预防阿尔茨海默病的使命
在美国，阿尔茨海默病是第三大死因。如果你活到 85 岁，患上痴呆症（通常是阿尔茨海默病）的风险接近 40% 多，几乎就像抛硬币的几率。而且女性患阿尔茨海默病的风险是男性的两倍。但人们可能没有意识到的是，它在很大程度上是可以预防的。这就是我必须传达出去的信息。我是一名拥有专科认证的神经内科医生，我见过很多大脑，也看过数千张影像扫描。阿尔茨海默病主要是一种大脑的代谢疾病。
英文原文
In America, Alzheimer's is the third leading cause of death. If you live to be age 85, your risk of developing dementia and generally Alzheimer's, it's close to a high 40% or a flip of a coin. And women have twice the risk of Alzheimer's in comparison to men. But what people may not be aware of is it is significantly preventable. And that's the message that I've got to get out. I'm a boardcertified neurologist and I've seen a lot of brains and thousands of scans. Alzheimer's is primarily a metabolic condition of the brain.我这里有一些卡片，我想让你写下你认为导致阿尔茨海默病和痴呆症的前五大因素。
英文原文
>> So, I've got some cards here and I want you to write the top five things that you think are contributing to Alzheimer's and dementia.第一，我们把对自己大脑的主导权移交给了制药业。所以，我向你们提出人们在保持大脑健康方面能做的最重要的事情。第二，久坐不动。这非常关键。锻炼和运动是大脑的多功能工具。然后是食物选择。你看，我这里有几样东西。这是一个大问题，因为如果……哇，太可怕了。这真令人担忧。所以，我们现在真正明白的是：基因负责上膛，生活方式扣动扳机。
英文原文
>> Number one, we have offloaded agency of our brains to the pharmaceutical industry. So, I'm putting forth to you the most important things people can be doing in keeping the brain healthy. And number two, being sedentary. This is huge. Exercise and movement is a multi-tool for the brain. Then there's food choices. You know, I've got a few things here. This is a big problem because if Wow, that's scary. That's worrisome. So, what we really understand now is genetics loads the gun. Lifestyle pulls the trigger.你知道，我们经常从家属那里听到，眼睁睁看着自己所爱的人逐渐离去究竟是怎样一种感受。
英文原文
>> You know, we often hear from the family what it was like to essentially lose the person they loved.我父亲身上也发生过这种情况。当你看到自己的父母变成那样，回想起他曾经是谁、是怎样一个人时，这……呃，很难受，我不想让其他人也经历这些。
英文原文
>> And I've been through this with my father and when you see your parent like that and you think back to who he was and what he was, it's uh difficult and I don't want people to go through that.你现在自己也是一位父亲了，你有一个优秀的儿子叫奥斯汀（Austin）。奥斯汀给你写了一封信。
英文原文
Well, you're a dad yourself now and you have this wonderful son called Austin. Austin wrote a letter for you.你看，呃，我现在正在想我的父亲，我正在竭尽全力，好让人们不必体会我此刻的感受。那么，这对我们意味着什么呢？
英文原文
You know, uh, I'm thinking of my dad right now and I'm doing my best so people don't have to experience what I'm feeling right now. So, what does that mean for us?我希望很多人能收到这个信息，那就是……
英文原文
>> My hope is that a lot of people get this message that在这期节目开始前，我想请大家帮个小忙。两个月前，观看这个频道的人中有 61% 没有订阅。现在这个比例降到了 58%。我的目标是 50%。所以，如果你喜欢过我们在这个频道上制作的任何视频，如果你喜欢这个频道，你能帮我一个小忙，点击订阅按钮吗？这对这个频道的帮助超乎你的想象。频道规模越大，我们就能在嘉宾和制作上投入越多。谢谢大家，请享受这期节目。
英文原文
Before this episode starts, I have a small favor to ask you. 2 months ago, 61% of the people that watched this channel weren't subscribed. We're now down to 58%. My goal is 50%. So, if you've ever liked any of the videos we've made on this channel, if you like this channel, can you do me a small quick favor and hit the subscribe button? It helps this channel more than you know. And the bigger the channel gets, the more we can invest in the guests and the production. Thank you and enjoy this episode.戴维·珀尔马特（David Pelato）医生，你的使命是什么？为什么这个使命对你个人如此重要？嗯，我的使命是让尽可能多的人知道，他们大脑的……呃……命运，实际上取决于他们今天选择如何生活。我们生活在一个被灌输这种观念的世界里：随遇而安，爱怎么过就怎么过，反正当你的大脑无法正常运转时，神经科学领域总会出现某种神奇的新成果来拯救你。我们还没走到那一步。我期盼那一天的到来，但我们现在还没到。事实上，我们现在真正明白的、也是神经科学中最伟大的发展是：我们的生活方式选择才是我们大脑命运的真正缔造者。
英文原文
Dr. David Pelato, what is the mission you are on and why does that mission personally matter to you? Well, the mission I'm on is to let as many people know that the the destiny of their brains uh is really based upon how they are choosing to live their lives today. So, we live in a world where we're sort of message to really live your life uh come what may, however you like, and there'll be some magic development in the world of neuroscience that will save you when your brain isn't working like it should. We aren't there yet. I welcome that day, but we aren't there yet. What we really understand now, in fact, the greatest development in neuroscience is that our lifestyle choices are really the architects of our brain's destiny.戴维医生，你是谁？你有什么经历，接受过怎样的教育？
英文原文
>> And who are you, Dr. David? What is your experience and what is the the education that you've had?我上了医学院，获得了医学博士学位，随后……呃，进入神经外科住院医师培训，并成为了一名拥有专科认证的神经内科医生。
英文原文
>> I went to medical school, got my MD, then became uh enrolled in a neurosurgery residency and became a boardcertified neurologist.为什么这一切对你个人来说如此重要？
英文原文
>> And why does this all matter so much to you personally?对我个人来说，我也经历过这个，经历过……
你刚刚出了那张牌，对吧？
我和我父亲一起经历过这些。并且，呃……
这很艰难。对我国 760 万阿尔茨海默病患者来说，这很艰难。说实话，对他们来说还不算最艰难的，对他们的家属来说才是最难受的。而且它在很大程度上是可以预防的。这就是我必须传达出去的信息。我们还没有治疗方法。我期盼有治疗方法吗？当然期盼。如果有一种药物，我会给我自己的父亲开吗？我当然会开。但我们还没走到那一步。
你的父亲遭遇了什么？我这里也有一张他的精彩画像。多风度翩翩的一位男士啊。
他曾是一位杰出的脑外科医生，富有同情心，医术精湛，是一位极其慈悲的……呃，长者。到了晚年，他患上了阿尔茨海默病。你知道，这很有意思，因为我是很晚才确诊他的。我记得最终意识到“天哪，他患上痴呆了”的那一刻，呃……我之前漏掉了。
英文原文
Personally, I've been through this well with You just played that card, didn't you? I've been through this with my father. And uh and it's rough. It's rough for in my country, the 7.6 million Alzheimer's patients. Not so rough for them as it is for their families, the truth be known. And it is significantly preventable. That's the message that I've got to get out. We don't have a treatment. Would I welcome a treatment? You bet. Would I have used a medication and prescribed it for my own father? Of course I would have. We aren't there yet. What happened to your father? Got a wonderful portrait of him here as well. What a suave man. So uh he was a brilliant brain surgeon, compassionate, skilled, wonderfully compassionate uh individual. And in his later years, he developed Alzheimer's. And you know, it's interesting because I diagnosed him late in the game. I remember the moment that I finally realized, my gosh, he's demented and uh I missed it.你怎么知道他患了阿尔茨海默病？那是什么病？你如何诊断它？
英文原文
>> How did you know he had Alzheimer's? What is that? How do you diagnose it?这是我的本职工作。我是说，我来见你的路上，在机场就能诊断帕金森病。我的意思是，这就是我的工作，是我的专业技能。你知道，就是他所经历的那种记忆问题，丢三落四，走进房间就忘了自己身在何处，这非常明显。我的意思是，这至少是痴呆症，而通常这意味着阿尔茨海默病。
英文原文
>> It's what I do. I mean, I I diagnose Parkinson's in the airport when I'm coming to see you. I mean, that's what I do. It's my skill set. You know, just the the type of memory issues that he was experiencing, losing things, walking into the room, forgetting where he was, it was very obvious. I mean, it it was at least dementia and generally that means Alzheimer's.就我个人的理解而言，区别是什么？因为我们……我经常听到痴呆症、阿尔茨海默病这些词，
英文原文
>> And just my knowledge, what is the difference? Because we I hear these words dementia, Alzheimer's,帕金森病。
英文原文
>> Parkinson.痴呆症大部分都是阿尔茨海默病。你也可能因为大脑供血不足而出现认知障碍，我们称之为血管性痴呆。也有一种痴呆与大脑中一种叫做路易体（Louis bodies）的物质积聚有关。人们还可能因为可逆的问题而出现认知障碍，例如由于他们可能正在服用的药物，或者……呃，其他类型的医疗问题。因此，痴呆症是一个总称。
英文原文
>> Most of dementia is Alzheimer's. You can be cognitively impaired because of poor blood supply to your brain. We call that vascular dementia. There is dementia that goes along with the accumulation of something called Louis bodies in the brain. People can be cognitively impaired with reversible issues like as a consequence of uh medications that they may be taking or uh other types of medical problems. So dementia is the sort of umbrella term.没错。痴呆症指的是跨越多个领域的认知功能障碍。
英文原文
>> Exactly. Dementia means you know this failure of cognitive function across multiple domains.好的。所以有阿尔茨海默病、血管性痴呆、路易体痴呆，还有……
英文原文
>> Okay. So Alzheimer's disease, vascular dementia, Louisibody dementia and额颞叶痴呆。
英文原文
>> fronttotemporal dementia.好的。所以归在痴呆症之下的所有东西，它是一组症状的统称。
英文原文
>> Okay. So everything underneath dementia, it's a general term for a group of symptoms.没错。
英文原文
>> That's right.好的。
英文原文
>> Okay.大脑免疫系统与代谢失衡
当你审视那些表面上截然不同的诊断时，让我感到极其着迷的是，它们确实各不相同，但它们都被一个共同的机制联系在一起，那就是大脑免疫系统的紊乱。这是最根本的。这是目前神经科学界巨大的顿悟时刻。大脑免疫系统的紊乱，是大脑由好变坏这一宏大图景中的核心特征。
英文原文
>> What has become so fascinating for me as you look at those seemingly very disperate diagnoses and they are but they're all united by one common mechanism and that is disruption of the brain's immune system. That's the fundamental. That is the the huge aha in neuroscience right now. That disruption of the brain's immune system is a central feature across this incredible panorama of what makes a good brain go bad.目前医学界相信的哪些东西是你不再认同的？大体上，我认为至少在阿尔茨海默病方面——随着我们交流的深入，我认为我们可以在更多神经退行性疾病中展开这一点——但我认为目前的传统观念依然认为，阿尔茨海默病的核心诱因是大脑中一种叫做 β-淀粉样蛋白（beta amaloid）的积聚。清除了 β-淀粉样蛋白，问题就解决了。那不是现实，这种看法是不公允的。那么有多少人一生中可能会患上某种形式的痴呆症？也就是说，有多少人会受到你所研究、致力解决并能诊断的这些神经退行性疾病的影响？
英文原文
>> What is it the current medical profession believes that you no longer believe? I think that by and large at least relating to Alzheimer's and I think we can flesh this out across more neurodeenerative conditions as we speak but I think still the party line is one that believes that the central player in Alzheimer's disease is the accumulation of a protein called beta amaloid in the brain. Get rid of the beta amalloid and problem solved. That is not reality and it's unfair. And how many people are likely to get a form of dementia in their life? Like how how many people are going to be affected by these neurodeenerative diseases that you have studied and worked on and can diagnose?很多人。我的意思是，如果你活到 85 岁，你患痴呆症（通常是阿尔茨海默病）的风险接近于抛硬币的几率。接近，你知道，40% 多的高位。那……那是非常令人担忧的。在美国，阿尔茨海默病是第三大死因。人们没有意识到这一点。而它在很大程度上是可以预防的。这就回到了我们的第一个问题：我为什么在这里？我是做什么的？我的使命是向人们传达：斯蒂芬（Stephen），在你这个年龄所做的事情，对于决定你大脑未来的命运有着巨大的影响。
英文原文
>> Lots. I mean, if you live to be age 85, your risk of developing dementia and generally Alzheimer's is close to a flip of a coin. It's close to, you know, high 40%. And that is uh that's very worrisome. In America, Alzheimer's is the third leading cause of death. People don't realize that. And it is largely preventable. That gets back to our first question. Why am I here? What do I do? And my mission is to message people that what you're doing at your age, Stephen, is hugely influential in terms of charting your brain's destiny.痴呆症是从什么时候开始的？通常我们讨论的观念是：你知道，一位患者——甚至还不是患者，只是某个人出现了一些状况，记不住名字，走进房间忘了自己要干嘛，丢东西——这时他们去看了医生，随后评估过程开始，并最终选择某种形式的治疗。但现实是，这……就像心脏病发作。我们不会等到你突发心脏病才开始检查你的血脂、测量你的血压、询问你：“你有运动吗？你的睡眠怎么样？你的体力活动情况如何？”而在面对痴呆症时，我们也应该做同样的事情。我们应该找三四十岁的人交谈，并询问完全相同的问题。阿尔茨海默病主要是一种大脑的代谢疾病。让我告诉你一件在你们国家发生的非常有意思的事情。呃，就在过去这周，在英格兰这里启动了一项名为 ADS smart trial 的新试验，政府已经……呃，出资了 3300 万……
英文原文
>> When does dementia start? Typically we discuss the idea that you know a patient becomes not even a patient yet but somebody is having issues forgetful of names going into the room forgetting why losing things that's when they go to the doctor and that's when the process begins of evaluation and ultimately choosing some form of treatment. And the reality is it it's like um a heart attack. We don't wait for you to have a heart attack to begin looking at your blood lipids, looking at your blood pressure, asking you, "Are you active? How are you sleeping? What's your physical activity like?" And we should be doing the same thing as it relates to dementia. We should be talking to people in their 30s and in their 40s and asking those very same questions. Alzheimer's is primarily a metabolic condition of the brain. Let me tell you something that's really interesting that happened in your country. Uh this past week there is a new trial being started right here in England called the ADS smart trial and the government has uh put up 33 million4400 万英镑的新药临床试验与阿尔茨海默病研究方向的转变
4400 万英镑用于启动一项针对两种治疗阿尔茨海默病药物的研究。一种叫做二甲双胍（metformin），是一种治疗糖尿病的药片；另一种其实是一种治疗多动症（ADHD）的药物，叫做思锐（Strattera）。这是一项大约 1000 人的试验，将耗时 18 个月来治疗阿尔茨海默病患者。我为什么要提起这个？事实上，你们的首相非常支持这项研究，因为他的父亲死于痴呆症。话虽如此，我提起它的原因在于二甲双胍是一种代谢类药物。它是一种糖尿病药物。想想看，他们已经不再把靶向 β-淀粉样蛋白作为唯一方向，终于认识到代谢在这里扮演着核心角色。请像对我这样一个 16 岁的人解释一样，给我讲讲这个。所以，β-淀粉样蛋白就是他们在患有阿尔茨海默病痴呆症的人脑中发现的那些棕色斑块。所以他们曾认为这是导致痴呆症的部分原因。
英文原文
pounds44
million
to
begin
a
study
of
two
medicines
in
the
treatment
of
Alzheimer's
disease.
One
is
called
metformin
which
is
a
diabetes
pill
and
the
other
is
actually
an
ADHD
drug
called
strata.
And
this
is
a
trial
of
about
a
thousand
people.
It's
going
to
take
18
months
to
treat
Alzheimer's
patients.
Why
I
bring
it
up?
As
a
matter
of
fact,
your
prime
minister
is
very
much
in
favor
of
it
in
that
um
his
father
died
of
dementia.
Uh
that
said,
the
reason
I
bring
it
up
is
metformin
is
a
metabolic
drug.
It's
a
diabetes
drug.
Think
about
that.
that
they've
moved
away
from
targeting
beta
amaloid
to
finally
recognizing
that
metabolism
is
a
central
player
here.
Explain
this
to
me
like
I'm
16
years
old.
So
beta
amalloid
are
these
these
brown
sort
of
plaques
they
found
on
the
brain
with
people
that
had
Alzheimer's
dementia.
Um
so
they
thought
that
it
was
part
of
the
cause
of
the
dementia.
随后他们发现，你可以有这些斑块，但仍然没有任何痴呆症状。所以我们现在知道，肯定还有别的原因，你可以有这些斑块——满脑子的斑块——但并没有痴呆。
英文原文
>> Subsequentlythey
found
out
that
you
can
have
those
plaques
and
still
not
have
the
dementia
symptoms.
So
we
now
know
it
must
be
something
else
and
you
can
have
the
plaques
a
a a
brain
load
of
plaques
and
not
be
demented.
所以现在的工作假说是还有其他原因在起作用。而你提出，这在很大程度上是基于代谢的。
英文原文
Sonow
the
working
hypothesis
is
that
it's
something
else
is
causing
it.
And
you're
positing
that
it's
largely
based
on
metabolism.
是的。
英文原文
>> Yes.而据我理解，代谢就是我们吃什么、我们做什么，比如我们的活动以及我们的生活、我们的生活方式决定。这是一个很好的问题，我认为严格的定义是：代谢是我们细胞产生能量和制造物质的方式。它们制造蛋白质，制造各种物质。所以，真正导致健康大脑变差的上游因素，其实是代谢的变化。代谢标志物，如我们的血糖、血压、身体脂肪、血脂。这些都是对大脑、心脏乃至整个人体都至关重要的代谢指标。因此，当我们说阿尔茨海默病从根本上讲是一种代谢状况时，让我们把它放在当前研究走向的背景下来看。例如，10 年前大约有三分之一的阿尔茨海默病研究真正聚焦于我们谈到的这种 β-淀粉样蛋白。现在这个比例已经下降到大约 14%，转向研究代谢这类事物，以及观察大脑的免疫系统——这些小胶质细胞（microglial cells）才是真正上游的关键所在，它不仅与阿尔茨海默病相关，而且关系到各种各样的神经退行性疾病。因此，当我们理解了代谢及其对小胶质细胞的影响时，我们实际上就撒开了一张非常广阔的网。这意味着，如果我们能在生命早期靶向调整我们的代谢，控制好血糖、锻炼身体、保证充足睡眠、与他人保持社交关系——谁曾想到这竟是对抗大脑健康问题如此强大的工具。我们确实正在营造一个有助于降低整个谱系中大脑退行性问题风险的环境，而不仅仅是阿尔茨海默病。我打算给你出一道稍微有点棘手的难题。
英文原文
>> Andmetabolism
as
I
understand
it
is
what
we
eat,
what
we
do
like
our
activity
and
our
life,
our
lifestyle
decisions.
It's
a
great
question
and
I
think
that
you
know
the
strict
definition
is
metabolism
is
the
way
that
our
cells
uh
create
energy
and
make
things.
They
make
proteins,
they
make
things.
So
really
uh
upstream
of
what
makes
a
good
brain
go
bad
are
changes
in
metabolism.
The
metabolic
markers,
our
blood
sugar,
our
blood
pressure,
our
body
fat,
our
blood
lipids.
These
are
the
metrics
of
metabolism
that
are
so
important
for
the
brain
and
the
heart
and
in
fact
your
entire
body.
So
when
we
say
that
Alzheimer's
is
fundamentally
a
metabolic
condition,
let's
let's
say
that
in
the
context
of
where
the
research
is
going.
For
example,
10
years
ago
about
a
third
of
Alzheimer's
research
was
really
focused
on
what
we
talked
about
this
beta
amalloid
protein.
That
number
is
down
to
about
14%
now
in
favor
of
looking
at
things
like
metabolism
and
looking
at
the
brain's
immune
system
these
micro
gal
cells
that
are
really
the
upstream
issue
as
it
relates
to
not
just
Alzheimer's
but
all
manner
of
neurodeenerative
condition.
So
when
we
understand
metabolism
and
its
effect
on
the
microgle
cells,
we're
throwing
a
very
wide
net
indeed.
Meaning
that
if
we
can
target
our
metabolism
earlier
in
life,
keep
our
blood
sugar
under
control,
exercise,
get
enough
sleep,
have
relationships
with
other
people,
who
knew
that
was
such
a
powerful
tool
uh
for
brain
health.
we
really
are
creating
an
environment
that
helps
us
reduce
the
risk
across
the
spectrum
of
brain
degenerative
issues,
not
just
Alzheimer's.
I'm
going
to
set
you
a
slightly
tricky
task.
生活方式对阿尔茨海默病的影响与主动权
好的。我这里有一些卡片，我希望你按照严重程度和后果的顺序，写下你认为从生活方式的角度来看，导致阿尔茨海默病和痴呆症的前五大因素。
英文原文
>> Okay.I
I've
got
some
cards
here
and
I
want
you
to
write
in
order
of
um
severity
and
consequence
the
top
five
things
that
you
think
from
lifestyle
perspective
are
contributing
to
Alzheimer's
and
dementia.
好的。如果你想补充更多，可以多加几条。只要告诉我你写了多少个就行。
英文原文
Okay.If
you've
got
more
that
you
want
to
add,
you
can
add
more.
Just
tell
me
how
many
you've
got
you've
done.
好的。那么，你写了几个？
英文原文
Okay.So,
how
many
have
you
got
there?
我有五个。再次重申一下我在这里做的事情：我正在向你提出我认为人们在掌控自己大脑命运方面可以做的最重要的事情。而这其实就是第一条。最大的问题在于没有接受一个事实——你自己才是大脑命运的缔造者。因为如果我们不做到这一点，这里的任何事情都不重要，这里的一切都不会发生。你必须接受这一点，必须认识到我们已经把大脑的自主权拱手让给了制药业以及其他形式的技术。再次强调，如果真有某种有效的东西，那很好。但目前还没有任何真正有意义的有效手段。约翰·肯尼迪曾说，修屋顶的时间应当是在阳光明媚之时。这就是我今天来到这里的原因。
英文原文
>> Ihave
five.
And
again,
let's
restate
what
I'm
doing
here.
I'm
putting
forth
to
you
what
I
think
are
the
most
important
things
people
can
be
doing
as
it
relates
to
being
in
charge
of
their
brain.
And
that
is
in
fact
number
one.
And
that
is
the
biggest
issue
is
not
embracing
the
fact
that
you
are
the
architect
of
your
brand's
destiny.
Because
if
we
don't
do
this,
nothing
here
will
matter.
nothing
here
will
take
place.
You've
got
to
embrace
that
and
you've
got
to
recognize
that
we
have
offloaded
agency
of
our
brains
to
the
pharmaceutical
industry,
if
you
will,
and
other
forms
of
technology.
And
again,
that's
great
if
there
were
something
that
were
effective.
There
is
not
anything
meaningfully
effective
right
now.
John
Kennedy
said
that
the
time
to
fix
the
roof
is
when
the
sun
is
shining.
And
that's
why
I'm
here
today.
所以第二条是久坐（sedentarity），也就是久坐不动的生活方式。这一点影响巨大。运动和身体活动对大脑来说是一把多功能工具。它针对胰岛素的功能，针对炎症，针对线粒体功能，也针对血流。这些都是维持大脑健康的极其重要的机制。你对大脑健康如此专注，部分是因为你父亲的原因吗？而且这是否从统计学上让你对同一种疾病具有易感性？
英文原文
Sonumber
two,
sedentarity,
meaning
being
sedentary.
This
is
huge.
This
exercise
and
movement
is
a
multi-tool
for
the
brain.
It
targets
the
function
of
insulin.
It
targets
inflammation.
It
targets
mitochondrial
function.
It
targets
blood
flow.
These
are
all
hugely
important
mechanisms
in
keeping
the
brain
healthy.
Are
you
somewhat
very
focused
on
brain
health
in
part
because
of
your
father
and
does
that
statistically
give
you
a
predisposition
to
the
same
disease?
