Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice.
Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice.
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DOI：
10.1016/j.cmet.2016.09.013
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发表时间：
2016-12-13
期刊：
影响因子：
29
通讯作者：
Imai SI
中科院分区：
文献类型：
--
作者：
Mills KF;Yoshida S;Stein LR;Grozio A;Kubota S;Sasaki Y;Redpath P;Migaud ME;Apte RS;Uchida K;Yoshino J;Imai SI
NAD+的可用性随着年龄的增长和某些疾病而下降。烟酰胺单核苷酸肽（NMN）是一种关键的NAD+中间体，已被证明可增强NAD+生物合成并改善小鼠疾病模型中的各种病理。在这项研究中，我们进行了为期12个月的NMN管理，以定期饲料喂养的野生型C57 BL/6 N小鼠在其正常老化。口服给药的NMN迅速用于在组织中合成NAD+。值得注意的是，NMN有效地减轻了小鼠中与年龄相关的生理衰退。无任何明显毒性或有害作用，NMN抑制年龄相关的体重增加，增强能量代谢，促进体力活动，改善胰岛素敏感性和血脂谱，并改善眼功能和其他病理生理学。与这些表型相一致，NMN阻止了关键代谢器官中与年龄相关的基因表达变化，并增强了骨骼肌中的线粒体氧化代谢和线粒体蛋白质失衡。NMN的这些作用突出了NAD+中间体作为人类有效抗衰老干预措施的预防和治疗潜力。
NAD+ availability decreases with age and in certain disease conditions. Nicotinamide mononucleotide (NMN), a key NAD+ intermediate, has been shown to enhance NAD+ biosynthesis and ameliorate various pathologies in mouse disease models. In this study, we conducted a 12 month-long NMN administration to regular chow-fed wild-type C57BL/6N mice during their normal aging. Orally administered NMN was quickly utilized to synthesize NAD+ in tissues. Remarkably, NMN effectively mitigates age-associated physiological decline in mice. Without any obvious toxicity or deleterious effects, NMN suppressed age-associated body weight gain, enhanced energy metabolism, promoted physical activity, improved insulin sensitivity and plasma lipid profile, and ameliorated eye function and other pathophysiologies. Consistent with these phenotypes, NMN prevented age-associated gene expression changes in key metabolic organs and enhanced mitochondrial oxidative metabolism and mitonuclear protein imbalance in skeletal muscle. These effects of NMN highlight the preventive and therapeutic potential of NAD+ intermediates as effective anti-aging interventions in humans.
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影响因子：
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作者：
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通讯作者：
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影响因子：
19
作者：
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通讯作者：
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