NMN:益处,副作用和剂量
由于现代医学的进步,世界各地的人们都活得更久了。除了降低死亡率和提高生存率外,生育率的持续下降也使老年人的比例上升。根据世界卫生组织的数据,到 2050 年,世界老年人口预计将达到 21 亿,使老年人口翻一番。
然而,更长的寿命并不能保证健康的生活。随着年龄的增长,我们的器官会受到损害并逐渐衰退,使我们容易患上疾病。这就是为什么许多科学家将注意力转移到寻找减缓、预防甚至逆转衰老的方法上。如果成功,所谓的抗衰老疗法可以降低与年龄有关的疾病的患病率,并帮助我们活得更久、更健康。
目前,正在研究的最有前途的抗衰老靶点之一是称为烟酰胺腺嘌呤二核苷酸(NAD+)的重要分子。NAD+ 介导我们细胞功能和生存所需的能量的产生,为修复 DNA 损伤的关键酶提供燃料。随着年龄的增长,这种不可或缺的分子逐渐减少。
许多科学家推测,与年龄相关的 NAD+ 下降是衰老特征器官衰退的基础。因此,通过恢复 NAD+,我们的细胞变得更健康,我们的器官变得更健康,我们变得更健康。如果能够实现这一目标,那么缺乏与年龄相关的高死亡率疾病,如心血管疾病、神经退行性疾病和癌症,将使我们活得更久。
我们如何恢复我们的 NAD+ 水平?由于 NAD+ 是自然发生的,因此我们的细胞具有自行制造所需的机制;他们只需要必要的生化成分。我们的细胞产生分子就像工厂装配线一样,其中每个组件都是下一个组件的前体。NAD+ 的生化前体称为烟酰胺单核苷酸 (NMN)。与 NAD+ 本身不同,NMN 可以口服摄入,因此可以以补充剂形式服用以提高 NAD+ 水平。
NMN的潜在好处
NMN 参与 NAD+ 的产生,为我们的细胞提供运作所需的能量。有几个因素被认为是衰老过程的基础,缺乏细胞能量就是其中之一。DNA损伤导致的遗传不稳定性也是这些因素之一。NAD+ 在激活维持 DNA 完整性的酶方面起着关键作用,从而促进遗传稳定性。鉴于其在这些细胞过程中的核心作用,用 NMN 增强 NAD+ 的潜在益处几乎延伸到所有身体系统。以下是一些比较著名的例子。
改善大脑功能
阿尔茨海默病也许是最具破坏性的与年龄有关的疾病之一,这种疾病使患者的记忆被剥夺。NMN 已被证明可以改善患有阿尔茨海默氏症的啮齿动物的认知能力,并减少阿尔茨海默氏症小鼠的脑斑块和神经退行性变。虽然阿尔茨海默氏症是一种终末期疾病,但许多老年人也患有认知障碍——无法正确学习、记忆和思考。NMN在小鼠中预防了这些与年龄相关的认知障碍。认知障碍有时与抑郁症有关,NMN也表明在小鼠中可以缓解抑郁症。
由于随着年龄的增长,我们的血管会变得功能失调,流向大脑的血液会受损,从而导致认知障碍。NMN 已被证明可以增加流向大脑的血流量并改善小鼠的认知功能。当我们大脑中的血管堵塞时,我们可能会中风,从而使我们的脑组织受损。NMN不仅可以延缓中风发作,还可以预防中风损伤,并改善啮齿动物中风后的认知和线粒体健康。
恢复血管健康
我们的血管将重要的营养物质输送到我们的每个细胞。随着年龄的增长,我们的血管变得僵硬,更容易阻塞,这可能导致心脏病发作或中风。NMN 已被证明可以通过恢复小鼠的血管弹性来逆转血管老化。衰老细胞——随着年龄的增长而积累的生长停滞细胞——会导致许多器官系统的老化,包括血管系统。在小鼠中,NMN阻止血管老化,减少衰老细胞,从而缓解高血压。衰老细胞促进衰老的方式之一是促进炎症,这几乎是所有与年龄相关的疾病的基础。NMN 已被证明可以通过减少小鼠的血管炎症来逆转血管功能障碍。
改善肌肉功能
我们依靠骨骼肌来运动、稳定和力量。随着年龄的增长,我们的肌肉会失去再生和生长的能力,导致与年龄相关的肌肉力量和大小下降,称为肌肉减少症。随着肌肉无力,我们也会变得更加疲劳,身体耐力也会降低。NMN似乎可以逆转这些情况,因为它的一种转运蛋白已被证明可以增加小鼠的力量和身体耐力。此外,NMN可改善老年男性的肌肉力量和表现,并增强中年跑步者的氧气利用率和运动耐力。另一方面,另一种称为烟酰胺核苷 (NR) 的 NAD+ 前体似乎确实可以改善肌肉功能。
促进心脏健康
在死亡接踵而至之前,我们的心脏可以承受大麦跳动,几乎没有空间去怀疑为什么心脏病是世界性的主要死亡原因。
随着年龄的增长,我们的心脏更容易受到不规则跳动的影响,这会产生毁灭性的后果,例如心力衰竭。NMN 已被证明可以预防小鼠的心力衰竭。我们的心脏组织是珍贵的,因为它不知道会再生。相反,受损组织表现为瘢痕形成(纤维化),导致心脏功能障碍。NMN通过减少瘢痕来恢复小鼠心脏功能。心脏不断跳动,需要大量的能量。为此,它需要健康的线粒体。NMN改善心脏新陈代谢并预防心力衰竭,部分原因是通过恢复线粒体的活力。
我们的心脏是心血管系统的一部分,将含氧血液泵送到我们的其他器官。当我们心脏周围的血管堵塞时,邻近组织会因缺氧而受损并死亡。这被称为缺血,通常会导致心脏病发作。在小鼠中,NMN保护心脏免受缺血性损伤。这种保护与干细胞疗法和褪黑激素协同改善。增强癌症抑制作用
