back to indexDr. David Sinclair: The Biology of Slowing & Reversing Aging | Huberman Lab Podcast #52
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Welcome to the Huberman Lab Podcast,
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where we discuss science and science-based tools
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for everyday life.
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I'm Andrew Huberman,
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and I'm a professor of neurobiology and ophthalmology
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at Stanford School of Medicine.
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Today, my guest is Dr. David Sinclair,
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professor of genetics at Harvard Medical School
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and co-director of the Paul F. Glenn Center
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for the Biology of Aging.
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Dr. Sinclair's work is focused on why we age
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and how to slow or reverse the effects of aging
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by focusing on the cellular and molecular pathways
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that exist in all cells of the body
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and that progress those cells over time
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from young cells to old cells.
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By elucidating the biology of cellular maturation and aging,
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Dr. Sinclair's group has figured out intervention points
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by which any of us, indeed all of us,
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can slow or reverse the effects of aging.
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What is unique about his work
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is that it focuses on behavioral interventions,
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nutritional interventions,
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as well as supplementation and prescription drug
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interventions that can help us all age more slowly
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and reverse the effects of aging in all tissues of the body.
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Dr. Sinclair holds a unique and revolutionary view
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of the aging process,
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which is that aging is not the normal and natural consequence
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that we all will suffer,
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but rather that aging is a disease
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that can be slowed or halted.
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Dr. Sinclair continually publishes
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original research articles
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in the most prestigious and competitive scientific journals.
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In addition to that,
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he's published a popular book
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that was a New York Times bestseller.
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The title of that book is a lifespan,
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why we age and why we don't have to.
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He is also very active in public facing efforts
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to educate people on the biology of aging
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and slowing the aging process.
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Dr. Sinclair and I share a mutual interest and excitement
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in public education about science.
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And so I'm thrilled to share with you that we've partnered
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and Dr. David Sinclair is going to be launching
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the lifespan podcast,
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which is all about the biology of aging
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and tools to intervene in the aging process.
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That podcast will launch Wednesday, January 5th.
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You can find it at the link in the show notes
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to this episode today as well.
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You can subscribe to that podcast on YouTube,
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Apple or Spotify or anywhere that you get your podcasts.
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Again, the lifespan podcast featuring Dr. David Sinclair
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begins Wednesday, January 5th, 2022.
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Be sure to check it out.
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You're going to learn a tremendous amount of information
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and you're going to learn both the mechanistic science
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behind aging, the mechanistic science
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behind reversing the aging process
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and practical tools that you can apply
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in your everyday life.
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In today's episode, Dr. Sinclair and I talk about
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the biology of aging and tools to intervene in that process.
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And so you might view today's episode
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as a primer for the lifespan podcast
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because we delve deep into the behavioral tools,
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nutritional aspects, supplementation aspects
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of the biology of aging.
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We also talk about David's important discoveries
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of the sirtuins, particular molecular components
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that influence what is called the epigenome.
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And if you don't know what the epigenome is,
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you will soon learn in today's episode.
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Coming away from today's episode,
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you will have in-depth knowledge about the biology of aging
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at the cellular, molecular and what we call
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the circuit level, meaning how the different organs
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and tissues of the bodies age independently
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and how they influence the aging of each other.
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Today's episode gets into discussion
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about many aspects of aging and tools to combat aging
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that have not been discussed on any other podcasts
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or in the book lifespan.
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Before we begin, I'd like to emphasize that this podcast
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is separate from my teaching and research roles at Stanford.
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It is however, part of my desire and effort
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to bring zero cost to consumer information about science
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and science related tools to the general public.
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In keeping with that theme,
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I'd like to thank the sponsors of today's podcast.
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Our first sponsor is Roca.
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Roca makes eyeglasses and sunglasses
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that are the absolute highest quality.
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I've spent a lifetime working on the visual system.
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I can tell you that the visual system has to contend
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with a number of different challenges,
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such as when you move from a bright area outside
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to an area where there are shadows,
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you have to adjust a number of things in your visual system
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so that you can still see things clearly.
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One problem with a lot of eyeglasses and sunglasses
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is they don't take that biological feature into account
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and you have to take off your glasses and put them back on
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Today's episode is also brought to us by Inside Tracker.
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Inside Tracker is a personalized nutrition platform
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that analyzes data from your blood and DNA
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And now with the advent of modern DNA tests,
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Today's episode is also brought to us by Magic Spoon.
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Magic Spoon is a zero sugar, grain-free,
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keto-friendly cereal.
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I don't follow a strictly ketogenic diet.
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What works best for me is to eat according to my desire
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to be alert at certain times of day
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and to be sleepy at other times of day.
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So for me, that means fasting until about 11 a.m.
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or 12 noon most days.
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And then my lunch is typically a low carb, keto-ish lunch,
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maybe a small piece of grass-fed meat,
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some salad, something of that sort.
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And then in the afternoon,
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I might have a snack that's also keto-ish.
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And then at night is when I eat my carbohydrates,
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which for me helps me with the transition to sleep
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and allows me to get great deep sleep.
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That's what works for me.
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What that means is that in the afternoon,
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I'm craving a snack and the snack for me is Magic Spoon.
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What I do lately is I put in some Bulgarian yogurt.
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Sometimes I just eat it straight.
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And as I mentioned before,
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I lately mix it with yogurt, put a little cinnamon on there.
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I'm getting hungry just talking about it now.
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Again, that's magicspoon.com slash Huberman
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and use the code Huberman to get $5 off.
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And now my conversation with Dr. David Sinclair.
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Thank you for coming.
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Thanks for having me here.
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It's good to see you.
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This is Mate, by the way, that we're toasting at 11 AM.
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Unlike other podcasts, well, I don't drink alcohol,
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so I'm boring that way.
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But truly, thanks for being here.
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I have a ton of questions for you.
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We go way back in some sense,
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but that doesn't mean that I don't have many,
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many questions about aging, longevity, lifespan,
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actionable protocols to increase how long we live, et cetera.
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And I just want to start off with a very simple question
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that I'm not even sure there's an answer to,
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but what is the difference between longevity,
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anti-aging and aging as a disease?
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Because I associate you with the statement,
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aging is a disease.
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Right, well, so longevity is the more academic way
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we describe what we research.
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Anti-aging is kind of the same thing,
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but it's got a bad rap because it's been used
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by a whole bunch of people
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that don't know what they're talking about.
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So I really don't like that term anti-aging,
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but aging as a disease and longevity
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are perfectly valid ways to talk about this subject.
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So let's talk about aging as a disease.
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When I started my research,
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disease here at Harvard Medical School,
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it was considered if there's something
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that's wrong with you and it's a rare thing,
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has to be less than 50% of the population,
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that's definitely a disease.
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And then people work their whole lives
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to try and cure that condition.
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And so I looked up what's the definition of aging
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and it says, well, it's a deterioration
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and in health and sickness and you can die from it,
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Something that sounds pretty much like a disease,
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but the caveat is that if more than half the population
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gets this condition, aging,
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it's put in a different bucket,
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which is first of all, that's outrageous
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because it's just a totally arbitrary cutoff.
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But think about this,
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that we're ignoring the major cause of all these diseases.
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Aging is 80 to 90% the cause of heart disease, Alzheimer's.
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If we didn't get old and our bodies stayed youthful,
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we would not get those diseases.
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And actually what we're showing in my labels,
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if you turn the clock back in tissues,
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those diseases go away.
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So aging is the problem.
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And instead through most of the last 200 years,
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we've been sticking band-aids on diseases
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that have already occurred because of aging
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and then it's too late.
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So there are a couple of things.
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One is we want to slow aging down
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so we don't get those diseases.
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And when they do occur, don't just stick a band-aid on,
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reverse the age of the body
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and then the diseases will go away.
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That clarifies a lot for me, thank you.
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Can we point to one specific general phenomenon in the body
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that underlies aging?
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Yeah, well, that's contentious
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because scientists like to come up with new hypotheses.
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It's how they build their careers.
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But fortunately during the 2000s,
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we settled on eight or nine major causes of aging.
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We called them hallmarks
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because causes was a little bit too strong.
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But these eight or nine causes,
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at least for the first time,
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allowed us to come around and talk together.
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We put them on a pizza
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so everyone got an equal weighting, equal slices.
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But before that, by the way,
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we were trying to kill each other in the field.
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Interesting that you guys work on aging
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and you're trying to kill each other.
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Well, kill each other's careers.
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I mean, I like to think I was fairly generous,
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but I was one of the kids
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and the old guard really didn't like the new guard.
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We just came along in the 1990s and 90s
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and said free radicals don't do much.
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There were actually genes called longevity genes
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and that caused a whole ruckus.
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And there was this competition for what never happened,
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which was a Nobel Prize for this.
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And it just led to a lot of competition.
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I would go to meetings
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and people would shout at each other and backstab.
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But then fortunately in the 2000s,
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we rallied around this new map of aging
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with these causes or hallmarks.
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But I think that there's one slice of the pizza
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that is way larger than the others.
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And we can get to that,
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but that's the information in the cell
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that we call the epigenome.
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Well, tell us a little bit more about the epigenome.
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Frame it for us, if you will.
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And then we'll get into ways
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that one can adjust the epigenome in positive ways.
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Yeah, so in science, what I like to do,
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I'm a reductionist, is to boil it down.
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And I actually ended up boiling aging down to an equation,
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which is the loss of information due to entropy.
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It's a hard thing to overcome
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the second law of thermodynamics, that's fair.
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But this equation really represents the fact
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that I think aging is a loss of information
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in the same way that when you Xerox something
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a thousand times, you'll lose that information,
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or you try to copy a cassette tape,
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or even if you send information across the internet,
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some of it will get lost.
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That's what I think is aging.
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And there are two types of information in the body.
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There is the genetic information, which is digital,
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ATCG, the chemical letters of DNA.
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But there's this other part of the information in the body
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that's just as important.
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It's essential, in fact.
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And that's the systems that control
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which genes are switched on and off,
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in what cell, at what time,
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in response to what we eat, et cetera.
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And it turns out that 80% of our future longevity
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and health is controlled by this second part,
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the epigenetic information, the control systems.
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I liken the DNA to the music that's on a DVD
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or a compact disc.
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For the younger people, we used to use these things.
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And then the epigenome is the reader that says,
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okay, in this cell, we need to play that set of songs.
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And in this other cell,
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we have to play a different set of songs.
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But over time, aging is the equivalent
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of scratching the CD and the DVD
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so that you're not playing the right songs.
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And cells, when they don't hear the right songs,
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they get messed up and they don't function well.
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And that is what I'm saying is the main driver of aging.
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And these other hallmarks
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are largely manifestations of that process.
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Can we go a little deeper into what these scratches are?
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Is it the way that the DNA are packed into a cell?
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Is it the way that they're spaced?
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What are the scratches that you're referring to?
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So DNA is six foot long.
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If you join your chromosomes together,
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you get about six foot per cell.
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So there's enough to go to the moon
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and back eight times in your body.
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And it has to be wrapped up to exist inside us.
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But it's not just wrapped up willy-nilly.
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It's not just a bundle of string.
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It's wrapped up very carefully in ways
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that dictates which genes are switched on and off.
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And when we're developing in the embryo,
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the cell marks the DNA with chemicals that says,
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okay, this gene is for a nerve cell.
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You, you cell, will stay a nerve cell
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for the next hundred years, if you're lucky.
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Don't turn into a skin cell.
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That would be bad.
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And those chemicals,
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there are many different types of chemicals,
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but one's called methylation.
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Those little methyls will mark which songs get played
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for the rest of your life.
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And there are other marks that change daily.
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But in total, what we're saying is that
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the body controls the genome through the ability
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to mark the DNA and then compact some parts of it,
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silence those genes, don't read those genes,
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and open others, keep others open that should stay open.
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And that pattern of genes that are silent and open,
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silent open, is what dictates the cell's type,
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the cell's function.
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And then the scratches are the disruption of that.
