The Plasma NAD(+) Metabolome Is Dysregulated in "Normal" Aging.
The Plasma NAD(+) Metabolome Is Dysregulated in "Normal" Aging.
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血浆NAD（+）代谢组在“正常”衰老中失调。
DOI：
10.1089/rej.2018.2077
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发表时间：
2019-04
影响因子：
2.6
通讯作者：
Braidy N
中科院分区：
文献类型：
--
作者：
Clement J;Wong M;Poljak A;Sachdev P;Braidy N
烟酰胺腺嘌呤二核苷酸（Nicotinamide adenine dinucleotide, NAD+）是一种重要的吡啶核苷酸，在细胞代谢中作为电子载体，在维持氧化还原平衡中起着至关重要的作用。NAD+:NADH和NADP+:NADPH比值的定量对多种细胞过程至关重要，包括细胞内CD38糖水解酶的次级信使信号传导、聚腺苷二磷酸核糖聚合酶（PARP）的DNA修复、NAD依赖的组蛋白去乙酰化酶（sirtuins）对基因表达的表观遗传调控以及氧化戊糖磷酸途径的调控。我们使用液相色谱-串联质谱联用技术定量分析了广泛年龄范围（20-87岁）的健康受试者血浆样品中NAD+代谢组的变化。我们的数据显示，随着年龄的增长，血浆中NAD+、NADP+和其他重要代谢物（如烟酸腺嘌呤二核苷酸（NAAD））的水平显著下降。然而，NAD+和NADP+ -NADH和nadph -烟酰胺（NAM）， n -甲基烟酰胺（MeNAM）以及腺苷二磷酸核糖化产物（包括腺苷二磷酸核糖（ADPR））的减少形式也有年龄相关的增加。然而，血浆中烟酸（NA）、烟酰胺单核苷酸（NMN）和烟酸单核苷酸（NAMN）的水平在不同年龄组之间没有统计学意义的变化。综上所述，我们的数据累积表明，年龄相关的损伤与细胞外血浆NAD+代谢组的相应改变有关。我们未来的研究将寻求阐明调节NAD+代谢物在治疗和预防年龄相关疾病中的作用。
Nicotinamide adenine dinucleotide (NAD+) is an essential pyridine nucleotide that serves as an electron carrier in cellular metabolism and plays a crucial role in the maintenance of balanced redox homeostasis. Quantification of NAD+:NADH and NADP+:NADPH ratios are pivotal to a wide variety of cellular processes, including intracellular secondary messenger signaling by CD38 glycohydrolases, DNA repair by poly(adenosine diphosphate ribose) polymerase (PARP), epigenetic regulation of gene expression by NAD-dependent histone deacetylase enzymes known as sirtuins, and regulation of the oxidative pentose phosphate pathway. We quantified changes in the NAD+ metabolome in plasma samples collected from consenting healthy human subjects across a wide age range (20–87 years) using liquid chromatography coupled to tandem mass spectrometry. Our data show a significant decline in the plasma levels of NAD+, NADP+, and other important metabolites such as nicotinic acid adenine dinucleotide (NAAD) with age. However, an age-related increase in the reduced form of NAD+ and NADP+—NADH and NADPH—and nicotinamide (NAM), N-methyl-nicotinamide (MeNAM), and the products of adenosine diphosphoribosylation, including adenosine diphosphate ribose (ADPR) was also reported. Whereas, plasma levels of nicotinic acid (NA), nicotinamide mononucleotide (NMN), and nicotinic acid mononucleotide (NAMN) showed no statistically significant changes across age groups. Taken together, our data cumulatively suggest that age-related impairments are associated with corresponding alterations in the extracellular plasma NAD+ metabolome. Our future research will seek to elucidate the role of modulating NAD+ metabolites in the treatment and prevention of age-related diseases.
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影响因子：
5.8
作者：
Adriouch, Sahil;Haag, Friedrich;Koch-Nolte, Friedrich
通讯作者：
Koch-Nolte, Friedrich
影响因子：
8.2
作者：
Kannt, Aimo;Pfenninger, Anja;Teichert, Lenore;Toenjes, Anke;Dietrich, Arne;Schon, Michael R.;Kloeting, Nora;Blueher, Matthias
通讯作者：
Blueher, Matthias
DOI：
10.1073/pnas.1718819115
发表时间：
2018-02-20
影响因子：
11.1
作者：
Hou, Yujun;Lautrup, Sofie;Bohr, Vilhelm A.
通讯作者：
Bohr, Vilhelm A.
影响因子：
29
作者：
Camacho-Pereira J;Tarragó MG;Chini CCS;Nin V;Escande C;Warner GM;Puranik AS;Schoon RA;Reid JM;Galina A;Chini EN
通讯作者：
Chini EN
影响因子：
7.3
作者：
Haffner, Curt D.;Becherer, J. David;Ulrich, John C.
通讯作者：
Ulrich, John C.