超级啰嗦的长生不老药也不能让你长生不老

“啰嗦”和“长生不老”两个词放在一起总让人想起《大话西游》里的唐僧。

整体来讲这是一本非常啰嗦的书。感觉作者没有分清科普读者和传记读者的区别，后者可能会对他研究的发现过程和整个来龙去脉，如何从某一次晚餐的愉快讨论发展到学术合作之类的等等细节很感兴趣，但是如果讲太多这些东西对前者来说就有点无聊了🥱，而且后面的一些内容感觉跟题目的关系都有点过于牵强了，我就非常迅速地扫过了。

我觉得我看这本书的两个主要的收获是：1. 了解到了“自由基抗衰老”基本上是在科学上站不住脚的纯商业宣传；2. 更多地了解了一下 epigenetics。（特别因为第二点给本书加一星）我们身体里所有的细胞都有（大致）一样的 DNA，那么是什么决定一些细胞变成神经元，另一些变成肝脏细胞、皮肤细胞等等的呢？这些就是由存储在一个叫 Chromatin 的结构中的 epigenetic 信息来决定的。第一次了解到相关的东西还是在 2018 年 NIPS 的一个 invited talk 上：What Bodies Think About: Bioelectric Computation Outside the Nervous System。那个 talk 讲得核心思想是，不同细胞的不同基因表达并不是一个简单的事先定好的表达计划，而是一个更复杂的自适应系统，这里所有的细胞组成一个计算系统，会根据细胞所处的环境、细胞之间的相互关系来动态地计算和决定哪一部分细胞进行怎样的基因表达——这个计算系统和我们的神经元组成的神经网络的运作方式是类似的（前者应该是后者的原型）。本书里提到基因里存储的信息是离散的，或者说是 digital 的，通过 ATGC 四种单元进行编码，从 analog 进化到 digital 的一个巨大突破就是信息在对噪音、错误、损害等的容忍性上得到巨大提升，基本上跟早期贝尔实验室为了避免电话信号在传输过程中逐渐被传输噪声破坏而做出的努力如出一辙：香农发展出了信息论，并由此推动信号由模拟信号转为数字信号。书中提到，epigenetic 的信息仍然是以模拟信号的方式存储的，会比基因信息更容易受到各种环境影响（宇宙射线、氧化等等），这个信息的损耗的过程，构成了我们衰老的一个重要原因。

到这里为止感觉都还讲得挺清楚的，后面感觉就各种散乱冗长地把各种只有一点点关系的东西也都拿过来说，什么长寿的社会影响啊之类的，整个书的结构也乱了。当然可能根本原因是本书的主题太大，这方面的研究应该还处在比较初期阶段，目前为止真正搞清楚了的东西也非常少，所以只能东扯扯西扯扯了。

书中提到的一个比较有趣的 hypothesis 是，寿命的长短并不是不同生物进化的完美与不完美的区别，因为进化的目的其实并不是让某一个体或者某一代的生命体活得更长，而是要让这个物种（的基因）能够长久延续下去。所以，比如比较容易被吃掉的动物（prey），经常会进化成寿命短+早生贵子的机制，只要完成基因传递的任务就大功告成了，反正指不定哪天就被抓去吃了，还不如早早死了把宝贵的生存资源留给下一代。

另外书中有列了几条关于长寿的具体建议：fasting，定期禁食一下下；运动，特别是 High Intensity Interval Training (HIIT)，和 diet 甚至 fasting 结合；时不时让自己受冻一下，也是不是让自己热一下（比如蒸桑拿）。总之就是时不时让自己有点危机感，多激活一下体内在远古时代还是单细胞的时候就进化出来的遗传信息自检、查错和修复机制。

以下是一些 quote

第一章：Viva Primordium

If old habits die hard, the free-radical idea is heroin. The theory was overturned by scientists within the cloister of my field more than a decade ago, yet it is still widely perpetuated by purveyors of pills and drinks, who fuel a $3 billion global industry. With all that advertising, it is not surprising that more than 60 percent of US consumers still look for foods and beverages that are good sources of antioxidants.

Aging, quite simply, is a loss of information.

The term epigenetics was first coined in 1942 by Conrad H. Waddington... In the same way that genetic information is stored as DNA, epigenetic information is stored in a structure called chromatin... It [the epigenome] instructs the newly divided cells on what type of cells they should be and what they should remain, ... that's why a neuron doesn't one day behave like a skin cell and a dividing kidney cell doesn't give rise to two liver cells... a digital chemical system was the best way to store long-term genetic data. But information storage was also needed to record and respond to environmental conditions, and this was best stored in analog format... Unlike digital, analog information degrades over time -- falling victim to the conspiring forces of magnetic fields, gravity, cosmic rays, and oxygen. Worse still, information is lost as it's copied.

第二章：The Demented Pianist

A caterpillar can’t be a human being, but it can become a butterfly by virtue of changes in epigenetic expression that occur during metamorphosis, even though its genome never changes.

Youth -> broken DNA -> genome instability -> disruption of DNA packaging and gene regulation (the epigenome) -> loss of cell identity -> cellular senescence -> disease -> death.

Our DNA is constantly under attack. On average, each of our forty-six chromosomes is broken in some way every time a cell copies its DNA, amounting to more than 2 trillion breaks in our bodies per day. And that’s just the breaks that occur during replication. Others are caused by natural radiation, chemicals in our environment, and the X-rays and CT scans that we’re subjected to.

第四章：Longevity Now

Intermittent fasting, or IF — eating normal portions of food but with periodic episodes without meals — is often portrayed as a new innovation in health.

Although many forms of exercise have positive health effects, it’s high intensity interval training (HIIT)—the sort that significantly raises your heart and respiration rates—that engages the greatest number of health-promoting genes, and more of them in older exercisers.