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So genes that were once silent,
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and you could say it's a gene that is involved in skin,
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it's starting to come on in the brain,
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shouldn't be there, but we see this happen,
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and vice versa, the gene might get shut off
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over time during aging.
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Cells over time lose these structures,
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lose their identity,
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they forget what they're supposed to do,
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and we get diseases.
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We call that aging, and we can measure that.
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In fact, we can measure it in such a way
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that we can predict when somebody's going to die
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based on the changes in those chemicals.
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Are these changes the same sorts of changes
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that underlie the outward body surface manifestations
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of aging that most of us are familiar with?
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Graying of the hair, wrinkling of the skin,
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drooping of the face.
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Walking around New York lately, it's amazing to me,
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there are certain people that seem to walk
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looking down at the sidewalk
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because their spine is essentially in a C-shape, right?
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A hallmark, if you will,
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of aging that most of us are familiar with.
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Are these same sorts of DNA scratches associated with that,
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or are we talking about people
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that potentially are going to look older,
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but simply live longer?
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Well, it's actually, you are as old as you look
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if you want to generalize.
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So let's start with centenarian families.
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These are families that tend to live over 100.
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When they're 70, they still look 50 or less.
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So it is a good indicator.
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It's not perfect because you can,
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like me, grow up in Australia
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and accelerate the aging of your skin,
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but in general, how you look.
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No one's ever died from gray hair,
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but overall, you can get a sense
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just from the ability of skin to hold itself up,
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how thin it is, the number of wrinkles.
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That is actually, a great paper just came out
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that said that an AI system looking at the face
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could very accurately predict someone's age.
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So I started off in developmental neurobiology.
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So one of the things that I learned early on
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that I still believe wholeheartedly
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is that development doesn't stop at age 12 or 15,
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or even 25, that your entire life
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is one long developmental arc, right?
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So in thinking about different portions
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of that developmental arc,
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the early portion of infancy and especially puberty
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seem like especially rapid stages of aging.
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And I know we normally look at babies and children
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and kids in puberty and we think,
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oh, they're so vital, they're so young.
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And yet the way you describe these changes in the epigenome
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and the way you have framed aging as a disease
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leads me to ask, are periods of immense vitality,
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the same periods when we're aging faster?
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Yes, yes, and this is something I've never talked about,
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at least not publicly, so this is a really good question.
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So those chemicals we can measure,
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it's also known as the Horvath clock,
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it's the biological clock,
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it's separate from your chronological age.
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So actually what I didn't mention is that
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when the AI looked at the faces of those people,
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they could predict their biological age, their internal age.
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So your skin represents the age of your organs as well.
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And the people that look after themselves,
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we can talk about how to do that later,
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but there are some people that are 10, 20 years younger
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than other people biologically.
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And it turns out if you measure that clock from birth
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or even before birth, if you look at animals,
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there's a massive increase in age
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based on that clock early in life.
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So you're right, so that's a really important point
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that you have accelerated aging
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during the first few years of life,
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and then it goes linear towards the rest of your life.
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But there's another interesting thing you brought up,
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which is that we're finding that the genes
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that get messed up, that get scratched,
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that are leading to aging
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are those early developmental genes.
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They come on late in life and just mess up the system,
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and they seem to be particularly susceptible
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to those scratches.
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So what's causing the scratches?
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Well, we know of a couple of things in my lab,
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we figured out one is broken chromosomes, DNA damage,
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particularly cuts to the DNA breaks.
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So if you have an X-ray or a cosmic ray,
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or even if you go out in the sun
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and you'll get your broken chromosomes,
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that accelerates the unwinding
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of those beautiful DNA loops that I mentioned.
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We can actually do this to a mouse.
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We can accelerate that process,
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and we get an old mouse, 50% older,
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and it has this bent spine kyphosis,
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it has gray hair, its organs are old.
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So we now can control aging in the forwards direction.
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The other thing that accelerates aging
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is massive cell damage or stress.
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So we pinched nerves,
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and we saw that their aging process
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was accelerated as well.
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Yeah, this is more of an anecdotal phenomenon.
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It is an anecdotal phenomenon,
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but this experience of in junior high school,
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you know, going home for a summer and you come back,
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high school in the US usually starts eighth or ninth grade
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or grade eight or grade nine for your Canadians.
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And then some of the kids,
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like they grew beards over the summer,
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or they completely matured quickly over the summer.
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Do you think there's any reason to believe
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that rates of entry into and through puberty
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can predict overall rates of aging?
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In other words, if a kid is a slow burner, right?
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They basically acquire the traits of puberty
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slowly over many years.
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Can we make some course prediction
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that they are going to live a long time
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versus a kid that goes home for the summer
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and comes back a completely different organism
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or appearing to be a completely different organism?
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Like they basically age very quickly in the summer.
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Does that mean they're aging very quickly overall?
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Well, yeah, I don't want to scare anybody.
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There are studies that show that
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the slower you take to develop,
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it also is predictive of having a longer, healthier life.
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And it may have something to do with growth hormone.
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We know that growth hormone is pro-aging.
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Anyone who's taking growth hormone, pay attention.
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We notice, look at someone who's taking growth hormone.
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They often will acquire these characteristics of vitality,
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like improved smoothness of skin,
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but their whole body shape changes.
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Yeah, I mean, you'll feel better for a short amount of time.
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You'll build up muscle, you'll feel great,
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but it's like burning your candle at both ends.
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Ultimately, if you want to live longer,
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you want less of that.
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And the animals that have been generated
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and mutants that have low growth hormone,
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sometimes these are dwarfs,
link |
they live the longest by far.
link |
A guy in my lab, Michael Bonkowski,
link |
he had the longest lived mouse.
link |
A mouse typically lives about two and a bit years.
link |
He had a mouse that lived five years
link |
and he gave it caloric restrictions for fasting
link |
combined with one of these dwarf mutations,
link |
low growth hormone.
link |
I think he called it Yoda.
link |
But you look at who lives the longest,
link |
it's the really small people.
link |
This is a bit anecdotal,
link |
but it sounds like it might be true
link |
is that the people who played the Munchkins
link |
in the Wizard of Oz,
link |
many of them went on to live into their 90s and beyond.
link |
Oh, there are some Laurent dwarfs as well.
link |
There are dwarf mutations in South America
link |
and they seem to be protected
link |
against many of the diseases of aging.
link |
You barely ever see heart disease
link |
or cancer in these families.
link |
So I, having owned a very large dog breed,
link |
a Bulldog Mastiff who lived a long life
link |
for a bulldog, 11 years,
link |
but there are many dogs that will live 12, 16 years
link |
that are smaller dogs.
link |
Can we say that there's a direct relationship
link |
between body size and longevity
link |
or duration of life?
link |
but that doesn't mean that you're a slave
link |
to your early epigenome,
link |
nor to your genome.
link |
The good news is that the epigenome can change.
link |
Those loops and structures can be modified
link |
by how you live your life.
link |
And so if you're born tall and I wasn't,
link |
and I wished at the time I did grow,
link |
but no matter what size you are,
link |
you can have a bigger impact on your life
link |
than anything your genes give you.
link |
80% is epigenetic, not genetic.
link |
So let's talk about some of the things that people can do.
link |
And I've kind of batched these into categories
link |
rather than just diving right into actionable protocols.
link |
So the first one relates to food, blood sugar, insulin.
link |
This is something I hear a lot about
link |
that fasting is good for us,
link |
but rarely do I hear why it's good for us.
link |
One of the reasons I'm excited to talk to you today
link |
is because I want to drill into the details of this,
link |
because I think understanding the mechanism
link |
will allow people to make better choices
link |
and not simply to just decide
link |
whether or not they're going to fast or not fast
link |
or how long they're going to fast,
link |
I think should be dictated
link |
by some understanding of the mechanism.
link |
So why is it that having elevated blood sugar,
link |
glucose, and insulin ages us more quickly?
link |
And or why is it that having periods of time each day
link |
or perhaps longer can extend our lifespan?
link |
Well, let's start with what I think was a big mistake
link |
was the idea that people should never be hungry.
link |
We live in a world now
link |
where there's at least three meals a day,
link |
and then we've got companies selling bars
link |
and snacks in between.
link |
So the feeling of hunger,
link |
some people never experience hunger in their whole lives.
link |
It's really, really bad for them.
link |
It was based, I believe, on the 20th century view
link |
that you don't want to stress out the pancreas
link |
and you try to keep insulin levels pretty steady
link |
and not have this fluctuation.
link |
What we actually found, my colleagues and I,
link |
across this field of longevity
link |
is that when you look at, first of all, animals,
link |
whether it's a dog or a mouse or a monkey,
link |
the ones that live the longest, by far, 30% longer
link |
and stay healthy are the ones that don't eat all the time.
link |
It actually was first discovered
link |
back in the early 20th century, but people ignored it.
link |
And then it was rediscovered in the 1930s.
link |
Clive McKay did caloric restriction.
link |
He put cellulose in the food of rats
link |
so they couldn't get as many calories even though they ate,
link |
and those rats lived 30% longer.
link |
But then it went away, and then it came back in the 2000s
link |
in a big way when a couple of things happened.
link |
One is that my lab and others showed
link |
that there are longevity genes in the body
link |
that come on and protect us from aging and disease.
link |
The group of genes that I work on are called sirtuins.
link |
There's seven of them.
link |
And we showed in 2005 in a science paper
link |
that if you have low levels of insulin
link |
and another molecule called insulin-like growth factor,
link |
those low levels turn on the longevity genes.
link |
One of them that's really important is called SIRT1.
link |
But by having high levels of insulin all day,
link |
being fed means your longevity genes are not switched on.
link |
So you're falling apart.
link |
Your epigenome, your information
link |
that keeps your cells functioning over time
link |
just degrades quickly.
link |
Your clock is ticking faster by always being fed.
link |
The other thing that I think might be happening
link |
by always having food around
link |
is that it's not allowing the cell to have periods of rest
link |
and reestablish the epigenome.
link |
And so it also is accelerating in that direction.
link |
There's plenty of other reasons as well
link |
that are not as profound,
link |
such as having low levels of glucose in your body
link |
will trigger your major muscles in your brain
link |
to become more sensitive to insulin
link |
and suck the glucose out of your bloodstream,
link |
which is very good.
link |
You don't want to have glucose flowing around too much.
link |
And that will ward off type 2 diabetes.
link |
So hunger, of course, is associated with low blood glucose
link |
Do you think there's anything
link |
about the subjective experience of hunger itself
link |
that could be beneficial for longevity?
link |
Though you get used to the feeling of not eating.
link |
So I'm kind of screwed that way.
link |
It's like cold water.
link |
You eventually adapt.
link |
You get used to it, unfortunately.
link |
But there are some studies that are being done
link |
at the National Institutes of Health
link |
that are able to simulate the effect of hunger,
link |
but still provide the calories.
link |
And it's looking like there's a small component
link |
that's due to hunger.
link |
But most of it, actually,
link |
is because you've got these periods of not being fed
link |
and then the body turns on these defensive genes.
link |
There's a really interesting experiment
link |
that was published maybe a couple of years ago
link |
by Rafael de Carbo down at the NIH.
link |
What he did was he took over 10,000 mice
link |
and gave them different combinations
link |
of fat, carbohydrate, protein.
link |
And he was trying to figure out what was the best combination.
link |
And then he also cleverly had a group,
link |
well, two groups, one that was fed all the time,
link |
or ate as much as they wanted,
link |
and the other group was only given food for an hour a day.
link |
And it turns out they ate
link |
roughly the same amount of calories.
link |
Because, of course, in an hour,
link |
they're stuffing their faces.
link |
It turns out it didn't matter what diet he gave them.
link |
It was only the group that ate within that window
link |
that lived longer and dramatically longer.
link |
So my conclusion is,
link |
and mice are very similar to us metabolically,
link |
I think that tells us that it's not as important
link |
what you eat, it's when you eat during the day.
link |
What is the protocol that people can extrapolate from that?
link |
Or maybe I should just ask you,
link |
what is your protocol for when to eat
link |
and when to avoid food?