确实如此。确实会。
英文原文
>> Itdoes.
It
does.
APOE 基因与运动对发病风险的干预
我想，当我们谈到我们在风险方面所继承的遗传因素时，现在很多人都关注克里斯·海姆斯沃斯（Chris Hemsworth）的故事，他携带了两个所谓的 APOE4 基因等位基因。你熟悉这个吗，还是需要我梳理一下？好的。我们有 APOE 等位基因。我们可以携带 2 型、3 型或 4 型。
英文原文
>> Ithink
you
know
when
we
talk
about
what
we
inherit
in
terms
of
risk
I
think
a
lot
of
people
these
days
are
focused
on
the
Chris
Hemsworth
story
that
he
carries
two
of
what
are
called
the
APOE4
genetic
alals.
Are
you
familiar
with
that
or
can
I
walk
through
it?
Okay.
So
we
have
the
the
APOE
alals.
We
can
have
a
two,
a
three
or
a
four.
嗯。
英文原文
>> Mhm.而且你有两次机会。
英文原文
>> Andyou
get
two
chances.
你说有两次机会是什么意思？
英文原文
>> Whatdo
you
mean
you
get
two
chances?
意思是你携带了其中的两个。所以你可以是 2/2，可以是 2/3、3/3、3/4、4/4 或者是 2/4。我想这就是可能发生的所有排列组合。携带较多的 APOE2 与发病风险显著降低有关。APOE3 是中性的，但大约 25% 的人携带的 APOE4 等位基因，则与阿尔茨海默病风险增加有关。如果你携带一个，风险大约增加 5 倍——
英文原文
>> Well,you
carry
two
of
them.
So
you
can
have
a
22,
you
can
have
a
2
three,
a
33,
a
34,
a
44,
and
a
I
guess
those
are
all
the
permutations
that
can
can
happen.
Carrying
more
of
the
APOE2s
is
associated
with
a
pretty
dramatic
risk
reduction.
APOE3
is
neutral,
but
carrying
the
APOE4
alil
like
about
25%
of
people
is
associated
with
an
increased
risk
of
Alzheimer's.
If
you
carry
one
by
about
fivefold
500%
英文原文
500%500%，五倍；如果你携带两个，换句话说，如果你是 APOE 4/4，风险增加可能高达 12 倍——
英文原文
>> 500%fivefold
and
if
you
carry
two,
in
other
words,
your
APOE
44,
the
risk
may
be
as
high
as
12fold
increase,
1200%。你说克里斯·海姆斯沃斯有这个情况，他对此非常公开。但这里有极其宝贵、而且是在你我尚未讨论的事项清单上极具价值的东西。为什么？因为现在人们到处都在做基因组测序。每个人都知道，在接受基因组测序的人中，有四分之一拿到结果并看到自己可能携带了一个 APOE4 等位基因。然后你读到了 AI 的简短打印报告，上面写着这会增加你患阿尔茨海默病的风险。这令人害怕，令人担忧。早些年，我们作为神经科医生被告知：当我们知道患者的 APOE 状态时，如果他们携带 APOE4，我们不应该告诉他们。那么，我们为什么要告诉他们呢？因为他们正走向阿尔茨海默病。事实绝非如此。如果你携带一个或两个 APOE4 等位基因，你并不一定注定会患上阿尔茨海默病。所以这极其重要。你的生活方式问题可以抵消这种遗传易感性。这是一种遗传易感性，我不否认这一点。但它并不是基因决定论。2025 年 11 月《美国医学会杂志》（Journal of the American Medical Association）发表了一项有趣的研究。作者名叫马力诺（Marino），他所做的是观察了来自弗雷明汉心脏研究（Framingham Heart Study）的人群，他将这组人分成了不同组别——总共有 4000 人，每组大约 1000 人——分为 25 至 44 岁的年轻人、45 至 64岁的中年人，以及 65 至 88 岁的老年人。那正是我的年龄段。他对这些人随访了若干年，确定了谁患上了痴呆症，谁没有患上。并将此与他们的身体活动水平进行了对比。他的发现确实非常引人注目：在中年人中，活动量最大的人与活动量最小的人相比，患这种目前尚无有效治疗手段的疾病——阿尔茨海默病——的风险降低了大约 45%。
英文原文
>> 1,200%.And
you're
saying
Chris
Hemsworth
has
he's
been
very
uh
public
about
it.
But
here's
what
is
so
valuable
and
on
the
list
of
things
that
you
and
I
have
not
covered
yet
and
incredibly
valuable.
Why
?
Because
people
are
getting
their
genome
sequence
now,
you
know,
left,
right,
and
center.
Everybody
knows
and
a
quarter
of
people
who
get
their
genome
sequence
are
getting
their
results
back
and
seeing
that
they
might
carry
an
APOE4
AL.
And
then
you
read
the
little
out
from
AI
that
says
this
puts
you
at
increased
risk
for
Alzheimer's.
That's
scary.
That's
worrisome.
Early
in
the
day,
we
as
neurologists
were
told,
well,
when
we
know
the
APOE
status
of
our
patients,
if
they
carry
APOE4,
we
shouldn't
tell
them.
Well,
why
should
we
tell
them?
Because
they're
on
the
road
to
Alzheimer's.
Nothing
is
further
from
the
truth.
If
you
carry
an
APOE4
alil
or
two,
you
are
not
necessarily
destined
to
get
Alzheimer's.
So
incredibly
important.
Your
lifestyle
issues
can
offset
this
issue
of
a
genetic
predisposition.
It's
a
genetic
predisposition.
I
won't
deny
that.
It
is
not
a
genetic
determinant.
There's
an
interesting
study
that
came
out
in
the
Journal
of
the
American
Medical
Association
in
November
of
The
author
was
named
Marino
and
what
he
did
was
looked
at
people
from
the
Frammingham
Heart
Study
and
he
divided
the
group
of
individuals
uh
there
were
about
a
thousand
in
each
group
4,000
total
into
younger
people
25
to
44
years,
middle-aged
people
45
to
64
and
older
65
to
That's
my
age
group.
And
he
followed
these
uh
individuals
uh
for
a
number
of
years
and
determined
who
got
dementia
and
who
did
not.
And
he
compared
that
to
their
level
of
physical
activity.
And
what
he
found
was
really
quite
remarkable
that
in
in
middle-aged
people,
those
who
were
the
most
active
compared
to
those
who
were
the
least
active
had
about
a
45%
risk
reduction
for
this
disease,
Alzheimer's,
for
which
there
is
no
meaningful
treatment.
这太重大了。在老年组中也发现了类似的结果。那些活动量最大并且携带 APOE4 的人，
英文原文
That'shuge.
Similar
results
in
the
older
age
group.
Those
who
are
most
active
and
carried
APOE4.
他们发展为阿尔茨海默病患者的风险降低了大约 67%——
英文原文
Theyhad
about
a
67%
reduced
risk
of
becoming
an
Alzheimer's
patient
如果他们锻炼的话。
英文原文
>> ifthey
exercised.
如果他们处于运动量最大的一组，与运动量最少的一组相比。再次说明，锻炼在这里就是一把多功能工具。对我们每一个人来说，它都是一个巨大且唾手可得的工具。这才是医生应该教给病人的。而不是说：“好吧，看起来你有认知障碍。我们将每 2 周给你做一次静脉输液治疗，然后听天由命吧。”
英文原文
>> Ifthey
were
in
the
the
group
that
exercised
the
most
in
comparison
to
the
group
that
exercised
the
least.
Again,
exercise
is
the
multi-tool
here.
It
is
a
a
huge
and
readily
available
tool
for
each
and
every
one
of
us.
That's
what
doctors
should
be
should
be
teaching
patients.
Not
well,
it
looks
like
you're
cognitively
impaired.
We're
going to
put
you
on
an
IV
uh
therapy
uh
every
2
weeks
and
hope
for
the
best.
运动在生理上起到了什么作用？它究竟是如何帮助大脑的？
英文原文
>> Whatis
the
exercise
doing
physiologically?
How
is
it
helping
the
brain?
嗯，它起到了很多作用。锻炼基本上意味着你在激活肌肉，对吧？你就是这样活动的。你需要肌肉工作，当……
英文原文
>> Well,it's
doing
a
lot
of
things.
Exercise
means
you're
basically
activating
muscle,
right?
That's
how
you
move.
You
need
your
muscle
to
to
work
when
肌肉作为内分泌器官与运动对大脑的益处
你运动。事实证明——你可能不知道这一点——你的肌肉其实是一个内分泌腺。
英文原文
you move. Uh, and as it turns out, you may not know this, but your muscles are an endocrine gland.那是什么意思？
英文原文
>> What does that mean?问得好，我也很高兴我们提到了这一点。我们知道内分泌腺包括肾上腺、甲状腺、垂体等。为什么它们被称为内分泌腺？因为它们产生化学物质，运送到别处发挥作用。你的肌肉会产生一套被称为“肌细胞因子”（myokine）的化学物质。Myo 代表肌肉，kine 意味着它们四处移动并在远距离发挥作用，而且它们会进入大脑。例如，它们有助于刺激大脑产生一种称为 BDNF（脑源性神经营养因子）的物质。这样它就会生长出新的脑细胞，滋养你的神经元，并滋养神经元之间的连接，也就是突触。
英文原文
>> Well, great question and and I'm glad we teed it up. We know our endocrine glands are, you know, the adrenals, the thyroid, the pituitary. And why are they called endocrine glands? Because they make chemicals that go elsewhere and do something. Your muscles create a suite of chemicals called myioind. Myom muscle kind means they move around and they do things at a distance and they make their way to the brain. For example, they help stimulate the brain to produce something called BDNF. So, it'll grow new brain cells and nurture your neurons and nurture the connections between neurons, which are the synapses.当我们激活肌肉时，能改善胰岛素的作用方式，让血糖保持在应有的水平。血糖升高是大脑退化的强风险因素。像测量平均血糖的糖化血红蛋白（A1C）这样简单的血液检查，如果数值升高，就是阿尔茨海默病风险的有力指标。运动时，我们能减轻炎症。炎症是一种关键机制，它会让我们大脑的免疫细胞从支持性转变为破坏性，我们稍后肯定会非常详细地探讨这一点。而且运动能改善流向大脑的血液。这绝对是一件好事。
英文原文
When we activate our muscles, we uh improve how insulin works so our blood sugar can remain where it needs to be. Elevated blood sugar is a powerful risk for brain degeneration. A simple blood test like the A1C, measuring your average blood sugar, is a powerful indicator, if it's elevated, of risk for Alzheimer's. When we exercise, we reduce inflammation. Inflammation is a key mechanism that changes our brain's immune cells from being supportive to being destructive, and we're going to certainly look at that in great detail. And exercise improves the blood going to your brain. That's got to be a good thing.是某种特定类型的运动，还是所有运动？
英文原文
any particular type of exercise or all exercises?我认为所有运动都很好。大家热议的问题是：对我的大脑来说，什么运动最好？是有氧运动，还是力量训练、抗阻训练？事实证明，最近的一项荟萃分析探讨了这个问题，并得出结论：两者皆需——我们既要强化肌肉，又要进行有氧运动，这样才能获得代谢方面的好处。但你想想看，如果肌肉产生的这些化学物质对大脑有益，那么拥有的这类化学物质越多就越好。所以，去锻炼肌肉吧。到了我这个年龄，保持肌肉量和增肌要困难得多，挑战大得多。所以，这确实是应该从年轻时就开始做的事情。
英文原文
>> I think all exercise is great. The big discussion is well, what's best for my brain? Is it aerobics or is it strength training, resistance training? And it turns out that a a recent meta analysis asked that question and came to the conclusion that it's both that we want to strengthen our muscles and we want to engage in uh aerobic activity such that we can gain the metabolic benefits. But you know, think about it. If these chemicals that your muscles are making are good for your brain that the more you have of these chemicals, the better. So, build muscle. When when you're my age, uh it's harder. It's much more challenging to keep your muscle mass and to build muscle. So, it's something that you really want to start at a younger age.下一张卡片是什么？我想我们这里还有一个工具箱，里面装了一些东西。
英文原文
>> What's the next card? I think I mean, we've got a tool box here as well, which has got some things in it.百宝箱。
英文原文
>> The goodie box.你知道其中有些东西和你刚才说的内容相关，对吧？
英文原文
>> You're aware that some of these are relevant to things you just said, right?确实相关。我要拿出一个非常高科技的设备，我认为大家都应该备一个。
英文原文
>> They are. And I'm going to pull out a um something a very very high techch device that I think people should get.好。
英文原文
>> Okay.那可能是他们能存钱买到的、用来改善大脑的最强有力工具。准备好了吗？
英文原文
>> That might be their most powerful tool that they can um save up for and get so that they can improve their brains. Ready?准备好了。
英文原文
>> Yeah.拿出一只。
英文原文
>> And here's one.嗯。
英文原文
>> Mhm.这是另一只。动起来。运动能推动一切指标发生改变。运动能改变一切。所以如果我用这双，你就不能用那双了。对你来说太小了。
英文原文
>> And here is the other. Get moving. Movement moves all the needles. Movement moves everything. So if I use these, you're not going to use those. are too small for you.这比我可能买到的任何药物或药品都好。
英文原文
>> This is better than any drugs or medicine that I could possibly buy.确实如此。这很有意思，因为我刚才向你描述的肌肉激活作用，与现在英国本土用于阿尔茨海默病临床试验的药物非常相似。想想看，二甲双胍（metformin）能起到运动所起到的很多作用。而运动起到的作用还要更多。
英文原文
>> It is. It's interesting because what I've just described to you in terms of the activity of muscle activation is very similar to the drug that's now being uh used in the Alzheimer's trial right here in in uh in England. Think about that. That metformin metformin does many things that exercise does. Exercise does more.我被说服了。
英文原文
>> Sold.你被说服了。
英文原文
>> You're sold.我买账了。
英文原文
>> I'm sold.社交联结与微胶质细胞表型
任务完成。缺乏社交联结。谁能料到呢？
英文原文
>> Mission accomplished. Lack of social connection. Who knew?真的吗？那是第三项。
英文原文
>> Really? That's the third thing.从这里开始，这些因素都是并列排名的。
英文原文
>> From here on out, these are all equally ranked.好的，所以这在前五位当中。
英文原文
>> Okay, so this is the in the top five.在前五位之中。
英文原文
>> In the top five.缺乏社交联结。有什么证据表明人际关系和社交联结与认知障碍症存在相关性？
英文原文
>> Lack of social connection. What evidence is there that relationships and social connection is correlates to dementia?这是一个很难衡量的指标，不是吗？一个人该如何衡量它？我们最早开始隐约意识到社交联结有益健康、有益身体、有益大脑，是来自关注长寿且认知障碍症风险较低人群的“蓝色地带”（Blue Zones）资料。这些人遵循某种特定饮食——我们稍后可以讨论——并且居住在起伏很大的地区，这意味着他们经常上下台阶。但我认为重要的是，我们从蓝色地带数据中了解到，这些人是与他人紧密相连的。他们融入了社区，而这对大脑有好处，对炎症有好处，对代谢也有好处。现在你可能会像我曾经问过的那样问：这其中的机制是什么，对吧？作为科学家，你会想明白这一点，对吧？机制是什么？因为除非我能看到机制，否则我是不会信服的。我们知道，当我们与人交往、建立关系时，我们的身体和大脑会增加一种名为催产素（oxytocin）的化学物质的分泌量。
英文原文
>> It's a tough metric, isn't it? How does one measure that? And we we first got an inkling that social connectivity was good for health, good for the body, and good for the brain. uh from the blue zones information that looked at uh people who lived long and had lower risk of dementia. And these are individuals who ate a certain diet, which we can talk about and uh lived in in areas that had a lot of verticality, meaning they were going up and down steps. But I think importantly what we learned from the blue zone data is that these are people who are connected to other people. They've insinuated themselves into community and that is good for the brain. It's good for inflammation. It's good for metabolism. Now you would you would ask as I have asked well what is the mechanism here right? You want to understand that as a scientist right? What's the mechanism because until I can see a mechanism I'm not going to I'm not buying in. And what we know when we connect to people and when we develop a relationship, our bodies, our brains uh increase the its output of a chemical called oxytocin.你听过催产素。它被称为爱的荷尔蒙。
英文原文
You've heard of oxytocin. It's called the love hormone.但它的作用不止于此。当我们对他人产生信任感、感受到与他人的连接时，这种催产素就会分泌出来。感受到。今天与你共度时光让我获得了催产素
英文原文
But it's more than that. This oxytocin is uh secreted when we're uh feeling trust for another individual, when we're feeling connected to another. we're feeling. I'm getting oxytocin from my time spent with you today我心存感激。为此谢谢你。
英文原文
>> and I'm grateful. Thank you for that.希望我也回馈了你一些。这种催产素能刺激我们大脑中的有益免疫细胞——也就是微胶质细胞，帮助它们保持支持、关爱和滋养的角色，而不是任由它们漂移演变成我所说的“邪恶双胞胎”，加重炎症，加剧我们突触的破坏。让我再铺垫解释一下，因为我认为我们接下来会依赖这个概念。我们大脑的微胶质细胞可以处于支持、关爱的状态。我们称之为 M2 构型。它们拥有长长的突起，能够伸展开来发挥效用，行使有益功能。
英文原文
And hopefully I'm giving some back to you. And this oxytocin um stimulates our good brain immune cells, these microgle cells, and helps keep them in their supportive, loving, nurturing role as opposed to letting them drift to becoming what I call uh the evil twin, increasing inflammation, increasing the destruction of our synapses. Let me set that up a little bit more because I think we're going to rely on that uh moving forward. Our brain's microgle cells can exist in a supportive loving. We call this the M2 configuration. We have long arms that are able to reach out and be effective and do good things.什么是微胶质细胞？
英文原文
>> What is a microgle cells?微胶质细胞是生活在大脑内部的免疫细胞。它们大约占大脑细胞的 10%。大家常说，脑细胞不就是神经元嘛。我以前常说，如果你喝一杯啤酒，就会失去 50,000 个脑细胞。实际上，大脑中除了神经元还有其他细胞。有免疫细胞，也有参与构成大脑结构的细胞。因此，这些极好、充满爱意和滋养功能的微胶质细胞（M2）四处巡查。它们在巩固我们的突触——也就是神经元之间的连接。它们确保我们极其珍贵的血脑屏障正常工作，将不良物质阻挡在外。它们确保我们的神经元功能正常且健康。它们基本上都在做有益的事，但它们会发生转变。它们可以变成我所说的邪恶双胞胎。
英文原文
>> So microgle cell is an immune cell that lives within your brain. Makes up about 10% of your brain cells. You know people say, well brain cells, those are neurons. I used to say, well if you drink a beer, you're losing 50,000 brain cells. Well, there are other cells in your brain aside from the neurons. There are immune cells. There are cells, you know, that are involved in in the structure of the brain. So, these wonderful, loving, nurturing micro gal cells, M2, are going around. They're shoring up our synapses, the connection of one neuron to the next. They are making sure that our very valuable bloodb brain barrier is working and keeping the bad things out. Uh they are making sure that our neurons are functioning appropriately and are healthy. They're basically doing good things, but they can shift. They can become what I call the evil twin.这就是邪恶双胞胎，即 M1 型微胶质细胞。我之所以称之为邪恶双胞胎，是因为它们在基因上完全相同，就像双胞胎一样。但这种细胞是具有破坏性的。正是这些细胞摧毁了我们的突触。当我们的突触被破坏时，我们就失去了连接。微观层面上我们当然失去了连接，因为突触连接丢失了；而在宏观层面上我们也失去了连接，导致我们不再能够与他人、与自己、与周围的世界建立连接。这就是正在发生的情况。这种从 M2 到 M1 的转变，是阿尔茨海默病根本的上游事件。这些细胞对我们的代谢非常敏感。
英文原文
And this is the evil twin, the M1 microgal cell. The reason I call it an evil twin is because they're genetically the same, like twins. But this is the cell that is destructive. These are the cells that destroy our synapses. And when our synapses are destroyed, we lose connection. We lose connection at a microscopic level of course because our synapses connections are lost and we lose connection at a macroscopic level whereby we no longer are able to uh connect to other people to ourselves to the world around us. That's what's going on. This shift from M2 to M1 is the fundamental upstream event in Alzheimer's disease. These cells are sensitive to our metabolism.这些细胞对炎症非常敏感。当我们的血糖升高时，会促使它们转变为破坏性状态。当身体任何来源的炎症传导至大脑时，都会促使支持性的 M2 微胶质细胞转变为破坏性状态。
英文原文
These cells are sensitive to inflammation. When our blood sugar is elevated, it shifts them to being destructive. When there's inflammation in the body making its way to the brain from any source, it shifts the M2 supportive microglea to being destructive.任何代谢问题，以及最重要、最重要的一点——这些细胞的能量代谢状态——都在其中发挥着基础性作用。支持性的细胞是通过线粒体的活跃功能来获取能量的。它含有大量的线粒体，负责产生被称为 ATP 的这种能量货币。
英文原文
Any metabolic issue and most importantly most importantly the energetics of these cells is playing a fundamental role. This is a cell that gets its energy from active function of the mitochondria. It contains a host of mitochondria that are producing this currency of energy called uh ATP.而那种细胞则使用完全不同的能量产生途径，称为糖酵解。因此，这种转变的上游是线粒体的变化。这就是上游所在。这是根本所在。线粒体的能量生成决定了 M2 和 M1 之间的转变。现在，我完全承认 M2 和 M1 之间存在无数的过渡状态。这不是一个非黑即白的二元问题，而是一个从支持性的 M2 向 M1 演变的连续模拟过程。但是再次强调，这一切的上游是能量代谢状态。是线粒体功能。而这正是对我们的代谢、对胰岛素，以及在积极方面对运动、对二甲双胍极为敏感的……
英文原文
This cell uses a totally different energy uh production facility called glycolysis. So upstream of this shift are changes in the mitochondria. This is what's upstream. This is the fundamental here. Mitochondrial energy production is what dictates the shift between M2 and M1. Now, I fully recognize that there are countless transitional states between M2 and M1. It isn't a binary issue. It's an analog issue going from M M2 supportive to M1. But again, upstream of all of this is the energetics. It's the mitochondrial function. And this is what is so sensitive uh to our metabolism, to insulin, to exercise on the positive side, to metformin on the小胶质细胞转变与线粒体损伤的恶性循环
药物方面。我们正在损伤自身的线粒体，从而导致它发生故障，进而从 M2 型转变成那个“邪恶的双胞胎”。
英文原文
medication side. We're damaging our mitochondria and that's causing it to malfunction and then change from the M1 to the evil twin.一点也没错。这里有两个输入途径。这些 M2 小胶质细胞，其实 M1 也是如此，都拥有接收信息的受体。来自体内任何部位的炎性化学物质，比如肠漏——你之前在节目中谈过这个——会在体内引发更多的炎症。那些化学物质可以进入大脑，小胶质细胞表面有受体，会促使它转变成更具破坏性的状态。
英文原文
That's exactly right. There are two inputs. These M2 microgle cells and M1 for that matter have receptors that are receiving information. inflammatory chemicals from anywhere in the body like a leaky gut. You've talked about that before on your program creates increased inflammation in the body. Those chemicals can make their way to the brain and there are receptors on the micro gal cell that will shift it to becoming more destructive.所以那是症状，或者说是结果吗？结果就是从 M2 转变成 M1。
英文原文
So is that the symptom like is that the effect? The effect is the shift from M2 to M1.从正常的双胞胎变成邪恶的双胞胎，
英文原文
>> From the normal twin to the evil twin,对吧？好的。因为我的能量生成系统出了问题，也就是我的新陈代谢。
英文原文
>> right? Okay. because something goes wrong with my energy production system i.e. my metabolism.是的。但同样，这里有两个输入因素。而且这是双向作用的。当这些小胶质细胞转变成更具破坏性时，它们会下调或降低自身线粒体的功能。
英文原文
>> Yes. But again there there are two inputs here. Uh and it goes both ways. When these microgleas shift to being more destructive they downregulate or reduce the function of their mitochondria.好的。所以它又反向影响到上游了。
英文原文
>> Okay. So it goes back upstream.它反向影响到上游，产生了一个前馈过程。而且极为重要的是，这些细胞是促炎性的，这意味着一旦被激活，它们就会在整个周围环境中分泌炎性化学物质，也就是它们在大脑中的局部环境。那些化学物质又反过来针对健康的小胶质细胞，进一步将它们拉向黑暗面，就像僵尸一样。
英文原文
>> It goes back upstream creates a feed forward process. And importantly, very importantly, these cells are pro-inflammatory, meaning that they are once they become activated, they're secretting chemicals of inflammation throughout their environment, their local environment in the brain. And those chemicals come back and target the healthy microbial cells and further shift them over to the dark side like zombies.TSPO 扫描与阿尔茨海默病大脑萎缩
我们怎么知道这些小胶质细胞与阿尔茨海默病以及痴呆症有任何关联呢？
英文原文
How do we know that these microbio cells are anything to do with Alzheimer's and dementia?我们实际上可以在一种名为 TSPO 扫描的特殊扫描上看到这一点。我们现在所看到的，这边是健康对照组。而当我们在正电子发射计算机断层显像（PET 扫描）上对阿尔茨海默病大脑进行 TSPO 成像时，你可以看到它完全被点亮了。
英文原文
>> We can actually see that on a special scan called a TSPO scan. And what we're looking at right now, uh, this is the healthy control right here. And when we image on this PET scan for TSPO in the Alzheimer's brain, you can see it is absolutely just lit up.格外赋予人力量、并且让这个故事覆盖范围变得极其广泛的是：我们在各种各样的神经退行性问题中，都看到了呈阳性的 TSPO 成像，这意味着大脑免疫细胞被激活了。
英文原文
And what is so incredibly empowering that takes this story uh to a very wide net that it throws is that we see positive tspo imaging meaning activation of the brain's immune cells across a wide variety of neurodeenerative issues.赋予人力量的部分在这里：这些细胞可以转变回去，重新变得具有支持性。而引导它们重新变回支持性的影响因素，是在我们掌控之中的。
英文原文
Here's the empowering part. These cells can shift back and become supportive again. And the influence that directs them back to being supportive is under our control.我见过几次这种照片。阿尔茨海默病患者的大脑真的长成那样吗？
