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生物钟
biological clock
地球上大多数生命体，包括人类
都有一种叫“生物钟”的生理机制
所谓“生物钟”就是机体
从白天到夜晚有一个24小时循环节律
与地球自转相吻合
生物钟是无形的“时钟”
由光-暗的周期决定
人体生理方方面面都牵涉到生物钟
Most life entities on earth including humans, have a physiological mechanism called the “biological clock”. The so-called 'biological clock' means that the body has a 24-hour cyclic rhythm from day to night, which is consistent with the rotation of the earth. The biological clock is an invisible 'clock', determined by the light-dark cycle. All aspects of human physiology are involved in the biological clock.
我们细胞里基因表达
组织、器官到个体行为
都会受到生物钟的调控
精细校准我们的生理活动
适应每天不同的时段
健康的生物钟意味着
身体该干嘛时就能干嘛
以人类作息为例
白天活动，晚上睡眠
表现为“昼夜节律”
当生物钟被扰乱
就会出现晚上睡眠变差
白天无原因地疲乏，容易变胖
易患代谢类疾病病
From gene expression in our cells, tissues, and organs to individual behaviors, they are all regulated by the biological clock, finely calibrating our physiological activities to adapt to the different time. A healthy biological clock means that that we can do what we want. Taking human as an example, work in the daytime and sleep at night are expressed as 'biological rhythms.' When the biological clock is disturbed, there will be poor sleep at night, easy to get fat, and easy to suffer from metabolic diseases.
1
生物钟会老
The biological clock will be old
生物钟老化使“白天”和“晚上”生理差别缩小
例如，年轻人的褪黑激素
（促进睡眠的生理激素）
在入夜时开始分泌，在白天起床停止
一天内有明显波动
中年人褪黑素分泌波动不再明显
老人褪黑素基本无波动
这便是很多老人睡眠难的原因
The aging of the biological clock narrows the physiological difference between 'daytime' and 'nighttime'. For example, young people's melatonin (a physiological hormone that promotes sleep) begins to secrete at night and stops when waking up, and there are several obvious fluctuations within a day; the fluctuation of melatonin secretion of the middle-aged is no longer obvious; and there is no fluctuation of melatonin for the elderly which is the reason why many elderly people have difficulty in sleeping.
生物节律稳态恢复变差
如果身体的昼夜作息被打乱
自我调节机制可以让节律恢复
年纪越大，恢复的时间越长
例如，大学时代熬夜唱K打游戏通宵不成问题
中年的时候熬次夜
恐怕都要一周才能缓过来
Biological rhythm recovery becomes worse. If our rhythm of day and night is disrupted, self-regulating mechanisms can restore it. The older people are, the longer the recovery time is. For example, staying up late to sing and play games during college is not a problem. Staying up late when being old may take people a week to recover.
生物钟老化使睡眠碎片化
夜间睡眠中断
这种情况的原因是机体不同组织出现
“不一致”的昼夜节律，导致半夜频繁醒来
典型的系统性生物钟失调
The aging of the biological clock fragments sleep and interrupts sleep at night. The reason for this situation is the occurrence of 'inconsistent' circadian rhythms in different tissues of the body, resulting in frequent waking in the middle of the night which is a typical systemic circadian clock disorder.
2
生物钟是由
基因蛋白调控的
The biological clock is regulated by genes and proteins
体内生物钟到底如何运作一直是未解之谜
2017年诺贝尔医学奖授予
来自美国的三位遗传学家：
杰弗里·霍尔 (Jeffrey C. Hall)
迈克尔·罗斯巴什 (Michael Rosbash)
以及迈克尔·扬 (Michael W. Young)
表彰他们“发现了调控昼夜节律的分子机制”
发现的基因命名为时钟（Clock）
和周期（Period）
顾名思义，这些基因的表达昼夜分明
促进了昼夜节律的形成
How the clock works remains to be a mystery. The 2017 Nobel Prize in Physiology and Medicine was awarded to three geneticists from the United States: Jeffrey C. Hall, Michael Rosbash, and Michael W. Young for discovering the molecular mechanisms regulating circadian rhythm. The genes they found were named Clock and Period. As the name implies, the expression of these genes is distinct, which promotes the formation of circadian rhythms.
3
NAD
调节人类生物钟
NAD regulates the human biological clock
已知人体内的代谢物就多达11万种
其中有一类具有“出类拔萃”的细胞功能
这类代谢物叫烟酰胺腺嘌呤二核苷酸
（Nicotinamide Adenine Dinucleotide
以下简称NAD）
NAD广泛参与了细胞代谢反应
是维持生命化学反应的关键节点
NAD可以和细胞内多达500种蛋白相结合
其中就包括了Clock基因和Period基因
这种蛋白NAD复合体
是蛋白行使功能所必需的
It is known that there are as many as 110,000 metabolites in the human body. One of them has an excellent cell function. This type of metabolite is called Nicotinamide Adenine Dinucleotide (NAD). NAD is widely involved in cellular metabolic reactions and is a key point in sustaining chemical reactions. NAD can be combined with up to 500 proteins in the cell, including the Clock gene and Period gene. This NAD complex is necessary for the protein function.