link |
Do you fast, do you ever fast longer than 24 hours?
link |
And what do you think is a good jumping off place
link |
if people want to explore this as a protocol?
link |
Well, if there's one thing I could say,
link |
if I would say definitely try to skip a meal a day,
link |
that's the best thing.
link |
Does it matter which meal?
link |
Or are they essentially equivalent?
link |
Well, as long as it's at the end
link |
or the beginning of the day,
link |
because then you add that to the sleep period
link |
where you're hopefully not eating.
link |
I think that that's an excellent point.
link |
I realize it's a simple one,
link |
but I think it's an excellent one
link |
because I think one of the things
link |
that people struggle with the most
link |
is knowing when and how to initiate
link |
this so-called intermittent fasting.
link |
And the middle of the day obviously
link |
is not tacked to the sleep cycle in the same way.
link |
So it's much harder as well for many people.
link |
Well, I'll tell you what I do.
link |
I have a tiny bit of yogurt or olive oil
link |
because the supplements I have need to be dissolved in it.
link |
And then I go throughout the whole day
link |
as I'm doing right now here with this glass of water here.
link |
I'm just keeping myself filled with liquids.
link |
And so I don't feel hungry.
link |
Beware that the first two to three weeks
link |
when you try that, you will feel hungry.
link |
And you also have a habit of wanting to chew on something.
link |
There's a lot of physical parts to it,
link |
but try to make it through the first three weeks
link |
and do without breakfast or do without dinner.
link |
And you'll get through it.
link |
And I did that for most of my life actually,
link |
mainly because I wasn't hungry in the morning.
link |
Some people are very hungry in the morning
link |
and they may want to consider skipping dinner instead.
link |
But I will go throughout the whole day.
link |
I don't get the crashes of the high glucose
link |
and the low glucose.
link |
Anyone who goes, oh man, it's three o'clock.
link |
I'm gonna need a sleep.
link |
If you do what I do, you will not experience that anymore.
link |
Because what my body does is it regulates
link |
blood sugar levels naturally.
link |
My liver is putting out glucose when it needs to
link |
and it's very steady and gives me pure focus
link |
throughout the day.
link |
And I don't even have to think about lunch.
link |
I'm just powering through.
link |
At dinner, I love food as much as anybody.
link |
So I will eat a regular, pretty healthy meal.
link |
I'll try to eat mostly vegetables.
link |
I can eat some fish, some shrimp.
link |
I rarely will eat a steak.
link |
In fact, my microbiome is so adapted to my diet.
link |
Now, if I eat a steak, it will not get digested very well.
link |
I'll feel terrible.
link |
If I don't eat a steak, I feel terrible.
link |
Argentine lineage.
link |
Well, we can talk about that.
link |
Well, everybody's different.
link |
I mean, that's the other thing.
link |
What works for me may not be perfect for you.
link |
And we do have to measure things to know what's working.
link |
I rarely eat dessert.
link |
I gave up dessert and sugar when I turned 40.
link |
And occasionally, I'll steal a bit of dessert
link |
because it doesn't hurt if you steal it, right?
link |
But other than that, I avoid sugar,
link |
which includes simple carbohydrates, bread I try to avoid.
link |
I've actually noticed, this is just a side note.
link |
I used to get buildup of plaque pretty easily.
link |
And every time I went to the dentist,
link |
they'd have to scrape it off.
link |
And I even bought tools to scrape it off
link |
because it was driving me nuts.
link |
I don't get plaque anymore.
link |
And I think it's because of my diet.
link |
I don't have those sugars in my mouth
link |
that the bacteria feed on
link |
and then form the biofilm on the teeth.
link |
Much better breath, by the way.
link |
So, do you ever fast longer than this?
link |
It sounds like if you go to bed,
link |
well, you tend to stay up late, I know,
link |
because I get texts from you at like two in the morning,
link |
my time, which means you're out very late
link |
and up early as well.
link |
But assuming that people go to sleep
link |
sometime around 11, 30, or 12, plus or minus an hour,
link |
and wake up sometime around 7 a.m.,
link |
plus or minus 90 minutes,
link |
you're eating more or less on a,
link |
it sounds like some like 20 hours of fasting,
link |
four hours of eating, or 16 hours of fasting,
link |
eight hours of food intake, et cetera.
link |
But do you ever do longer fasts,
link |
like 48 hours or 72 hours or week-long fasts?
link |
Occasionally I do.
link |
So my typical day,
link |
I would only eat within a two-hour window,
link |
just usually I'm either eating out or-
link |
Yeah, yeah, but I love, well-
link |
And if you exercise, do you feel like,
link |
then you just power through and maintain that fasted state?
link |
Absolutely, I can exercise.
link |
And now my body's so used to it,
link |
I don't feel like I need food after exercising.
link |
But have I gone longer?
link |
Yes, but not very often.
link |
I find it quite difficult to go more than 24 hours.
link |
But when I do it, maybe it's once a month,
link |
I'll go for two days.
link |
After two, and actually even better,
link |
if you go for three days without eating,
link |
it kicks in even greater longevity benefits.
link |
So there's a system called the autophagy system,
link |
which digests old and misfolded proteins in the body.
link |
And there's a natural cleansing
link |
that happens when you're hungry.
link |
Macro-autophagy, its name is.
link |
But a good friend of mine, Anna Maria Cuervo
link |
at Albert Einstein College of Medicine,
link |
discovered a deep cleanse called the chaperone-mediated
link |
autophagy, which kicks in day two, day three,
link |
which really gets rid of the deep proteins.
link |
And what excites me is she just put out a big paper
link |
that said, if you trigger this process in an old mouse,
link |
it lives 35% longer.
link |
Yeah, so it's a big deal.
link |
If I could go longer, I would.
link |
But I just find that with my lifestyle,
link |
and I'm going always day 110%, I need to eat
link |
at least once a day, unfortunately.
link |
One more practical question
link |
than a mechanistic question related to this.
link |
The practical question is when you are fasting,
link |
regardless of how long,
link |
I know you're ingesting fluids like water
link |
and presumably some caffeine.
link |
I heard you had several or more espresso today,
link |
which is impressive.
link |
But are you also ingesting electrolytes?
link |
Like I know some people get lightheaded,
link |
they start to feel shaky when they fast,
link |
and that the addition of sodium to their water
link |
or potassium, magnesium is something
link |
that's becoming a little more in vogue now.
link |
Is that something that you do
link |
or that you see a need for people to do?
link |
Well, it makes sense, but I haven't had a need to do it.
link |
So I don't, I just, I drink tea during the day
link |
and coffee when I'm first awake and I don't get the shakes.
link |
So, you know, I don't fix what's not broken.
link |
And I do add things to my protocol
link |
that I think will improve me
link |
and avoid those things, of course, that won't.
link |
But yeah, because I don't have a need for it, I don't try it.
link |
But it does make sense,
link |
especially if you've had a big night the night before,
link |
you probably want to supplement with that.
link |
But I think there's fair amount of good stuff
link |
in tea and coffee as it is.
link |
Okay, so then the mechanistic question is,
link |
you've told us that there's ample evidence
link |
that keeping your blood sugar low for a period of time,
link |
each 24 hours, can help trigger some of these
link |
pro-longevity anti-aging mechanisms
link |
and that extending them out two or three days
link |
can trigger yet additional mechanisms
link |
of gobbling up of dead cells and things of that sort.
link |
How is it that blood glucose triggers these mechanisms?
link |
Because we've said, okay,
link |
remove glucose and things get better.
link |
You've talked before, maybe we could talk more now
link |
about some of the underlying cellular
link |
and genetic mechanisms, things like the sirtuins,
link |
but how are glucose and the sirtuins
link |
actually tethered to one another mechanistically?
link |
Yeah, there's a really good question.
link |
That proves you're a scientist or world leading on.
link |
So what we now know is that these longevity pathways,
link |
we call them, these longevity genes talk to each other.
link |
And we used to say,
link |
oh, my longevity gene's more important than yours.
link |
It was ridiculous, because they're all talking to each other.
link |
You pull one lever and the other one moves.
link |
And the way to think of it is that there are systems set up
link |
to detect what you're eating.
link |
So the sirtuins will mainly respond to sugar and insulin.
link |
And then there's this other system called mTOR,
link |
which is sensing how much protein
link |
or amino acids are coming into your body.
link |
And they talk to each other.
link |
We can pull one and affect the other and vice versa.
link |
But together, when you're fasting,
link |
you'll get the sirtuin activation, which is good for you.
link |
And you'll also, through lack of amino acids,
link |
particularly three of them, leucine, isoleucine, valine,
link |
the body will downregulate mTOR.
link |
And it's that up sirtuin, down mTOR
link |
that is hugely beneficial
link |
and turns on all of the body's defenses,
link |
the chewing up the old proteins,
link |
improving insulin sensitivity, giving us more energy,
link |
repairing cells, all of that.
link |
And so these two pathways,
link |
I think are the most important for longevity.
link |
You mentioned leucine.
link |
Within the resistance training,
link |
slash bodybuilding, slash fitness community,
link |
leucine gets a lot of attention
link |
because there are longstanding debates
link |
about how much protein one needs per day
link |
and how much one can assimilate at each meal.
link |
It makes for many YouTube videos and not much else, frankly.
link |
However, it's clear that because of leucine's effects
link |
on the mTOR pathway, that there are many people,
link |
not just people in these particular fitness communities
link |
that are actively trying to ingest more leucine
link |
on a regular basis
link |
in order to maximize their wellness and fitness
link |
and in some cases muscle growth, but also just wellness.
link |
But what I interpret your last statement to mean
link |
is that leucine, because it triggers cellular growth,
link |
is actually pro-aging in some sense.
link |
Well, it could be.
link |
That's what the evidence suggests.
link |
And again, it goes back to the debate, should you supplement
link |
with growth hormone or testosterone,
link |
all of these activities will give you immediate benefits.
link |
You'll bulk up more, you'll feel better immediately.
link |
But based on the research,
link |
it's at the expense of long-term health.
link |
So my view of longevity, the way I treat my body,
link |
is I don't burn both candles.
link |
I have one end of the candle lit.
link |
I'm very careful, I don't blow on it.
link |
But I also do enough exercise
link |
that I'm building up my muscle, but I'm not huge.
link |
Anyone who's seen me knows
link |
that I'm not a professional bodybuilder.
link |
But I tried to actually, here's the key,
link |
and I haven't said this publicly that I can remember.
link |
I pulse things so that I get periods of fasting
link |
and then I eat, then I take a supplement,
link |
then I fast, then I exercise.
link |
And I'm taking the supplements and eating
link |
in the right timing to allow me
link |
to build up muscle sometimes.
link |
Because you can't just expect to take something constantly
link |
and do something constantly for it to work.
link |
And that's why it's taken me about 15 years
link |
to develop my protocol.
link |
And there's a lot of subtlety to it.
link |
Yeah, it sounds like a very rational protocol.
link |
Does the name Ori Hofmeckler mean anything to you?
link |
Just briefly, I discovered Ori Hofmeckler
link |
about 15 years ago.
link |
He was in Israeli special forces.
link |
He's now got to be close to 70.
link |
Forgive me, Ori, if that number is inflated.
link |
He wrote a book called The Warrior Diet,
link |
which got very little attention at the time.
link |
But what he said was,
link |
when he was in Israeli special forces,
link |
they rarely ate more than once per day
link |
and sometimes once every second or third day.
link |
And this is a guy who maintains
link |
an incredible physical stature.
link |
You know, he's very lean, very strong,
link |
and very vital at, you know,
link |
I wouldn't say an advanced age,
link |
but he's getting up there
link |
and he just seems to be getting better and better.
link |
Ori Hofmeckler was the person
link |
who essentially founded, if you will,
link |
although our ancestors founded, to be completely fair,
link |
the so-called intermittent fasting diet.
link |
He called it The Warrior Diet
link |
and this book didn't get much attention.
link |
But one of the things that you just said
link |
really reminded me of Ori.
