NMN进入体内变成NAD+后对能量和物质代谢产生重要作用。仅就三羧酸循环而言，三羧酸循环是人体三大营养（糖类、脂类、氨基酸）的最终代谢通路，也是糖类、脂类和氨基酸代谢联系的枢纽，三羧酸循环同时为有机体提供了大量能量是有机体能量枢纽。线粒体内的辅酶I（NAD）在TCA循环中接受电子传递还原成还原型辅酶I(NADH)，1 mol辅酶I(NAD)可以生成3 mol ATP，是细胞生命活动能量的重要来源。
2， 预防年龄相关的生理衰退
许多研究已经证实，NAD+在人体内的含量降低随着年龄降低[1][2]，补充NMN的小鼠表现出体重减少、能量增加、更好的血糖控制水平，NMN扭转了年龄造成的生理性衰退。而NAD+的消耗酶（PARP、cADPR和Sirtuins）在代谢，炎症，应激和损伤反应的生物过程中发挥重要作用，对调节细胞周期和抗衰老有重要作用。一般研究认为NMN抗衰老的机制是通过以下三个利用NAD+的酶来发挥作用。
2.1， DNA修复酶
NAD+是ADP核糖基转移酶或核糖基聚合酶（PARP）的唯一底物，PARP位于多种细胞细胞核内，当自由基和氧化剂对细胞造成损伤时，DNA单链会发生断裂，PARP会被激活。激活的PARP利用辅酶I(NAD+)作为底物转移ADP核糖基到目标蛋白上，同时生成烟酰胺(Nam)，这些目标蛋白参与DNA修复、基因表达、细胞周期进展、细胞存活、染色体重建和基因稳定性等多种功能。[3][4]有研究表明PARP对治疗癌症有积极作用，在各种癌症相关过程中发挥多功能作用，包括DNA修复，重组，细胞增殖或细胞死亡。[5]哈佛大学医院的Sinclari博士研究发现：补充NMN修复了辐射对小鼠DNA的损伤，使得它与健康小鼠无异。[6]
2.2， 环ADP核糖合成酶
NAD+是环ADP核糖合成酶(cADPRsynthases)环核糖聚合酶（cADP合酶）的唯一底物。环ADP核糖合成酶由一对细胞外酶组成，称为淋巴细胞抗原CD38和CD157，它们以NAD为底物生成环ADP核糖，是细胞周期和胰岛素的第二信使。[7]
2.3，去乙酰化
NAD+是长寿Ⅲ蛋白型赖氨酸去乙酰化酶Sirtuins的唯一底物。Sirtuins存在于哺乳动物中，由275个氨基酸组成，有7种不同的亚型（SIRT1-SIRT7)，SIRT3-SIRT5存在线粒体中，SITR6和SITR7存在于细胞核中，SITR1存在于细胞质中。Sirtuins在细胞抗逆性、能量代谢、细胞凋亡和衰老过程中具有重要作用，故被称为长寿蛋白。[8][9]SIRT1可激活PARP-1来进行DNA双链的高效修复，SIRT13~5可以作为肿瘤的抑制物。[10]
来源：Sirtuinsin mammals: insights into their biological function
3， 改善2型糖尿病
2型糖尿病是现在社会的一种流行病，研究认为是高热量和久坐摧毁了我们身体对糖的天然代谢途径。一种机制认为高热量食物的摄取摧毁了NAD+的合成代谢，补充NMN可以增加胰岛素的敏感性，改善年龄诱导的葡萄糖耐受不良。[11]
4，预防神经退行性疾病（帕金森、老年痴呆症）
现在研究普遍认为轴突变性是引发神经退行疾病（如帕金森病，阿尔茨海默病（AD）和肌萎缩侧索硬化）的原因。在神经元损伤之后诱导多个转录物，包括NRK2增加超过20倍，其催化合成NAD +，以补偿应答来提高NAD +水平。实验证明通过补充NAD+，提高了对创伤脑损伤[12]、帕金森[13]和肌萎缩侧索硬化症[14]的神经保护，是神经肌肉正常化延缓记忆衰退。[15]阿尔茨海默病表现出NAMPT减少和神经干细胞分化受损，极高NAMPT活性或补充NAD+后，减少了β-淀粉样蛋白含量的增加[16]，通过PGC-1α介导的β-分泌酶（BACE1）降解和诱导线粒体生物合成来改善阿尔茨海默病。[17]
5， NMN功效概览
Cell和Nature越来越多的文章对NMN的功能进行了揭示，将NMN的功能概览如下：
| 方向 | 相关文献 | 相关应用 |
| 抗衰老 |
NMN减轻了小鼠的生理性衰退，服用NMN扭转了小鼠的生理指标[18] 提高NAD+水平可使小鼠线粒体恢复至年轻水平，22月的小鼠服用NMN恢复至6月大小鼠水平[19] NMN可激活长寿蛋白Sirtuins1~7[20][21] |
改善睡眠、提高记忆力、抗衰老；延缓衰老 |
| DNA修复 | 补充NMN可修复受辐射损伤细胞的DNA，服用一周后老年老鼠与年轻小鼠无差异[22] |
a, 放化疗患者； b，辐射人群 |