英文原文
I've seen this kind of photo a few times. Um, is that really what an Alzheimer's brain looks like?确实是。
英文原文
>> It is.你见过很多大脑。
英文原文
>> And you've seen a lot of brains.我见过很多大脑。
英文原文
>> I've seen a lot of brains.你觉得你见过多少个大脑？
英文原文
>> How many brains do you think you've seen?嗯，真实的大脑，几百个。
英文原文
>> Well, uh, real brains, um, hundred.那是你捧在手里的真实人类大脑。
英文原文
>> And now that's real human brains in your hands.在我的实验室里捧在手心的大脑。是的。
英文原文
>> Brains in my hands in my laboratory. That's right.还有扫描图呢。成千上万张扫描图。
英文原文
>> And then scans. Thousands of scans.那你见过阿尔茨海默病的大脑吗？
英文原文
>> And have you seen an Alzheimer's brain?见过了无数次。我认为这是一个极端的例子，但我们在这里看到的，我们称之为萎缩。山峰之间的山谷变得更宽了，因为山峰萎缩了；然后在大脑内部这里，这些叫做脑室。它们充满了脑脊液，正在扩大以填补空出来的空间。
英文原文
>> Oh, countless times. Well, I think this is an extreme example, but what we're seeing here is we call it atrophy. The valleys between the mountains are are wider because the mountains have shrunken and then the inside of the brain here, these are called the ventricles. They are filled with spinal fluid are expanding to take up the empty space.现在，我们必须始终保持谨慎。我们只看这张图像，而没有综合去看整幅画面。这可能是一种被称为脑积水的情况的表征，脑积水是指大脑中的液体增多，使得这些脑室变大。这里它之所以扩大，纯粹是因为大脑基本在萎缩。
英文原文
Now, we always have to be careful. We only look at this image uh and and don't look at the the whole picture in in aggregate. This could be an indication of something called hydrophilis where fluid is increasing in the brain and makes these ventricles larger. It's just expanding because the brain is basically shrinking.好的。所以大脑萎缩可能有很多种原因。
英文原文
>> Okay. So, and the brain could be shrinking for any number of reasons.是的。不过你要知道，随着年龄增长，你的大脑确实会萎缩，但你在这些图像中看到的程度确实非常广泛。因此，这是阿尔茨海默病大脑在宏观层面上的一个特征。你知道，除了宏观特征，还有微观特征，也有血液学特征。
英文原文
>> Yes. But uh you know, keep in mind that your brain will shrink as you age, but the extent that you're seeing in in in these images is really extensive. So, this this is a characteristic macroscopically of an Alzheimer's brain. You know, you there are microscopic characterizations as well and there are blood characterizations as well.突触修剪与发育机制的异常再激活
我嫂子刚生了孩子。我依稀记得本节目中某位神经科学家跟我提过的一项统计数据。所以我去谷歌查了一下，上面说我们在两岁时拥有的大脑连接比成年时还要多。大约在两岁之前，大脑基本上拥有所有这些不可思议的连接，这大概解释了为什么小孩子学东西厉害得要命。然后大脑会逐渐失去部分连接，以便强化那些重要的连接。在一定程度上，我当时是想弄明白这是否解释了为什么小孩会有“可怕的两岁”。我们现在要切入一个非常精彩的内容了。好的。
英文原文
My sister-in-law just had a baby. I vaguely remembered some stat that some neuroscientist on this show had told me. So, I Googled it and it said that we have more brain connections at 2 years old than we do when we're an adult. And the brain basically up until two sort of has all these incredible connections which probably explains why kids are so bloody good at learning stuff. And then the brain kind of loses the connections so it can reinforce the ones that matter. And I in part I was trying to figure out if this explains why kids have terrible twos. We are going to go to a really cool place right now. Okay.让我先来铺垫一下背景。你所描述的过程叫做突触修剪。在这个过程中，大脑对它最终需要做的事情会变得熟练得多。在一岁时，突触或连接形成的速率大约是每秒形成 100 万个突触。
英文原文
>> And let me set it up first of all. So what you're describing is something called synaptic pruning. And it is where the brain, you know, becomes much more adept at what it's ultimately going to need to do. the the rate of synapse or connection formation at age one year is about 1 million synapses being formed every second.那意味着什么？
英文原文
>> So what does that mean?这意味着在这个大脑中，神经正在建立网络，它们彼此连接，在一岁幼儿体内达到每秒 100 万个连接的速率。现在，突触修剪这一概念——也就是精简优化的部分——是以大约该速率 20% 的速度在进行的。这意味着当这些连接建立的同时，大约 20% 的那些连接或其他连接实际上正在被破坏。所以大脑正在自我优化，我们在非常迅速地失去连接。
英文原文
>> That means that in this brain nerves are wiring up they're wiring up connecting to each other uh at the rate of a million connections per second in the one-year-old. Now this idea of synaptic pruning the refinement part is happening at about 20% that rate means that while these connections are being made about 20% of them of those connections or others are actually being destroyed. So the brain is refining itself. We're losing connections very rapidly.这种突触修剪、这种精细化过程是通过什么机制发生的呢？是小胶质细胞。小胶质细胞正是以恰当方式破坏或清除这些突触的主体，这是一种正常的生理活动，是我们希望发生的事情。
英文原文
What is the mechanism whereby this synaptic pruning this refinement takes place? The microgal cells. The microgleal cells are the ones that are appropriately destroying or taking away these synapses which is a normal activity. It's what we want to happen.在某些情况下，突触修剪不充分，就会产生后果。自闭症谱系障碍就是其中之一，脆性 X 综合征是另一个。在这些情况下，大脑没有进行充分的突触修剪，它们被称为过度连接综合征，大脑实际上处于过度连接状态。
英文原文
There are situations when there's not enough synaptic pruning and there are consequences. Autism spectrum disorder being one of them. Fragile X syndrome is another. These are situations where the brain doesn't adequately synaptic prune and they're called hyperconnection syndromes where the brain is actually overconnected.不过想想看：在我们成长过程中、在儿童时期参与恰当突触修剪的那些小胶质细胞，与我们在年老时以不当方式吞噬消化或破坏我们突触的，是同一种小胶质细胞，而这可能表现为阿尔茨海默病。所以神经科学界现在有一种观点，认为阿尔茨海默病是一种正常发育过程的再激活。
英文原文
Think about it though. These same micro gal cells that are involved in appropriate synaptic pruning when we are growing up in our when we're children are the same microgal cells that inappropriately digest away or destroy our synapses uh when we are older. and that can manifest as Alzheimer's disease. So the there's a thinking now in neuroscience that Alzheimer's is the reactivation of a normal developmental event.这有多奇妙？阿尔茨海默病——突触的丧失，也就是这种疾病的特征——竟然是我们童年时期本属正常的机制的再激活。
英文原文
How cool is that? That Alzheimer's, the loss of our synapses, which is what's characteristic of this disease, is a reactivation of what would have been normal when we were children.所以大脑正在对自身进行修剪，
英文原文
So the brain is printing itself不当地修剪。
英文原文
>> inappropriately.为什么它会那样做呢？
英文原文
>> Why might it be doing that?这是一个最关键的大问题。它那样做是由多种原因导致的。首先是因为这些小胶质细胞的激活，这种激活是不恰当的。客观来说，与小胶质细胞从支持性转变成破坏性相关的最大输入因素，是我们的历法年龄。我这么说是因为数据是这样显示的，但我认为它应该是我们的生物学年龄。
英文原文
>> That is the million-dollar question. It's doing that for a number of reasons. Uh first because of the activation of these microgle cells, which is not appropriate. I mean, you know, to be fair, the biggest input that relates to the shift of the microgle cell from supportive to destructive is our chronological age. And I say that because that's what the data says, but it should I I believe it should be our biological age.我之所以说它可能是我们的生物学年龄，是因为这样一来就为我们留出了干预生物学年龄的大门，比如通过运动和饮食。但话虽如此，这是衰老带来的结果，并有助于我们理解为什么阿尔茨海默病的第一大风险因素是我们度过生日的次数。这一点确实无法改变，但我们肯定可以改变其他那些输入因素。
英文原文
And the reason I say it's our bi could be our biological age is because it opens the door then for us to target our biological age like exercise and diet. But that said, um it is, you know, a consequence of aging and helps us understand why the number one risk factor for Alzheimer's is the number of birthdays we've had. Can't really change that, but we can change these other input sets for sure.风险因素：非恢复性睡眠
那么，第几项来着？是第四项吗？
英文原文
>> So, what is number? Is it four?让我看看。非恢复性睡眠。
英文原文
>> Uh, let's see. Non-restorative sleep.非恢复性睡眠。
英文原文
>> Nonrestorative sleep.非恢复性睡眠。谈到睡眠时，我们会有很多讨论内容，比如我们如何衡量自己的睡眠。但它是非恢复性的。我们睡眠时间不够，而且质量也不高。你怎么能知道呢？等等。标签：广告。
英文原文
>> Non-restorative sleep. So, sleep has there are a lot of things we talk about when we're talking about sleep, how we metricize our sleep. But it's non-restorative. We don't get enough and it's not high quality. How would you know? Wait. Hashtag ad.我不知道。你可以戴一个穿戴设备，对吧？你可以去接受一次正式的多导睡眠图监测，这意味着你要走进实验室，这很瘆人。我做过。你身上要佩戴各种各样的东西来测量你的心率、脑电波、血氧，而且你睡觉时整晚都有人在看着你、记录你。我觉得那很瘆人。但是你可以用 Oura 智能戒指、Apple Watch、Whoop，你可以测量自己的睡眠，并且以相当不错的可靠性去了解它的质量和数量。
英文原文
I don't know. Well, you'd wear a a wearable device, right? I mean, you could subject yourself to a formal uh polyomnog, which means you're going into a lab, and it's creepy. I've done it. And you wear all kinds of things measuring your heart rate, your brain waves, your your blood oxygenation, and somebody's watching you and recording you all night long when you're sleeping. I found it very creepy. But you you have access to an Aura ring, an Apple Watch, a Whoop, and you can measure your sleep and with pretty good reliability get a sense as to its quality and its quantity.这就是恢复性睡眠的核心所在。恢复性睡眠太重要了。它让我们能够在快速眼动睡眠中巩固我们的记忆和经历。正如你所知，它允许激活脑类淋巴系统，从而让我们能够
英文原文
That's what restorative sleep is all about. Restorative sleep is so important. It allows us to consolidate our memories, our experiences in REM sleep. It allows activation, as you know, of the glimpmphatic system that allows us to基本上就是清理垃圾，新研究表明，当我们活动时也会发生这种情况。这也是运动这个多功能工具的又一个组成部分。
英文原文
take out the garbage basically, which new research indicates happens when we move as well. Yet another part of the uh motion multi-tool.但睡眠也能帮助我们减轻炎症。它能改善胰岛素的功能。这些都是关系到大脑功能以及大脑健康功能保护的关键因素。
英文原文
But sleep helps us reduce uh inflammation as well. It improves insulin functionality. These are key players that relate to brain function and brain health function preservation.所以，哪怕只是一晚糟糕的睡眠，也会极大地改变胰岛素的功能，对我们的血糖控制产生重大影响，并切实为退行性变埋下伏笔。不仅如此，仅仅经历一晚糟糕的睡眠后，我们的决策能力就会受到显著影响。
英文原文
So you know uh even one night's poor sleep dramatically changes the function of insulin has a significant effect upon our blood sugar control and really does set the stage for degeneration. Not only that but it significantly affects our decision-m ability after just one night of poor sleep.胶质淋巴系统与深睡眠
我听说过胶质淋巴这回事。自从我了解到胶质淋巴引流系统后，我的睡眠质量明显变好了，但我也变得有点让身边的朋友觉得烦，因为我跟他们讲过很多次。我描述它的方式——当然我这么说肯定在科学上不够严谨——就是到了晚上，大脑里就好像有环卫清扫工出来了一样。
英文原文
I've heard about this glimpmphatic thing. And ever since I heard about the glimpmphatic drainage system, I have slept significantly better, but I've also become a little bit of an with my friends because I I've told them about it many times. And the way that I kind of describe it, which I'm sure is um being scientifically butchered when I say it, is that at night time it's almost like the street cleaners come out in our brain.那是一个非常完美的比喻。他们出来清扫街道。
英文原文
That is a perfect metaphor. And they come out and sweep up the streets.但只有当你处于深度睡眠时，他们才会出来。
英文原文
>> But they're only coming out if you're in deep sleep.好的。那需要多长时间才能进入深度睡眠呢？
英文原文
>> Okay. And how long it does it take to get into deep sleep?进入深睡眠？通常这是在你睡眠周期的较后阶段才会发生的。
英文原文
>> To get into it? What's something that typically happens later on in your sleep cycle?对我来说大概是在第5个半小时左右。
英文原文
>> So for me it's around hour 5 and 1/2.5个半小时。好的。所以你在夜间更晚的时候会有更多的深度睡眠。
英文原文
>> Hour 5 and a half. Okay. So you have more deep sleep further into the night.没错。
英文原文
>> That's right.睡眠是呈周期性波动的，对吧？就像……
英文原文
>> And you sleep in these cycles, right? Like确实是分周期睡眠的。
英文原文
>> you do sleep in cycles.好的。这些周期大概是90分钟一个周期，还是60到90分钟？
英文原文
>> Okay. And the cycles are like 90 minute cycles or 60 to 90.当然因人而异。但事实是，我们会在不同阶段之间循环，就像交响乐团准备演奏乐曲一样，各个声部都会稍加练习，最终汇聚在一起，带来有益健康的睡眠。“Salubrious”是一个形容词，意思是促进健康的。我过去常认为睡眠是不容妥协的，但现在我真的把它放在优先位置。早年间我曾认为睡觉是缺乏效率的表现，而现在我把这种想法反过来了，如果我没睡好，我反而觉得自己没有生产力。
英文原文
>> Depends on pe on the person of course. But you know the fact is we cycle through various aspects as you know as the orchestra is is getting ready to play its music. each each area gets to practice a little bit and it all converges on and ultimately cubrious uh sleep cubrious means uh it's an adjective it means health providing I used to really think of sleep as non-negotiable but now you know I really do prioritize it and um you know I used to think in my earlier years that if I slept I was being unproductive and now I've kind of inverted that where I feel like I'm being unproductive if I haven't slept前额叶皮层与杏仁核的博弈
另一件我觉得可以进一步充实的内容是：睡眠会极大地影响你第二天的决策能力。大脑中有两个区域对我们如何做决策至关重要。前额叶皮层，在这里，属于额叶——
英文原文
>> you know the other thing I think that uh fleshes out a little bit is the the idea that sleep dramatically affects your decision-m ability the next day. There are two areas of the brain that are fundamental for how we make our decisions. The uh prefrontal cortex which is here is the frontal lobe前额叶皮层包含了皮层的这一部分。它大约占整个大脑皮层（即大脑外层）的三分之一。另一个负责决策的区域位于颞叶深处。这些是颞叶，它呈杏仁状，被称为杏仁核。有人称它为恐惧中心。但这些区域……哦，找到了。好的。在颞叶内，也就是这里，颞叶内部有这个杏仁状的器官，或者更准确地说是叫作杏仁核的杏仁状区域。这两个区域在决策中都起着重要作用。杏仁核是一个冲动的、自我中心的区域，会快速做出决定。
英文原文
>> and the prefrontal cortex involves this part of the cortex. It's uh takes up about onethird of the entire cortex or outside of the brain. And another area for decision-m is deep within the temporal loes. These are the temporal loes and it's uh shaped like an almond. It's called the amygdala. Some people call it the fear center. But these areas are Oh, here we go. Okay. So, within the temporal lobe, uh which is here, the temporal lobe, inside of it is this almond shaped uh organ, or rather this almond shaped area that's called the amydala. And both of these areas play important roles in decision- making. The amygdala is an impulsive, self-centered area that makes rapid decisions.比如“我累了”。
英文原文
>> Well, I'm tired.我们等会儿会讲到那儿。我正要引到那个话题。我们——
英文原文
>> Well, we'll get there. I'm leading up to that. We're我只是……我只是深有体会。
英文原文
>> I just I just can relate to我知道你深有体会。我们大家都能体会。
英文原文
>> I know you can. We all can.前额叶皮层，再次强调，额头后方的这个区域，基本上就是“房间里的成年人”。随着我们进入青少年时期，这个前额叶皮层就会开始掌控局面。“房间里的成年人”有望变得越来越有影响力，并对杏仁核施加我们所说的自上而下的控制。这样我们就会减少冲动，明白自己行为的后果，能够规划未来，能够做事并思考这不仅会对我产生何种影响，还会对你产生何种影响，对这个星球产生何种影响。这就是前额叶皮层。我们高度依赖前额叶皮层自上而下抑制杏仁核的这种控制。问题在于，有些因素会威胁到这种连接，其中之一就是炎症。炎症会极大地降低“房间里的成年人”掌控局面的功能和能力。如果你处于慢性炎症状态，那么你的决策日复一日都在受损。让我把这个说得更深入一点，因为这里有一个有趣的观点：食物在炎症中扮演着某种角色。我们过去称之为标准美国饮食。我觉得这有点像是把当今世界上糟糕的饮食习惯都归咎于美国。但起初是标准美国饮食，后来变成了西方饮食，而现在它几乎成了全球饮食，极其大量地充斥着促炎的超加工食品。
英文原文
>> The prefrontal cortex, again, this area behind your forehead is the adult in the room, basically. And what happens as we reach our teenage years is this prefrontal cortex sort of takes control. The adult in the room hopefully becomes more and more influential and exerts what we call top- down control over the amydala. So we're less impulsive. We understand the consequences of our actions. We can plan for the future. We can do uh things that we can think about how it's going to affect not just me but how it's going to affect you, how it's going to affect the planet. That's the prefrontal cortex. We depend highly upon this top- down control of the prefrontal cortex reigning in the amydala. The problem is things can threaten that connection and one of the things is inflammation. Inflammation can dramatically reduce the functionality the ability of the adult in the room to be in charge. And if you are chronically inflamed, then your decision-m is suffering day in and day out. Let me take this a little bit further because it's it's an interesting uh concept here that food has a role in inflammation. We used to call it the standard American diet. I think kind of blaming America for the crappy diet of the world today. But it was the standard American diet then became the western diet and now it's pretty much the global diet that so aggressively features these ultrarocessed foods that are pro-inflammatory.现在想想我刚才说的话。全世界都在吃加剧炎症的食物。而炎症切断了“房间里的成年人”与那种冲动的、“唯我独尊”、“我想全归我所有”、“就得按我的方式来”的全球化冲动之间的连接。
英文原文
Now think about what I just said. The world is eating foods that are increasing inflammation. And inflammation separates the connection between the adult in the room and the impulsive, we're the best. I want it for me. That's it. It's going to be my way globally.这使我们能够将全球营养结构的改变与当今世界上所看到的一些现象联系起来。
英文原文
This allows us to relate the change in global nutrition to some of the things we're seeing happening in our uh in our world today.饮食中的糖分与认知健康
这是否和你列出的前五项中的第五张卡片有关？不良饮食。我这里带了几样东西。食物方面。来看看我这里有什么。一些橙汁。
英文原文
And does this link to card number five of your top five? Poor diet. I've got a few uh few things here. Terms of food. Let's see what I have. Some orange juice.一罐啤酒。一大盘食物。我们很接近了。我们进展得很好。我们要尽最大努力避免糖分。那么，假设这是12盎司，史蒂芬，你来告诉我这里面有多少糖？我会把它倒进这边的玻璃杯里。告诉我什么时候停下。这里面有多少糖？你知道答案吗？
英文原文
Can of beer. Big tray of food. We're close. We're doing great. We want to do our best to avoid sugar. So, how much Let's say this is 12 ounces. Why don't you tell me, Stephen, how much sugar? I'll put it in this glass here. Tell me when to stop. How much sugar is in here? Do you know the answer?你知道吗？我现在做了这个播客之后，可能更接近答案了。如果你在我年轻的时候问我，我会说一勺。
英文原文
>> Do you know what? I probably I'm closer to the answer now I've done this podcast. I If you'd asked me when I was younger, I would have said one.好，一勺。在我做这个播客之前，我也会以为，对，就一勺糖。
英文原文
>> Okay, one. Before I did this podcast, I would have thought, yeah, there's one sugar.不，比那要多一点。你告诉我什么时候停。这是两勺。好的，接着来。现在三勺。我可以停了吗？
英文原文
>> No, there's a little bit more than that. You tell me when to stop. That's two. All right, here we go. All right, now three. Can I stop?我觉得……
英文原文
>> I mean,四勺。好的，继续。五。六。看看这个。七。八。如果这是一罐汽水，再加两勺就行。看吧。你那杯美妙的橙汁里含有八茶匙糖。“哦，但里面的维生素C怎么办？膳食纤维怎么办？”这根本无法抵消它对你身体造成的损害。
英文原文
>> four. Okay, here we go. Five. Six. Look at this. Seven. Eight. And if this were a can of soda, just two more. There. Eight teaspoons of sugar in your wonderful glass of oranges. Oh, but what about the vitamin C? What about the fiber? It doesn't offset what this is doing to your body.想想看，我们早上醒来，然后喝下8茶匙的糖，这不是很疯狂吗？
英文原文
>> Isn't it crazy that, you know, we wake up in the morning and then we we drink 8 teaspoon of sugar?曾经一度有种说法认为它对健康是有益的。就像在喝阳光甜橙（Sunny D）的年代，我以为如果我喝橙汁……
英文原文
And there was a narrative at one point that it was healthy for you. So, like back in the Sunny D days, I I thought if I drank orange juice.是的。喝阳光甜橙的年代。那并不一定算是果汁。我的意思是，阳光甜橙到底是什么？
英文原文
>> Yeah. Sunny D days. That's not necessarily juice. I mean, what is Sunny D?我当时以为那算是我每天必吃五种果蔬里的一份呢。
英文原文
>> I thought it was like one of my five a day fruit and veg.是啊。是的。
英文原文
>> Yeah. Yeah.确实很疯狂。
英文原文
>> You Yeah. It's crazy.你多大了？34岁。
英文原文
>> How old are you? 34.34岁。34岁。好的。你正是最需要接收到这一信息的人群，因为你现在的代谢正在形成。如果我们能把这个信息传递给你这个年龄段的人，将会产生巨大的成效；等到你到了我这个年纪——而且你一定会到我这个年纪的——你就会庆幸自己当年了解了这些。
英文原文
>> 34. 34. Okay. You are the perfect population that needs to get this message because right now you know your metabolism is is being formed. If we can get this message to your age group, uh it will have a huge uh outcome and you know when you get to be my age and you will get to be my age, you will wish you had had known this.为什么？
英文原文
>> Why?因为你将为拥有一个健康的大脑打下基础。前几天我在不列颠哥伦比亚省的温哥华做了一场演讲，开场时我让现场的所有观众闭上眼睛。我说，我想让你们想象一下，当你们睁开双眼时，你们已经85岁高龄了。我说，现在睁开眼睛。现在环顾这个房间，我打算在房间正中间画一条线。你们当中有一半人现在已经被确诊患有痴呆症。
英文原文
>> Because you'll have set yourself up for a good brain. I gave a talk the other day in uh Vancouver, British Columbia and I started off by asking everybody in the audience to close their eyes. I said, I want you to imagine when you open your eyes, you're 85 years of age. I said, now open your eyes. Now look around the room and I'm going to draw a line right down the middle of the room. Half of you have now been diagnosed with dementia.你将会处于这个房间的哪一半？
英文原文
Which half of the room are you going to be in?而我们现在所讨论的内容，能让你成为仲裁者，让你成为构建者和决策者，决定你将身处那个房间的哪一半。这些问题可能会在你的60多岁发生，也可能在你的70多岁发生；这并不是说目前没有一些非常有前景的研究正在推进，如果有时间我们可以聊一聊。从这个角度来看，未来是一片光明的。但正如本杰明·富兰克林所言，一盎司的预防胜过一磅的治疗，这完全是至理名言。我认为这可能是我所讲过的最重要的事情之一……
英文原文
And what we're talking about right now allows you to be the arbiter, allows you to be the architect uh and the decision maker in terms of which half of that room are you going to be in. Now, you know, these issues can happen in your 60s, they can happen in your 70s, which is not to say that there are not some very promising things in development right now that if we have time we can talk about. The future looks bright from that perspective. But again, you know, Benjamin Franklin said that an ounce of prevention is worth a pound of cure and it makes all the sense in the world. I think this is probably one of the most important things that I对……有好处
英文原文
>> Good for你……
英文原文
you在弄清我喜爱的那些食物的真相方面做到了。你为什么认为这个……呃……这么有用？
英文原文
>> didin
terms
of
figuring
out
the
truth
about
the
foods
that
I
loved.
