Placeholder Image

字幕表 動画を再生する

  • Thanks, Brian.

  • I am at the National Institute on Aging, and as many of you know--

  • people are getting older, and there have been

  • advances in cancer research, cardiovascular disease research--

  • many people who would have died in their 50s and 60s from those diseases

  • are living into the danger zone for Alzheimer's and Parkinson's diseases.

  • It's projected that by 2050, the number of people

  • with Alzheimer's disease will triple from what it is today.

  • It's 5 million today, it'll be 15 million by 2050.

  • In my lab, we use a number of different animal models

  • that are relevant to age-related neurodegenerative disorders.

  • We have mice that accumulate amyloid in their brain as they get older,

  • and they have learning and memory problems.

  • We have mice that have damage to dopamine producing neurons,

  • that control body movements-- that's Mylo-Parkinson's disease.

  • And we also have models of stroke, which is again another major-rate problem

  • and cause of death.

  • Well, it has been known for a long time that one way to extend

  • the life span of laboratory animals is simply to reduce their energy intake.

  • And, in rats and mice one can increase their life span by 30 or 40%.

  • We started looking at the effects of energy restriction on the brain

  • in the context of age-related neurodegenerative disorders,

  • and found that we could slow down, for example,

  • the abnormal accumulation of amyloid, or the degeneration of dopamine neurons

  • in the Alzheimer's and Parkinson's myel by reducing energy intake.

  • Now, there's a number of ways you can reduce energy intake.

  • You can simply eat less at each meal,

  • or you can do what we call intermittent fasting.

  • So, reduce the frequency of the meals.

  • And, what I am going to tell you today

  • is that fasting does good things for the brain.

  • In the animals we have insight into a lot of the neurochemical changes

  • that are occurring in the brain that we think explain

  • why fasting is good for the brain.

  • But I am going to start out

  • and talk a little bit about anecdotal evidence

  • that fasting is good for the brain,

  • and also evolutionary prospective

  • on why fasting might be good for the brain.

  • OK. So everybody knows that in certain religions

  • people will fast periodically.

  • Down through history

  • many famous people with good brains

  • have fasted regularly.

  • Up on the top here is a quote from Plato,

  • he fasted for greater physical and mental efficiency.

  • There are some quotes there,

  • including one from about 6,000 years ago,

  • an Egyptian pyramid inscription that says,

  • "Humans live on one-quarter of what they eat;

  • on the other three-quarters live their doctors."

  • And in this country, as you know, being overweight is a big problem.

  • It's not only a risk factor for cardiovascular disease and diabetes,

  • certain cancers, but emerging evidence suggests

  • that it's also a risk factor for age-related cognitive impairment,

  • and possibly Alzheimer's disease.

  • In the lower right, there is a reference to a book

  • written over a hundred years ago by Upton Sinclair.

  • Many of you may know Upton Sinclair is the author of "The Jungle",

  • a book on meatpacking industry, but he also wrote and published the book

  • that you can find in the full text online, it's called "The Fasting Cure".

  • In that book he interviewes 250 people who had some ailment

  • and went on fast for various lengths of time,

  • and except in a handful of cases,

  • their health condition improved.

  • OK, before I focus on the brain, which will be the main part of my talk,

  • I just want to point out

  • that there is evidence not just from animals,

  • but from humans that fasting is good for the body.

  • It will reduce inflammation,

  • it will reduce oxidative stress in organ systems throughout the body,

  • and one thing that happens when you fast, that does not happen

  • when you eat three meals a day, is that your energy metabolism shifts

  • so that you start burning fats.

  • Every time you eat a meal the energy goes into your liver

  • and it's stored in the form of glycogen--

  • and it's always tapped into first.

  • And it takes about 10 to 12 hours before you deplete the glycogen stores

  • in your liver.

  • So, if you eat three meals a day you never deplete the glycogen stores

  • in your liver, although if you exercise you can.