通过精细的比较和测量发现在年老过程中
多个器官组织中NAD的水平显著下降
（以程度排序），肾（下降80%）
肺（下降75%）
心脏（下降60%-70%）
脾脏（下降60%）
肌肉组织（下降50%-70%）
脂肪组织（下降30%-40%）
肝脏（下降20%-30%）
胰腺（下降15%-20%）
脑脊液（下降10%）
Through careful comparison and measurement, it was found that during aging, the level of NAD in multiple organs and tissues decreases significantly in different organs (in order of degree): kidney (80%), lung (75%), heart (60%-70 %), spleen (60%), muscle tissue (50%-70%), adipose tissue (30%-40%), liver (20%-30%), pancreas (15%-20%), cerebrospinal fluid (10%).
以上数据只是基于自然衰老
（即没有明显的病理情况）
采集的在疾病状态下
NAD下降的幅度更为明显
NAD的降低
必然影响蛋白NAD复合体的形成
进而影响生物钟的昼夜节律
The above data was only collected based on natural aging (with no obvious pathology). In a disease state, the decline of NAD is more obvious. The reduction of NAD will inevitably affect the formation of the NAD complex, which in turn affects the circadian rhythm of the circadian clock.
除此以外
最新研究发现NAD体内合成关键
基因烟酰胺磷酸核糖转移酶
（NAMPT基因）
的表达也遵循昼夜节律
具有周期性
昼夜节律失调
NAMPT基因表达会紊乱
In addition, the latest research found that the expression of nicotinamide phosphoribosyltransferase (NAMPT gene) which is a key gene for the synthesis of NAD also follows the circadian rhythm and has periodicity. The disorder of circadian rhythm leads to disordered NAMPT gene expression.
衰老个体中NAMPT基因表达低于年轻个体
这解释了为什么随着年龄增大
NAD水平会降低
NAMPT下调直接影响体内NAD的水平
NAD的改变会进一步传递到生物钟的调控
早期的负循环在时间的尺度上
叠加放大最终导致生物节律的彻底失衡
同时提示年轻人作息更要规律
不然生物钟老化的进程会加快的
The expression of NAMPT gene in aging individuals is lower than that in young individuals, which explains why NAD levels decrease with age. NAMPT down-regulation directly affects the level of NAD in the body, and changes in NAD will further affect the circadian clock. The early negative cycle amplifies on the time scale which eventually leads to a complete imbalance of biological rhythm. At the same time, it reminds young people to work more regularly, otherwise, the aging process of the biological clock will accelerate.
通过补充NAD
可以对人体的健康和寿命产生深远的影响
遗憾的是NAD不是稳定的代谢物
所以直接补充NAD不可行
比较而言，补充NAD稳定前体是可行的
如烟酰胺单核苷酸（简称NMN）
NMN是天然化合物
通过口服补充NMN
即可快速增强体内NAD的水平
Supplementing NAD has a profound impact on human health and longevity. Unfortunately, NAD is not unstable, so it is not feasible to supplement NAD directly. In comparison, it is feasible to supplement stable precursors of NAD, such as nicotinamide mononucleotide (NMN for short). NMN is a natural compound, and NMN supplementation can rapidly increase the level of NAD in the body.
最近五年内，NMN相关工作出现了爆发
有数十篇高水平学术文章
充分证明补充NMN
对包括睡眠在内的生理机能
具有显著的改善作用
遗憾的是食物中的NMN极少
远远不能满足人体需求
In the past five years, NMN-related work has surged. Dozens of high-level academic articles have fully proved that supplementing NMN can significantly improve physiological functions including sleep.
就算NMN含量最高的牛油果
每100克也只有1毫克左右
而一个成年人每天需要的至少500毫克NMN
相当于50斤牛油果！
单纯从食物中摄取NMN是不现实的
需要通过膳食补充剂
来提供每天所需的NMN
从而转化为NAD，促进个体“年轻化”
恢复昼夜节律的稳态
白天精神抖擞迎接挑战
晚上让你睡的像个婴儿
Unfortunately, there is very little NMN in food, which is far from meeting human needs. Even avocado with the highest NMN content only contains about 1 milligram per 100 grams, and adults need at least 500 milligrams NMN per day, equivalent to 50 pounds of avocado! It is unrealistic to eat NMN from food alone. It is necessary to supplement NMN every day, which is converted into NAD, promoting the 'rejuvenation' of the individual and restoring the steady state of the circadian rhythm. Have a good state in the day and have a good sleep at night.
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