癌症治疗中的辅助工具
免疫疗法是对抗癌症的更新和最有前途的疗法之一。这些疗法利用免疫细胞来抑制肿瘤生长。免疫疗法并不完美,但在啮齿动物中,NMN 已被证明可以增强几种不同类型的肿瘤杀伤能力,包括自然杀伤细胞疗法、CAR-T 细胞疗法和 PD-1 介导疗法。
虽然免疫疗法在不久的将来可能是一种癌症疗法,但化学疗法仍然被广泛使用,但会带来许多有害的副作用。NMN 已被证明可以减少这些不必要的副作用,例如小鼠的心脏组织损伤和认知障碍。
预防肥胖和糖尿病
肥胖与多种代谢缺陷有关,包括胰岛素抵抗——当细胞由于胰岛素信号受损而无法利用葡萄糖时——这可能导致糖尿病。线粒体是我们吃的食物转化为能量的最终细胞目的地,使它们在新陈代谢和相关疾病中至关重要。NMN已被证明可以使肥胖小鼠肝脏中的线粒体数量增加一倍,这可以防止肥胖。用NMN刺激脂肪分解也可以帮助肥胖的人减掉脂肪。此外,NMN改善了肥胖母亲所生小鼠的新陈代谢和健康。
吃得太多和肥胖会严重破坏我们的新陈代谢,并可能导致糖尿病。衰老会使这两种情况变得更糟。在小鼠中,NMN已被证明可以逆转饮食和衰老诱发的糖尿病,并预防与糖尿病相关的肾脏疾病和神经元变性,这表明NMN可以防止这些代谢障碍。为了支持这一点,NMN 已被证明可以改善老年女性的肌肉胰岛素敏感性。因此,虽然持续锻炼和健康饮食等生活方式调整至关重要,但 NMN 可以预防肥胖和糖尿病。
可以治疗眼睛老化和受伤
黄斑变性是一种与年龄有关的疾病,涉及视网膜区域的退化,使我们能够清楚地看到。因此,更严重的黄斑变性会导致失明。NMN 已被证明可以修复与小鼠黄斑变性相关的线粒体功能障碍。
随着年龄的增长,我们的眼睛会变得干燥和发炎。NMN 已被证明可以减少炎症和增加油脂分泌,治疗小鼠干眼症。NMN 还被证明可以减少眼外伤后的细胞死亡和伤口大小。
促进器官健康
除了减缓衰老的大脑、脉管系统、肌肉、心脏、新陈代谢和眼睛的各个方面外,NMN 还被证明可以使骨干细胞恢复活力并促进啮齿动物的骨形成。它还可以逆转肠道衰老,防止与年龄相关的肾脏退化,并抑制啮齿动物肝纤维化的发生。因此,NMN还可以减缓骨骼、肠道、肾脏和肝脏的衰老。
振兴繁殖
随着年龄的增长,生育问题也随之而来,尤其是女性。这源于卵母细胞(卵子)质量的问题。NMN 已被证明可以改善与年龄相关的卵母细胞质量和数量的下降,以及小鼠的雌性生育能力。NMN还可以保护卵母细胞免受猪毒素的侵害。
增强DNA修复的维持
我们的DNA编码为我们细胞的组成部分,但随着年龄的增长,损伤会累积。修复DNA损伤可以预防与年龄有关的疾病。NAD+ 为称为 sirtuins 的酶提供燃料——有时被认为是我们健康寿命的守护者。Sirtuins 在修复 DNA 中起着关键作用。
此外,每次我们的细胞分裂时,染色体末端的DNA(端粒)都会变短。在某个时候,这种端粒缩短开始损害我们的基因和细胞。Sirtuins通过稳定端粒长度来减缓这一过程。
由于 sirtuin 依赖于 NAD+ 发挥作用,因此一直在努力通过 NAD+ 增强方法增强 sirtuin 活性。沿着这些思路,研究表明,喂食小鼠NMN可以激活sirtuins。NMN还可以修复小鼠因辐射和衰老而导致的DNA损伤。此外,在小鼠和人类中,NMN都会增加端粒长度。
来自哈佛大学和华盛顿大学等研究所的 NMN 研究表明,补充该分子或增强 NMN 合成可促进啮齿动物衰老期间的长寿和健康。Sinclair及其同事发现,当老年小鼠喝NMN浸泡的水时,它们的跑步耐力几乎翻了一番。进一步的研究表明,给小鼠注射NMN可以在衰老过程中保持认知能力。此外,Imai及其同事的一项研究表明,NMN合成的激增使小鼠的剩余寿命增加了一倍以上。





供人食用的推荐剂量
动物研究表明,增加 NAD+ 水平可以逆转各种与年龄相关的疾病,如心脏病、糖尿病和神经退行性疾病.增强分子甚至延长了酵母、蠕虫和小鼠的寿命。NMN在动物体内的NAD+增强能力及其促进健康的特性使科学家们相信该分子的治疗潜力。现在,科学家们正在开始临床试验,以了解NMN是否安全,我们应该服用多少,以及它对我们的身体有什么影响。
NMN安全性的临床试验
一个国际研究小组在日本进行了首次NMN人体临床研究,以调查该分子的安全性。尽管 1 期临床试验的规模很小,但研究表明,高达 500 毫克口服 NMN 的剂量对人类是安全的,这意味着潜在的治疗策略。研究结果发表在2019年11月的《内分泌》杂志上。
NMN 作为膳食补充剂的安全性已在许多 FDA 批准的临床试验中得到证明。
在世界卫生组织 (WHO) 注册的其他临床试验也在研究 NMN 的安全性和有效性。在美国,华盛顿大学医学院的研究人员正在进行一项临床试验,以测试NMN对心血管和代谢健康的影响,每日剂量为250毫克。波士顿布莱根妇女医院的另一项临床研究也在测试补充剂对身体的影响,以及是否有任何副作用。