link |
I sat down with him.
link |
I actually went to his home and sat down with him
link |
and he said, fasting is wonderful,
link |
but these pulses where you nourish the body
link |
or even slightly overnourish the body,
link |
provided they aren't too frequent,
link |
have a tremendous effect on vitality.
link |
And so I want to use that as kind of a segue
link |
to address this issue of vitality versus longevity,
link |
because here you're telling me,
link |
and certainly the evidence supports that, you know,
link |
growth hormone will make you feel better and younger,
link |
taking testosterone or estrogen, we should probably say.
link |
women who take hormone therapies later in life
link |
who take estrogen,
link |
they experience a strong increase in vitality
link |
if it's done correctly.
link |
But there is an effect of aging the body more rapidly.
link |
It's sort of a second puberty, if you will.
link |
But this idea of restriction and then pulsing,
link |
not necessarily feast and famine,
link |
but certainly famine and feast in lowercase letters,
link |
there really seems to be something about that.
link |
So at a cellular level,
link |
like we kind of go back to mTOR and the sirtuins,
link |
how do you think that the cells might be reacting
link |
to this kind of lowercase feast
link |
and uppercase famine type protocol?
link |
Well, the pulsing, I think,
link |
is what you want to do is to get the cells
link |
to be perceiving adversity, okay?
link |
Because our modern life, we're sitting around,
link |
we're eating too much, we're not exercising,
link |
our cells respond.
link |
They go, hey, everything's cool, no problem.
link |
And they become relaxed
link |
and they don't turn on their defenses and we age rapidly.
link |
We can see it in the clock.
link |
People who exercise and eat less
link |
have a slower ticking clock.
link |
But my protocol is different than most people's
link |
because I am pulsing it.
link |
Now, first of all, let's get to why did I even think
link |
that might be possible?
link |
Because I didn't read the warrior diet.
link |
What I found in my research was that
link |
if we gave resveratrol, this red wine molecule
link |
that became well-known in the 2000s,
link |
if we gave it to mice, their whole lifespan,
link |
they were protected against a high fat diet,
link |
which we call the Western diet.
link |
They had lean organs.
link |
They lived slightly longer, but not a lot.
link |
And if we gave them a high fat diet without resveratrol,
link |
they actually lived a lot shorter.
link |
So resveratrol protected them against the high fat diet.
link |
We gave it to them on a normal diet.
link |
They just ate it when they wanted
link |
and there wasn't much effect.
link |
This is what's not known,
link |
though it's in the supplemental data of the paper
link |
that nobody ever reads.
link |
The mice that were given resveratrol every second day
link |
on a normal diet lived dramatically longer
link |
than any other group.
link |
So people out there, you know, my critics say,
link |
oh, resveratrol didn't extend the lifespan
link |
of mice on a normal diet, therefore it's not aging.
link |
It's just protecting against a high fat diet.
link |
Well, look at the supplemental data, please.
link |
If you give it to the mice every other day,
link |
we had mice living over three years.
link |
Wow, that's a long time.
link |
I have got many, many mice in my ownership
link |
in my lab at Stanford,
link |
and that's a very long life for a mouse.
link |
And so it was a long lifespan extension.
link |
And what that told me is that probably
link |
you don't want to be taking a supplement every day.
link |
You can take it either every other day
link |
or give your body a rest.
link |
And I do the same with my meals.
link |
I rest during the day and then I give a nutritious dinner
link |
to my body and then give it a rest.
link |
Same with exercise.
link |
And then I try to time it because there are times
link |
when I'm taking the drug metformin,
link |
which mimics low energy. For those of you who don't know,
link |
metformin is a drug given to type 2 diabetics
link |
to bring down their blood sugar levels.
link |
But it's been found that looking at tens of thousands
link |
of veterans and others,
link |
that those two type 2 diabetics live longer than people
link |
that don't even get type 2 diabetes.
link |
So it's a longevity drug.
link |
Right now you have to get it from your doctor in the US
link |
and most other countries,
link |
you can just get it over the counter.
link |
And you protect it, it looks like,
link |
based on epidemiological data, cancer, heart disease,
link |
frailty, what else, dementia.
link |
So I take metformin.
link |
You take metformin and your fasting each day.
link |
So when do you take it relative to the fasting?
link |
Yeah, I always take metformin in the morning,
link |
along with the resveratrol,
link |
because for a number of reasons,
link |
but mainly because my body responds better
link |
and I've been measuring my body for 12, 13 years.
link |
But here's the thing, if I'm going to exercise that day,
link |
I will skip the metformin.
link |
And a lot of people who do pay attention
link |
to this kind of thing,
link |
think that they should stop taking metformin
link |
because they're never going to get muscle
link |
or it's going to affect their ability to build up muscle.
link |
But that's not true.
link |
What metformin does to you,
link |
it actually just reduces your ability to have stamina
link |
because it's inhibiting your body's ability
link |
And so what happens is when you're on metformin,
link |
you do fewer reps, but guess what?
link |
Those muscles that you do build up on metformin
link |
have the same strength and have much lower inflammation
link |
and other markers of aging.
link |
You just won't have that extra 5% size of muscles.
link |
So if you want large muscles, don't take metformin
link |
and you'll be fine during your exercise.
link |
But for me, I'm not trying to get giant.
link |
I want strong muscles and I want to live longer
link |
So I just try to time it so that I get the most reps
link |
out of my exercise regime.
link |
But sometimes in scientific literature,
link |
it's worth bringing this up.
link |
If there's a 5% difference in a graph,
link |
then either the press release or some reporter will say,
link |
oh my goodness, big difference,
link |
5% can't take metformin during exercise.
link |
That's the headline.
link |
And then you go in and it's barely significant.
link |
And the graph is distorted because they've changed the axes
link |
to make it look bigger.
link |
And now it's become a myth that metformin
link |
greatly inhibits your ability to exercise,
link |
which is not true.
link |
But in an abundance of caution,
link |
I skip my metformin on days I'm going to exercise.
link |
And not only that, I'm one of the 20% of people
link |
that has a stomach sensitivity to it.
link |
So if I'm not feeling great that day,
link |
I don't take it either.
link |
You mentioned metformin is available only by prescription
link |
from a doctor, at least in the US.
link |
Berberine, this is a substance that comes from tree bark,
link |
who I also learned about many years ago from Ori.
link |
He said, if ever I'm going to overeat
link |
like a Thanksgiving meal or something, I take berberine.
link |
Those were his words.
link |
And what's remarkable about berberine
link |
is that you can eat enormous quantities of food
link |
and not feel as if you've eaten enormous quantities of food.
link |
I'm not necessarily recommending people do this,
link |
but what I noticed was if I took berberine,
link |
which my understanding is it works very similarly
link |
to metformin, works on the AMPK pathway
link |
and the mTOR pathway, et cetera,
link |
that if I didn't ingest food in particular carbohydrates,
link |
I would feel a little dizzy and kind of get a headache,
link |
like almost hypoglycemic.
link |
What are your thoughts on berberine
link |
as an alternative to metformin?
link |
And are there any cautionary notes?
link |
I mean, obviously people should talk to their doctor
link |
before adding or subtracting anything from their life,
link |
including breath work or anything that comes up.
link |
But with all that set aside,
link |
what are your thoughts about berberine
link |
and timing of low blood sugar and these sorts of things?
link |
Well, before I had access to metformin,
link |
I was taking berberine.
link |
It's often known as the poor man's metformin.
link |
He just called me poor.
link |
Women can take it too.
link |
So the thing with berberine, and we started it in my lab,
link |
it is effective at boosting energetics in the body,
link |
just like AMPK and metformin does.
link |
And we've actually given it to rats and mice
link |
and seen that they are very healthy,
link |
especially on a high-fat diet.
link |
So I think it's likely to be good.
link |
There are some human studies that exist,
link |
clinical trials showing that it increases
link |
insulin sensitivity.
link |
You have to take high doses.
link |
Which is a good thing, right?
link |
I think when people hear insulin sensitivity,
link |
sometimes people think, oh, well, that's bad, right?
link |
No, but you want your cells to be insulin sensitive.
link |
You don't want a lot of blood sugar floating around
link |
that can't be sequestered into cells.
link |
So this is anti-type 2 diabetes.
link |
And so this berberine does have wonderful effects
link |
on the metabolism of animals and in some clinical trials
link |
on dozens of people it's been tested.
link |
Now there's one cautionary tale, which just came up.
link |
Matt Kaeberlein's lab published that berberine
link |
reduced the lifespan of worms.
link |
But I'm not sure worms trump human clinical trials
link |
Not in my opinion.
link |
But no disrespect to my C. elegans colleagues,
link |
or rather my colleagues that work on C. elegans.
link |
Well, what I like to do is to give all the information
link |
people can decide what they want.
link |
But I would say if, based on the worm data,
link |
I wouldn't panic just yet.
link |
I think berberine has been shown
link |
to be really safe in humans.
link |
You mentioned resveratrol.
link |
I think now would be a great time to talk a little bit
link |
about protocols for resveratrol,
link |
grape seed extract, et cetera.
link |
Let's start with the obvious one
link |
that I know you get a lot.
link |
But for the record, can't I just drink red wine
link |
and get enough resveratrol, David?
link |
You need to drink about 200 glasses a day.
link |
I'm sure it's been tried.
link |
And I drink a glass of red wine a day if I get the chance.
link |
But any more than that, it's a lot of calories
link |
and your liver will get fatty and it's all bad.
link |
So realistically, you can only get the thousand milligrams
link |
that I take a day from a supplement that's pure.
link |
Now, there are a lot of people selling resveratrol.
link |
If it's not light gray or white in color, throw it away.
link |
The brown stuff has gone bad or is contaminated.
link |
And the contaminated stuff, beware, it'll cause diarrhea.
link |
But regular resveratrol should not do that.
link |
So a thousand milligrams per day is what you do?
link |
Yeah, and I have for about 15 years now.
link |
And you ingest that with some fatty substance
link |
like olive oil or yogurt, is that right?
link |
Yeah, you have to.
link |
And other supplements, quercetin, curcumin,
link |
these are crunchy things.
link |
They're not going to get through your gut.
link |
And I'm not just making this up.
link |
I always base my statements on human studies.
link |
So we've done a lot of studies on resveratrol
link |
as have others since.
link |
And we know that from, we found out early,
link |
I was one of the first people to take a high dose
link |
And when we included it with food,
link |
the levels in my blood went up fivefold.
link |
And so you want to have something in there.
link |
If you just drink it with water,
link |
it's not going to get through.
link |
And unfortunately, some people have done clinical trials
link |
without even thinking that they might need
link |
to dissolve it in something.
link |
So are you taking this all at once in the morning
link |
and chasing it with some olive oil?
link |
Or are you dissolving it in yogurt?
link |
What's the specific protocol?
link |
Yeah, I've been improving, perfecting what I do.
link |
For about 10 years, I would take some Greek yogurt,
link |
a couple of spoonfuls, put the resveratrol on there,
link |
mix it around, make sure it's dissolved,
link |
and put that in my mouth and swallow that.
link |
These days, what I like to do,
link |
because I've realized that olive oil,
link |
and particularly oleic acid,
link |
one of the monounsaturated fatty acids,
link |
is also an activator of the sirtuin defenses.
link |
So I'm trying to ingest more oleic acid.
link |
So I switched to olive oil.
link |
What I do is I put a couple of teaspoons of olive oil
link |
in a glass, mix around the resveratrol,
link |
and maybe some quercetin, a similar molecule,
link |
make sure it's dissolved.
link |
I put a little bit of vinegar,
link |
and if I have a basil leaf, I'll put that in,
link |
and it's like drinking some salad dressing, and it's great.
link |
That raises a question that I want to ask
link |
before we get to NMN and NR and vitamin B3,
link |
which is, by doing that,
link |
do you think that it breaks your fast?
link |
And I want to just frame this question of breaking the fast
link |
in a more general scientific theme,
link |
and I'd love your thoughts on this.