Why
do
you
think
this
is
um
so
useful?
正是因为你刚才描述的原因，那就是我们正在讨论的持续葡萄糖监测仪。所以，呃，我不知道这里面是不是真有一个，但这是……
英文原文
>> Forthe
reason
that
you
just
described,
and
that
is
we're
talking
about
a
continuous
glucose
monitor.
So,
uh,
I
don't
know if
there's
really
one
in
here,
but
this
is
It
很可能有。
英文原文
>> probablyis.
持续葡萄糖监测与个体化差异
是的，这是个体化医疗。你的食物选择如何影响你的血糖，而你的血糖又如何影响你大脑的命运、你的心脏以及就此而言的整个身体？但这就是你能了解它的方式。对我而言，那是腰果。我根本不知道腰果这种坚果会像那样升高我的血糖。我当时戴着血糖仪，每次吃腰果它就会报警提示。我过去有吃腰果过量的倾向，我还以为它们是安全的。我也对运动时血糖升高的程度感到非常惊讶，尽管在我刚开始运动时那是短暂的。这是一种正常反应，我也知道这一点。我算是有所预期，但呃，当我跑步时终于在智能手机上亲眼看到这一幕上演，那感觉……那确实令人印象深刻。
但是，你知道，我并不是说你需要在任何时候都佩戴持续葡萄糖监测仪（CGM），但我认为它呃……它非常有价值，而且现在无需处方就能买到。在美国曾有过很大的阻力，反对让人们在无需处方的情况下获得持续葡萄糖监测仪。你知道，有期刊发表社论说：“天哪，人们会变得神经质的。他们不应该知道这些信息。这属于医生的职权范围。”而我的论点是，好吧，如果情况真是那样，如果人们不应该拥有自己的数据，那我们就不应该允许人们购买体重秤。一回事。我的意思是，那种说法太疯狂太疯狂了，但是……持续……是的，这里面确实有一个。
英文原文
>> Yeah,it's
personalized
medicine.
How
do
your
food
choices
affect
your
blood
sugar
and
your
blood
sugar
affects
your
brain's
destiny
and
your
heart
and
and
and
your
body
for
that
matter?
But
this
is
how
you
will
know.
For
me,
it
was
cashews.
I
had
no
clue
that
cashews,
nuts,
would
raise
my
blood
sugar
the
way
they
did.
And
I
had
the
Lucas
Monzer
on,
and
it
lit
up
when
I
ate
cashews.
I
had
a
tendency
to
overeat
cashews.
I
thought
they
were
safe.
I
was
also
very
surprised
at
the
degree
of
my
blood
sugar
elevation
with
exercise,
though
it
was
transient
while
I
was
beginning
to
exercise.
That's
a
normal
response
and
I
knew
it.
I
kind
of
expected
it,
but
um
when
I
finally
saw
it
play
out
on
my
smartphone
while
I
was
running,
it
was
it
was
impressive.
But,
you
know,
and
I'm
not
saying
you
need
to
wear
a
a
CGM
at
all
times,
but
I
think
it's
uh
it's
extremely
valuable
and
and
now
available
without
a
prescription.
There
was
a
big
push
back
uh
in
America
about
making
CGM's
continuous
glucose
monitors
available
to
people
without
a
prescription.
You
know,
there
were
editorials
written
in
journals
saying,
"Oh
my
gosh,
people
are
going
to
be
neurotic.
They
shouldn't
know
this
information.
This
is
the
purview
of
the
doctor."
And
my
argument
was,
well,
if
that's
the
case,
if
people
shouldn't
have
their
data,
then
we
shouldn't
allow
people
to
buy
a
bathroom
scale.
Same
thing.
I
mean,
that's
a
crazy
crazy
thing
to
say,
but
the
continuous
click.
Yeah,
there
is
one
in
here.
这些小设备，呃，它们花不了多少钱，20美元、30美元。你可以在亚马逊和很多其他地方买到。呃，你把它贴在手臂上。呃，或者你……这个设备你是扎手指的，但我认为最好的是那种持续型的，贴在身上的。你可以记录你的数据，并且可以上传到呃……
英文原文
>> Theselittle
devices,
um,
they
don't
cost
a
lot
of
money.
They're
$
20
$30.
You
can
get
them
on
Amazon
and
lots
of
other
places.
Um,
you
stick
it
to
your
arm.
Um,
or
you,
this
one,
you
prick
your
finger,
but
I
think
the
best
ones
are
the
continuous
ones
where
you
stick
to
them.
You
can
record
your
data
and
you
can
upload
it
to
uh
你懂的
英文原文
>> youknow
直接推送到你的手机上
英文原文
>> putson
your
phone
directly
to
your
phone
但你可以用这些数据做很多事情，而且你知道最主要的是……
英文原文
>> butyou
can
do
a
lot
with
that
data
and
you
know
the
main
thing
is
除非你能够衡量它们，否则你怎么知道自己的改变起到了什么作用？我的意思是，如果你想减肥，你可以经常去站上浴室体重秤，呃，看看它是不是起效了。你想把血糖控制住，而且你也应该这么做。你怎么会知道呢？我的意思是，每年去看一次医生，做一次空腹血糖检测，呃，我不是说它毫无用处。我的意思是，它会给你提供线索，但我们完全可以做得更好。
我查看自己的持续葡萄糖监测仪时发现了几件让我吃惊的事情，都是我过去喜欢的东西，但我现在，你知道，我变得稍微更注意了。其中之一是烧烤酱，我以前很喜欢。它含有40%到50%的糖，这让我很震惊。香醋浓缩汁，40%到50%的糖。我吃过这种市售的无脂法式沙拉酱，结果发现它含有35%的糖。
英文原文
>> howdo
you
know
what
your
changes
are
doing
unless
you're
able
to
measure
them.
I
mean
if
you
want
to
lose
weight
you
can
you
go
on
the
bathroom
scale
uh
frequently
and
see
if
it
if
it's
working.
You
want
to
get
your
blood
sugar
under
control
and
you
should.
How
would
you
know?
I
mean,
to
go
to
the
doctor
once
a
year
and
have
a
fasting
blood
sugar
measurement,
uh,
I'm
not
going
to
say
it's
useless.
I
mean,
it'll
give
you
a
clue,
but
it's
we
can
do
so
much
better.
A
few
things
that
I've
discovered
from
looking
at
my
own
continuous
glucose
monitor
that
surprised
me
and
things
that
I
liked,
but
I
am
now,
you
know,
I'm
a
little
bit
more
conscious
of.
One
of
them
is
barbecue
sauce,
which
I
loved.
It's
40
to
50%
sugar,
which
shocked
me.
Balsamic
glaze,
40
to
50%
sugar.
had
this
commercial
fat-ree
French
dressing
which
was
turned
out
to
be
35%
sugar.
为什么选无脂？
英文原文
>> Whyfat
free?
上面写着无脂。我以为它很健康。
英文原文
>> Itsaid
fat
free
on
it.
I
thought
it
was
healthy.
是的，他们在标签上玩弄了很多这类花招。
英文原文
>> Yeah,they
they
do
a
lot
of
those
sort
of
tricks
on
labels.
你竟然会倾向于选择无脂的东西，这真令人担忧。我的意思是，你知道，无脂饼干、无脂……而另一个则是无麸质。我的意思是，杂货店的无麸质货架上净是垃圾食品。
英文原文
>> That'sreally
worrisome
that
you
gravitated
towards
something
that
was
fat
free.
I
mean,
you
know,
fat-ree
cookies,
fatree,
and
the
other
one's
gluten-ree.
I
mean,
there's
crap
on
the
gluten-free
aisle
in
the
grocery
store.
麸质敏感与消化道误区
是的。呃，我从这个播客学到的另一件事是，呃，我了解到全世界大约只有1%的人是真正类似麸质不耐受的，然而我们中却有20%的人（包括我自己在内）在购买无麸质产品。我过去实际上常常到处跟人说我是无麸质饮食者，但在从这个播客了解了一些事情之后，我觉得我实际上可能是果糖不耐受。
好吧，我谨在此提出，对麸质敏感的人数可能不止于此。呃，现在有一个确定的病症实体，称为非乳糜泻麸质敏感。所以，你知道，典型的麸质问题当然是乳糜泻，那是一种自身免疫性疾病。它有血液标志物，呃，也有通过内窥镜检查小肠来做出的诊断。
而现实情况是，呃，患有非乳糜泻麸质敏感的人比患有完全性乳糜泻的人要多得多。所以我认为这是一个很大的数字。很多年前，马里乌斯·哈吉瓦西利乌（Marius Hadjivassiliou）医生的研究让我深受触动，他实际上就在英格兰谢菲尔德医院工作，他描述了呃……与大脑相关但与乳糜泻无关、却与麸质摄入相关的问题。这极大地激发了我去关注麸质，探究它与某些人摄入麸质后的神经系统后果之间的关系。我记得有一阵子，随着我开始了解这一点并呃……阅读他的著作，他当时描述了一些人是如何因摄入麸质而头痛的。谁能想得到？我当时有一位常年头痛的患者，一直在服用麻醉性止痛药来缓解头痛。我对她说：“嘿，管它呢，我们试试看吧。尝试一下无麸质饮食，看看会发生什么，6周后再回来。”她在6周后复诊，令人瞩目的是，她的头痛消失了。她简直高兴坏了。她没有头痛了，她停掉了麻醉药。
于是她去了……她看了一位胃肠病医生，因为她也有麸质问题，可能也伴有胃肠道症状。呃，她说：“我看了普穆特（Perlmutter）医生，他让我采用无麸质饮食。现在我的头痛消失了。”那位医生对她说：“这太荒谬了。为了向你证明这一点，我要做一次内窥镜检查。我要看看你的小肠，证明你没有乳糜泻。”
他做了内窥镜检查。她没有乳糜泻的特征。于是他对她说：“恢复摄入麸质吧。”她说：“但……但……但好吧。”她重新开始摄入麸质。结果怎样？头痛变本加厉地复发了。
于是她又回到了诊所，你知道，难为情地把这个故事向我解释了一番。
英文原文
>> Yeah.Uh
this
another
thing
I
learned
from
this
podcast
is
um
I
learned
that
roughly
1%
of
the
world
are
truly
like
gluten
intolerant
yet
20%
of
us
including
me
buy
gluten-free
stuff.
I
actually
used
to
go
around
saying
I
was
gluten-free
but
having
learned
a
few
things
on
this
podcast
I
think
I
might
actually
be
fru
intolerant.
Well
I
would
say
respectfully
that
the
number
of
people
who
are
gluten
sensitive
is
probably
more
than
that.
uh
there
is
an
entity
a
defined
entity
now
called
non-seliac
gluten
sensitivity.
So
you
know
the
classic
gluten
issue
is
of
course
celiac
disease
which
is
an
autoimmune
condition.
There
are
blood
markers
for
it.
There
are
um
diagnoses
made
by
looking
at
the
small
bowel
with
an
endoscope.
And
the
reality
is
that
uh
a
lot
more
people
have
non-seliac
gluten
sensitivity
than
have
a
full-on
celiac
disease.
So
I
think
it's
it's
a
big
number.
I
was
very
taken
by
the
work
many
years
ago
of
a
Dr.
Marius
Hajivasalu
who's
actually
here
in
England
at
Sheffield
Hospital
as
well
who
described
uh
issues
related
to
the
brain
that
weren't
related
to
celiac
disease
but
were
related
to
gluten
consumption.
That
got
me
launched
uh
in
a
big
way
to
looking
at
gluten
as
it
relates
to
the
neurological
consequences
in
some
people
of
of
consumption
of
gluten.
I
remember
one
time
as
I
was
beginning
to
learn
this
and
uh
reading
his
work
and
he
was
describing
how
some
people
have
headaches
from
consuming
gluten.
Who
knew?
And
I
had
a
patient
with
lifelong
headaches
was
on
narcotics
for
her
headaches.
And
I
said,
"Hey,
what
the
heck?
Let's
give
it
a
shot.
Let's
go
gluten-free.
See
what
happens.
Come
back
in
6
weeks."
She
came
back
in
6
weeks
and
remarkably,
she
was
headache
free.
She
was
just
over-the-top
happy.
She
was
headache.
She
was
off
narcotics.
So
she
went
to
she
had
a
gastroanerologist
because
she
had
gluten
issues
probably
related
to
GI
symptoms
as
well.
And
uh
she
said,
"I
saw
Dr.
Prutater
and
he
put
me
on
a
gluten-free
diet.
Now
my
headaches
are
gone."
And
the
doctor
said
to
her,
"That's
preposterous.
And
to
prove
it
to
you,
I'm
going
to
do
an
endoscopy.
I'm
going
to
look
at
your
small
intestine
and
prove
that
you
don't
have
celiac
disease.
He
does
an
endoscopy.
She
doesn't
have
the
hallmarks
of
celiac
disease.
And
he
says
to
her,
"Go
back
on
gluten."
And
she
said,
"But
but
but
okay."
She
goes
back
on
gluten.
What
happens?
Headaches
returned
with
a
vengeance.
And
so
she
returns
to
the
office,
you
know,
bashfully
and
explain
that
story
to
me.
我读到的是，普通人群中大约有0.5%的人患有非乳糜泻麸质敏感。就乳糜泻而言，它影响大约1%的人。然后有0.1%的人对小麦过敏。但是当你询问人们、调查普通人群中关于践行无麸质饮食的情况时，多达20%的成年人报告说在无麸质饮食下感觉好得多。然而，双盲安慰剂对照食物激发试验显示，只有极少数自我诊断的个体对麸质有特异性反应。而且总的来说，我认为在这份报告中提到，误解在于很多人是对果糖和低聚果糖过敏，而低聚果糖与麸质总是同时出现。
我认为这也解释了为什么当你去某些国家吃到非常好的原料时——我经常举例如意大利的意面等类似食物，由于那里没有低聚果糖，你就不会有同样的反应。但也可能纯粹是总净碳水化合物导致你有那种感觉……可能是热量摄入减少导致你感觉……呃，或者是很多其他因素，比如你知道，安慰剂效应就是他们认为可能的原因之一。
英文原文
>> WhatI
read
was
that
roughly
0.5%
of
the
general
population
have
non-siliac
gluten
sensitivity.
In
terms
of
ciliac
disease,
it
affects
roughly
1%
of
people.
And
then
0.1%
of
people
have
a
wheat
allergy.
But
when
you
ask
people,
the
general
population,
if
you
survey
them
around
being
gluten-free,
up
to
20%
of
adults
report
feeling
much
better
on
a
gluten-free
diet.
However,
double
blind
placeboc
controlled
food
challenge
trials
show
that
only
a
fraction
of
self-dagnosed
individuals
react
specifically
to
gluten.
And
generally,
I
think
the
um
in
this
report
it
says
that
the
misunderstandings
are
a
lot
of
people
are
allergic
to
fructes
and
fruins
and
gluten
always
appear
at
the
same
time.
And
I
think
this
also
explains
why
when
you
go
to
certain
countries
and
have
really
good
ingredients,
I
often
citing
um
Italy
for
like
the
pasta
and
things
like
that
where
they
don't
have
fruans,
you
don't
have
the
same
response.
But
also
it
could
just
be
the
total
net
carbohydrates
that
causing
you
to
feel
Could
be
the
calorie
reduction
that's
causing
you
to
feel
Um
or
many
other
things
like
you
know
so
like
placebo
is
one
of
the
things
they
think
it
might
be.
草甘膦与肠道菌群
我再告诉你另外一件未被提及的事情，那就是在美国，呃，虽然我们没有转基因小麦——转基因作物培育出来的目的是为了能够喷洒草甘膦或农达来杀死杂草，而作物具有抗性并能够存活下来。所以他们目前还没有真正搞转基因小麦那套东西。因此你会认为小麦上不会有任何草甘膦。这种假设是错误的。在美国，草甘膦被喷洒在小麦上是为了使其干燥、脱水，以便他们能更迅速地将更多小麦推向市场。这可能是另一个因素。为什么？因为在我们吃的这些食物中存在草甘膦残留。而草甘膦对肠道微生物组具有显著影响。
英文原文
I'llgive
you
one
other
thing
not
mentioned
and
that
is
that
in
America
um
though
we
don't
have
GMO
wheat
GMO
genetically
modified
u
crops
are
created
such
that
glyphosate
or
Roundup
can
be
sprayed
to
kill
the
weeds
but
the
plant
is
resistant
and
will
survive.
So
they've
not
really
done
the
GMO
wheat
thing
yet.
So
therefore
you
would
think
there
wouldn't
be
any
glyphosate
on
the
wheat.
That's
a
wrong
assumption.
Glyphosate
in
America
is
sprayed
on
the
wheat
to
desiccate
it,
to
dry
it
out
so
they
can
get
more
wheat
to
market
more
quickly.
And
that
might
be
another
factor.
Why?
Because
glyphosate
is
residual
in
these
foods
that
we
eat.
And
glyphosate
has
a
significant
effect
on
the
gut
microbiome.
呃好吧。所以这也可能是他们喷洒在食物上的化学物质所致。
英文原文
>> Uhokay.
So
it
could
be
the
chemicals
they're
spraying
on
the
food
as
well.
没错。而且你知道，过去呃别人告诉我们的科学解释是：草甘膦只影响植物，既然你是人类，你就不必担心它。好吧，它确实影响植物，而且也影响细菌。但话又说回来，我们人类为什么要关心呢？因为我们体内生活着成百上千亿的细菌，我们依靠它们来维持健康。所以……
英文原文
>> That'sright.
And
you
know,
we
were
told
uh
that
the
science
was
that
the
glyphosate
only
affects
plants
and
since
you're
a
human,
you
shouldn't
worry
about
it.
Well,
it
affects
plants
and
it
affects
bacteria.
But
again,
we
humans,
why
should
we
care?
Well,
we've
got
billions
and
billions
of
bacteria
that
live
within
us
we
depend
upon
to
be
healthy.