尽管研究人员仍需要进行更多的研究来确定人类的有效剂量,但其他 NAD 助推器的临床试验表明,每天 1 克口服补充剂可以刺激健康的中老年人的 NAD+ 代谢。
科学家使用 NMN 吗?
随着临床研究仍在进行中,一些科学家对NAD+对衰老的益处有足够的信心,并且已经在服用补充剂。
研究衰老的哈佛大学教授大卫·辛克莱(David Sinclair)在《乔·罗根体验》(The Joe Rogan Experience)播客中谈到了服用NMN以保持健康和预防衰老。Sinclair 每天服用 1 克 NMN,以及其他补充剂,包括白藜芦醇、二甲双胍和阿司匹林。当被问及补充剂是否有任何缺点时,辛克莱说,到目前为止,除了胃部不适之外,他还没有经历过任何事情,对他来说,“任何事情都比即将到来的要好”——衰老。
补充NMN的副作用
目前,尚未在人类中记录烟酰胺单核苷酸的副作用。研究人员对啮齿动物的 NMN 进行了大部分研究,揭示了对新陈代谢、大脑功能、肝脏、皮肤、肌肉、骨骼结构、心脏健康、生殖、免疫力和寿命的积极影响。长期小鼠研究也显示,在整个 12 个月的干预期间,没有毒性、严重副作用或死亡率增加。
一项关于人体 NMN 的研究表明,单次口服 100、250 和 500 mg NMN 后没有安全问题。单次口服NMN五小时后,科学家们发现心率、血压、血氧水平或体温没有变化。对血液的实验室分析没有显示显着变化,除了血液中四种分子的水平在正常范围内。这项研究还测量了睡眠质量,发现服用 NMN 前后没有差异。
科学家需要对人类的NMN给药进行进一步研究,以确定食用NMN是否会产生副作用。科学家可以研究高于500毫克的剂量,以确定它们是否会引起副作用。研究还可以研究长期食用NMN是否会引起副作用。
活跃的NMN临床试验
由于 NMN 在各种人类疾病小鼠模型中具有益处,因此已经进行了多项 NMN 临床试验以研究其临床适用性
NMN的未来研究
几千年来,世界各国都在叙述,皇帝和国王都在寻找他们能到达的每一个角落,寻找青春之泉。直到今天,这个故事仍然是一个谜,但科学家不是探险家,而是科学家。
动物研究表明,NMN 在 NAD+ 促进和抗衰老方面具有很有前途的特性。现在,研究人员正在推进临床试验,以调查该分子在人体中的安全性和有效性。随着机构和私人实体在抗衰老领域的研究工作,研究人员将很快开始得到答案。对于科学家来说,最终目标是开发减缓、阻止甚至逆转衰老的治疗方法,让人们过上健康长寿的生活。
服用NMN可能为对抗与年龄有关的疾病和病症提供了一种有前途的手段。以下是阐明 NMN 潜在益处的主要研究摘要。
研究类别 | 总结/结论 | 小鼠/大鼠 | 人 | 猪 |
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骨修复 |
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癌症 |
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心血管 |
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DNA修复 |
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眼睛保护 |
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免疫 |
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长寿 |
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新陈代谢 |
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神经学上的 |
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繁殖 |
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皮肤和肌肉 |
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器官健康 |
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机制 |
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参考链接
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