| 糖尿病 | 对饮食和年轻所引起的2型糖尿病能有效干预[23] | 糖尿病患者 |
| 运动与减肥 |
NMN促进脂肪分解，增加运动耐力[24] 补充NAD+增加骨骼肌的形成和线粒体氧化代谢。[25] |
运动员 |
| 神经认知 |
NMN可减低脑细胞死亡和氧化应激，这进一步证明了NMN对神经系统的保护作用[26] NMN恢复了线粒体的功能[27] NMN恢复了患有AD的老鼠的认知功能[28] NMN修复了认知障碍[29] |
老年痴呆、帕金森、肌萎缩侧索硬化 |
| 心血管 |
NMN显著增加了心脏NAD+的水平，保护心脏免受I/R损害；[30] NMN减少了血管氧化应激，使老鼠主动脉恢复正常，代表了治疗动脉老化的新策略；[31] NMN可降低心肌炎症；[32] 服用NMN后小鼠的FXN-KO恢复至正常水平。[33] |
心血管慢性疾病 |
| 解酒护肝 | NMN可促进酒精代谢，并增强人体对酒精的耐受性；[34] | 解酒护肝 |
| 保护视力 | NMN防止感光细胞变性并恢复视力，拯救视网膜障碍[35] | 视力保护 |
| 保护听力 | 增加耳部神经元和组织中NAD +水平的方法可以提供对创伤引起的听力损失的保护[36] | 听力保护 |
6，参考文献
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[2] Specific ablation of Nampt in adult neural stem cells recapitulatestheir functional defects during aging. Stein, L.R. and Imai, S. EMBO J. 2014;33: 1321–134
[3] Crosstalk between poly(ADP-ribose) polymerase and sirtuin enzymes.Cantó, C., Sauve, A.A., and Bai, P. Mol. Aspects Med. 2013; 34: 1168–1201
[4] New insights into the molecular and cellular functions ofpoly(ADP-ribose) and PARPs.
Gibson, B.A. andKraus, W.L. Nat. Rev. Mol. Cell Biol. 2012; 13: 411–424
[5] Therapeutic applications of PARP inhibitors: anticancer therapy andbeyond. Curtin, N.J. and Szabo, C. Mol. Aspects Med. 2013; 34: 1217–1256
[6] A conserved NAD+ binding pocket that regulates protein-proteininteractions during aging
[7] Evolution and function of the ADP ribosyl cyclase/CD38 gene familyin physiology and pathology. Malavasi, F., Deaglio, S., Funaro, A., Ferrero,E., Horenstein, A.L., Ortolan, E., Vaisitti, T., and Aydin, S. Physiol. Rev.2008; 88: 841–886
[8] Sirtuin 1-mediated effects of exercise and resveratrol onmitochondrial biogenesis. Menzies, K.J., Singh, K., Saleem, A., and Hood,D.A.J. Biol. Chem. 2013; 288: 6968–6979
[9] SIRT1 metabolic actions: Integrating recent advances from mousemodels. Boutant, M. and Canto, C. Mol. Metab. 2014; 3: 5–18
[10] Mitochondrial sirtuins and their relationships with metabolicdisease and cancer.
