Nicotinamide Improves Aspects of Healthspan, but Not Lifespan, in Mice

Mitchell Sarah J.; Bernier Michel; Aon Miguel A.; Cortassa Sonia; Kim Eun Young; Fang Evandro F.; Palacios Hector H.; Ali Ahmed; Navas-Enamorado Ignacio; Di Francesco Andrea; Kaiser Tamzin A.; Waltz Tyler B.; Zhang Ning; Ellis James L.; Elliott Peter J.; Frederick David W.; Bohr Vilhelm A.; Schmidt Mark S.; Brenner Charles; Sinclair David A.; Sauve Anthony A.; Baur Joseph A.; de Cabo Rafael

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Nicotinamide Improves Aspects of Healthspan, but Not Lifespan, in Mice

机译：尼古林酰胺改善了卫生骨的方面，但在小鼠中没有寿命

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The role in longevity and healthspan of nicotinamide (NAM), the physiological precursor of NAD(+), is elusive. Here, we report that chronic NAM supplementation improves healthspan measures in mice without extending lifespan. Untargeted metabolite profiling of the liver and metabolic flux analysis of liver-derived cells revealed NAM-mediated improvement in glucose homeostasis in mice on a high-fat diet (HFD) that was associated with reduced hepatic steatosis and inflammation concomitant with increased glycogen deposition and flux through the pentose phosphate and glycolytic pathways. Targeted NAD metabolome analysis in liver revealed depressed expression of NAM salvage in NAM-treated mice, an effect counteracted by higher expression of de novo NAD biosynthetic enzymes. Although neither hepatic NAD(+) nor NADP(+) was boosted by NAM, acetylation of some SIRT1 targets was enhanced by NAM supplementation in a diet-and NAM dose-dependent manner. Collectively, our results show health improvement in NAM-supplemented HFD-fed mice in the absence of survival effects.

机译：尼古林酰胺（NAM）的寿命和健康血管中的作用，NAD（+）的生理前体，是难以捉摸的。在这里，我们报告说，慢性NAM补充在没有延伸寿命的情况下改善了小鼠中的卫生血措施。肝脏衍生细胞的肝脏和代谢通量分析的未确定代谢物分析揭示了小鼠葡萄糖稳态上的Nam介导的改善，其高脂饮食（HFD）与降低的肝脏脂肪变性和伴随糖原沉积和通量伴随的炎症相关通过戊糖磷酸盐和糖酵解途径。肝脏中的靶向NAD代谢分析显示NAM处理小鼠中NAM抢救的抑郁表达，抗De Novo NAD生物合成酶的表达抵消了效果。虽然NAM既不能升高肝NAD（+）也不会提高NADP（+），但NAM补充剂以饮食和NAM剂量依赖性方式增强了一些SIRT1靶的乙酰化。统称，我们的结果显示在没有生存效应的情况下在NAM补充的HFD喂食小鼠中出现健康。

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《Cell metabolism》 |2018年第3期|共14页
作者
Mitchell Sarah J.; Bernier Michel; Aon Miguel A.; Cortassa Sonia; Kim Eun Young; Fang Evandro F.; Palacios Hector H.; Ali Ahmed; Navas-Enamorado Ignacio; Di Francesco Andrea; Kaiser Tamzin A.; Waltz Tyler B.; Zhang Ning; Ellis James L.; Elliott Peter J.; Frederick David W.; Bohr Vilhelm A.; Schmidt Mark S.; Brenner Charles; Sinclair David A.; Sauve Anthony A.; Baur Joseph A.; de Cabo Rafael;
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NIA Expt Gerontol Sect Translat Gerontol Branch NIH Baltimore MD 21224 USA;

NIA Expt Gerontol Sect Translat Gerontol Branch NIH Baltimore MD 21224 USA;

NIA Expt Gerontol Sect Translat Gerontol Branch NIH Baltimore MD 21224 USA;

NIA Lab Cardiovasc Sci NIH Baltimore MD 21224 USA;

NIA Expt Gerontol Sect Translat Gerontol Branch NIH Baltimore MD 21224 USA;