link |
One of the questions I get asked all the time is,
link |
does ingesting blank break the fast?
link |
Does eating this or drinking this, coffee,
link |
if I walk in the room and someone else is eating a cracker,
link |
does it break my fast?
link |
People get pretty extreme with this.
link |
My sense, and please tell me if I'm wrong,
link |
but my sense is that it depends on the context
link |
of what you did the night before,
link |
whether or not you're diabetic, lots of things.
link |
So for instance, if I eat an enormous meal at midnight,
link |
go to sleep, wake up at 6 a.m.,
link |
I could imagine that black coffee
link |
or coffee with a little bit of cream
link |
might quote unquote break my fast,
link |
but the body doesn't have a breaking the fast switch.
link |
The body only speaks in the language of glucose,
link |
AMPK, mTOR, et cetera.
link |
So do you worry that ingesting these calories
link |
is going to quote unquote break your fast?
link |
And more generally, how do you think about the issue
link |
of whether or not you're fasting enough
link |
to get these positive effects?
link |
Because not everybody can manage on just water or just tea,
link |
or we should say not everybody is willing to manage
link |
on just water or just tea for a certain part of the day.
link |
Well, my first answer is not scientific, it's philosophical.
link |
If you don't enjoy life, what's the point?
link |
And so I'd like a cup of coffee in the morning,
link |
little bit of milk, spoonful of yogurt's not gonna kill me.
link |
Olive oil doesn't have protein or carbs in it, not many.
link |
And so I'm probably not affecting
link |
those longevity pathways negatively.
link |
But without that, first of all,
link |
I wouldn't enjoy my life as much.
link |
Well, the olive oil is not as great as the yogurt,
link |
but I'm trying to optimize.
link |
And there's no perfect solution to what we're doing.
link |
And we're still learning.
link |
We don't know what's optimal for me,
link |
let alone everybody else.
link |
But I'm with you, I don't believe that taking
link |
a couple of spoonfuls of something
link |
unless it's high fructose corn syrup is gonna hurt you
link |
because I've now got the rest of the day
link |
till about eight, nine p.m. of not eating anything.
link |
And I forgive myself for that.
link |
And there's a really good point here.
link |
You and I were discussing this earlier.
link |
The point about doing this is that you try to do your best.
link |
If you go from regular living to don't eat the whole day,
link |
you're gonna fail, like quitting smoking cold turkey.
link |
It's easier to chew gum and stick the patch on
link |
because your body has to get used to all sorts of habits.
link |
And it's social, it's physical,
link |
putting stuff in your mouth, chewing,
link |
not just the low blood sugar levels.
link |
And your brain will fight it.
link |
Your limbic system is gonna go, hey, do it, do it, do it.
link |
And you're gonna have to fight it.
link |
But once you get through it, you'll be better.
link |
But you do it in stages.
link |
Do breakfast first, then do small lunch,
link |
and then eventually cut lunch out.
link |
Don't go cold turkey because everyone knows
link |
it's a fact that if you try to do a strict diet
link |
right out of the gates, you'll almost always fail.
link |
No, I think that captures the essence of fasting rationally
link |
and a rational approach to supplementation very well.
link |
Along the lines of supplementation,
link |
what about NMN, NR, and B3 niacin?
link |
I want to know what you do.
link |
I also want to know what I should do.
link |
And I think most people want to know what they should do.
link |
I mean, these are molecules that impact the sirtuin pathway,
link |
impact the pathways that control aging
link |
or rates of aging in the epigenome.
link |
How do they do that?
link |
And how does one incorporate that
link |
into a supplementation protocol,
link |
should they choose to do that?
link |
Well, disclaimer is that I don't recommend anything,
link |
but I talk about what I do.
link |
So a bit of scientific background.
link |
These sirtuin genes that we discovered,
link |
first in yeast cells when I was at MIT,
link |
and then in animals as I moved to Harvard in the 2000s.
link |
And one of my first postdocs,
link |
actually literally my first postdoc, Chaim Cohen,
link |
published a great paper just a couple of months ago
link |
and found that turning on the sirtuin 6 gene,
link |
remember the 7, number 6 gene is very potent.
link |
It extended the lifespan dramatically of mice
link |
that he engineered, both males and females, which is great.
link |
So what you want to do is,
link |
so naturally boost the activity of these sirtuins.
link |
They are genes, but they also make proteins.
link |
That's what genes typically make or encode.
link |
And then those proteins take care of the body
link |
in many different ways, as we've discussed.
link |
So how do you turn on these genes
link |
and make the proteins they make even more active?
link |
You want to rev up that system.
link |
So exercise will do it, fasting will do it.
link |
What about supplementation?
link |
Well, the first activator of the sirtuins
link |
that we discovered that acts on the enzyme
link |
to make it do a better job of cleaning up the body
link |
and protecting was resveratrol.
link |
We looked at thousands of different molecules,
link |
eventually tens of thousands.
link |
And the one that was the best was resveratrol in the dish.
link |
And then we gave it to little organisms, worms,
link |
and then flies and mice, eventually humans.
link |
And we saw that it activated that enzyme.
link |
So resveratrol is one way to activate it.
link |
You can think of it as the accelerator pedal on a car.
link |
It revs it up, but there's something else
link |
that the sirtuins need to work, and that's NAD.
link |
NAD is a really small molecule,
link |
a little chemical in the body that we need for life.
link |
It's used by the body for chemical reactions,
link |
400 different reactions in the body,
link |
and without it, you're dead within seconds.
link |
The problem that we've seen is that NAD levels decline
link |
as you become obese, as you get older,
link |
if you don't ever get hungry.
link |
And the body not only doesn't make enough of it,
link |
it's chewing it up as well.
link |
There's an enzyme called CD38 that Eric Verdin over at UCSF
link |
showed chews up, oh, he's now at the Buck Institute
link |
in California, chews up NAD.
link |
As you get older, so it's a double whammy.
link |
You don't make as much, you chew it up,
link |
which is really bad because what we've shown in my lab
link |
and so have others is that NAD levels are really important
link |
for keeping those sirtuin defenses at a youthful level.
link |
And you can give a lot of resveratrol,
link |
but if you don't have the fuel,
link |
you're basically accelerating a car
link |
that doesn't have enough gas.
link |
So you wanna do both, and that's what I do.
link |
I take a precursor to NAD called NMN,
link |
and the body uses that to make the NAD molecule in one step.
link |
And so I know from measuring dozens of human beings
link |
that if you take NMN for the time period that I do,
link |
I've been taking it for years,
link |
but if you take it for about two weeks,
link |
you will double, on average,
link |
double your NAD levels in the blood, okay?
link |
That's not public information.
link |
That's from clinical trials that are not yet published
link |
over the last two years.
link |
There are other ways to increase NAD levels
link |
in someone like me who's getting older, I'm 52 now.
link |
You can take NR, which is used to make NMN,
link |
which is used to make NAD.
link |
And both NMN and NR are sold by companies in the U.S.
link |
NR lacks the phosphate.
link |
Phosphate's a small chemical that the body needs.
link |
You've probably heard of the atom phosphorus.
link |
Let's go back one step.
link |
How do you make NR?
link |
NR gets made from vitamin B3 often.
link |
You can also find it in milk and other foods.
link |
But sometimes people ask me,
link |
why don't you just take vitamin B3
link |
and won't that just force the body to make NAD?
link |
And the answer is no, it doesn't work very well.
link |
We know this just by doing the experiment.
link |
But the reason I think is, is that NAD is a,
link |
I said it's a small molecule,
link |
but relative to vitamin B3, it's big.
link |
It's got those phosphates on there.
link |
It's got the vitamin B attached.
link |
So you've got all these components that come together
link |
to make this very complicated little molecule called NAD.
link |
And when you give NMN, it contains all three components
link |
that the body needs to make NAD.
link |
If you give NR, or just vitamin B3,
link |
which is an even smaller molecule,
link |
the body has to find these other components
link |
from somewhere else.
link |
So where do you get phosphate?
link |
Well, body needs it for DNA, needs it for bones.
link |
So high doses of something
link |
that requires additional phosphate
link |
makes me a little concerned.
link |
And we have compared NMN and NR head-to-head
link |
For instance, NMN we've shown in a cell paper
link |
a few years ago, makes mice run further.
link |
Old mice can run 50% further
link |
because they had better blood flow, better energy.
link |
NR at the same dose did not do that.
link |
In fact, it had no effect.
link |
I see, dosage-wise, if I were elect to take NMN
link |
in supplement form to increase my NAD levels
link |
and presumably slow my aging,
link |
how much NMN should I take?
link |
What's the protocol that you do?
link |
And are the various forms that are out there,
link |
are some better or some worse?
link |
Well, I'm always happy to tell you what I do
link |
and what my father does, my 82-year-old father.
link |
We take a gram of NMN every day.
link |
So it's a gram of resveratrol and a gram of NMN.
link |
Okay, 1,000 milligrams.
link |
Now, another important point,
link |
which is I'm not the same as everybody else.
link |
I have a different microbiome, age, sex, right?
link |
And so I've been measuring myself.
link |
And so I know if something's,
link |
or I think I know if something's making me better or worse
link |
based on measuring 45 different things.
link |
So I just want people to be aware
link |
that what I do may not perfectly work at all for others.
link |
But I have studied, as I said,
link |
dozens of people who take NMN at a gram,
link |
sometimes two grams.
link |
And I know by looking at all those people
link |
that without any exceptions,
link |
that if you do what I do,
link |
your NAD levels go up by about twofold or more.
link |
And so I do that every day, the 1,000 milligrams.
link |
Now, people sell it.
link |
Now, I never get into brands and all that.
link |
First of all, I don't have the time to measure products.
link |
I don't know, though I should say,
link |
I do want to say I'm working on a solution
link |
for people to know what works
link |
and what's real and what isn't, but I'm not there yet.
link |
And in the meantime, I would say,
link |
if you do want to buy this,
link |
let's say you want to buy NMN,
link |
look for a company that is well-established,
link |
that has high levels of quality control.
link |
Look for three letters, GMP,
link |
which is good manufacturing practices.
link |
And so that means they make it
link |
under a certain level of quality control.
link |
You're not going to find iron filings in there,
link |
and it probably has the stuff in it that they say it does.
link |
So that's all I can say right now.
link |
I'm working on something that's going to be much more helpful.
link |
But overall, make sure it's white, crystalline, NMN,
link |
and that to me, it tastes like burnt popcorn.
link |
You crack open the capsules and you'll take a little sample
link |
to make sure it tastes like burnt popcorn.
link |
Well, when I'm making my capsules, I'll taste it.
link |
And I do a lot of quality control on the stuff that I take.
link |
Do you take that gram all at once with the resveratrol
link |
or do you take it spread throughout the day?
link |
It's all in the morning for those things.
link |
So if I take metformin, it's NMN
link |
and the resveratrol all together.
link |
And there's a good reason for that.
link |
It's all scientific, I try to be.
link |
The levels of NAD go up in the morning
link |
in our bodies naturally.
link |
Our bodies actually have a cycle of NAD, it's not steady.
link |
In fact, NAD controls your clock.
link |
This was shown by Shin, MI, and colleagues
link |
in a nice science paper about a decade ago
link |
that if you disrupt the NAD cycle,
link |
which is controlled by the sirtuin gene that we worked on,
link |
that is what's telling your body, oh, it's time to eat,
link |
it's time to go to sleep.
link |
And if you take the NMN late at night,
link |
for example, you can disrupt your circadian rhythms.
link |
Conversely, when I travel and I want to reset my clock
link |
to the time zone, I will take a boost of NMN in the morning
link |
Does this protocol for you,
link |
does it produce any immediate effects
link |
of increased energy, et cetera?
link |
You mentioned that one would, if it's right for them,
link |
would have to take it for at least two weeks
link |
to start to see the NAD levels increase.
link |
At that point, when NAD levels increase,
link |
could one possibly expect an increase
link |
in overall energy focus, et cetera?