So,
如今我们摄入的这种化学物质——它存在于我们所有人身体里——会影响生活在我们体内的细菌。
英文原文
here we are now consuming a chemical and it's in all of us that can affect the bacteria that live within us.这里还有一个稍微有点引申、但我认为确实非常引人入胜的事实：线粒体原本是细菌。而这些线粒体目前在很大程度上仍然与细菌非常相似。它们和细菌一样拥有环状DNA，并且对草甘膦敏感。草甘膦是一种线粒体毒素。所以，当我们食用喷洒了这种除草剂的食物时，摄入的正是这种物质。
英文原文
And here's another bit of a stretch, but I think really fascinating. Mitochondria were originally bacteria. And these uh mitochondria are very much still like bacteria. They have a circular DNA like bacteria and they are sensitive to glyphosate. Glyphosate is a mitochondrial toxin. So that's what we are consuming when we are consuming foods that have been sprayed with this herbicide.赞助商插播
我这里有一项着实让我感到震惊的统计数据。数据显示，销售团队大约50%的时间都花在行政杂务和手动更新CRM系统上，而不是用在销售上。这对他们的利润底线是致命的。这也是为什么十年前在我的上一家公司，我转而使用赞助了本期节目的Piperive。如果你从未使用过Pipedrive，它是一款智能的AI驱动型销售CRM系统。他们刚刚推出了全新的会议智能功能，比如直接内置在CRM中的AI笔记记录器。
英文原文
I um have a stat here that genuinely shocked me. It says that sales teams spend about 50% of their time on admin and manual CRM updates rather than selling. That is deadly for their bottom line. And that is part of the reason why a decade ago at my previous company I switched to using Piperive who are our sponsor. If you've never used Pipe Drive, it is an intelligent AI powered sales CRM. And they just launched new meeting intelligence features like an AI noteaker built right into the CRM.Pipedrive现在能自动化处理更多阻止你从事自己最热爱工作的行政杂务。在开会前，它会将交易历史记录、电子邮件记录和先前的对话汇总成一份简报，让你做好准备。它还会与你一起参加会议。它在那里负责记笔记，这样你就不需要自己动手了；它还会将记录的这些笔记转化成准确的自动起草的CRM更新记录。
英文原文
Pipe Drive now automates more of the admin that stops you from doing the work that you love to do best. Before your meeting, it pulls deal history, email records, and previous conversations into a single brief so you're prepared. And it joins your meetings with you. It's in there to take notes so you don't need to. and it turns those notes that it takes into accurate autodraft CRM updates.已经有100,000家公司使用它来管理销售业务。你可以在 piperive.com/ceeo 注册，获取独家的30天免费试用，而不是通常的14天。完全不需要信用卡。如果你从事销售并且管理着一个销售团队，只需访问 piperive.com/ceo 即可开始体验。我想你不会后悔的。
英文原文
100,000 companies are already running their sales on it. You can sign up at piperive.com/ceeo where you'll get an exclusive 30day free trial instead of the usual 14 days. Absolutely no credit card needed. Just head to piperive.com/ceo to get started if you're in sales and you run a sales team. I don't think you'll regret it.我接下来要说的是一则广告。赞助这则广告的公司确确实实改变了我的业务。在我给团队发送了那条表示我对这款产品有多着迷的特定Slack消息之后大约三周，他们主动联系了我。告诉你们这件事我甚至觉得有点像泄露了秘密，但我还是想说，因为我很喜欢他们。
英文原文
What I'm about to say is an ad. the company paying for it really, really, really have changed my business. They reached out to me about three weeks after I posted this particular Slack message to my team saying how obsessed I was with this product. I almost feel like I'm letting the cat out the bag by telling you guys about it, but I'm going to because I like them.Crockbot现在赞助了本节目，而且我已经投资了拥有Grockbot的公司SpaceX。Grockbot是我手机上的一个应用，但它也在我的电脑上。基本上我拥有所有这些不同的智能体，你可以把它们看作现在正与我协同完成工作的团队成员。比如这里的这个图表，显示的是我以及我的团队的使用情况。在4周内，单人的日均使用量从100次请求上升到了大约63,000次请求。它已经扎下根来。
英文原文
Crockbot now sponsors this show and I've already invested in SpaceX, which is the company that owns Grockbot. Grockbot is an app on my phone, but it's also on my computer. And basically I have all of these different agents. You can think of them like team members that are working with me to do work right now. Like this graph here is a graph showing my usage and my team's usage. In 4 weeks, daily use rose from 100 requests by one person to about 63,000 requests. It has taken hold.它再次让我解脱出来，去从事作为创作者、创业者和投资者只有我该做的事情，也就是关于品味、创造力、判断力等更高层次的事情。你今天就可以使用Grockbot完成更多工作。访问 x.ai/ac，即 x.ai/doac，首月可享受50%的折扣优惠。
英文原文
It's freed me up again to do the things that only I should be doing as a creative, as an entrepreneur, as an investor, which is the sort of higher level things around taste, creativity, judgment. You will get more done with Grockbot today. And you can get 50% off your first month by heading to x.ai/ac. x.ai/doac.多酚类食物与肠道健康
那其他这些东西呢？你对这里展示的另外一些食物有什么看法？
英文原文
What about these other things? What's your take on some of these other foods here?我在这里看到的是非常棒的食物。这看起来像是巧克力、洋葱、黑莓，我想这个应该是喜马拉雅苦荞。所以这些是富含……我们先把盘子里的酒暂且放在一旁。这些是富含所谓多酚的食物。多酚赋予了它们颜色。这就是为什么黑莓是黑色的，为什么洋葱是有颜色的。我们还有蓝莓，我想还有树莓。你知道，它们含有糖分吗？是的，它们确实含有糖分。但它们所含糖分释放进体内的速度较慢，而且同样与多酚结合在一起。
英文原文
What I'm seeing here are wonderful foods. This looks like chocolate, on uh onions, uh blackberries, uh I think this is supposed to be Himalayan tartar, buckwheat. So, these are foods that are rich in We'll leave the alcohol here off the plate for just a moment. These are rich that are foods that are rich in what are called polyphenols. That's what gives them their colors. Uh that's why the blackberry is black. It's why the onions are colored. We have blueberries and I guess raspberries as well. You know, do they contain sugar? Yes, they do. But they contain sugar in a way that is released more slowly into the body and again coupled with the polyphenols.这些化学物质会被我们的肠道细菌读取。换句话说，它们在向我们的肠道细菌发出信号，促使它们发挥良好作用，增加抗氧化剂的生成，产生对全身有益的化学物质。因此，从某种意义上说，我们既是在滋养我们自己，同时也是在滋养我们的肠道细菌。这种喜马拉雅苦荞大概是地球上这些多酚最丰富的来源之一。
英文原文
These are are chemicals that are read by our gut bacteria. In other words, these are signaling our gut bacteria to do good things to increase their antioxidant production to create chemicals that are good for the entire body. So, uh we're in a sense nurturing ourselves but we're also nurturing our gut bacteria. This Himalayan tartery buckwheat is probably one of the richest sources of these polyphenols on the planet.什么是多酚，它又是如何帮助我的大脑的？
英文原文
What's a polyphenol and how does that help my brain?再次说明，多酚是一种靶向分子，它能激活在体内生成抗氧化剂的通路。它们激活一条被称为NRF2通路的机制，从而增强我们的解毒功能，增加抗氧化剂的生成，并减轻炎症反应。所以全都是有益的方面。我在这里没有看到的，是地球上（至少就消费量而言）排名第一的多酚来源。那就是咖啡。所以投咖啡一票。好吧，差不多了。
英文原文
>> So again, a polyphenol is a a targeting molecule that uh activates pathways to create antioxidants in the body. They activate a a pathway called the NRF2 pathway and that increases our detoxification. It increases our production of antioxidants and it reduces inflammation. So all the good things. What I'm not seeing here is the number one source of polyphenols on the planet at least in terms of consumption. That is coffee. So there's a vote. Oh, well close enough.所以投咖啡一票。但是在这些高度加工或我们所说的超加工食品中，多酚的含量极少。在美国，成年人摄入的热量有60%来源于超加工食品。这些食品经过加工，使得这些多酚在加工过程中被去除掉了，而我们得到的食品大体上都添加了甜味剂，而且在与……哪怕仅仅是加工过程本身就存在各种各样的问题。
英文原文
>> So there's a vote for coffee. But there's very little polyphenols in these uh highly processed or what we call ultrarocessed foods. In America, 60% of the calories that adults consume are derived from ultrarocessed foods. They're processed such that these polyphenols are processed out of the foods and what we're getting are foods that by and large have added sweetener and have all kinds of issues uh related to their even just the processing of them.我现在会把所有多酚含量高的食物列在屏幕上，让大家都能看到。我会按照每100克含有多少多酚来进行排序，这样你就能看看自己平时是否会吃其中的一些食物。特级初榨橄榄油就是我喜爱并且经常食用的一种，因为它含有大量的多酚。
英文原文
I'll put up all the foods with strong levels of polyphenols on the screen now so everyone can see. Um and I'll rank them by how much polyphenols they contain per 100 g in order so you can see if you eat some of those. Um, extravirgin olive oil is one of them that I love and I eat a lot of because I had it contains lots of polyphenols.确实如此。而且你知道，这确实是我们现在所认识到的所谓地中海饮食的关键之一。不过你知道，令人遗憾的是，现在如果你去地中海一带旅行，你会发现他们吃的已经不再是地中海饮食了。顺便说一句，我很高兴看到你的盘子里有巧克力。巧克力很好。
英文原文
>> It does. And you know, it's really one of the keys we've now come to understand of the so-called Mediterranean diet. Uh, you know, unfortunately now, if you travel the Mediterranean, you'll see that they're eating not the Mediterranean diet anymore. And I'm I like that you have chocolate on the plate, by the way. Chocolate's good.巧克力很好。多酚。
英文原文
>> Chocolate's good. Polyphenols.不过我想应该是黑巧克力吧。
英文原文
>> Dark chocolate, though. I'm guessing黑巧克力。所以你要寻找的指标是希望超过80……
英文原文
>> dark chocolate. So the number that you look for is you want to go north of 8080%。
英文原文
>> 80%.80%。是的。因为这个比例越高，通常含糖量就越低。
英文原文
>> 80%. Yes. Because the higher that is, the lower generally is going to be the sugar content.巧克力制作与进化错配
我曾有机会在秘鲁亲手制作过巧克力，我永远也忘不了那一天。
英文原文
>> I had the opportunity to make some chocolate in uh Peru, and it I'll never forget the day.展开讲讲吧。我以前讲过这个故事，但当时他们给了我这么大一个巨大的大盆。然后他说：“我们先来做白巧克力。”那里有一大碗像这样的白糖。他说：“往盆里倒进60%，或者可能是70%的白糖。”当时我心想：“什么？”他当时就是说：“倒进去70%的糖。”我把糖倒到了这么高的位置。然后他说：“然后我们倒进去了这种液体。”
英文原文
>> Well, tell me about it. I've said this story before, but they gave me this like massive tub that was like this big. And he and he was like, "We're going to make white chocolate first." And there was a big bowl of sugar like this. And he goes, "Pour in 60% or it might have been 70% of the white sugar into the into the bowl." And I was like, "What?" He was like, "Pour 70% of the sugar." And I filled it up to here with sugar. And then he was like, "And then there was this liquid we poured in."我心想：“哇，我吃的白巧克力竟然有70%都是糖。牛奶巧克力……”
英文原文
>> And I was like, "Wow, the white chocolate I eat is 70% sugar. Milk chocolate."我喜欢白巧克力。
英文原文
>> I love white chocolate.真的吗？
英文原文
>> Really?当然。为什么不呢，为什么会不喜欢呢？
英文原文
>> Abs. Why wouldn't why wouldn't you?我懂。你的大脑天生就被设定去寻找甜味。那是你的生存机制。它告诉你自然界中的食物没有毒，并帮助你的身体为过冬储存脂肪。我的意思是，这就是我们的基因所起的作用。那是通过尿酸的激活来实现的。
英文原文
>> I know. Your brain is programmed to find sweet. That's your survival mechanism. It tells you that the food in nature is not poisonous and it helps your body store fat for for the winter. I mean, it's that's what our genetics do for us. That's through activation of uric acid.然后牛奶巧克力的比例大概是其一半。大约是50%，接着显然黑巧克力就是……
英文原文
>> And then milk chocolate was like half the size. It was about 50% and then obviously dark chocolate is对。而且你知道，任何这些东西你都可能会吃过量，当然巧克力也完全可能吃过量。但是你知道，人类和原始人类所食用的传统饮食富含纤维——正如你在这里看到的各种不同颜色所展示的那样，这些食物富含多酚——而且含有非常适宜的脂肪水平；而我们曾经被深深设定去追逐的，却是备受指责的脂肪、低脂这个、低脂那个。而且你知道，我认为这触及了一个更广泛的主题——我们过一会儿再聊酒的事——
英文原文
>> right. And and you know, you could go overboard on any of this and certainly go overboard on the chocolate. But you know the traditional diet that humans and protohumans consumed was one that was rich in fiber uh which these foods are rich in polyphenols as demonstrated by the different colors that you see here and and had very good levels of fat the the castigated fat the lowfat this the lowfat that that we were so programmed to gravitate towards and and you know it gets I think to the broader theme we'll do we'll do some alcohol in a moment这个关于究竟是什么让我们生病的核心问题，其更广泛的主题在于：我们的基因预期与我们的基因实际面对的环境之间存在错配。换句话说，我们从先于我们存在的所有前人那里传承下来的基因组，是在我们的基因组中经过一代又一代的千锤百炼而成的。当下，我们正在经历我们的进化（也就是我们的基因）与我们的环境之间极其惊人的错配。我的意思是，我认为这是与现代疾病相关的一个核心问题，即我们过着一种根本无法向我们的基因组发送适宜信号的生活。而我从15岁起就一直对这个问题充满兴趣。我听你说过人们……
英文原文
broader theme of of really the central issue here in terms of what's making us sick is this mismatch between what our genetics expect and what our genetics are seeing. In other words, our genome that we are gifted from all generations who've come before us, it's been refined generation after generation. in our genome. Right now, we are experiencing this incredible mismatch between our evolution, meaning our genes, and our environment. I mean, I think that's a central issue related to modern ailments, that we are living a life that just doesn't send the appropriate signals to our genome. And I've been interested in this for since I was 15. I've heard you say that people患有2型糖尿病的人患阿尔茨海默病的风险要高出300%到400%。一些研究已经表明了这一点。我认为，我们完全可以通过较新的数据来支持的一个数字，是至少增加75%到85%的风险。哇，那是一个很大的数字。但人们可能没有意识到的是，即便是帕金森病，在2型糖尿病患者中的发病率也增加了大约85%。为什么会这样？因为当你观察患有帕金森病的大脑时——这些数据在20世纪80年代末开始显现——你会看到小胶质细胞的激活，摧毁了大脑中被称为黑质、即产生多巴胺的黑质部分。这是小胶质细胞的激活。最初的研究非常吸引人。那是……那是在斯坦福大学观察到的，当时突然开始有在一天之内就患上帕金森病的人出现在急诊室，起因是注射了一种被一种叫做MPTP的物质污染的静脉注射设计毒品。那是一种线粒体毒素，它基本上烧毁了他们大脑中产生多巴胺的那些细胞，并变成了一个强大的研究工具。我上周参加了一个会议，会上MPTP被用于实验室小鼠，以造成……破坏大脑的那一部分，诱发帕金森病。现在他们已经为此开发出了一种抵消手段。他们给小鼠注射MB... MPTP，但同时给它们另一种叫做RNS60的物质，它能够通过阻止小胶质细胞的激活，来防止小鼠发生这种损伤。那么，这是什么？
英文原文
with type 2 diabetes have a 300 to 400% higher risk of Alzheimer's. Some studies have shown that. I think a number that we can uh absolutely support by more recent data is at least 75 to 85% increased risk. Wow, that's a big number. But what people may not be aware of is that even Parkinson's disease is increased in the type 2 diabetic by about 85%. Why would that be? Because when you look at the the Parkinson's brain, and this data became evident in the late 1980s, you see activation of the microgal cells destroying that part of the brain called the substantion, the black substance that makes dopamine. It's an activation of the microgle cells. The original work was was fascinating. It was uh it was seen at Stanford University when suddenly people started showing up in the emergency room who developed Parkinson's in one day from shooting an IV designer drug that was contaminated with something called MPTP and that was a mitochondrial toxin and it it basically fried those cells in their brains that made dopamine and became a powerful research tool. I was at a conference last week where MPTP was used in laboratory mice to create uh to damage that part of the brain, create Parkinson's. And now they've developed a an offset for that. They're giving the mice MBT, but giving them something else called RNS60 that was able to keep these mice from having that damage occur by activation of their microgal cells. So, what is this?嗯，它看起来像一条很长的动物（比如短吻鳄）的大脑，但我认为这是身体脂肪，或者我觉得它是脂肪。
英文原文
Well, it looks like a brain of a very long animal like an alligator, but I think it's body fat or I think it's fat.>> 看起来不那么舒服。这是一磅脂肪。
英文原文
>> Not that pleasant. That's a pound of fat.而且你不会想让它长在这里。你绝对不想让它长在这里。
英文原文
And you don't want it here. You do not want it here.>> 你不会想让它长在你的肚子上。
英文原文
>> You don't want it on your belly.>> 不，你不想让它长在肚子上。你不想让它长在你的器官周围。那被称为内脏脂肪。所以，嗯，你知道，当你超重30磅，超过理想体重时，那就是30个这样的东西。想想看。而且这很普遍。我的意思是，这极其普遍。所以，这是一个器官。它看起来只是普通的一团东西。我们过去常常认为脂肪是相当惰性的，只是作为卡路里的储备，如果我们挨饿、需要卡路里，我们就可以调用体内脂肪。这就是它的初衷。但它正在产生对全身都有作用的化学物质。总的来说，这些都是具有破坏性的化学物质。它们是促炎化学物质，称为细胞因子。我们过去认为脂肪只是我们吃下的食物储存的副产品，
英文原文
>> No, you don't want on your belly. You don't want it around your organs. That's called visceral fat. So, um, you know, when you're 30 lb overweight, over ideal body weight, that's 30 of these. Think about that. And that's common. I mean, it's so incredibly common. So, this is an organ. It looks like just stuff. We used to consider fat as being pretty inert, but as a resource for calories, we could tap into body fat if we needed calories if we were starving. That's what it's intent is. But it is creating chemicals that have function throughout the body. And by and large, these are chemicals that are damaging. They're pro-inflammatory chemicals called cytoines. We think of flat fat as just being the byproduct of its storage for the food we ate,>> 对吧？而且我们不认为它是一个器官，或者它会分泌东西，或者有任何活动。但你现在告诉我它会释放出化学物质？
英文原文
>> right? And it we don't think of it as an organ or that it's secretreting or doing anything. But you're telling me there's chemicals coming off this?>> 确实如此。体内脂肪会分泌促炎化学物质。而且它们不一定总是坏的。我的意思是，甚至对于炎症总是坏的这种观念，我们都是提出质疑的。我们需要炎症。如果我们突然能够立即减少你体内的所有炎症，你就会丧命。你必须具备炎症反应。这是一种救命的活动。带来麻烦的是过度的炎症，或者是较长时期内维持的较低水平的炎症。你知道，人们谈到过COVID中的细胞因子风暴。COVID中的细胞因子风暴伴随着细胞因子的突然爆发，遍布全身的炎症破坏着一切。而且我……我认为我们应该将像阿尔茨海默病这样的情况不视为细胞因子风暴，而是视为细胞因子小雨，这仍然是炎症的上升，虽然轻微，但它是在很长一段时间内发生的。我们桌上也放着酒精。你对酒精有什么看法？我的意思是，他们过去常说少量的酒精是有益的。
英文原文
>> You bet there are. There are pro-inflammatory chemicals that are secreted by uh by body fat. And they're not necessarily always bad. I mean, even the notion of inflammation always being bad, we challenge. We need inflammation. If we suddenly were able to reduce uh all the inflammation in your body immediately, you would perish. You need to have the inflammatory response. It's a life-saving activity. It's the excessive inflammation that gets us into trouble or lower levels of inflammation over a longer period of time. You know, people talked about the cytoine storm in COVID. the cytoine storm in COVID with this sudden explosion of cytoines, inflammation throughout the body damaging uh everything. And I I think that we should consider things like Alzheimer's as not a cytoine storm, but as a cytoine drizzle, that this is still an uptick of inflammation, though slight, but it happens over a long period of time. And we've got alcohol there as well on the table. What is your point of view of alcohol? I mean, they used to say that a little bit of alcohol is contributing.酒精与小胶质细胞
嗯，有许多数据表明，在痴呆风险方面存在我们所谓的U型曲线。什么是U型曲线？在极低水平，即不饮酒的情况下，存在一定的痴呆风险。随着摄入，风险稍微下降了一些。女性每天一杯红酒，男性每天两杯红酒，但随后U型曲线又重新上升了。所以，我们曾经以为存在一个最佳平衡点。呃，结果重新评估表明，实际上任何酒精摄入对大脑可能都不好，即便……而且我认为背景语境很重要。争论曾经是，红酒含有多酚类物质，对应我们之前的讨论，你知道，喝一杯红酒，我们知道，许多在蓝区的人，例如，会喝一些红酒，我有时也会喝，但是……呃，我觉得它具有威胁性，酒精本身就是一种神经毒素，而且我认为，还是让我们从你刚才描述的、刚才展示的咖啡和特级初榨橄榄油中获取多酚吧。我想我在这里得谨言慎行，冒着变成网络迷因的风险，但是……嗯，酒精是如何损害大脑的？
英文原文
Well, there was a lot of data that showed that there was what we call a U-shaped curve in terms of dementia risk. What is a U-shaped curve? The very lowest level, i.e. no consumption of alcohol, there was a certain risk for dementia. With consumption, then the risk went down a bit. One glass of wine per day for women, two glass wine per day for men, but then the U comes back up. So, we thought there was a sweet spot. uh and it turns out that reassessing that indicates that really any alcohol consumption is probably not good for the brain even and I think context is important. The argument was well red wine has polyphenols visav our previous discussion you know have a glass of red wine we know that uh many people in the blue zones for example will drink some wine as do I from time to time but uh I find it threatening alcohol itself is a neurotoxin and I think it's let's get our polyphenols from what you just described what you just showed from coffee and extravirgin olive oil I think I'll tread lightly here at risk of becoming an internet meme but Um, how does alcohol harm the brain?>> 它对神经元有直接的毒性，而且呃从我的角度来看，我想你可能已经猜到了，通过我如今看待脑科学的视角，它有助于使我们的小胶质细胞极化，使其脱离支持性状态。
英文原文
>> It is directly toxic to neurons and uh from my perspective, I think you probably guessed through the lens through which I see brain science these days, it helps polarize our microgal cells away from being supportive.>> 这些东西。是的。
英文原文
>> These things. Yep.>> 坏双胞胎，好双胞胎。
英文原文
>> The bad twin, the good twin.>> 那是好的。那是坏的。
英文原文
>> That's the good. That's the bad.>> 好双胞胎和坏双胞胎。所以，它把这些变成了这些。
英文原文
>> The good twin and the bad twin. So, it turns these into these.>> 没错。这些遍布整个大脑吗？它们遍布整个大脑，而且它们会四处移动。它们会四处移动。
英文原文
>> That's right. Are these all over the brain? They're all over the brain and they move around. They move around.>> 是的。呃，那就是令人非常兴奋的地方，那个发现，你知道，最初当它们刚被发现时，你会看到这些小细胞散布在载玻片上的神经元之间，你知道，死体载玻片上。人们当时认为它们很小，被称为micro，而glia的意思是胶水。人们当时认为它们把大脑粘合在一起。把脑细胞粘合在一起。后来技术发展了，允许在活体组织中进行观察，并注意到它们在四处移动。它们到处游弋，寻找事情可做，寻找需要修复的东西，或者相反，寻找可以摧毁的东西。我们要说清楚，这是我们可以控制的事情。所以这个好的小胶质细胞是M2型。
英文原文
>> Yeah. Uh that was what was so exciting, that discovery that, you know, originally when when they were first discovered, you would see these little cells interspersed between the neurons on a slide, you know, that of a dead slide. And it was thought that they are small, they're called micro, and they're ga meaning glue. It was thought that they glued the brain together. Glu glued the brain cells together. Then technology evolved that allowed the observation in living tissue and noted that they're moving all around. They're swimming around looking for something to do, looking for something to repair or conversely looking for something to destroy. And let's be clear, that is something over which we have control. So this good micro gleo cell is the M2.>> 没错。然后坏的那个，邪恶的双胞胎是M1型。
英文原文
>> That's right. And then the bad one, the evil twin is the M1.>> 没错。而酒精会把M2型翻转成M1型。酒精、高血糖、炎症、压力、久坐不动的生活方式、呃缺乏恢复性睡眠，所有这些因素，甚至社会孤立。那么当我们有了M1型，这个邪恶的双胞胎时，这又是如何直接增加我们患痴呆的几率的？机制是什么？那些小胶质细胞在大脑中造成了破坏。它们破坏我们神经元的稳定性。它们破坏血脑屏障的稳定性。所以现在我们让那些可能使问题进一步恶化的物质进来了。最根本的是，它们摧毁突触。
英文原文
>> That's right. And alcohol flips the M2 into the M1. Alcohol, high blood sugar, inflammation, stress, sedentarity, um lack of restorative sleep, all the things, even social isolation. And then when we have the M1, the evil twin, how does this then directly increase our probability of getting dementia? What's the mechanism? Those microgle cells create uh havoc in the brain. They destabilize our neurons. They destabilize the bloodb brain barrier. So now we're letting things in that can make the problem even worse. Most fundamentally, they destroy synapses.突触病变与补体信号
所以神经科学界现在正把阿尔茨海默病看作一个新名词所指的疾病，即突触病变（synaptopathy），一种突触的疾病，突触的丧失。而且你知道，有趣的是，我为你连接这个过渡。对于这个问题，我们的答案是什么：为什么女性患阿尔茨海默病的风险是男性的两倍？是因为她们寿命更长吗？并不尽然。女性大脑中到底在发生什么？最近所明确的是，绝经期雌激素的急剧下降，特别是一种叫做雌二醇的雌激素，会导致突触被贴上名为补体的信号分子标签。那基本上就是呃被称为“吃掉我”的信号。哈佛大学的贝丝·史蒂文斯（Beth Stevens）博士做了一些了不起的工作。
英文原文
So neuroscience is now looking at Alzheimer's as what is a new term, a synaptopathy, a disease of the synapses, a loss of the synapses. And you know, interestingly, I'll connect this segue for you. What is our answer for the question, why do women have twice the risk of Alzheimer's in comparison to men? Is it because they live longer? Not really. What's going on in the female brain? And what has recently been identified is this sudden drop of estrogen, particularly one estrogen called estradiol at menopause causes the synapses to be labeled with signaling molecules called compliment. That is basically uh what what is called an eat me signal. There's a Dr. Beth Stevens at Harvard who's done some amazing work.>> 你说的“吃掉我”信号是什么意思？
英文原文
>> What you mean eat me signals?>> 摧毁我。突触结合一种叫做补体的化学物质。而补体会触发这些小胶质细胞，向它们发出信号：作为M1型小胶质细胞的你，来摧毁这个突触吧。我的意思是，她已经……她已经证实了这一点。你实际上可以看到这一幕的发生。这相当令人惊叹。所以这个邪恶的双胞胎接收到了一个信号，前来摧毁大脑的各个部分。
英文原文
>> Destroy me. The syninnapse binds a chemical called compliment. And compliment triggers these microglea and it says for you M1 micro ga come and destroy this syninnapse. I mean she's she's demonstrated this. You can actually see it happening. It's pretty breathtaking. So the evil twin is receives a signal to come and destroy parts of the brain.>> 它被直接指引到该突触，去摧毁那个突触。
英文原文
>> It's directed right to the syninnapse to destroy that syninnapse.>> 大脑为什么要这么做？
英文原文
>> Why would the brain be doing that?>> 问得好。这些细胞因为我们谈到过的那些原因而被激活。这些代谢变化、炎症、暴露于受污染的空气、吸入野火产生的这些PM2.5颗粒，所有已知会激活这种小胶质细胞并导致它做出那种行为的因素。但我认为更重要的是，你知道，这解释了为什么呃随着年龄的增长，我们面临更高的风险。这真的是我认为目前神经科学研究中最令人兴奋且最基础的呃领域。那么，到底如何……
英文原文
>> Well, good question. These cells are activated for the reasons we've talked about. These metabolic changes, the inflammation, the exposure to polluted air, breathing these PM2.5 particles from wildfire, all of the things that are known to activate this microgle and cause it to do that. But I think more importantly, you know, this explains why uh when we age, we're at higher risk. It's really, I think, the most exciting and fundamental uh area of neuroscience research right now. So, how does40赫兹光声刺激与阿尔茨海默病研究
它起作用吗？目前的研究进展如何？
嗯，正在发生各种各样很棒的事情。麻省理工学院（MIT）有位蔡立慧（Li-Huei Tsai）博士，她做了什么呢？她证实了非阿尔茨海默病患者的大脑具有一种美妙的背景节律，称为伽马振荡（gamma oscillation），一种构成大脑活动基础的优美正弦节律。而阿尔茨海默病患者的大脑节律被打乱了，没有那种美妙的正弦节律。她偶然发现，根据放置在实验动物面前的光的频率，脑节律会发生改变。她在一只注定会患上阿尔茨海默病的实验啮齿动物——这是我们使用的实验工具之一——身上发现，以每秒40次、即40赫兹闪烁的光……
我们到底是怎么发现这些东西的？谁知道呢。它恢复了背景伽马节律。于是她说：“嗯，这很有意思。我想知道这对人类会产生什么影响。”她发现的是40赫兹的光和40赫兹的声音。她有一个能做到这一点的设备。它能恢复大脑中的这种伽马振荡，并让小胶质细胞恢复到支持性状态。
英文原文
it work? What's the research doing now?Well, all kinds of cool things are happening. There's a Dr. Leeway Sai at MIT, and what has she done? She's demonstrated that the nonAlzheimer's brain has a beautiful background rhythm called gamma oscillation, a beautiful syosoidal rhythm underlying the brain. The Alzheimer's brain has a disrupted rhythm. It doesn't have that beautiful syosoidal rhythm. and she stumbled upon the idea that brain rhythms change based upon frequencies of light that are put in front of a laboratory animal. And she found in the laboratory uh rodent that is geared to get Alzheimer's that is one of the experimental tools that we use that a light flashing at 40 times per second 40 hertz.