NIA Lab Mol Gerontol NIH Baltimore MD 21224 USA;

NIA Expt Gerontol Sect Translat Gerontol Branch NIH Baltimore MD 21224 USA;

NIA Expt Gerontol Sect Translat Gerontol Branch NIH Baltimore MD 21224 USA;

NIA Expt Gerontol Sect Translat Gerontol Branch NIH Baltimore MD 21224 USA;

NIA Expt Gerontol Sect Translat Gerontol Branch NIH Baltimore MD 21224 USA;

NIA Expt Gerontol Sect Translat Gerontol Branch NIH Baltimore MD 21224 USA;

NIA Lab Mol Gerontol NIH Baltimore MD 21224 USA;

Cornell Univ Dept Pharmacol Weill Cornell Med New York NY 10065 USA;

Sirtris 200 Technol Sq Cambridge MA 02139 USA;

Sirtris 200 Technol Sq Cambridge MA 02139 USA;

Univ Penn Dept Physiol Inst Diabet Obes &

Metab Philadelphia PA 19104 USA;

NIA Lab Mol Gerontol NIH Baltimore MD 21224 USA;

Univ Iowa Dept Biochem Carver Coll Med Iowa City IA 52242 USA;

Univ Iowa Dept Biochem Carver Coll Med Iowa City IA 52242 USA;

Harvard Med Sch Glenn Labs Biol Mech Aging Boston MA 02115 USA;

Cornell Univ Dept Pharmacol Weill Cornell Med New York NY 10065 USA;

Univ Penn Dept Physiol Inst Diabet Obes &

Metab Philadelphia PA 19104 USA;

NIA Expt Gerontol Sect Translat Gerontol Branch NIH Baltimore MD 21224 USA;

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中图分类内分泌腺疾病及代谢病;
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1. Nicotinamide Improves Aspects of Healthspan, but Not Lifespan, in Mice [J] . Mitchell Sarah J., Bernier Michel, Aon Miguel A., Cell metabolism . 2018,第3期

机译：尼古林酰胺改善了卫生骨的方面，但在小鼠中没有寿命
2. Late-life targeting of the IGF-1 receptor improves healthspan and lifespan in female mice [J] . Kai Mao, Gabriela Farias Quipildor, Tahmineh Tabrizian, Nature Communications . 2018,第1期

机译：IGF-1受体的晚期靶向改善雌性小鼠的健康寿命和寿命
3. Metformin improves healthspan and lifespan in mice [J] . Alejandro Martin-Montalvo, Evi M. Mercken, Sarah J. Mitchell, Nature Communications . 2013,第2016期

机译：二甲双胍可改善小鼠的健康寿命和寿命
4. Measurement of similarity in C. elegans healthspan using dynamic time warping on movement features [C] . Arun G. Govindaswamy, Wahhaj Farooq, Yiyang Wang, International Conference on Bioinformatics and Computational Biology . 2020

机译：使用动态时间在运动功能上使用动态时间翘曲的C. elegans Healthspan的相似性测量
5. Young Hematopoietic Stem Cells Ameliorate Age-Associated Phenotypes and Extend Lifespan in Mice [D] . Guderyon, Michael James 2019

机译：年轻的造血干细胞可改善小鼠的年龄相关表型并延长其寿命
6. Nicotinamide improves aspects of healthspan but not lifespan in mice [O] . Sarah J. Mitchell, Michel Bernier, Miguel A. Aon, -1

机译：烟酰胺可改善小鼠的健康状况但不能改善寿命
7. Long term consumption of green tea EGCG enhances healthspan and lifespan in mice by mitigating multiple aspects of cellular senescence in mitotic and post-mitotic tissues, gut dysbiosis and immunosenescence [O] . Rohit Sharma, Ravi Kumar, Anamika Sharma, 2021

机译：通过减轻有丝分裂和薄脑病组织，肠道脱敏和免疫倒期，通过减轻细胞衰老的多个方面，长期消费绿茶EGCG增强了小鼠的疗效和寿命

Nicotinamide Improves Aspects of Healthspan, but Not Lifespan, in Mice

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