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Age-related NAD+ decline.
Experimental Gerontology ( IF 3.9 ) Pub Date : 2020-02-22 , DOI: 10.1016/j.exger.2020.110888
Melanie R McReynolds 1 , Karthikeyani Chellappa 2 , Joseph A Baur 2
Affiliation  

Nicotinamide adenine dinucleotide (NAD+) is an essential metabolite that is reported to decline in concentration in tissues of aged animals. Strategies to increase NAD+ availability have shown promise in treating many conditions in rodents, including age-related degeneration, which has in turn driven intense interest in the effects of supplements on human health. However, many aspects of NAD+ metabolism remain poorly understood, and human data are limited. Here, we discuss the state of the evidence for an age-related decline in NAD+, along with potential mechanistic explanations, including increased consumption or decreased synthesis of NAD+ and changes in the composition of cells or tissues with age. Key challenges for the field involve the development of better tools to resolve information on the NAD+ content of specific cells and subcellular compartments as well as determining the threshold levels at which NAD+ depletion triggers physiological consequences in different tissues. Understanding how NAD+ metabolism changes with age in humans may ultimately allow the design of more targeted strategies to maintain its availability, such as inhibition of key consumers in specific tissues or direct delivery of precursors to sites of deficiency. In the meantime, human clinical trials with oral supplements are poised to provide some of the first direct evidence as to whether increasing NAD+ availability can impact human physiology. Thus, it is an exciting time for NAD+ research, with much remaining to be learned in terms of both basic biology and potential therapeutic applications.

中文翻译:

与年龄相关的 NAD+ 下降。

烟酰胺腺嘌呤二核苷酸 (NAD+) 是一种必需的代谢物,据报道其在老年动物组织中的浓度会下降。增加 NAD+ 可用性的策略在治疗啮齿动物的许多疾病方面显示出希望,包括与年龄相关的退化,这反过来又引起了人们对补充剂对人类健康影响的浓厚兴趣。然而,NAD+ 代谢的许多方面仍然知之甚少,人类数据也很有限。在这里,我们讨论了与年龄相关的 NAD+ 下降的证据状态,以及潜在的机制解释,包括 NAD+ 的消耗增加或合成减少,以及细胞或组织的组成随年龄的变化。该领域的主要挑战包括开发更好的工具来解析特定细胞和亚细胞区室的 NAD+ 含量信息,以及确定 NAD+ 消耗在不同组织中触发生理后果的阈值水平。了解 NAD+ 代谢如何随着人类年龄的增长而变化可能最终允许设计更有针对性的策略来维持其可用性,例如抑制特定组织中的关键消费者或将前体直接输送到缺乏部位。与此同时,口服补充剂的人体临床试验有望提供一些关于增加 NAD+ 可用性是否会影响人体生理的第一个直接证据。因此,对于 NAD+ 研究来说,这是一个激动人心的时刻,
更新日期:2020-02-23
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