Kumar, S. andLombard, D.B. Antioxid. Redox Signaling. 2015; 22: 1060–1077
[11] Nicotinamide mononucleotide, a key NAD+ intermediate, treats thepathophysiology of diet- and age-induced diabetes in mice
[12] P7C3 neuroprotective chemicals block axonal degeneration andpreserve function after traumatic brain injury. Yin, T.C., Britt, J.K., DeJesús-Cortés, H., Lu, Y., Genova, R.M., Khan, M.Z., Voorhees, J.R., Shao, J.,Katzman, A.C., Huntington, P.J. et al. Cell Rep. 2014; 8: 1731–1740
[13] Neuroprotective efficacy of aminopropyl carbazoles in a mouse modelof Parkinson disease. De Jesús-Cortés, H., Xu, P., Drawbridge, J., Estill, S.J.,Huntington, P., Tran, S., Britt, J., Tesla, R., Morlock, L., Naidoo, J. et al.Proc. Natl. Acad. Sci. USA. 2012; 109: 17010–17015
[14] Neuroprotective efficacy of aminopropyl carbazoles in a mouse modelof amyotrophic lateral sclerosis. Tesla, R., Wolf, H.P., Xu, P., Drawbridge,J., Estill, S.J., Huntington, P., McDaniel, L., Knobbe, W., Burket, A., Tran,S. et al. Proc. Natl. Acad. Sci. USA. 2012; 109: 17016–17021
[15] NAD+ Replenishment Improves Lifespan and Healthspan in AtaxiaTelangiectasia Models via Mitophagy and DNA Repair Substance with the potentialto postpone aging
[16] Neuronal SIRT1 activation as a novel mechanism underlying theprevention of Alzheimer disease amyloid neuropathology by calorie restriction.Qin, W., Yang, T., Ho, L., Zhao, Z., Wang, J., Chen, L., Zhao, W.,Thiyagarajan, M., MacGrogan, D., Rodgers, J.T. et al. J. Biol. Chem. 2006; 281:21745–21754
[17] Nicotinamide riboside restores cognition through an upregulation ofproliferator-activated receptor-γ coactivator 1α regulated β-secretase 1degradation and mitochondrial gene expression in Alzheimer’s mouse models.Gong, B., Pan, Y., Vempati, P., Zhao, W., Knable, L., Ho, L., Wang, J., Sastre,M., Ono, K., Sauve, A.A., and Pasinetti, G.M. Neurobiol. Aging. 2013; 34:1581–1588
[18] NAD+ and sirtuins in aging and disease (Imai, 2014)
[19] Declining NAD+ Induces a Pseudohypoxic State DisruptingNuclear-Mitochondrial Communication during Aging (Gomes, Sinclair,2013)
[20]un Li,Zhenkun Lou, Vera Gorbunova, L. Aravind, Clemens Steegborn, David A. Sinclair.A conserved NAD+ binding pocket that regulates protein-protein interactionsduring aging. Science 355：1312,(2017)
[21] Mouchiroud L., Houtkooper R.H., Moullan N., et al.. TheNAD+/Sirtuin pathway modulates longevity through activation of mitochondrialUPR and FOXO signaling. Cell 154: 430-441 (2013).
[22] Nicotinamide Mononucleotide, a Key NAD+ Intermediate, Treats thePathophysiology of Diet- and Age-Induced Diabetes in Mice (Yoshino, 2011)
[23] Head to Head Comparison of Short-Term Treatment with the NAD(+)Precursor Nicotinamide Mononucleotide (NMN) and 6 Weeks of Exercise in ObeseFemale Mice (Uddin, 2016)
[24] Evidence for a direct effect of the NAD+ precursor acipimox onmuscle mitochondrial function in humans. van de Weijer, T., Phielix, E., Bilet,L., Williams, E.G., Ropelle, E.R., Bierwagen, A., Livingstone, R., Nowotny, P.,Sparks, L.M., Paglialunga, S. et al. Diabetes. 2015; 64: 1193–1201
[25] Nicotinamide mononucleotide attenuates brain injury afterintracerebral hemorrhage by activating Nrf2/HO-1 signaling pathway (Wei, 2017)
[26] Nicotinamide mononucleotide protects against β-amyloidoligomer-induced cognitive impairment and neuronal death (Wang, 2016)
[27] Nicotinamide mononucleotide inhibits JNK activation to reverseAlzheimer disease (Yao, 2017)
[28]Nicotinamidemononucleotide, an intermediate of NAD+ synthesis, protects the heart fromischemia and repercussion (Yamamoto, 2014)
[29].Nicotinamide mononucleotide, an intermediate of NAD+ synthesis, protects theheart from ischemia and repercussion
[30] Nicotinamide mononucleotide supplementation reverses vasculardysfunction and oxidative stress with aging in mice (de Picciotto, 2016)
[31]Short-termadministration of Nicotinamide Mononucleotide preserves cardiac mitochondrialhomeostasis and prevents heart failure (Zhang, 2017)
[32] Nicotinamide mononucleotide requires SIRT3 to improve cardiacfunction and bioenergetics in a Friedreich’s ataxia cardiomyopathy model
[33] Samuel W.French. Chronic alcohol binging injures the liver andother organs by reducing NAD⁺ levels required for sirtuin's deacetylaseactivity. Experimental and Molecular Pathology 100:303-306(2016)[34]NAMPT-mediatedNAD+ biosynthesis is essential for vision in mice (lin, 2016)
[35] Brown KD, Maqsood S, Huang JY, Pan Y, Harkcom W, Li W, Sauve A,Verdin E, Jaffrey SR. Activation of SIRT3 by the NAD(+) precursor nicotinamideriboside protects from noise-induced hearing loss. Cell metabolism.2014;20:1059–1068