NAD⁺ and its derivatives NADH, NADP⁺, and NADPH are essential cofactors in redox reactions and electron transport pathways. NAD serves also as substrate for an extensive series of regulatory enzymes including cyclic ADP-ribose hydrolases, mono(ADP-ribosyl)transferases, poly(ADP-ribose) polymerases, and sirtuin deacetylases which are O-acetyl-ADP-ribosyltransferases. As a result of the numerous and diverse enzymes that utilize NAD as well as depend on its synthesis and concentration, significant interest has developed in its role in a variety of physiologic and pathologic processes, and therapeutic initiatives have focused both on augmenting its levels as well as inhibiting some of its pathways. In this article, we examine the biosynthesis of NAD, metabolic processes in which it is involved, and its role in aging, cancer, and other age-associated comorbidities including neurodegenerative, cardiovascular, and metabolic disorders. Therapeutic interventions to augment and/or inhibit these processes are also discussed.

Impact statement

NAD is a central metabolite connecting energy balance and organismal growth with genomic integrity and function. It is involved in the development of malignancy and has a regulatory role in the aging process. These processes are mediated by a diverse series of enzymes whose common focus is either NAD’s biosynthesis or its utilization as a redox cofactor or enzyme substrate. These enzymes include dehydrogenases, cyclic ADP-ribose hydrolases, mono(ADP-ribosyl)transferases, poly(ADP-ribose) polymerases, and sirtuin deacetylases. This article describes the manifold pathways that comprise NAD metabolism and promotes an increased awareness of how perturbations in these systems may be important in disease prevention and/or progression.

中文翻译：

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衰老和癌症中的 NAD 代谢。

NAD ⁺及其衍生物 NADH、NADP ⁺和 NADPH 是氧化还原反应和电子传递途径中必不可少的辅助因子。NAD 还可作为一系列调节酶的底物，包括环状 ADP-核糖水解酶、单（ADP-核糖基）转移酶、聚（ADP-核糖）聚合酶和作为 O-乙酰基-ADP-核糖基转移酶的沉默调节蛋白脱乙酰酶。由于利用 NAD 并依赖于其合成和浓度的众多不同的酶，人们对其在各种生理和病理过程中的作用产生了浓厚的兴趣，并且治疗计划的重点是提高其水平以及作为抑制其某些途径。在这篇文章中，我们研究了 NAD 的生物合成、它所涉及的代谢过程，以及它在衰老、癌症、和其他与年龄相关的合并症，包括神经退行性疾病、心血管疾病和代谢疾病。还讨论了增加和/或抑制这些过程的治疗干预。

影响陈述

NAD 是一种将能量平衡和有机体生长与基因组完整性和功能联系起来的中心代谢物。它参与恶性肿瘤的发展，并在衰老过程中发挥调节作用。这些过程由一系列不同的酶介导，这些酶的共同焦点是 NAD 的生物合成或其作为氧化还原辅因子或酶底物的利用。这些酶包括脱氢酶、环状 ADP-核糖水解酶、单（ADP-核糖基）转移酶、聚（ADP-核糖）聚合酶和沉默调节蛋白脱乙酰酶。本文描述了包含 NAD 代谢的多种途径，并提高了人们对这些系统中的扰动在疾病预防和/或进展中的重要性的认识。