Nicotinamide adenine dinucleotide (NAD⁺) is a vital coenzyme in redox reactions. NAD⁺ is also important in cellular signalling as it is consumed by PARPs, SARM1, sirtuins and CD38. Cellular NAD⁺ levels regulate several essential processes including DNA repair, immune cell function, senescence, and chromatin remodelling. Maintenance of these cellular processes is important for healthy ageing and lifespan. Interestingly, the levels of NAD⁺ decline during ageing in several organisms, including humans. Declining NAD⁺ levels have been linked to several age-related diseases including various metabolic diseases and cognitive decline. Decreasing tissue NAD⁺ concentrations have been ascribed to an imbalance between biosynthesis and consumption of the dinucleotide, resulting from, for instance, reduced levels of the rate limiting enzyme NAMPT along with an increased activation state of the NAD⁺-consuming enzymes PARPs and CD38. The progression of some age-related diseases can be halted or reversed by therapeutic augmentation of NAD⁺ levels. NAD⁺ metabolism has therefore emerged as a potential target to ameliorate age-related diseases. The present review explores how ageing affects NAD⁺ metabolism and current approaches to reverse the age-dependent decline of NAD⁺.

烟酰胺腺嘌呤二核苷酸 (NAD ⁺ ) 是氧化还原反应中的重要辅酶。NAD ⁺在细胞信号传导中也很重要，因为它被 PARP、SARM1、sirtuins 和 CD38 消耗。细胞 NAD ⁺水平调节几个基本过程，包括 DNA 修复、免疫细胞功能、衰老和染色质重塑。维持这些细胞过程对于健康的衰老和寿命很重要。有趣的是，在包括人类在内的几种生物体中，NAD ⁺水平在衰老过程中会下降。NAD ⁺水平下降与几种与年龄有关的疾病有关，包括各种代谢疾病和认知能力下降。减少组织NAD ⁺浓度被归因于二核苷酸的生物合成和消耗之间的不平衡，例如，由于限速酶 NAMPT 的水平降低以及 NAD ⁺消耗酶 PARPs 和 CD38 的活化状态增加。一些与年龄有关的疾病的进展可以通过治疗性增加 NAD ⁺水平来停止或逆转。因此， NAD ⁺代谢已成为改善与年龄有关的疾病的潜在目标。本综述探讨了衰老如何影响 NAD ^{+代谢，以及目前逆转 NAD +}随年龄增长而下降的方法。