How how do we discover this stuff? who knows, restores the background gamma. And she said, "Well, that's interesting. I wonder what effect that's going to have in humans." And what she found was 40 Hz light and 40 Hz sound. She has a device that does this. Restores this gamma oscillation in the brain and reverts microgle cells back to being supportive.
那些邪恶孪生细胞，
英文原文
>> The evil twin cells,把邪恶孪生细胞转变回支持性状态。所以她实际上已经在患有阿尔茨海默病的人类身上应用了这项技术。
英文原文
>> the evil twin back to being supportive. So she's actually done this technique in humans with Alzheimer's.那这对我们意味着什么？比如对普通人来说，
英文原文
>> So what does that mean for us? Like for the average person,我的桌子上就有一个40赫兹的光发生器，你知道的。
英文原文
>> I have a 40 Hz light generator on my desk, you know.哦，真的吗？所以你可以直接去买——
英文原文
>> Oh, really? So you can go and buy确实可以，我买了。我是说，
英文原文
>> that I do. I mean,根据科学研究，那对你有什么作用呢？
英文原文
>> what what does that do for you according to the science?哦，根据科学研究，它能让我的小胶质细胞保持履行它们应尽的职责。她实际上已经在现存的阿尔茨海默病患者身上做过干预性试验，她的结果比任何针对β-淀粉样蛋白的药物都要好。那些β-淀粉样蛋白药物是FDA批准的针对β-淀粉样蛋白的疗法。我在我最近的新书里明确指出，这些药物在很大程度上是无效的，而且极其危险。我的态度是坚决不要使用它们。
最著名的通过频闪照明、闪烁LED或听觉咔哒声开创的40赫兹感官刺激，已经成为招募小胶质细胞来清理大脑的最引人入胜的非侵入性方法之一。
英文原文
>> Oh, according to the science, it is keeping my micro GA uh doing what they need to do. She's actually done interventional trials in patients with existing Alzheimer's disease, and her results are better than any drug that targets beta amaloid. The beta amaloid drugs are the FDA approved treatment for beta amalloid. And I make it very clear uh in my recent book that these drugs are for the most part ineffective and significantly dangerous. And my vote is that they are not to be used.40 Hz sensory stimulation most famously pioneered through strobe lighting, flickering LEDs or audiary clicks, has emerged as one of the most intriguing non-invasive approaches to recruiting micro glear to clean up the brain.
哇。你能想象吗？我是说，那真是一个——为什么这太棒了，“我的天哪”时刻。这太惊人了。你闪烁一下光，听一听声音，你的小胶质细胞就会变回支持你的一方。所以我……我把一个设备就放在我的电脑屏幕旁，它被动地把那种光照进我的眼睛里。我能证明它正在为我带来什么奇妙的效果吗？不能。但我相信这项科学吗？你猜对了，我确实相信。
在动物模型中，每天仅仅1小时的40赫兹光刺激就能显著降低斑块和缠结负担。嗯，我是说这种研究不胜枚举。我会把其中的一些数据展示在屏幕上。呃，最后收尾一下关于酒精的话题，你在书中的第102页提到了这项研究，呃，他们发现暴露在酗酒级别酒精中24小时的小胶质细胞，清理β-淀粉样蛋白的能力下降了15%。一点没错。
所以有人酗酒24小时，小胶质细胞的能力就下降15%……呃，就其清除那种与阿尔茨海默病相关的斑块——β-淀粉样蛋白的能力而言。
英文原文
>> Wow. Can you imagine? I mean, that is a why that's fantastic #WTF a moment. It's breathtaking. You flash a light and you hear a sound and your micro gle cells revert back to being on your side. So I I keep a device right by my by my computer screen and it's passively shining that light into my eyes. Can I prove that it's doing anything wonderful for me? No. But am I a believer in the science? You bet I am.In animal models, just 1 hour of daily 40 Hz light stimulation drove significant drops in plaque and tangle burden. H I mean it goes on and on and on. I'll put some of that data on the screen. Um just closing off on this subject of of alcohol, you said in your book on page 102 about this study uh where they found that microia exposed to binge level alcohol for 24 hours showed a 15% decrease in their ability to clean out beta amalloid. Exactly.
So someone binge drinks for 24 hours and the microia drop in their ability by 15%. um as it relates to their ability to clean out that beta amaloid which is the plaque associated with Alzheimer's.
睡眠、饮食与阿尔茨海默病预防的起点
是的，它是相关联的斑块。它不是核心关键角色，但它很重要。我是说，呃，我们需要进一步剖析一下关于靶向β-淀粉样蛋白的这种误区。它是一个参与者，这毫无疑问。但我承担不起15%的能力下降。我是说，因为我的年龄，它们已经被下调偏向M1表型了。所以，你知道，呃，这就是反对饮酒的理由。而且你知道，即使是一晚无法恢复精力的睡眠也会造成同样的结果，甚至更严重。
英文原文
>> Yeah, it's the plaque associated. It's not the pivotal player, but it's important. I mean, uh we need to unpack a little bit more about this kind of misdirection of targeting beta amaloid. It's a player. There's no question. But I can't afford uh a 15% reduction. I mean, they're already downregulated uh towards M1 because of my age. So, you know, uh that's the vote against alcohol. And you know, even one uh night of non-restorative sleep does the same thing. Even more so.很有意思。
英文原文
>> Interesting.一晚没睡个好觉，就会急剧降低你清除β-淀粉样蛋白的能力。
英文原文
>> One night of not getting a good night's sleep dramatically reduces your ability to clear beta amaloid.你能从中恢复过来吗？因为会有很多人在想：“糟糕，我上周有七个晚上都没睡好。”
英文原文
>> Can you recover from that? Cuz there's going to be a lot of people thinking, "Fuck, I had, you know, seven bad nights last week."或者……或者这会……
英文原文
>> Or or does我跟你说一件事。我是说，我知道你经常在洛杉矶、纽约和周一之间来回奔波，我真不知道你是怎么做到的。
英文原文
>> I'll tell you one thing. I mean, I know you travel a lot between LA, New York, and Monday, and I don't know how you do it.是的，行程很多。是的。然后再飞回欧洲。但我……我确实如此，这就是为什么我对所有这些事情思考得如此之多，因为我觉得，我现在34岁所做的事情真的会产生复利效应。
英文原文
>> Yeah, it's a lot. Yeah. And then fly back to Europe. But I I do this is why I think about all this stuff so much because I'm like what I do now at the age of 34 really is going to compound.是的。确实、确实如此。
英文原文
>> Yep. It really really is.我会弄清楚自己犯过的错误。
英文原文
>> And I'm gonna figure it out the mistakes I made.是的。我是说，你知道，在神经病学院里，他们又会教你：“好吧，一旦问题已经开始，你该为阿尔茨海默病患者做些什么？”这挺好的，我很高兴有人在关注并做这项研究，但在你这个年纪播下种子，才是这一切真正开始的时候。
让我来说说这个。有一项刚刚发表的有趣研究，简直让我大吃一惊。它的研究对象是1953年受孕的女性，就在此时此刻你我坐着的这里，在英格兰这里，以及她们当时是否有糖配给制。二战时期的糖配给制在1953年依然在实行。
它关注了一大群女性，并对她们进行了多年的随访，追踪到了人们达到……我想至少随访了50、60、70年，它的发现是：那些处于糖配给制下、在怀孕期间以及随后的1000天内（也就是贯穿整个怀孕期以及孩子生命的最初几年）无法获得糖的女性，她们的孩子现在已经60、70、80岁了，患阿尔茨海默病的风险降低了40%，仅仅因为母亲在怀孕时无法接触到糖。
哇。我是说，你知道，人们总是在问：“那么，珀尔穆特（Perlmutter）博士，阿尔茨海默病的预防计划应该从什么时候开始？”你知道，我的标准回答是：“嗯，你知道，我们在三四十岁时就得开始注意了。”呃，但这项研究真的把时间往前拨了极多，不是吗？
不过其机制是什么？我认为存在多种机制。我认为，你知道，糖本身会升高血糖，呃，从而损害大脑功能甚至大脑的发育生成。但我认为糖还会改变肠道细菌的微环境与构成，这项研究实际上并没有对此作出评价，但我对此类问题比较敏感。饮食中更高水平的糖会改变肠道内生存的细菌和其他生物（例如酵母菌）的种类、功能和多样性。
英文原文
>> Yeah. I mean, you know, in neurology school they again they teach you, well, how do you what do you do for the Alzheimer's patient once the problem has begun? And great. I'm glad people are looking at the doing research, but it's setting, you know, sewing the seeds at your age is when it really begins.Let me take this. There's one interesting study that was just published and it just blows my mind. It was done uh looking at women who conceived in the year 1953 right where you and I are sitting right now here in England and whether they had sugar rationing or they didn't have sugar rationing at that time. The sugar rationing from World War II was still in place in 1953.
And it it looked at a large cohort of uh women and followed them for a number of years uh to when people became I guess so followed at least 50 60 70 years and what it found was the women who had sugar rationing who weren't able to get sugar while they were pregnant and for one uh thousand days so through pregnancy and then the first couple years of life the risk of that child now that that child is 60 70 80 years old developing Alzheimer's was reduced by 40% because mother didn't have access to sugar when she was pregnant.
Wow. I mean, you know, people are always saying, "Well, Dr. Promoter, when should the Alzheimer's prevention program begin?" You know, my standard response is, "Well, you know, we got to be paying attention in our 30s and 40s." Uh, but this really winds the clock back, doesn't it?
What is the mechanism though? I think there are multiple mechanism. I think you know sugar in and of itself raising blood sugar uh compromises brain function and even the genesis of the brain. But I think sugar also changes the millu the makeup of the gut bacteria and the study actually didn't really comment on that but I'm kind of sensitive to that. Higher levels of dietary sugar change the array, the function, the diversity of the bacteria and other organisms that live within the gut like yeasts for example.
肠道微生物组与大脑健康
而婴儿拥有母亲的肠道微生物组。
英文原文
>> And the baby has the mom's gut microbiome.呃，实际上不是的，婴儿在出生之前其实并没有多少微生物组。分娩方式对于新生儿微生物组的发育至关重要。换句话说，剖宫产与顺产有着巨大的影响。当婴儿通过产道时，会受到产道中一种特殊混合物、一组特殊微生物群的“涂油礼”。
英文原文
>> Uh actually no, the baby does not really have much of a microbiome until such time as it's born. The method of birth is really fundamentally important for the development of that newborn's microbiome. In other words, cesareian section versus a vaginal delivery has a huge impact. When a baby passes through the birth canal, it's being anointed with a special concoction, a special array of organisms in the birth canal.细菌，
英文原文
>> Bacteria,细菌、病毒和酵母菌，各种进入婴儿眼睛、鼻子和嘴巴里的微生物。我称之为“涂油礼”。这是一种恩赐，对吧？新生儿正是在那一刻，根据其出生方式开启并播种了他或她的微生物组。呃，通过剖宫产出生的新生儿，其发育出的微生物组将取决于婴儿出生时外科医生手套上的残留物。事实上，有研究……我想是在纽约大学（NYU）正在进行的，许多女性可能对此很熟悉，如果她们要进行剖宫产，医生会拿棉签擦拭产道、阴道。婴儿通过剖宫产出生。然后，将那根仍含有这些分泌物的棉签涂抹在婴儿的鼻子和嘴巴里，以帮助恢复那种特定类型的微生物组。
英文原文
>> bacteria and viruses and yeast, all kinds of organisms that get in the baby's eyes and its nose and its mouth. And it I call it an anointment. It's it's a blessing, right? that this newborn gets his or her microbiome started seated at that moment based on how it's birth uh birthed being born by cesareian section that newborn will develop a microbiome based upon what was on the surgeon's glove at the time that baby was delivery delivered in fact there is research uh being done I think at NYU many women are probably familiar with this where if they're going to have a C-section they take a swab of the birth of the vagina. Baby is born by C-section. Then that swab which still contains those secretions is placed in the baby's nose and its mouth to help restore that um specific type of of microbiome.微生物组与阿尔茨海默病及痴呆症之间有什么联系？
英文原文
>> What is the link between the microbiome and Alzheimer's and dementia?嗯，我认为这种联系是……是相当深远的。我认为我们必须明白，这些微生物正在制造对大脑有益的物质。呃，比如它们正在制造各种类型的短链脂肪酸，这些对大脑功能非常重要。微生物组——这些微生物分泌的化学物质正在改变我们全身的基因表达，当然也包括大脑中的基因表达。我认为最大的问题是当我们体内的这些微生物发生变化时，而这种变化可能例如由服用某些药物引起。哦……
英文原文
>> Well, I think the link is is uh is quite profound. And I think that we've got to understand that these organisms are making things that are good for the brain. uh they're making very types of short- chain fatty acids for example that are important for brain functionality. The microbiome these organisms are secretreting chemicals that are changing gene expression throughout our bodies and of course in the brain. I think the biggest issue when we have uh changes in these microbes that can be brought on for example by taking certain medications. Oh我们这里碰巧就有，例如质子泵抑制剂类药物。这些是抑酸药，人们吃它，是因为他们根据在电视上或别处看到的内容，觉得自己需要降低胃酸。而当你改变了肠道的 pH 值，你就改变了生活在其中的微生物及其功能。当你这样做时，就可能导致肠道内壁漏损或通透性增加。这为体内的炎症埋下了伏笔。
英文原文
we we happen to have them here for example proton pump inhibiting drugs. These are acid blocking drugs that people take because they think they need to lower their stomach acid based upon what they're seeing on television or elsewhere. And when you change the pH of the gut, you're changing the organisms that live there and their function. And when you do that, it can lead to increased leakiness or permeability of the gut lining. That sets the stage for体内的炎症。那些炎症化学物质随后会传遍全身，并进入大脑。它们在那里做什么？它们使我们具有支持性、关爱性的 M2 小胶质细胞发生极化，变成破坏性的。还记得那些显示出……的 TSPO 影像吗？
英文原文
inflammation in the body. Those inflammatory chemicals can then make their way throughout the body and make their way into the brain. What do they do there? They polarize our supportive loving M2 microg GA to being destructive. Remember those TSPO images that showTSP？
英文原文
>> TSP?那些显示出……的 TSPO 影像。
英文原文
>> TSPO images that show那是什么？
这些是那种受体的影像——在具有危险性的 M1 小胶质细胞上发现的 TSPO 受体，我们实际上可以把某种物质结合上去，然后进行扫描。呃，正电子发射计算机断层显像（PET 扫描），记得那个吗？它显示了这些小胶质细胞的活化，解释起来就像在第 14……所以再说一次，TSPO 纯粹是在活人身上证明其小胶质细胞活化的一种方式，
英文原文
>> what's that? These are the images the the type of receptor the TSPO receptor that is found on the M1 dangerous micro glea that we can actually attach something to and then scan it. Uh PET scan remember that that shows activation these micro ga explain it's like on 14. So again, the TSPO is simply a way in living humans to demonstrate activation of their microgal cells,它们也就是这些……
英文原文
>> which are these免疫细胞，
英文原文
>> immune cells,这些邪恶双胞胎一样的东西。
英文原文
>> these evil twin things.是的。让我对我们的 M1 小胶质细胞稍微客气一点。它们是有特定时机和场合的。当我们出现急性损伤、急性感染时，我们需要这种小胶质细胞来发挥作用，去消灭或中和。例如，当我们头部受伤时，我们会激活我们的 M1 小胶质细胞，
英文原文
>> Yeah. Let me let me be a little kinder to our M1 microglea. There's a time and a place when we have an acute injury, acute infection, we want to have that type of microbial cell to do its job to destroy or to neutralize. When we have a head injury, for example, we activate our our M1 microglea,但我们必须能够恢复为具有支持性的小胶质细胞，
英文原文
>> but we have to be able to revert back to being the supportive microgle cell,那个健康的小胶质细胞。
英文原文
>> the the healthy one.当我们在事件发生之后，仍让小胶质细胞保持在破坏性的表型或构型中，就会导致好转延迟，甚至完全不见好转。
英文原文
>> When we keep our micro glea in their destructive um phenotype or configuration after the event has occurred, it leads to delays in improvement or even lack of improvement.是哪方面的好转？
英文原文
>> Improvement in what?问得好。例如，我们知道这些橄榄球运动员会患上这种脑病，当他们在打橄榄球时头部撞击过多，就会经历这种渐进性的神经退行性病症，最终可能会夺去他们的生命，但他们已经不再撞击头部了。为什么会这样？因为那些做出恰当反应的小胶质细胞没有恢复回去。
英文原文
>> Good question. We know that these uh football players for example get this encphylopathy that when they bang their heads playing football too many times they experience this progressive neurodeenerative condition that ultimately may kill them but they're not banging their heads anymore. Why so? Because the micro gleal cells that appropriately responded don't revert back.每当我与新的创始人交谈时，他们都持有同样的信念，认为他们的小微企业面临的最大威胁是产品糟糕。其实不是。他们面临的最大威胁是为小团队招错了人。因为糟糕的雇员会拖慢发展的脚步，并迅速毒化公司文化。我完全理解。刚起步时，你需要顶尖员工来发展公司，但你没有 40 个小时的闲暇时间耗在筛选面试上。所以，你为了填补空缺而匆忙招人，但长远来看这最终会让你付出更大代价。任何小微企业真正需要的是一种可靠且高效的方式来寻找合适的人才，而不会延缓发展势头。
英文原文
Whenever I talk to new founders, they all carry the same belief that the biggest threat to their small business is having a bad product. It's not. The biggest threat they face is hiring the wrong person for their small team. Because bad hires put the handbreak on growth and rapidly infect company culture. And I get it. When you're starting out, you need a players to grow your company, but you don't have 40 spare hours to spend sifting through interviews. So, you hire fast to fill the seat, but this ends up costing you even more in the long term. What any small business actually needs is a reliable and efficient way to find the right talent without stalling momentum.这正是我们长期的赞助商领英（LinkedIn）和 LinkedIn Hiring Pro 能为你提供帮助的地方。它简化了整个招聘流程，从起草职位描述，到筛选候选人短名单，再到利用 AI 进行初筛面试。使用过该工具的招聘人员中，近 60% 在一周内就找到了可供面试的候选人。从一开始就招对人，立即前往 linkedin.com/doac 免费发布你的第一个职位。网址是 linkedin.com/doac，条款和条件适用。
英文原文
That's where our long-term sponsor LinkedIn and LinkedIn Hiring Pro can help you. It streamlines the entire hiring process from drafting a job description to shortlisting candidates and conducting AI powered interviews for initial screenings. Nearly 60% of hirers who've used this tool have found a candidate to interview within a week. Hire right the first time around and get started by posting your first job for free at linkedin.com/doac. That's linkedin.com/doac and terms and conditions apply.你可能会觉得 Nespresso 的前总裁会是一个很难被转化去接受一家新咖啡公司的人。但仅尝了一口 Cometeer 咖啡就让他决定投资。
英文原文
You'd think the former president of Nespresso would be a pretty hard person to convert to a new coffee company. But just one sip of Cometier coffee made him invest.不过让我告诉你我成为投资人的原因。我当时收到了一大箱这东西，寄到我在伦敦办公室的办公桌上。然后我想大约在一个半小时内，我们的 Slack 频道就开始炸锅了，大家都在问：“放在厨房里的那个到底是什么鬼东西？”太不可思议了。所以与其试图在家里自己冲煮并平衡风味，他们是在最完美的时刻对其进行速冻。所以你要做的就是把它从这里弹入杯中，倒入热水，它的味道就像你以前从未尝过的美味。你也可以制作美味的冰咖啡饮品。直接倒进去就行。
英文原文
But let me tell you the reason why I became an investor. So I had a big box of this arrive on my desk in the London office. And then I'd say within about an hour and a half, the Slack channel that we have starts blowing up with people asking, "What the hell is that thing that's been left in the kitchen?" It is unbelievable. So instead of trying to make it yourself at home and balance the flavors, they flash freeze it at the perfect moment. So all you have to do is pop it out of here into a cup, pour hot water on it, and it tastes like nothing you've tasted before. You can also make delicious iced coffee drinks as well. Just pour it in.无需机器，无需用塑料和所有那些讨厌的东西冲泡。今天你可以在 cometier.com/stephven 享受首单优惠 30 美元。网址是 cometier.com/stephven。
英文原文
No machine, no brewing with plastic and all that nasty stuff. And you can get $30 off your first order at cometier.com/stephven today. That's cometier.com/stephven.噢，所以有点像拳击手打完拳赛，然后你逐渐看着他们恶化。你看着他们口齿不清……
英文原文
>> Oh, so it's kind of like boxers who finish boxing, but then gradually you watch them deteriorate. You watch their speech slur记忆力也是。
英文原文
>> memories.我们俩现在都在想着穆罕默德·阿里。
英文原文
>> We're both right now thinking about Muhammad Ali.那多令人痛心啊？对吧。那被称为拳击手帕金森综合征。Pugilist 的意思就是拳击手。但是对头部的任何撞击，呃，你知道，无论是踢足球……呃，上周发表的一项研究将 F1 赛车手列为面临风险的人群。我想第一位患上慢性创伤性脑病（CTE）的 F1 赛车手就在一周前上了新闻。我是说，你知道，开着车以那么快的速度行驶时，我想你的头肯定会晃来晃去地撞击。但是你必须保护好你的头部。你真的必须保护它免受创伤。
英文原文
>> How tragic was that? Right. That's called pugilistic Parkinsonism. Impugilist means a boxer. But any bump to the head uh you know whether it's uh playing soccer uh there was a study that came uh out last week that looked at F1 drivers as being at risk. The first F1 driver I think that developed the CTE chronic traumatic encphylopathy made the news uh just a week ago. I mean you know I guess you're banging your head around when you're in in that car going that fast. But you got to protect your head. You really got to protect it against trauma.有项有趣的研究表明，如果你受到头部创伤——你知道，这可能发生在我们所有人身上——如果你碰巧在头部创伤之前就患有 2 型糖尿病，你预后不良的风险就会增加。2 型糖尿病患者受到头部创伤的预后要糟糕得多。为什么？因为 2 型糖尿病正在转变他们的小胶质细胞，阻止它们恢复并发挥有益、支持性的作用。把它转变成了那个邪恶的双胞胎。
英文原文
interesting study that shows that if you have head trauma, it's going to happen, you know, to all of us maybe that your risk of poor outcome is increased if you happen to have been a type 2 diabetic prior to the head trauma. Outcome of head trauma in type 2 diabetics is much worse. Why? Because that type 2 diabetes is shifting their micro GA, preventing them from coming back and being uh being helpful, being supportive. Shifting it to the evil twin.邪恶的双胞胎。确实如此。没错。
