NAD(+) Intermediates: The Biology and Therapeutic Potential of NMN and NR.

NAD(+) Intermediates: The Biology and Therapeutic Potential of NMN and NR.
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DOI:
10.1016/j.cmet.2017.11.002
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发表时间:
2018-03-06
期刊:
影响因子:
29
通讯作者:
Imai SI
Imai SI
中科院分区:
生物学1区
文献类型:
--
作者:
Yoshino J;Baur JA;Imai SI

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NAD+的生物学研究一直在获得动力,为年龄相关的功能衰退和疾病的发病机制提供了许多重要的见解。特别是,两个关键的NAD+中间体,烟酰胺核苷(NR)和烟酰胺单核苷酸(NMN),已被广泛研究,在过去几年。补充这些NAD+中间体已显示出预防和治疗作用,改善与年龄相关的病理生理学和疾病状况。尽管NMN和NR的药代动力学和代谢结局仍在深入研究中,但这些NAD+中间体可能表现出不同的行为,其结局似乎取决于NAD+生物合成酶、核苷酸酶和推定转运蛋白的组织分布和表达水平。一个将NAD+代谢与哺乳动物衰老和长寿控制联系起来的综合概念已经提出,现在的阶段是测试这些令人兴奋的临床前结果是否可以转化为改善人类健康。
Research on the biology of NAD+ has been gaining momentum, providing many critical insights into the pathogenesis of age-associated functional decline and diseases. In particular, two key NAD+ intermediates, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), have been extensively studied over the past several years. Supplementing these NAD+ intermediates has shown preventive and therapeutic effects, ameliorating age-associated pathophysiologies and disease conditions. Although the pharmacokinetics and metabolic fates of NMN and NR are still under intensive investigation, these NAD+ intermediates can exhibit distinct behavior and their fates appear to depend on the tissue distribution and expression levels of NAD+ biosynthetic enzymes, nucleotidases, and presumptive transporters for each. A comprehensive concept that connects NAD+ metabolism to the control of aging and longevity in mammals has been proposed, and the stage is now set to test whether these exciting preclinical results can be translated to improve human health.
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