Zhang Jianying, Wang He-Ling, Lautrup Sofie, Nilsen Hilde Loge, Treebak Jonas T, Watne Leiv Otto, Selbæk Geir, Wu Lindsay E, Omland Torbjørn, Pirinen Eija, Cheung Tin Cho, Wang Jun, Ziegler Mathias, Tysnes Ole-Bjørn, Zapata-Pérez Rubén, Bruzzone Santina, Canto Carles, Deleidi Michela, Janssens Georges E, Houtkooper Riekelt H, Scheibye-Knudsen Morten, Koshizaka Masaya, Yokote Koutaro, Verdin Eric, Bohr Vilhelm A, Tzoulis Charalampos, Sinclair David A, Fang Evandro Fei
Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, Lørenskog, Norway.
Key Laboratory of Oral Health Research in Hunan Province, Xiangya School of Stomatology, Central South University, Hu'nan, China.
Nat Aging. 2025 Sep 9. doi: 10.1038/s43587-025-00947-6.
Beyond their classical functions as redox cofactors, recent fundamental and clinical research has expanded our understanding of the diverse roles of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) in signaling pathways, epigenetic regulation and energy homeostasis. Moreover, NAD and NADP influence numerous diseases as well as the processes of aging, and are emerging as targets for clinical intervention. Here, we summarize safety, bioavailability and efficacy data from NAD-related clinical trials, focusing on aging and neurodegenerative diseases. We discuss the established NAD precursors nicotinic acid and nicotinamide, newer compounds such as nicotinamide riboside and nicotinamide mononucleotide, and emerging precursors. We also discuss technological advances including in industrial-scale production and real-time detection, which are facilitating NAD research and clinical translation. Finally, we emphasize the need for further large-scale studies to determine optimal dose, administration routes and frequency, as well as long-term safety and interindividual variability in response.
除了作为氧化还原辅因子的经典功能外，最近的基础研究和临床研究拓展了我们对烟酰胺腺嘌呤二核苷酸（NAD）和烟酰胺腺嘌呤二核苷酸磷酸（NADP）在信号通路、表观遗传调控和能量稳态中多种作用的理解。此外，NAD和NADP影响众多疾病以及衰老过程，并正成为临床干预的靶点。在此，我们总结了NAD相关临床试验的安全性、生物利用度和疗效数据，重点关注衰老和神经退行性疾病。我们讨论了已确定的NAD前体烟酸和烟酰胺、较新的化合物如烟酰胺核糖和烟酰胺单核苷酸以及新兴的前体。我们还讨论了包括工业规模生产和实时检测在内的技术进步，这些进步正在推动NAD研究和临床转化。最后，我们强调需要进一步开展大规模研究，以确定最佳剂量、给药途径和频率，以及长期安全性和个体间反应差异。