英文原文
>> The evil twin. Exactly. Right.线粒体、二甲双胍与生活方式干预
好的。那么，从这次谈话中得到的一大要点是，我在日常生活中做出的决定，我吃进嘴里的东西，我做或不做的运动，我喝或不喝的酒，嗯，最终都会对这产生影响。
这就是那个事件。而在此之前的上游环节，
英文原文
>> Okay. So, one of the big takeaways from this conversation is the decisions I make in my everyday life, what I put in my mouth, the exercise I do or don't do, the alcohol I do or don't drink, um is all going to impact this ultimately. That's that's the event. And upstream of that是线粒体的变化，是这里所发生情况的能量学机制。这在其中起着非常重要的作用，以至于你知道，我们现在正在研究我们能做些什么来增强线粒体功能，因为在线粒体功能恢复时，它有助于维持我们的小胶质细胞处于支持性角色。现在已经有将健康线粒体移植到人类心脏中的移植技术，而且很快也会移植到人类大脑中。我们有一些方法可以增加我们的线粒体数量、改善其功能，并提升我们清除有缺陷线粒体的能力。运动可以做到这一点，二甲双胍也能做到这一点。这种药物目前就在英国这里被用作阿尔茨海默病治疗方案的一部分。二甲双胍是……那个二甲双胍补充剂。
英文原文
are the changes in the mitochondria, the energetics of what is going on here. That is playing a really important role such that you know we are now looking at what can we do to enhance mitochondrial function because when mito mitochondrial function is restored it helps keep our microglea in their supportive role. There are transplant uh techniques now for transplanting healthy mitochondria into human hearts and very soon into human brains. There are ways that we increase our our mitochondria in terms of their numbers, in terms of their function, and in terms of our ability to get rid of defective mitochondria. Exercise does it and metformin does it as well. This drug that is being used right here in England now as part of a treatment pro protocol for Alzheimer's. Metformin is that metformin supplement.它是一种糖尿病药物。它针对的不是 β-淀粉样蛋白，
英文原文
>> It's a diabetes drug. It's not targeting beta amaloid,但普通人不应该服用它，对吧？
英文原文
>> but the average person shouldn't be taking that, should they?问得太好了。我之前参加过一个关于健康寿命和衰老的会议，那是一个规模很小的会议，大约 20 人。有人问了一个问题：你们当中有多少人在服用二甲双胍？这大约是在八年前，我想 80% 的科学家都举手了。
你现在从我这里听到的并不是说我们都应该跟风去服用二甲双胍。我更倾向于运动。但是有一项名为 TAME 试验的大型研究。阿尔伯特·爱因斯坦医学院的 Nir Barzilai 正试图启动这项研究，但一直在寻找资金。我想这是一个大约 7000 万美元的项目。他拿不到资助，因为二甲双胍已经过专利期了，所以最终没人能获得巨额收益。但该研究着眼于服用二甲双胍这种药物的干预措施，以观察它对长寿以及痴呆症有什么影响。
英文原文
>> That's a great question. I was at a um at a conference uh dealing with uh a health span uh aging and it was very small uh conference about 20 people. The question was asked, how many of you are taking metformin? This about eight years ago and I think 80% of the scientists raised their hands. What you're not hearing from me right now is that we should all jump on board and take metformin. I prefer to exercise. But there is a a big study called the TAME trial. Neil Barzai at Albert Einstein is trying to get this started but looking for funding. It's uh I think about a $70 million project. He can't get funding because metformin has gone off patent so nobody's going to get the the brass ring at the end of the day. But it's looking at the intervention of taking this drug metformin uh to see what effect it has on longevity and and dementia for that matter.对于普遍健康的非糖尿病人群，目前的科学共识是不建议服用二甲双胍，因为存在一些潜在的后果。为什么在健康成年人中常规使用会存在问题：第一，它会削弱运动带来的益处。显然，运动是目前唯一经过最充分验证、最具可重复性的长寿干预手段。多项随机对照试验证明，二甲双胍会主动干扰机体对运动的适应。第二，在长期的临床数据中存在掩盖生活方式根本要素的风险。在降低心血管风险方面，强化的生活方式改变始终优于二甲双胍。依靠药物来模拟代谢健康，无法复制全身性血管和心理……
英文原文
For generally healthy non-diabetic people, the current scientific consensus is not to take metformin because there are some potential consequences. Why routine use in healthy adults is problematic. Number one, it blunts the benefits of exercise. Apparently, exercise is the single most validated reproducible longevity intervention available. Multiple randomized control trials have demonstrated that metformin actively interferes with exercises adaptations. Number two is risk of masking lifestyle fundamentals in long form clinical data. Intensive lifestyle modification consistently outperforms metformin in reducing cardiovascular risk. relying on a pill to simulate metabolic health cannot replicate the systemic vascular and psychological……运动、睡眠和天然全食物带来的益处，而且还有一大堆其他已知的副作用。好的。
英文原文
benefits of movement, sleep, and whole foods and there's a bunch of other known side effects. Okay.这很有意思。这几乎就像是在复制运动的部分效果。
是的。但正如你极好地指出的那样，看看其潜在的弊端。而且我认为这篇文章里没有提到服用二甲双胍（metformin）的人群中我们所见到的 B12 缺乏的可能性。你知道，戴维·辛克莱博士（Dr. David Sinclair），你曾请他上过这个节目，上过这个播客。他最近几个月前发表了一篇论文，研究了所有这些与他谈到的衰老钟相关的很酷的干预措施，并对它们进行了排名。其中描述了二甲双胍，也描述了雷帕霉素（rapamycin）。名列前茅的——你知道他是个狂热的 NAD 倡导者，如你所知——在这些衰老钟方面名列前茅的是运动。所以这又回到了这个问题：我们的祖先是怎么做的？他们很活跃。他们没有受到这种久坐不动之苦——整天屁股坐在那里、在电脑前东奔西跑的这种状态。对我来说，这一直是我理解我们为什么会生病的核心焦点。我 15 岁时就写过一篇关于这个的短文。而且……
英文原文
So, interesting. It's almost like replicating some of the effects of exercise.Yes. But as you wonderfully point out, look at the potential downsides. And I I don't think mentioned in this uh article was the uh possibility of B12 deficiency that we see uh in people taking metformin. you know, um, Dr. David Sinclair, you've had him on the program on the podcast. He recently put out a paper several months ago that looked at all these kind of cool interventions as it relates to these aging clocks that he he talked about and uh, it ranked them and Mitt Foreman was described and rap was described. what led the list and you know and he's a big NAD guy as you know uh what led the list was exercise in terms of these age aging clocks so again it gets back to this what did our ancestors do they were active they didn't suffer from you know this sedentarity this idea that we're just sitting on our butts all day flying here and there in front of the computers and you know I to me this has been the the central focus of my understanding as to Why we are sick? I wrote a paper about this when I was 15. And
15岁。
英文原文
>> 1515岁。我想你这里甚至有一张照片，在你的其中一张照片里。是的，我写了一篇短文，发表在《迈阿密新闻》（Miami News）上。我想那份报纸现在在迈阿密已经不存在了。但我当时的结论很简单：在我们所生活的世界里，我们在基因上无法足够快地适应，以便在这个突然对我们反客为主的世界中生存下去，我们无法……看，就在那儿，致编辑信。
英文原文
>> 15 I think you may even have a you have a picture here of it uh in in one of your photographs. Uh yeah, I wrote a paper uh about it and it was published in the Miami News. I think that is no longer uh a newspaper in Miami. But I I I I simply concluded that the world in which we live, we are not able to adapt uh quickly enough, genetically enough to be able to survive in the world that has suddenly, you know, turned the tables on us that we are not able to uh there it is to the editor.那么这是什么？这是你 15 岁的时候写的。
确实是。
“也许人类在接下来的几个世纪里会迅速改变，使自己适应啤酒罐、混凝土和震耳欲聋的噪音。我们的每一代人都在为抗污染肺部的进化做出贡献。但今天那些被困在过时生理结构中的人又该怎么办呢？”这是这位年轻人写的。你那时差不多 17 岁，差不离。
英文原文
>> So what is what is this? This is when you were 15 years old.It is.
Perhaps the human will change rapidly in the next centuries to adapt himself to beer cans, concrete, and shattering noise. Our generations are each contributing to the evolution of pollution resistant lungs. But what about the people of today who are stuck with the outdated machinery? And that was written by this young man. You're about 17 years old there, but nearly.
不，对，我猜是……不，到 17 岁时我已经留长发了。
英文原文
>> No. Yeah, I guess. Uh I No, by 17 I had grown long hair.好的。
英文原文
>> Okay.是的，我当时是个圆滚滚的小家伙，不是吗？顺便说一句，那也是我受诫礼时系的领带。是的。
英文原文
>> So, yeah. Uh, I was a pudgy little one, wasn't I? That was my bar mitzvah tie, too, as a matter of fact. Yeah.这里还有一张你儿子的照片。
英文原文
>> Got a picture here of your son as well,奥斯汀（Austin）。
英文原文
>> Austin.奥斯汀，你们看起来很像。
英文原文
>> Austin, you look very similar.你们现在看起来比……还要像。
英文原文
>> You look more similar now than好吧，我会把这当作非常大的夸奖。不仅如此，我想说他教了我很多。
英文原文
>> Well, I'm going to take that as a very big compliment compliment. And uh more than that, I would say uh uh he's taught me a lot.他确实教了很多。在很多方面他都是一位导师，看着他为人父真是太美妙了。
英文原文
>> He really has. uh in many ways he's a mentor and it it's so wonderful watching him become a father.这以他自己尚无法完全体会的方式改变了他。我想现在还没完全体会，但他会体会的；还有我们的女儿，看着她在世界舞台上绽放为一名艺术家。看着他们两个真是令人叹为观止。再次说，当你有了自己的孩子时，我会回来的，或者我不知道我们会怎样，我想保持联系，因为对你来说那将是一个真正的转折点。
英文原文
>> Uh it has it's changed him in ways he you know he cannot uh begin to to appreciate. I think not yet but he will and our daughter um watching her blossom as a an artist on the world stage. It's just breathtaking to watch the two of them. And again when when you have your children I'm I'm going to come back or I don't know what we'll do. I want to stay in touch cuz that's it's going to be a real gamecher for you.现在你有了孙子……孙女，这是否在很大程度上改变了你对大脑、身体、长寿以及我们今天谈论的所有这些话题的看法？改变了你对自我保养的看法？
我会说我加倍努力了——为了当好爷爷，我对我所做的一切绝对都是加倍投入。我是说，我当爷爷的时间算比较晚的。你看，我 71 岁才当上爷爷。你知道，我大多数有孙辈的朋友，他们的孙辈都已经快二十岁了。所以，我必须全力以赴。而且我觉得，我不想成为那种“照我说的做，别照我做的做”的人。我不想成为那样的人。我想对自己的缺点保持尽可能透明，对我认为重要的事情也保持透明。我认为从根本上讲，我们今天谈论的内容改变了主导权和责任归属。
也许会有人对此提出批评，但我的目标是赋予掌控力。你知道，我们常常把自己的掌控力寄托在开发出疗法的希望上，对吧？电影导演詹姆斯·卡梅隆（James Cameron）曾有一句名言：希望不是一种策略。我想提供一种策略，来增加你免遭认知衰退的几率；这种衰退不仅对你来说是毁灭性的打击，而且到那时，谁知道呢，对你的妻子、你的孩子也是如此，那是一个可怕的境地，代价极其沉重。
所以当我说这些药物在寄望于“未来会有有效药物”的语境下是无效的时候，我恰好看到古巴哈瓦那竟然出炉了一项强有力的研究：采用鼻内给药一种名为促红细胞生成素（erythropoietin）的物质——这是一种由肾脏产生的物质——对现有的阿尔茨海默病患者产生了令人震惊的效果。我是说，那些原本会衰退、在安慰剂组中按照我们使用的标准量表衰退了 4 分的患者，竟然改善了 4 分。所以他们不仅是稳定下来，而是病情好转了。
英文原文
>> Did it change a lot of how you think about the brain and the body and longevity and all the subjects we've talked about today? Preserving oneself now that you've got a grandson um a granddaughter.I would say that I've doubled down uh I I have absolutely doubled down on everything that I do uh to to be a grandfather. I mean I became a grandfather kind of late in life. You know, here I am 71 become my grandpa. Most of, you know, my friends who have grandchildren, you know, their grandchildren are, you know, in her late teens already. So, I got to do the best I can. And I think, you know, I don't want to be do as I say, not as I do. I don't want to be that person. I want to be as transparent as possible with my foibless and, you know, with the things that I I I think are important. You know, I think fundamentally that what we're talking about today changes the ownership and the responsibility.
And perhaps there's a criticism there, but my my goal is to give agency. You know, we offload our agency to the hope of the development of cures, right? And and James Cameron, the movie director, famously said that hope is not a strategy. I want to provide a strategy to improve your odds of not experiencing this cognitive decline that is not just you know the a devastating issue for you but by that time who knows your wife your children and uh it's an awful situation and the cost is profound.
So when I say that the drugs are ineffective in the context of hope that there will be effective drugs, I just saw a powerful study come out of Havanic Huba of all places giving an intraasal treatment of something called ariththrop poetin which is something made by the kidneys that had effects in existing Alzheimer's patients that were mind-blowing. I mean patients who would have declined who did decline in the placebo group by four points on a standard scale that we use improved four points. So what didn't just stabilize they they got better.
对于那些目前患有阿尔茨海默病、或者有亲属患有阿尔茨海默病的人——我想听众中有很多这样的人。我之所以知道，是因为每当我就这一主题展开讨论时，评论区通常都填满了故事。有被确诊的人，有亲人被确诊的人。他们点击这些视频的很大一部分原因，就是因为他们刚刚拿到了诊断书，或者正忍受着疾病，正在寻找答案。对于那些不幸正在家庭中或自身大脑里面对痴呆症的人，我们能提供些什么？
英文原文
For those people that do have Alzheimer's or have a relative that has Alzheimer's now I imagine there's a lot of them listening. I I know that because when I have conversations on this subject matter the comments typically fill with stories. People who have been diagnosed, loved ones have been diagnosed. A lot of the reasons why they click on these videos is because they've just received a diagnosis or they're living with it and they're in search of answers. What what is there that we can offer to people who unfortunately are now dealing with dementia in their family or within their own brain?阿尔茨海默病的干预与生活方式
那么我们能提供什么？而且你为什么要相信我，对吧？你为什么要相信出现在你节目里的某个人？要知道，我在这里是在逆流而上。我正在指出，至少在美国，FDA 所批准的那些并不是出路。我是在指出，当我们看一下哈佛大学一项规模相对较小的研究——显然由备受尊敬的鲁道夫·坦齐（Rudolph Tanzi）和迪安·奥尼什（Dean Ornish）主持——他们选取了 51 名患有阿尔茨海默病或即将发展为阿尔茨海默病的轻度认知障碍人群，改变了他们的生活方式。他们增加了运动量，改变了饮食，减轻了压力，并且每天必须冥想一小时。结果这些人不仅在短短 20 周的干预期内减缓了衰退，而且其中 70% 的人病情要么稳定，要么得到了改善。
英文原文
Well, what what do we offer? And why should you believe me, right? Why should you believe some guy that's on your show that is, you know, I'm swimming upstream here. I am indicating that what at least in America the FDA has approved is not the way to go. I'm indicating that when we look at a relatively small study from Harvard University obviously well respected by Tany and Rudolph Tany Dean Ornish where they took a group of 51 individuals who have Alzheimer's disease or mild cognitive impairment going to have Alzheimer's and they changed their lifestyle. They increased their exercise. They changed their diets. They reduced their stress and they had to meditate for an hour a day. So these people didn't just slow their decline in the relatively short intervention of 20 weeks, but 70% of them either stabilized or improved.他们对饮食做了什么调整？
英文原文
What did they do to their diet?他们让他们采用了偏植物性、更接近地中海式的饮食。这种饮食富含我们刚刚看过的那些成分：富含多酚，色彩丰富；重新接纳脂肪，但是是优质脂肪；并且鼓励社交互动。人们的状况好转了。所以这就是我要对这个假设情况所说的话。这就是我要对正在收听的任何人说的话：密切注意你的血糖，减轻你的体重。最重要的是，我们之前看过的这个强有力的工具：一双跑鞋。在我看来，那就是拯救之道。
刚发表的考克兰（Cochrane）系统评价对这些阿尔茨海默病药物是怎么评价的？我们必须谈谈这个，因为我在上一本书中就写过我不赞成使用这些针对淀粉样蛋白的药物这一观点。我为什么会说这样的话呢？毕竟它们可是获得了 FDA 批准的。我这么说是因为它们在很大程度上是无效的，而且具有显著的风险特征。这项考克兰评价对 17 项不同研究中的 20,342 名受试者进行了分析，每项研究历时 18 个月，并提出了两个简单的问题：这些针对 β-淀粉样蛋白的药物在阿尔茨海默病患者身上有效吗？它们安全吗？对吧？这就是风险与获益。对吧？他们发现，这些药物在延缓疾病进展方面基本没有显著效果，更谈不上带来改善了。
英文原文
>> They put them on a plantforward more Mediterranean type diet. A diet rich in the things that we just looked at. Rich in polyphenols, rich in color. welcome back to the table fat but the good fats and encourage social interaction is people improved. So that's what I say to this hypothetical. That's what I say to anyone who's listening that pay close attention to your blood sugar. Get your weight down. And most importantly, this powerful tool that we looked at, a pair of running shoes. That is the salvation in my opinion.What did the Cochran analysis that was just published say about these Alzheimer's drugs? We've got to talk about it because I wrote in my last book the idea that I am not in favor of the use of these amalloid targeting drugs. And why would I say such a thing? I mean after all they are FDA approved. I said it because they are for the most part ineffective and they have a significant risk profile. So this cockrine analysis looked at 20,342 individuals in 17 different studies 18 months each study and asked two simple questions. Do the drugs work in the Alzheimer's patient that target beta amalloid and are they safe? Right? Those are risk and benefit. Right? They found that the drugs basically have no meaningful effect in slowing the progression, much less leading to improvement.
那么生酮饮食作为应对痴呆症症状的一种方式又如何呢？
英文原文
>> What about the ketogenic diet as a way to deal with the symptoms of dementia?嗯，我认为不仅是症状。我认为当你在谈论生酮饮食时，正如你所清楚知道的，你针对的是线粒体。生酮饮食加上运动，我们针对的是线粒体功能。请记住，那是决定小胶质细胞是发挥支持作用还是破坏作用的关键枢轴点。
英文原文
>> Well, I think more than the symptoms, I think when you're talking about ketogenic diet, you're targeting, as you well know, the mitochondria. Ketogenic diet along with exercise, we're targeting mitochondrial function. And remember that that is a the pivot point for determining supportive versus destructive microglea.而且通过……
英文原文
>> And by生酮饮食与大脑能量代谢
生酮饮食——对不了解的人来说——我们基本上指的是极低碳水化合物饮食，每天碳水摄入大概少于 50 克。
英文原文
keto diet, for anyone that doesn't know, we basically mean a very low carb diet, less than maybe 50 grams of carbs per day
同时在饮食中显著增加更多脂肪，优质脂肪，特级初榨橄榄油以及坚果和种子。在针对轻度认知障碍和早期阿尔茨海默病的临床试验中，生酮饮食或酮体补充剂（可以通过各类酮体口服液获取）能挽救大脑大约 10% 到 18% 的总能量供应，直接填补受损葡萄糖代谢所遗留燃料缺口的最高达 80%。这种能量提升转化为标准记忆和测试成绩最高达 15% 的改善，以及日常功能最高达 20% 的提高，帮助患者以更大的独立性应对基本自我照料和日常事务。不好意思，谁曾想到呢？当你针对线粒体时，这对大脑是件好事。我的意思是，这是一个代谢问题。大脑需要葡萄糖，当我们产生胰岛素抵抗时，大脑的某些部位就会受损。并非所有脑细胞都需要胰岛素，但有些部位确实需要。海马体——记忆中心；控制我们代谢的下丘脑；让我们做出良好决策并帮助引导行为的前额叶皮层；最后还有一个叫做嗅球的区域，参与嗅觉功能。当你仔细想想，我刚才提到的这一切在阿尔茨海默病中都是问题。我们变得健忘、代谢乱套、失去执行功能，并且丧失嗅觉。所以你指出这一点太对了：这是一种上游的能量匮乏，即大脑利用能量的能力出现问题。你可以通过生酮饮食来绕过这个问题，在帕金森病中也是如此。新西兰有一位名叫 Matthew Phillips 的研究人员，他发表了关于这两种疾病的研究论文，我还与他合写过一章关于生酮饮食在帕金森病中应用的书籍章节。
英文原文
significantly with the addition of more fat to the diet, good fat, the extra virgin olive oil with nuts and seeds. In clinical trials on mild cognitive impairment and early Alzheimer's, a keto diet or ketone supplementation, which you can get through various ketone shots, rescues roughly 10 to 18% of the brain's total energy supply, directly closing up to 80% of the fuel gap left by impaired glucose metabolism. This energetic boost translates up to 15% improvement in standard memory and test scores alongside a 20 up to 20% gain in daily functioning, helping patients manage basic self-care and everyday tasks with greater independent independence. Sorry, who knew? When you target mitochondria, it's a good thing for the brain. I mean, it's a metabolic issue. The brain requires glucose and when we become insulin resistant, certain parts of the brain suffer. Not all of the brain cells require insulin, but some parts do. The hippocampus, the memory center, the hypothalamus that controls our metabolism, the prefrontal cortex, which allows us to make good decisions and helps direct our behavior, and finally an area called the olfactory bulb, which is involved in smell. When you think about it, everything I just mentioned are are issues in Alzheimer's. We become forgetful. our metabolism goes catawwampus, we lose executive function and we lose our sense of smell. So you are so right to point that out that this is an upstream energy deficiency, the inability of the brain to use energy. You can bypass that with the keto ketogenic diet and also in Parkinson's. There is a researcher in New Zealand named Matthew Phillips who has published papers on each of those and I wrote a book chapter with him on the use of the ketogenic diet in in Parkinson's.