link |
I realize we're not making promises here,
link |
but I'm just wondering whether or not the only measure
link |
of whether or not this protocol is working
link |
is whether or not you die at age blank or blank plus 20.
link |
And of course, once you're dead,
link |
you can't really know if you would have lived longer
link |
if you'd done something differently and vice versa.
link |
Sure, well, there was a study, again, by Shina Mai,
link |
my good friend at Washington University in St. Louis,
link |
that showed that it improves,
link |
remember, this insulin sensitivity, which is a good thing.
link |
But you can't know your insulin sensitivity
link |
unless you're measuring a glucose,
link |
have a glucose monitor on your arm.
link |
Do you have one on right now?
link |
Yeah, last time I saw you had this thing.
link |
It looks like a small leech, not a large leech,
link |
and it was measuring your blood glucose.
link |
They're very informative
link |
because you learn what your body reacts to,
link |
and grapes were really bad.
link |
Rhonda Patrick agrees with that.
link |
But the issue was what, where were we, Andrew?
link |
The issue is whether or not
link |
you can expect any immediate effects
link |
on energy, vitality, focus, just even subjective.
link |
So what do you feel is the question?
link |
because I've been taking this for a long time,
link |
if I don't take it, I start to feel 50 years old.
link |
I can't think straight.
link |
It may be placebo, but who knows?
link |
But what we're doing now are very careful clinical trials.
link |
We've done the safety for two years,
link |
and we're now treating elderly patients
link |
at Harvard Medical School with some wonderful colleagues.
link |
And those people are actually going to be,
link |
and currently in MRIs,
link |
so you can measure the energetics and the NAD levels
link |
in their legs as they exercise in real time.
link |
And that will tell us if what we see in the mice,
link |
this increased endurance, actually works.
link |
In the meantime, it's fun to talk about anecdotes.
link |
I have a number of athlete friends,
link |
some of which have increased their,
link |
lowered their time in marathons, for example.
link |
There's a good friend of ours in our circle
link |
that is winning marathons at age 50 now.
link |
And he attributes that to the protocol that he's on.
link |
I haven't started taking NMN,
link |
but I'm planning to do that when my next birthday arrives,
link |
which is in a couple of months.
link |
But I do experiments on my sister and have for years,
link |
I have a sister who's three years older than I am,
link |
who is very enthusiastic about these protocols.
link |
And I'll tell you that after reading your book,
link |
I started purchasing for her
link |
and giving her an NMN supplement.
link |
And she claims, and I believe her,
link |
she has a quite sensitive system
link |
and she's very tuned into it.
link |
She feels far and away better when she takes it
link |
as opposed to when she doesn't.
link |
And I've done the control experiment of removing her supply
link |
and then giving it back to her and this kind of thing.
link |
So that's my other laboratory.
link |
This is what younger brothers do to older sisters.
link |
I have a question about something that,
link |
if it has no relevance,
link |
we can just treat it as a speed bump and then move right on.
link |
And the artificial sweeteners, these things that,
link |
or I should say non-glucose increasing sweeteners.
link |
So you've got stevia, which is a plant basically,
link |
and then you've got sucralose and aspartame
link |
and all these things.
link |
There is some evidence that I know we're both aware of,
link |
they've been published in quite reputable journals
link |
showing that they can disrupt the gut microbiome
link |
in certain cases, in particular saccharin,
link |
the one that basically nobody uses anymore.
link |
And it's questionable as to whether or not stevia
link |
has the same negative effects, et cetera.
link |
That's not what this is about.
link |
But in terms of the sensation of,
link |
or the perception of sweet taste,
link |
is that itself a possible detriment to these pro-longevity,
link |
forgive me for using the term, the pathways.
link |
If I were to drink a Diet Coke during a fast,
link |
am I somehow disrupting this?
link |
And I'm asking this question
link |
because I get asked this question a lot.
link |
Well, there may be small effects.
link |
I don't think they're worth worrying about.
link |
Joe Rogan laughed at me
link |
because I was drinking a Diet Coke
link |
during the first interview I did with him.
link |
I will drink Diet Coke.
link |
I've read the scientific literature.
link |
And again, it's this 5% thing
link |
that I think is blown out of proportion.
link |
If I was to put a number on it,
link |
I would say if eating a high sugary meal
link |
or drinking a sugar-filled soda,
link |
what is that, 30 grams of sugar,
link |
let's say that's a 10 out of 10 bad for you.
link |
A Diet Coke might be a one.
link |
And if I'm, you know, which am I gonna do?
link |
I could have a 10 or a one or go without in my life.
link |
I'll do the one on occasion.
link |
I try to avoid them because I don't like the ones as much.
link |
But you can't say that sucralose
link |
is equivalent to drinking a sugary soda.
link |
There's just no comparison.
link |
And I think, what is it, stevia.
link |
I do use stevia whenever I can
link |
because it's a naturally sourced product.
link |
And I haven't seen any good evidence yet
link |
that it's bad for you.
link |
But I think a lot of this is overblown.
link |
And a lot of it's the media trying to give equal weight
link |
to stories, as you know, as a scientist,
link |
it can be frustrating when something's a 10
link |
and something's a one and they're equated.
link |
How do I say this respectfully?
link |
I think if science journalists were required
link |
to post their credentials alongside their name,
link |
people would take the articles
link |
with an additional grain of salt, right?
link |
I mean, in other words,
link |
that I think that the science media
link |
is mainly generated around two specific goals.
link |
One is to make people very, very afraid
link |
or get people very, very excited.
link |
And oftentimes the get people excited part
link |
is sponsored content.
link |
And I think that's overlooked.
link |
In any case, thank you for that.
link |
I want to talk about iron and iron load.
link |
We were talking earlier about ferritin
link |
and of course women mend straight.
link |
And so their iron needs are greater
link |
than people, men that don't mend straight
link |
or women that don't mend straight.
link |
I don't think we can get right down
link |
into how much iron somebody needs
link |
because it'll vary person to person.
link |
But I was surprised to learn that iron
link |
is actually going to accelerate the aging process
link |
in various contexts.
link |
Well, this is a new finding out of Spain.
link |
Manuel Serrano's lab has found that excess iron
link |
will increase the number of senescent cells in the body.
link |
And senescent cells are these zombie cells
link |
that accumulate as you get older
link |
and they sit there and they cause inflammation mainly
link |
and also can cause cancer.
link |
And it's found that if you get rid of these cells
link |
or never accumulate them, you stay younger in animals.
link |
And there's some really interesting studies
link |
out of Mayo Clinic in humans as well.
link |
So iron is a pro-senescent metal.
link |
And so what I think is that if you're taking excess iron
link |
as a supplement, you're probably accelerating
link |
your aging process.
link |
The other thing that I found really interesting
link |
is I've looked at hundreds of thousands of people's
link |
metabolism and their blood biomarkers.
link |
I was one of the first people in Inside Tracker
link |
as a board member and I'm still a scientific lead guy.
link |
So I can look anonymously at hundreds of thousands
link |
of people's blood work.
link |
And we also know how fit they are, how old they are.
link |
Some of them are marathon runners,
link |
some of them are CrossFit.
link |
And there's a signature of health that actually
link |
is different than your average person.
link |
Now, I'm not gonna say bad things about MDs
link |
because a lot of my best friends are MDs
link |
and I work with them at Harvard Medical School.
link |
The issue though is that with MD training,
link |
there's a scale of what's normal.
link |
And if you're out of that normal range,
link |
something must be wrong.
link |
That's the paradigm that they work under.
link |
But first of all, everybody's different
link |
and you wanna know their baseline and track people
link |
over years to know what's normal for them.
link |
And what I find, for example,
link |
is people who are really healthy and live the way I do
link |
and have a diet that's fairly vegetarian but not strict
link |
still have slightly low hemoglobin levels,
link |
slightly low iron, slightly low ferritin,
link |
but we have super amounts of energy.
link |
We're not anemic and we're getting along with great in life.
link |
But a doctor who just looks at that might say,
link |
oh, we need to give you more iron, right?
link |
So what I'm getting at is an example of
link |
we need to personalize medicine
link |
and look at people over the long run
link |
to know what works for them and what's healthy for them,
link |
and not just work towards the average human
link |
but work towards what's optimal for human.
link |
I love that answer.
link |
You mentioned tracking and tracking over time,
link |
and this is a really interesting area
link |
that I know you have been focused on for a long time.
link |
I've been getting blood work done about every six months,
link |
frankly, since I was in college.
link |
I like data and I got interested in supplementation
link |
and exercise because it made me feel better,
link |
but I also want to know what was going on under the hood.
link |
So you get numbers back.
link |
You get this hormone, that hormone,
link |
this blood glucose measure, et cetera.
link |
How do you make sense of the data?
link |
I mean, what Inside Tracker is doing aside,
link |
how do you personally make sense of the data
link |
in ways that might differ from the way
link |
that a standard MD might look at one of these charts?
link |
Because the standard practice is to say,
link |
is it red, yellow, or green, right?
link |
Is it basically too high or too low?
link |
Is it somewhere close to the margins or are you okay?
link |
Are you in these ranges?
link |
Are there any things that you pay attention to
link |
that you think are particularly interesting
link |
for people to just take note of?
link |
I mean, we're not asking you
link |
to go against anybody's physician,
link |
but what sorts of things should people
link |
start to educate themselves about
link |
in terms of what these molecules are on their charts
link |
if they choose to get them and what do you look at?
link |
Yeah, well, there's a lot there.
link |
The first is that you should be tracking things
link |
because one measurement isn't enough.
link |
These things vary and over time,
link |
and if you can have a decade or more of data,
link |
it's super informative as you know well know, as you know.
link |
So the physician, interestingly, my physician,
link |
let's take him as an example.
link |
So he sees me, he says, how are you feeling?
link |
I'm feeling great, okay, see you next year.
link |
Anyway, so I say, okay, stop.
link |
Let's talk a little bit about-
link |
Let me educate you.
link |
That's what David tells his physician.
link |
I imagine that the like 12-year-old David Sinclair
link |
says to his physician, listen,
link |
let's have a different discussion.
link |
Is that how it works?
link |
It is, he finds me pretty annoying as does my dentist.
link |
But so I said, stop, hang on, I've got this data.
link |
I've got the inside tracker data.
link |
So I pull that up on the screen
link |
and I'm showing him the changes in my cholesterol,
link |
in my CRP, which is inflammatory marker, as you know,
link |
and we're going through it
link |
and you can see things change over time
link |
and I've corrected them as they go slightly
link |
out of the optimal range for me,
link |
which is different than what he would do, of course.
link |
But what was funny is that he says, this is great.
link |
I love this data, but I'm not allowed to get this
link |
because of course the insurance companies won't pay for it.
link |
So again, you can pay out of pocket.
link |
It's not super expensive.
link |
I would say if you save a bit of money on a coffee,
link |
you can afford this kind of stuff.
link |
But the main point is that doctors do like this data.
link |
It's just that they're unable to spend the money
link |
on every one of their patients to get it.
link |
Is there a code word that someone can use
link |
with their physician that will trigger
link |
a comprehensive blood test?
link |
I keep trying to figure out what's the code
link |
that one needs to ask or tell their doctor,
link |
like I'm feeling blank so that they get a full blood panel.
link |
Well, do you have to be hemorrhaging
link |
from the gut or something?
link |
Well, I usually use the WTH method, which is what the hell?
link |
And then he says, okay, we'll do it.
link |
Cause I think a lot of people out there are thinking,
link |
look, I'd love to have blood work repeatedly over time,
link |
but that's hard to get for financial reasons.
link |
But also a lot of people just don't know
link |
how to approach the conversation.
link |
And this is one of the things
link |
that I hope that we can educate people on,
link |
that they deserve to know what's going on inside their body
link |
and that it makes a doctor's visit worthwhile
link |
and that you don't have to feign illness in order to do it.
link |
Right, yeah, and a lot of people do.
link |
So I would say if you can afford these tests,
link |
there are an increasing number of companies
link |
that offer these tests.
link |
Insight Tracker is one of them.