  • And once you deplete the glycogen stores in your liver

  • then you start burning fats,

  • and you produce what are called ketone bodies.

  • It turns out ketone bodies are very good for your brain,

  • and I'll talk about that in a minute.

  • Now, we've done a lot of work on animals

  • in the 90s, between 15 and 20 years ago,

  • showing that intermittent fasting was good for the brain,

  • then we started collaborating with some investigators,

  • did some human studies looking at effects on the body,

  • some that were shown on the last slide.

  • And then a producer at the BBC named Michael Mosley

  • made a program on intermittent fasting that was aired on the BBC,

  • it's been aired on PBS.

  • He wrote a book called "The Fast Diet".

  • And just in the last two years there's been a flurry of books

  • on intermittent fasting for health,

  • and it's becoming what, I think-- some people may think it's a fad,

  • but hopefully people find some of these--

  • What do I mean by intermittent fasting, and intermittent energy restriction?

  • There's a lot of variations, that there've been on used on this.

  • One sort-- a harsh one is every other day only eat 500 calories.

  • And in our human studies we've been doing what's called the 5:2 diet,

  • where 2 days a week you only eat 500 calories,

  • the other 5 days you eat normally.

  • Eat healthy if you can.

  • In this book called "The 8-Hour Diet" there's evidence that if you restrict

  • the time window that you eat each day to 8 hours or less,

  • it'll have health benefits,

  • again, that's long enough to shift the energy metabolism.

  • OK, why does fasting bolster brain power?

  • During development of your brain, but also in the adult,

  • neurons are generated from stem cells.

  • They grow out their axons and dendrites, they form connections with each other,

  • synapses, and communicate with each other.

  • During aging, many people-- their brain ages successfully,

  • they stay cognitively intact,

  • whereas, unfortunately, others develop diseases.

  • We think the reason, the main take-home message of this talk,

  • is fasting is a challenge to your brain,

  • and your brain responds to that challenge

  • of not having food by activating adaptive stress response pathways

  • that help your brain cope with stress, and resist disease.

  • Does this make sense in evolutionary terms?

  • Anything we talk about in biology, we always have to ask the question,

  • "Why is it that way?

  • Why when we take animals and put them on an intermittent fasting diet,

  • are their neurons protected, in mice, of Alzheimer's and Parkinson's disease?

  • Why do they perform better when we test their learning and memory?"

  • It amazes.

  • Well, if you're hungry and haven't found food,

  • you better figure out how to find food.

  • You don't want your brain to shut down if you're hungry.

  • And, in fact, that's what we find in the animals:

  • Nerve cell circuits are more active.

  • Some of the changes in the brain that occur with intermittent fasting

  • also occur with vigorous exercise.

  • Now, most people, and Jeff this morning gave a nice talk

  • on showing the benefits of exercise on him.

  • I think you probably found that it benefited your brain too? OK.

  • So, when we start looking at

  • what are the neurochemical changes in the brain with intermittent fasting.

  • They are very similar to exercise.

  • Now on this slide, in the upper left picture,

  • the third boy on the right running, that's my son, he is in the audience.

  • You can tell by the faces of the 3 kids-- they are in a cross-country race,

  • that's a challenge, right?

  • They are probably saying to themselves during the race--

  • I used to run races myself, I still occasionally do--

  • "Why am I doing this?"

  • However, when they get done with the race, they feel great, and they feel relaxed.

  • During the cross-country season my wife and I--

  • It's very obvious our son's mood was better.

  • On the right, my daughter is in the white.

  • Her mood was better during cross-country season.

  • Why is that?

  • Exercise and intermittent fasting both increase the production of proteins

  • in the brain that are called neurotrophic factors.

  • We discovered this many years ago, back when I was a postdoc

  • in Colorado in 1980s.

  • We found that these neurotrophic factors, such as FGF, and one called BDNF,

  • brain-derived neurotrophic factor, promote the growth of neurons,

  • promote the connection of neurons, and the strengthening in synapses.