不过生酮饮食很难坚持，不是吗？
英文原文
It's hard to adhere to the ketogenic diet though, isn't it?
我并不是说一个人必须一直保持那种状态。我认为你想努力建立的是灵活性，这样当你决定断食一天或两天，或者只吃一顿饭，并且坚持极低碳水和较高脂肪的饮食方案时，你就能够相对快速地进入酮症状态，而不是必须去适应那种可能需要两周时间的生酮状态。David 医生，关于阿尔茨海默病、痴呆症，以及总体上拥有健康大脑，对于那些可能没有过多考虑疾病、只是想在日常生活中展现最好状态的人来说，我们还没聊到但本该聊到的最重要的事情是什么？我的意思是，我自己就是其中之一，因为显然我有时会与医生交谈，并且……
英文原文
And I'm not saying one needs to do that at all times. I think what you want to try to establish is flexibility such that when you do decide you're going to fast for a day or two or one meal and and stick to the very low carb and higher fat regimen that you're able to jump into ketosis relatively quickly as opposed to having to adapt to uh ketogenic state which may take you know a couple of weeks. Dr. David, what is the the most important thing we haven't talked about that we should have talked about as it relates to Alzheimer's, dementia, and generally just having a healthy brain for those that maybe aren't thinking so much about a disorder, but just want to be able to show up in their lives on a daily basis and be their best. I mean, I'm one of those people because obviously, you know, I have conversations with doctors sometimes and
是的。但谁又不是这种人呢？
英文原文
Yeah. But who isn't one of those people?
确实。你能跟谁去聊，对方会说“你知道，我其实不太在意让自己大脑发挥状态”呢？
英文原文
I mean, true. Who could you speak to uh who would say you know I really am not so invested in having my brain perform?
大脑表现与个性化补充剂
关于大脑退化我们今天所谈论的一切，在大脑表现方面具有同等价值。所以这是一个极好的转折过渡。因此，如果你希望自己的大脑在最佳状态下运转，这些完全就是通往王国相同的钥匙。
英文原文
Everything that we have talked about today in terms of brain degeneration is equally valuable in terms of brain performance. So that was a wonderful segue. So if you want your brain to perform at its optimal level, these are the exact same keys to the kingdom.
我们还有几个……
英文原文
We've got a few
你这里还有些好东西。你的工具箱里还有其他东西。我们已经触及了其中一些。嗯，你支持服用补充剂吗？
英文原文
you've got some goodies in here. There's other things in your toolbox here. We've touched on some of them. Um, are you a fan of supplements?
我支持。
英文原文
I am.
你支持？
英文原文
You are?
我绝对支持。
英文原文
I absolutely am.
你具体服用哪些补充剂？
英文原文
What particular supplements do you take?
嗯，这个回答的个性化医疗部分首先是，我自身有一点基因上的特殊性。
英文原文
Well, I have a bit of a first the personalized medicine part of that answer is I have a little bit of a genetic quirk.
呃，名字叫做 MTHFR。这意味着我对 B 族维生素的处理不像应有的那么好。正因如此，这是一个复杂的情况，但我的同型半胱氨酸水平升高了。同型半胱氨酸水平——同型半胱氨酸本身是一种氨基酸，是心脏病和阿尔茨海默病的显著危险因素。
英文原文
Uh, goes by the name of MTHFR. And what that means is I don't handle B vitamins as well as I should. And as such it's a complicated story but my homocyine level was elevated. Homocyine level homocyine itself is an amino acid that is a significant risk factor for heart disease and Alzheimer's.
好的。
英文原文
Okay.
所以因为我独特的基因，我必须服用一种不同类型的 B 族维生素，称为甲基化 B 族维生素。所以这对我来说是首要的……
英文原文
So because of my unique genetics I have to take a different type of B vitamin called methylated B vitamin. So that's first and foremost for me
甲基化维生素 B。对，
英文原文
vitamin B methylated. Yeah,
甲基化，对我以及可能占全球约 25% 的人口而言。
英文原文
methylated for me and for probably about 25% of the global population.
你还吃什么？
英文原文
What else do you take?
我服用来自鱼油的 DHEA。
英文原文
I take DHEA from fish oil.
那么，那是欧米伽-3 吗？
英文原文
So, is that omega-3?
欧米伽-3。但我们想看的是 DHA 含量。所以我服用的鱼油……我每天摄入大约 1,000 毫克 DHA。当我们谈论那些与阿尔茨海默病患者共同生活的人时，你知道，我们经常从家属那里听到实质上失去他们所爱之人是怎样的感受。
英文原文
Omega3. But we want to look at the DHA content. So, my fish oil that I take uh contains uh I'm getting about 1,000 milligs a day of uh DHA. When we talk about people that are living with someone with Alzheimer's, you know, we often hear from the family what it was like to essentially lose the person they loved.
是的。
英文原文
Yeah.
阿尔茨海默病的病程与亲历体验
患有阿尔茨海默病的人本身会是怎样的体验？这是个很好的问题。我认为在早期，这是极其令人痛苦的。你问人们最害怕什么疾病？绝大多数回答是阿尔茨海默病。不是癌症，不是心脏病，不是任何其他疾病，我认为是失去做出自主决定和自我照料的能力。
英文原文
What is it like for the person that has Alzheimer's? It's a great question. I think early on it's incredibly distressing. And you ask people what disease do you fear most? Overwhelmingly the answer is Alzheimer's. It's not cancer. It's not heart disease. It's not anything else. It's losing the ability. I think uh to make your own decisions and selfcare.
他们知道自己正在失去这种能力吗？
英文原文
Do they know that they're losing it?
早期是知道的。
英文原文
Early on, yes.
早期他们知道，之后会发展到一个他们意识不到的阶段，那算是一种解脱。我看着这发生在我父亲身上。
英文原文
Early on they do and it gets to a point where they don't realize and that's a blessing. I watched that happen to my dad.
真的吗，
英文原文
Really,
他，你知道，最终变得毫无察觉。你知道，当你在早期失去这些细微的认知功能时，你心里非常清楚有什么不对劲。
英文原文
he was, you know, ultimately became unaware. You know, when you lose these subtle cognitive functions early on, you know damn well something's going on.
在他的情况下这经历了多久？
英文原文
How long did that take in his case?
是的。从确诊到去世，我应该说从他的行为发生改变到他离世，大概经历了 5 年。
英文原文
Yeah. between diagnosis to his death I should say from when you know when his behavior changed to his passing took about 5 years
5 年，最终导致患者死亡的是这种疾病本身，还是其他原因？是这种疾病，就是这种疾病。是的，最终一切机能都会停止运转。他不——我认为他并不携带 APOE4。我不知道他的基因图谱是怎样的，我不知道，我也并不了解我母亲，所以我无法弄清我父亲是否确实携带了 APOE4，或者——可以确定的是，还有 80 种其他与阿尔茨海默病风险相关的基因问题。但话说回来，基因负责装弹，生活方式、生活方式扣动扳机。
英文原文
5 years and is it the disease that ends up killing the person or is it something else it's the disease it's the disease yeah everything ultimately just shuts down he did not I don't believe carry AP E4 I don't know what his genetic profile looked like I do not and I don't know my mother so I can't figure out what whether my dad did carry the APOE E4 or and to be sure there are 80 other genetic issues that relate to Alzheimer's risk. But again, genetics uh loads the gun. Lifestyle lifestyle pulls the trigger.
就他的变化而言，那五年是什么样的？
英文原文
What were those five years like in terms of how he changed?
嗯，你必须从他的基准状态说起。他是一个高大伟岸的人。仅仅就你知道的他的贡献和他的同理心而言，并且平心而论，对他人甚于对家人，实事求是地挑明情况，这是我一直在努力化解的一点，我认为这有助于解释为什么我一生都如此有干劲，去获得或许早年就本可以获得的认可。我不确定我是否计划过在我们的对话中深入到这个话题，但管他呢。不过话虽如此，当他能意识到这一点时，他是会去否认和推卸责任的人。“我从来没说过那个”，或者“你一定是把这个放错地方了”，并且对他身边发生的事情变得有些指责。当他找不到东西时，他会指责别人把东西搬来搬去。然后随着病情的进展，你知道，他的这些问题对他自己而言越来越不成问题，而对我们其余所有人而言越来越成为严重的问题。
英文原文
Well, you have to start at his baseline. He was a towering human. uh just in terms of you know his contribution and his compassion and to be fair to others more so than to family call it out like it was which is something I've I've worked through which I think helps explain why I've been as driven as I have been throughout my life to um get recognition that perhaps I could have gotten earlier in life. I'm not sure I had planned on going to this part of uh this topic in our conversation, but what what the heck. But that said, um when he was aware of it, uh his uh he was one to deny uh and off offload blame. I never said that or you must have misplaced this or and became a bit accusatory of things that were happening. When he couldn't find things, he would accuse people of of moving things around. And then as um as it progressed, you know, his uh issues became less and less of an issue for him and more and more of an issue for all the rest of us.
是否有过那么一个时刻，他意识到自己的大脑正在发生变化？
英文原文
Was there a moment where he realized he had his brain was changing?
是的。那么他是否脱离了那种充满指责的状态，开始理解到这是……
英文原文
Yes. And so did he shift out of that accusatory state and start understanding that this was
不，我认为他那时已经不具备应对的认知工具了。巧合的是，他住的那家养老院，他在养老院的公寓正好隔着停车场对着我的临床神经学阿尔茨海默病诊所，以至于我可以从我的诊室看到他的房间。我会在诊室里会见患者家属，在谈话进行的同时，我能看到他的房间。他们会说：“医生，你根本不知道我们和母亲或父亲经历了什么。”而我会停下来对他们说：“让我在此打断一下，只是为了让我们能在人性层面彼此共情。你看到隔着停车场的那个房间了吗，那就是我父亲现在住的地方，他正因这种疾病走向死亡。所以我懂。现在你知道谁是你的团队队友了。”渐渐地，这种衰退意味着他不知道自己是谁了。哦，除此之外，他没办法，你知道，他完全无法自理。那就是阿尔茨海默病的最终结局。那是完全丧失与他人进行任何有意义互动或开展任何有意义活动的能力。你只是躺在床上，脸上带着茫然的凝视。这是……
英文原文
No, I don't think he had the tools at that point. and and um by circumstance the nursing home in which he lived, his apartment in the nursing home was across the uh parking lot from my clinical neurology Alzheimer's practice such that I could see his room from my examining room and I'd be meeting in the examining room with families of patients and um I could see his room while the conversation ations are going on. And they'd say, "Doc, you have no idea what we're going through with mom or dad." And I would stop and I would say, "Let me hold you right there just so we can relate as humans. That room that you see across the parking lot, that's where my father lives now and he's dying from this disease. So, I get it. So, now you know who your team player is." And gradually the decline meant that he didn't know who he was. Oh, beyond that, he didn't, you know, he was totally unable to function. That's the end endgame in in Alzheimer's. It's a a total lack of ability to engage any meaningful interaction with others or any meaningful activity. You're just in bed with a blank stare on your face. It's
这……呃，当你看到自己的父亲变成那样，回想……回想起他曾经是什么样的人、曾拥有怎样的人生，这真的很难受。我真的不想让其他人也经历这些，真的不想。如果我总是说“不要寄希望于药物，今天就做出这些改变，因为这并不容易，我真希望医学界能去推行这些”，从而让人觉得我很讨人嫌，我也不会为此道歉。因为这正是对你最初那个问题的回答——我到底在做什么？我正在倾尽全力，让其他人不必再去经历我此刻正在体会的心情。你知道，虽然那是很久以前的事了，我现在也是一个71岁的老人，但我依然没有释怀。而且我意识到，我可能永远都无法释怀。但这不是坏事，因为……它在激励着我。它给了我站在你广大听众面前的勇气，去说出这些话。因为只要有一个人听进去了这个信息，我的使命就完成了。而我的希望是，能有很多人接收到这个信息：我们需要重获自主权，不要被说服去寄希望于外面存在某种特效药。那种想法根本不切实际，是错误的，而且极其残忍，我对此坚决反对。
英文原文
it's uh and when you see your parent like that and think and you think back to uh to who he was and what he was, it's uh it's difficult and I don't want people to go through that. I really don't. And if I'm a pain in the ass by saying the things that I say about don't put your faith in the drugs and make these changes today cuz they're hard and I wish medicine would do these things. I'm not going to apologize cuz that's what answers your very first question. What am I doing? I'm doing my best so people don't go through to have to experience what I'm feeling right now. And you know I'm this was a long time ago and I'm a 71y old man and I'm not over it. And I realize I'm not ever going to be over it. And that's not a bad thing because it's um it motivates me. It gives me the courage to go before your audience. I know that it is vast and to make these statements because if one person gets this message, then I've done my job. And my hope is that a lot of people get this message that we need to regain agency and not be persuaded to hope that there's a wonder drug out there. That's just inappropriate. It's wrong and it's absolutely cruel and I object to it.好吧，你自己现在也是一位父亲了，你有一个优秀的儿子叫Austin。我其实私下联系了Austin，Austin写了……为你写了一封简短的信。给你，这是来自你儿子Austin的信。
英文原文
Well, you're a dad yourself now and you have this wonderful son called Austin. I actually spoke to Austin and Austin wrote uh wrote a little letter for you. Here you go. This is from uh your son Austin.好的。
英文原文
Okay.获奖者是……你可以读出来。
我会读的。
英文原文
And the winner is you can read it. I will.Austin的信
“……在我整个人生中，你始终是‘充满热情’的人格化典范。无论对待患者、家人，还是通过类似这样的播客节目触达的数百万人，你总是全心全意地去帮助他人，赋予我们改善生活的工具。看到你帮助人们理解并改善他们的大脑健康，我感到无比自豪。这至关重要。
我从收到的无数留言中看到了这一点，人们告诉我，你为他们及其家人带来了多么巨大的改变。在学术会议上我也能听到，人们向我讲述你在几十年前为他们做过的事情。能成为你的儿子，我倍感荣幸。
最近，看到你成为一名杰出的祖父，我心中更是充满了喜悦。
你以令人惊叹的方式延续了你父亲的事业。
迫不及待想很快见到你。
来自大洋彼岸我们全家的爱。
Austin。”
英文原文
that for the entirety of my life, you've been an example of passion personified. Whether it was for your patients, your family, or the millions of people you reach on podcasts like this one, you've always cared so much about helping others and empowering us with tools to make our lives better. I'm so proud to watch as you help people understand and improve their brain health. It matters. I see it in the messages I get from people telling me just how much you did for them and their families. I hear it at conferences when people tell me about the things you did for them decades ago. I'm honored to have you as my father. And most lately, I'm filled with the joy to see become an exceptional grandfather. You are an incredible continuation of the work of your father. I can't wait to see you soon. Love from all of us across the pond. Austin.使命与顿悟
好吧，呃，Stephen，你……你真是太懂怎么触动人心了，不是吗？
呃，你知道，我此刻正在想着我的父亲。我们一生都在努力去做正确的事，而他树立了非常高的标杆，真的极高。达赖喇嘛曾说过，如果你想让别人快乐，就要心怀慈悲；如果你想让自己快乐，也要心怀慈悲。
在很多层面上，这些都是喜悦的泪水。我对现状的发展感到非常欣慰，因为我走在属于自己的轨道上。能够身处自己的赛道，明确自己的专业技能并穷尽毕生精力去发挥它，这种感觉真的很好。这就是一切的意义所在。这或许是对你开场提问的一个更好的回答。我认为这就是一种顿悟：找到你的专长，并用它来做出贡献。
事情就是这样。我想只要我的大脑还能正常运转，只要我继续坚持做所有正确的事情，我就会一直走下去。希望它能一直保持下去。
英文原文
Well, uh, Stephen, you you you really did it here, didn't you? Um, you know, uh, I'm thinking of my dad right now and we go through our lives trying to, um, do the right thing and he set a very high bar. He really did. You know the Daly Lama said that if you want others to be happy, be compassionate. And if you want to be happy, be compassionate. In many ways, these are tears of joy. I am so happy with how it's playing out because I'm in my lane. It feels really good to be in my lane and doing having identified what my skill set is and exploiting it to the ends of the earth. That's what it's all about. Probably a better answer to your uh opening question. I think that's enlightenment. I think enlightenment is identifying your skill set and using it to contribute. And uh and there you go. And I guess uh I will continue as I'll continue as long as my brain holds up and I'm doing all the right things. So hoping that it it does.正如Austin所说，你精彩地延续了你父亲的事业。
在他老人家的悼词中，我唱了一句，我想那是Dan Fogelberg的歌……只是Dan Fogelberg歌曲里的一句词，我想我没记错创作者。歌词是：“我的一生不过是在拙劣地模仿他，我只是那个乐队领队的鲜活遗赠。”
既然如此，为什么不把这份精神遗产传承下去，身体力行地去施教呢？“Doctor”（医生）的本义是教师，并不是治愈者。所以这就是我们该做的事，也是你正在做的事。你看，这个播客节目里探讨的所有内容，核心都在于传道解惑。无论是探讨我们是否应该服用肌酸、剂量应该是多少、相关研究有哪些，还是探讨衰老的成因是什么。这个问题你问过无数次：“你如何定义衰老？”这就是在施教。它将好奇心与慈悲心结合在一起，这是一种绝佳的结合，因为好奇心赋予了你真正践行慈悲的工具，至少在医学领域确实如此。
阿门。
英文原文
As Austin said, you are a wonderful continuation of your father's work. Um, at his eulogy, um, I sang, I think it's a Dan Fogelberg song. Um, just a line from a Dan Fogberg song. I think I got that right. Attribution. And it was, uh, my life has been a poor attempt to imitate the man. I'm just a living legacy to the leader of the band. And why not, you know, why not uh continue on the legacy and teach by example? Doctor means teacher. It doesn't mean healer. So that's what we do. That's what you do. You know, all the things that go on on this podcast, it's all about teaching. whether it's about you know um should we take creatine or or should we not take creatine and what's our dosage and what's the research or what is the cause of aging. You've asked that question so many times. How do you define aging? It's teaching and it's it's um it marries curiosity with compassion and that's a great marriage because curiosity gives you the tools to really be compassionate and at least in medicine it sure does. Amen.终极建议：重新连接
我们今天探讨的所有内容，最终都归结到了大脑这个关键器官上。关于人们的大脑，你有什么总结性的话要对大家说吗？我们能对他们说些什么，以确保他们在听完这次对话后，会竭尽全力去保护它？
我来从个人层面和全局层面对此作一点延伸，谈谈什么才是真正重要的。简而言之，就是：重新连接。
如果我们能重新与他人建立联结，重新维系人际关系，这将极大改善我们的生活、提升我们的大脑健康，并改善我们生存的星球。
正如你所知，Austin和我合著了一本书，名叫《Brain Wash》，就在那最上面放着。我们在书中从微观层面定义了一种叫做“断联综合征”（disconnection syndrome）的现象，探讨了大脑如何与其前额叶皮层失去连接——那是人类独有的天赋；而在宏观层面上，我们彼此之间又变得多么疏离。重新连接有切实的个人益处，正如我们探讨催产素时提到的那样。但我们必须彼此重新建立连接，重新与地球建立连接，我们所有人都是休戚与共的。我想，这就是我最重要的核心信息。
英文原文
Everything we've uh talked about today comes back to this old fella, the brain. What are your closing words for people about their brain? What can we say to them to to make sure that they walk away from this conversation and they do everything they can to protect this? And I'm going to amplify that a bit uh from a personal perspective, what matters and from a global perspective. In a word, reconnect. If we reconnect with others and reconnect with relationships, it will go a long way to improving our lives, improving our brain health, and improving the planet. Austin, as you know, and I wrote a book uh called Brainwash. It's right there on top. And we define in this book something called disconnection syndrome at a microscopic level. And we talked about that how the brain gets disconnected from its prefrontal cortex. Our gift as humans and on a macroscopic level how disconnected we're becoming from each other. There's personal benefit. We talked about that through oxytocin. But we've got to reconnect with each other. We got to reconnect with the planet. And we're all in this together. That would be I think my most important message.好吧，你确实非常擅长传递深刻的信息。我是说，你已经写了这么多精彩的著作。你最新的这本书叫《Brain Defenders》，我想是在我生日后的一天，也就是8月27日出版的。我会在下方附上链接。《Brain Defenders: Harness the power of your immune cells to protect your brain for life》。我知道我的许多听众都格外渴望远离痴呆症和阿尔茨海默病，因为他们的家族中有此类病史。他们亲眼目睹了这种疾病带来的可怕后果。而这是一本极好的书，能让人正如你所描述的那样，重新夺回一些主动权，让人觉得面对这种看似令人无能为力的疾病时，我们其实是有一定控制力的。
英文原文
Well, you certainly are one for a message. I mean, you've written so many incredible books here. Your most recent book called Brain Defenders um is came out I think the day after my birthday, August 27th. I'll link it below. Brain Defenders: Harness the power of your immune cells to protect your brain for life. And I know there's lots of my audience that are especially keen to avoid dementia and Alzheimer's because it runs in their family. Um and they've seen the horrific consequences of of of the disease. And this is a wonderful book to feel to sort of take back a bit of agency as you describe and feel like there is some control over something that feels so helpless.当然。你是一个很好的人，一个非常贴心的人。今天能与你相识并共度这段时光，我真的很感激。
我也同样深感荣幸。你所做的事业太不可思议了。我想，你父亲的生命在你身上得到了延续，也延续在千千万万被你触及并提供帮助的人们身上。你为他们带来了知识，点亮了他们的生活，从而赋予了他们我们所谈到的那种掌控感。我认为，在我们感到绝望的时候，这种掌控感是最为珍贵的。你为这么多人做到的正是这一点：不仅给出了切实可行的行动方案，更带给了大家希望，这真的是一件无比美好的事情。所以，感谢你所做的一切，David医生。
谢谢你，Steven。
英文原文
>> You bet. And um you're a good man. You're a sweetheart. And um I'm sure grateful to to meet you and spend time with you today.I am too. It's wonderful what you've done. you know, the consequence of, I guess, your father is is you and the millions and millions of people that you've reached and helped, given them some information, turned the lights on in their life, which gives them that agency that we describe. And I think agency's most valued at times when we feel hopeless and that's certainly what you've done for so many is give them both actions that they can take, but a sense of hope and that's really truly a wonderful thing. So, thank you for doing that work, Dr. David.
Thank you, Steven.
这太不可思议了。我们确实有一个收尾传统：上一位嘉宾会为下一位嘉宾留下一个问题。
噢，哇。
在完全不知道留给谁的前提下。留给你的问题是……
噢，天哪。
我通常不会让嘉宾直接看到，但这次我要破例一次。这就是留给你的问题。
天哪。这是Mark Cuban留下的，而且我们刚才正好回答了这个问题。
问题是——Mark，为了回答你的问题——“什么会让你情绪激动？”这是一个极好的问题，但我想我们刚才已经回答了。
David医生，非常感谢你。
谢谢。
YouTube现在推出了这种非常强大的全新算法，能基于人工智能和你所有的观看习惯，精准判断出你接下来最想看什么视频。算法显示，眼前这个视频对你来说就是最完美的选择。对此刻收看的每一个人来说，推荐的视频都是不一样的。不妨去看看那个视频，我敢打赌你一定会喜欢它。
英文原文
>> It's incredible. We we do have a closing tradition where the last guest leaves a question for the next.Oh, wow.
Not knowing who they're leaving it for. And the question left for you is
Oh, no.
I usually don't let guests see this, but I'm going to break the tradition in this case. This is the question left for you.
Oh my gosh. So, it's from Mark Hubin and we've answered the question. The question is, Mark, to answer your question, what makes you emotional? It's an excellent question, but uh I think we've answered your question,
Dr. David. Thank you.
Thank you.
YouTube have this new crazy algorithm where they know exactly what video you would like to watch next based on AI and all of your viewing behavior. And the algorithm says that this video is the perfect video for you. It's different for everybody looking right now. Check this video out and I bet you you might love it.