link |
And you just do it a couple of times a year at a minimum,
link |
and then you can share that with your doctor.
link |
If you can't afford that, then I would say to your doctor,
link |
here are the main ones that Andrew and David do.
link |
Yeah, and we must.
link |
And there's an email that is something like a phone number,
link |
rather it's 555-5555.
link |
I think if they have any complaints,
link |
they can just call that number.
link |
David will pick up on East Coast business hours
link |
and I'll pick up outside of those hours.
link |
But there were some main ones.
link |
I would say your blood sugar levels,
link |
you want to do your HbA1c,
link |
which is your average glucose levels over the month.
link |
There's CRP, which I mentioned for inflammation.
link |
Let's talk about C-reactive protein for a second,
link |
because I think it's been shown to be an early marker
link |
of macular degeneration, of heart disease,
link |
of a variety of different things.
link |
CRP is something that we don't hear enough about, I think.
link |
Maybe, what do you know about CRP that I don't?
link |
I'm guessing a lot, but.
link |
Oh, it was originally picked up as something
link |
that was associated with heart disease
link |
in the Framingham study, I believe.
link |
It is the best marker for cardiovascular inflammation
link |
and is also, we use it as a predictor of longevity.
link |
And its levels go up with mortality.
link |
And so this is an association,
link |
but there's enough data that I would say,
link |
if you have high levels of CRP,
link |
you need to get your levels down quickly.
link |
And the levels usually go up with age
link |
and with levels of inflammation.
link |
So the ways to get it down would be to switch the diet,
link |
eat less, try to eat more vegetables.
link |
You'll find it will come down.
link |
There are also drugs that can do it.
link |
Anti-inflammatories can do it as well.
link |
But CRP is, it's actually HCRP.
link |
There's a high-sensitive or HSCRP.
link |
Your doctor will know.
link |
Get one of those readings,
link |
because if you've got normal blood sugar levels,
link |
your doctor, or fasting blood sugar levels,
link |
your doctor might say you're fine.
link |
But a lot of people have normal blood sugar,
link |
but have high CRP, which is just as bad for you long-term
link |
and can predict a future heart attack.
link |
On the lines of heart attack,
link |
I want your thoughts on cholesterol,
link |
and serum cholesterol, and dietary cholesterol.
link |
I cannot, for the life of me,
link |
get my arms around this literature.
link |
And even if I ignore all the essentially nonsense
link |
that's out there in various social media groups
link |
that saying cholesterol is the worst thing in the world,
link |
or cholesterol is not, or dietary cholesterol
link |
has nothing to do with serum cholesterol
link |
and nothing to do with longevity,
link |
I can't seem to sort through the very basic data
link |
that essentially ask,
link |
is having high levels of LDL going to kill me earlier?
link |
Should I be striving to always reduce LDL and increase HDL?
link |
Is that a reasonable goal?
link |
And if so, is dietary cholesterol
link |
the primary determinant of that?
link |
And just as a final point about this,
link |
I am aware of quite good data that shows that anorexics,
link |
people that essentially eat no food
link |
unless you force them to,
link |
can often have very high LDL.
link |
So their dietary cholesterol is essentially zero,
link |
and so they're manufacturing a lot of their own.
link |
So realize this isn't your primary area of expertise,
link |
but you're a smart guy.
link |
You think about this kind of stuff a lot.
link |
What do you think is going on
link |
with the cholesterol literature,
link |
and will we ever get to the bottom of this
link |
as a scientific and medical community?
link |
Because to me, it is rather perplexing.
link |
It is, but you can get through the politics.
link |
I know a fair bit about cholesterol
link |
because it's in my family history,
link |
and I was headed for an early death.
link |
My grandmother had a stroke at 30.
link |
That's how bad I am in terms of my genetics.
link |
So I went on a statin,
link |
and I know there's a lot of people
link |
who say that statins long-term are bad.
link |
It's associated with Alzheimer's disease.
link |
I've been taking a statin since I was 29,
link |
and that's because I forced my same doctor
link |
to give me the statin.
link |
The conversation was something like this.
link |
You're too young to be on a statin.
link |
I said, what, you want me to have a heart attack
link |
before you give me something?
link |
Give it to me now.
link |
So 29, I've been on a statin,
link |
and my cholesterol was way up beyond 300,
link |
which is a massive, massive.
link |
Basically, my blood was creamy to look at.
link |
So I've now got my cholesterol down to low, low levels
link |
to what would it be?
link |
You could check on my inside tracker,
link |
but so my ratio of HDL to LDL,
link |
which you want to be less than five, is now two,
link |
and the LDL is below 100.
link |
And I've measured my cardiovascular health with an MRI.
link |
I've got a movie of my heart beating.
link |
I've still got a heart of a 20-year-old.
link |
So that's working.
link |
I'm willing to forego the risk
link |
that the statin is causing problems later
link |
because of my family history.
link |
But other people, I would say,
link |
be aware that statins aren't perfect drugs.
link |
There are some interesting new ones.
link |
There's one called the PSK-9 inhibitor,
link |
which is, I think, fortnightly, every two weeks, injection.
link |
That blocks the release of LDL from the liver.
link |
And then that seems to be great for lowering cholesterol,
link |
but also has other benefits that might be pro-longevity.
link |
And there were some people that I was just talking to
link |
are on the cutting edge of this,
link |
and their doctors are trying them on this drug
link |
instead of the statin.
link |
So you could talk to your doctor about that.
link |
Do you avoid dietary cholesterol for that reason also?
link |
I mean, I happen to love butter.
link |
I realize there's some people who don't.
link |
My cholesterol is a little bit high,
link |
but I'm working to bring that down a bit,
link |
although not by altering my food intake yet.
link |
But what do you think is the relationship
link |
between dietary cholesterol and serum cholesterol?
link |
And what's going on with the liver?
link |
Why are anorexics, why is their serum cholesterol so high
link |
when they're eating nothing?
link |
Well, there've been a number of papers over the years
link |
that have been ignored.
link |
And our friend, Peter Atiyah,
link |
brought to my attention recently a new study
link |
that I think definitively said
link |
that dietary cholesterol has almost zero impact
link |
on blood cholesterol levels.
link |
Yeah, so I'm annoyed,
link |
because I've been avoiding eggs and butter
link |
for most of my life, and I didn't have to.
link |
So I had eggs plenty of time, at least in your case.
link |
Yeah, yeah, so that's the thing.
link |
You can eat these foods that were once banned,
link |
because it's very difficult to take cholesterol up
link |
into the body from the gut,
link |
and most of it's being synthesized in the body.
link |
Wow, I'm just pausing there for a second,
link |
because I think that it's what we've been told,
link |
six meals a day, eat a lot of grains and fruits
link |
and this kind of thing, avoid cholesterol.
link |
I mean, basically everything we learned in the 80s and 90s
link |
and early 2000s is getting flipped on its head now.
link |
But, and I think this is a very strong caveat
link |
that's important to mention, amino acids,
link |
in particular the amino acids
link |
that come from animal products, right?
link |
Seem to have some pro-aging effect on them, right?
link |
At least the way that I've heard you describe your diet.
link |
And I'm somebody who enjoys meat, I like it.
link |
But, so I'm by no means a vegan at all.
link |
But I've heard you say you eat mostly plants,
link |
but a little bit of fish or chicken
link |
or something of that sort, or eggs or,
link |
but is that specifically to avoid
link |
excessive amino acid intake?
link |
Or is it something specific about plants
link |
that excites you with respect to,
link |
I mean, vegetables are delicious too, but what is it?
link |
Is it something great about plants
link |
or is it something bad about, when I think of meat,
link |
I guess the biologist in me thinks amino acids, right?
link |
I don't think top sirloin, I think amino acid.
link |
No, I think top sirloin as I'm eating it,
link |
but really what they are are amino acids, including leucine.
link |
Yeah, well, there are two good things about plants
link |
and neither of them is taste for me.
link |
I would eat steak all the time if I could.
link |
I did when I was a kid, I'm an Australian.
link |
But plants have two benefits.
link |
One is that they're highly nutritious
link |
and they'll give you a lot of the vitamins
link |
and nutrients that I need.
link |
I don't take a multivitamin, I don't wanna
link |
have the excess iron in my body.
link |
So there's that high density nutrition.
link |
So those dark leaves, if it's a spinach salad, great.
link |
Second is that there is what's called
link |
xenohormatic molecules in plants.
link |
That term xenohormesis is a term that I came up with
link |
with my friend Conrad Howitz, which means
link |
stressed plants make molecules that benefit your health.
link |
I'll break it down.
link |
Xeno means between species and hormesis is the term
link |
whatever doesn't kill you makes you stronger
link |
And the idea is that when plants are stressed out,
link |
think of a grapevine that's dried out
link |
and they're starting to harvest the grapes,
link |
which is typically how it's done.
link |
They are full with resveratrol because resveratrol
link |
is a plant defense molecule that I think is made
link |
to activate those sirtuin genes in a plant.
link |
So plants have sirtuins just like we do.
link |
But by purifying or at least concentrating
link |
in a light proof bottle and keeping it out of the air,
link |
we stabilize this xenohormatic molecule,
link |
or it's a cocktail, not just one, there's others in wine.
link |
We then ingest those and get the benefits
link |
of activating our own defenses
link |
because our food was getting stressed out.
link |
And by stressed, I don't mean psychologically stressed,
link |
I mean biologically stressed.
link |
And so I try to eat plants that have gone through
link |
a bit of stress, they might be brightly colored,
link |
they've had too much sun or got nibbled on by a caterpillar.
link |
So you go to places where it's organic or it's fresh,
link |
local, and those are the plants that aren't perfect
link |
and they probably have high concentrations
link |
of these molecules.
link |
And in addition, I also buy the supplements
link |
to make sure I'm getting enough of those as well.
link |
Which supplements mimic that?
link |
Well, so resveratrol will,
link |
there's another one called chrysotin,
link |
or chrysotin, some people call it,
link |
which you find in trace amounts in apples and onions.
link |
And we also showed back in 2003
link |
that it activates sirtuins as well,
link |
but others have, 20 years later,
link |
found that it kills senescent cells
link |
or helps kill senescent cells.
link |
So it's a double whammy with that molecule.
link |
And are you actively picking out the peaches
link |
that look like they were nibbled on by a caterpillar?
link |
No, but I don't worry if they've been banged up a bit.
link |
What's the story with antioxidants?
link |
Are they of any value whatsoever?
link |
Because the way that you described them at the beginning
link |
and what I've heard recently is that
link |
they are not all the rage for anti-aging.
link |
What are they doing that's useful?
link |
Should we be seeking out antioxidants anyway
link |
for other cellular health purposes?
link |
Well, yeah, antioxidants are not going to hurt you
link |
unless you take mega doses.
link |
We do need some oxidants for our immune system.
link |
And there's even what's called mitohormesis,
link |
which is your mitochondria power packs
link |
need to have a little bit of these free radicals
link |
to be able to function.
link |
So you don't want to overdose on these antioxidants,
link |
vitamin C, vitamin E, don't overdo it.
link |
You don't take a multivitamin, correct?
link |
I think I'm going to stop after this conversation
link |
because I've always just taken one
link |
for the kind of insurance purpose,
link |
which is a stupid purpose, not actual insurance,
link |
but just thinking, oh, you know,
link |
I'll top off on my ACBD.
link |
Right, and I'll pee out what I don't need.
link |
Right, but that never bothered me.
link |
The whole expensive pee thing never got,
link |
that argument never got me
link |
because a good vitamin is not that expensive.
link |
I just figured better safe than sorry,
link |
but it may be that it's detrimental.
link |
Well, it can in the case of iron,
link |
as we discussed, and the antioxidants.
link |
So when I came into the aging field in the early 1990s,
link |
it was all about antioxidants.
link |
And we thought that enzymes by the name of catalase
link |
and superoxide dismutase
link |
were going to be the key to longevity.
link |
It turns out that it's largely been a failure
link |
that giving animals and humans antioxidants
link |
haven't had the longevity benefits that we dreamed of.
