NAD+产生和消耗途径对于更精确地理解和治疗与年龄相关的病理过程，如糖尿病、缺血再灌注损伤、心力衰竭、阿尔茨海默病和视网膜变性至关重要。