  • OK, so here is the idea:

  • Challenges to you brain, whether it's intermittent fasting,

  • vigorous exercise, or what we are doing now,

  • hopefully if you haven't fallen asleep, is cognitive challenges.

  • When this happens, neurocircuits are activated,

  • levels of neurotrophic factors such as BDNF increase.

  • That promotes the growth of the neurons,

  • the formation and strengthening of synapses.

  • Also shown in the lower left, it turns out both,

  • exercise and intermittent fasting, and using your neurons, using your brain

  • can increase the production of new nerve cells from stem cells,

  • at least in one region of your brain, called the hippocampus,

  • which is shown here.

  • I mentioned ketones, which come from burning fat,

  • and that happens during fasting.

  • The Romans discovered ketones even though they had no idea,

  • they haven't taken any chemistry course, or didn't know what it was.

  • People with epileptic seizures back then,

  • they thought they were possessed by demons.

  • And they found if they take these people and shut them in a room,

  • and don't feed them, the demons will go away.

  • What's happening is:

  • ketones go up, and it's well known that ketons suppress seizures,

  • and in fact, ketogenic diets are used to treat, even today,

  • patients with severe epilepsy.

  • We are doing my work in my lab

  • trying to understand why ketones are good for neurons.

  • One reason is they provide an alternative fuel for the neurons,

  • they boost the energy levels in the neurons.

  • Recently we discovered that fasting,

  • by increasing BDNF levels in the brain, as a neurotrophic factor,

  • can increase the number of mitochondria

  • in your nerve cells.

  • And I am not going to go into details of this slide,

  • but the mechanism is very similar to the mechanism

  • where by exercising your muscles increases the number of mitochondria

  • in your muscles.

  • The fasting is a mild energetic stress, and the neurons respond adaptively

  • by increasing mitochondria, which helps them produce more energy,

  • and in this paper cited down here, "Nature Communications",

  • we recently showed that

  • by increasing the number of mitochondria in neurons,

  • it can increase the ability of the neurons to form and maintain synapses,

  • and thereby increase learning and memory ability.

  • In addition to the increasing neurotrophic factors

  • and increasing neuronal bioenergetics,

  • we've found that intermittent fasting

  • will enhance the ability of your nerve cells to repair DNA,

  • so right now-- and also probably exercise,

  • and also intellectual challenges.

  • And again, what's happening in this case when you are using your neurons,

  • exercising your neurons,

  • it causes a mild oxidative stress,

  • and at the same time that there is increased oxidative stress

  • the cells are enhancing their ability to repair oxidative damage to DNA.

  • Why is it that the normal diet is three meals a day plus snacks?

  • It isn't that it's the healthiest way, eating pattern,

  • and that's my opinion, but I think there's a lot of evidence to support that.

  • There are a lot of pressures to have that eating pattern.

  • There's a lot of money involved.

  • The food industry, are they going to make money

  • from skipping breakfast like I did today?

  • No, they are going to lose money.

  • If people fast the food industry loses money.

  • What about the pharmaceutical industries?

  • What if people do some intermittent fasting,

  • and exercise periodically, and they are very healthy?

  • Is the pharmaceutical industry going to make any money on healthy people?

  • So, one challenge for a society,

  • and this is one of the purposes of these TED Talks, hopefully,

  • is that communication is the way to improve health.

  • People understanding what they can do to improve their health

  • and then taking action, like Jeff talked about

  • in his own talk this morning.

  • So, I would urge you to communicate, and spread the word

  • that there are ways for people to be healthy,

  • and maybe we can do this even with--

  • Of course, I am working for NIH, and one thing about NIH is

  • we are using your tax payer's money to try to help your health.

  • We don't have a profit motive.

  • So, really one of the main reasons I've got interested

  • in things like intermittent fasting, exercise,

  • trying to understand at the cellular molecular level,

  • what's happening in the brain.

    <