link |
And the main reason is that there's a lot more going on
link |
than just free radical damage.
link |
The epigenome gets disrupted.
link |
We've got these proteins misfolding.
link |
So the problem really has been that we didn't realize
link |
that you need to turn on the body's natural defenses
link |
against that plus a whole host of other things
link |
to get the true benefits.
link |
But I'm not going to say it's a problem
link |
taking an antioxidant drink.
link |
Pomegranate juice for one is full of good stuff,
link |
including xenochromatic molecules.
link |
But resveratrol is a good case in point,
link |
which is when I worked on resveratrol
link |
as a longevity molecule,
link |
first we showed it in yeast and worms and flies and mice.
link |
Before that, it was thought that resveratrol
link |
was good for your heart in red wine,
link |
when you drink red wine, because it's an antioxidant.
link |
So then we showed that it extended the lifespan
link |
of yeast cells through this genetic pathway, the sirtuins.
link |
And we then tested whether resveratrol,
link |
if we changed one atom to make it not an antioxidant,
link |
It still worked fine.
link |
So it wasn't its antioxidant activity
link |
that was extending lifespan.
link |
It was its ability to turn on the yeast's defenses
link |
Conversely, when we gave the yeast antioxidants,
link |
they lived shorter.
link |
So yeah, that was the beginning of my transformation
link |
into thinking, turn on the body's defenses,
link |
don't give it the antioxidants.
link |
This is an opportunity for me to say
link |
something that I've been wanting to say for a long time,
link |
which is that what's so wonderful about science
link |
is that because the goal is mechanism,
link |
you can really start to understand, as you just described,
link |
what actually mediates a process
link |
is very different than what modulates a process.
link |
I mean, if a fire alarm goes off in the building right now,
link |
it's going to modulate our attention.
link |
That doesn't mean that it controls our attention.
link |
It's not mechanistically relevant.
link |
And so I think this thing about antioxidants
link |
is one of these cases, it sounds like,
link |
where it's in the right ballpark,
link |
but until one really unveils the mechanism as you have,
link |
you can be, one can or a field can be badly wrong
link |
for a very long period of time.
link |
It sounds like the sirtuins,
link |
and really getting down to the guts of the machinery
link |
of what causes cells to age is really what it's about.
link |
Zooming way out, what are the behavioral tools
link |
that one can start to think about
link |
in terms of ways to modulate these,
link |
basically the way that DNA is being expressed
link |
I've heard you talk before about hormesis of other sorts,
link |
cold exposure, we talked about fasting.
link |
We talked about exercise in broad terms,
link |
but what about any evidence, if it exists,
link |
as to whether or not aerobic training
link |
versus weight training, these sorts of things.
link |
In other words, what are the sorts of things
link |
that people can do to improve the sirtuin pathway?
link |
And I realize that they're caveats.
link |
We can't go directly from a behavior to sirtuins,
link |
but in the general theme, what can people do?
link |
Well, we know that aerobic exercise in mice and rats
link |
raises their NAD levels and their levels of sirt,
link |
one of the genes goes up to actually number one
link |
What we don't know yet is what type of exercise
link |
is optimal to get them to change.
link |
We will learn, we're doing work.
link |
Now it's revealed that we're doing work
link |
with the military in the US
link |
to try and understand that kind of thing.
link |
And I'll always tell you and the public
link |
when I don't know something, I'm not gonna extrapolate.
link |
I base my exercise on the scientific literature,
link |
which has shown that maintaining muscle mass
link |
is very important for a number of reasons.
link |
The two main ones are,
link |
you wanna maintain your hormone levels.
link |
I'm an older male losing my testosterone
link |
and muscle mass over time.
link |
And by exercising, I will maintain that and have.
link |
In fact, I probably haven't had a body like this
link |
So that's one of the benefits of having this lifestyle.
link |
Sorry to interrupt you, we did an episode on hormones
link |
and there are data in humans that show
link |
that there are some males in their 80s and 90s
link |
where their testosterone is equivalent
link |
to the average of 25 and 30 year olds.
link |
I can get you that information.
link |
It is really impressive studies.
link |
Unfortunately, they didn't include a lot of information
link |
about the lifestyle factors, et cetera.
link |
But this idea that testosterone goes down with age,
link |
it might be the trend
link |
but it's not necessarily a prerequisite.
link |
Right, I believe in naturally increasing
link |
and maintaining these hormone levels.
link |
And I've been measuring them for a long time.
link |
And I could see for me,
link |
my testosterone levels were steadily,
link |
levels were going down.
link |
And then you got tenure and they went back up again.
link |
No, I actually became complacent and it was the worst.
link |
Actually, my age changed in the wrong direction after that
link |
because I was relaxed and not worried about the future.
link |
But then I got serious.
link |
And I actually, according to the inside tracker algorithm,
link |
got my age down from 58 to 31 in a matter of months.
link |
That was a big drop.
link |
And I've been getting steadily younger
link |
over the last 10 years,
link |
according to that measurement, the blood tests.
link |
What about estrogen?
link |
Because women are different in the sense that they do,
link |
the number of eggs and the ovaries change over time, right?
link |
Do you think that they can maintain estrogen levels
link |
in over longer periods of time
link |
using some of these same protocols?
link |
Well, yeah, I get into trouble from a certain university
link |
when I talk about this too much.
link |
Just about fertility and long story.
link |
I don't want to get too much into the anecdotes,
link |
but I'll tell you the science,
link |
which is that if you take a mouse
link |
and put it on fasting or caloric restriction
link |
for up until the point where it should be infertile,
link |
so that's about it at a year of age,
link |
a mouse gets infertile, a female mouse.
link |
Due to fasting or due to simply to aging?
link |
Due to aging, due to aging.
link |
The fasting, it's not an extreme fast,
link |
it's just less calories.
link |
Then you put them back on a regular food
link |
and they become fertile again
link |
for many, many months afterwards.
link |
So the effect on slowing down aging
link |
is also on the reproductive system.
link |
And so I wouldn't say to any woman,
link |
I wouldn't think that they should become super skinny
link |
to try and preserve fertility.
link |
That's not what I'm saying.
link |
But these pathways that we work on,
link |
these sirtuins, are known to delay infertility
link |
in female animals.
link |
Case in point, I'm one of the lead authors on a paper
link |
where we used NMN.
link |
Remember, this is the gas, the fuel,
link |
the petrol for the sirtuins.
link |
We gave old mice, one group of mice was 16 months old.
link |
Remember, they came infertile at 12,
link |
gave them NMN, and I think it was only six weeks later,
link |
they had offspring.
link |
They became fertile again,
link |
which goes against biology, a textbook biology,
link |
which is that female mammals run out of eggs.
link |
Turns out that's not true.
link |
You can rejuvenate the female reproductive system
link |
and even get them to come out of mouse support,
link |
So that's a whole new paradigm in biology as well.
link |
That's super interesting.
link |
Sorry to interrupt you,
link |
but I'm reminded of a set of studies that were done
link |
by your former colleagues, because they're no longer there,
link |
David Hubel and Torrance Wiesel,
link |
my scientific great-grandparents, won the Nobel Prize
link |
for discovering what are called critical periods,
link |
this phase of early development
link |
when the brain is extremely plastic.
link |
And a big part of their work was to show
link |
that after a certain point,
link |
the critical period shuts down,
link |
essentially the brain can't change or not nearly as much.
link |
And then people came along later
link |
and showed that you could open up
link |
these critical periods again, but very briefly,
link |
and it takes a very specific stimulus, essentially,
link |
high degrees of focus, et cetera.
link |
However, there's a well-known phenomenon in this literature
link |
where if you take an animal, and to some degree,
link |
this has been shown in humans as well,
link |
and you let them pass through the critical period,
link |
but then you essentially sensory deprive them.
link |
You take away experience, you close both eyes.
link |
You essentially reopen the critical period.
link |
So it seems like, and I couldn't help but mention this,
link |
that there's this parallel between what we're talking about
link |
here with fertility and neuroplasticity,
link |
where, yes, there's a timer where certain things
link |
are available to the organism early in life,
link |
and then they tend to taper off.
link |
It's not an open and shut, but they taper off.
link |
But then a deprivation can actually reactivate
link |
the availability of that process.
link |
Forgive me, I just couldn't help but mention it,
link |
but to me, both of those things are associated with youth,
link |
fertility and neuroplasticity.
link |
And so I think that it'd be so interesting,
link |
I'd love to collaborate with you on this
link |
to explore how neuroplasticity might actually be regulated
link |
by these things like the sirtuins.
link |
Right, and the sirtuins do control memory
link |
in neurons as well.
link |
So what I think is really interesting is that
link |
what we're learning from the research is that
link |
from work that you and your colleagues have done
link |
and in my lab as well,
link |
is that the body has remarkable powers of healing
link |
and recovering from illness and injury.
link |
And what we once thought was a one-way street
link |
and you just can't repair,
link |
you can't get over these diseases,
link |
you can reset the system.
link |
And the body can really get rejuvenated
link |
in ways that in the future will wonder
link |
why didn't we work on this earlier?
link |
The future of humanity is more like
link |
us walking around like Deadpool.
link |
We'll probably be cleaner and we won't smell as badly,
link |
but Deadpool, if you don't know,
link |
can get injured and just recover.
link |
It's very hard to injure this guy.
link |
And we're gonna be the same.
link |
There are many species, you cut off the limb,
link |
the limb grows back.
link |
Salamanders, yeah.
link |
We are now learning how to tap into that system.
link |
And in part, what we're doing is reversing the age
link |
of those cells and telling them
link |
how to read the genes correctly again,
link |
reversing the age of that epigenome.
link |
And when you do that, the cells,
link |
the brain, for instance, the skin,
link |
we did the optic nerve.
link |
Now let's talk about those results for a second.
link |
Then I want to make sure that we return
link |
to some of these behavioral protocols.
link |
You had this amazing paper at the end of last year,
link |
cover article, full article in Nature,
link |
showing that essentially a small menu
link |
of transcription factors,
link |
which control gene expression, et cetera,
link |
could essentially reverse the age of neurons in the eye
link |
and rescue those cells against damage,
link |
essentially allow blind mice to see again
link |
and offset degeneration of these retinal cells.
link |
Incredible paper and such a boon to the field.
link |
Where does that stand now
link |
in terms of human clinical trials?
link |
I mean, what are you envisioning
link |
in terms of the trajectory of those data
link |
from mice into humans someday?
link |
Right, well, to get to the point immediately,
link |
we're going to be testing the treatment on monkeys,
link |
just for safety reasons.
link |
And then the first patient should be done
link |
sometime in 2022, early 2023,
link |
and we're going to try to recover blindness.
link |
This involves making an injection
link |
of a virus into the eye, right?
link |
Right now, there's no way that I am aware of
link |
to manipulate these transcription factors
link |
through a pill or some other.
link |
That's what we're working on in my lab at Harvard right now.
link |
Pill-based modulation of transcription factors.
link |
It will be a proper pill
link |
and the whole body gets rejuvenated by 20 years.
link |
That's what we're aiming for.
link |
Now we do it with gene therapy in the eye and other places.
link |
So in the eye, yes, it's single injection.
link |
The genes go into the retina
link |
and we can turn it on with a drug called doxycycline.
link |
And we do that in the mice for four to eight weeks.
link |
Then the eye gets younger.
link |
We can measure that because we can measure the clock.
link |
And then the vision comes back in those mice.
link |
And I don't see any reason why it shouldn't work in people
link |
because it's the same structures and mechanisms
link |
that are on in the human as well.
link |
And it's one injection.
link |
As you mentioned, injections into the eye,
link |
obviously nobody should do this
link |
outside of an ophthalmology clinic.
link |
And they're definitely by an ophthalmologist.
link |
But the injections into the eye are painless
link |
if done correctly by the right person.
link |
It sounds dreadful, but it's actually,
link |
I've seen it done hundreds of times.
link |
I've done it thousands of times,
link |
and it's not to myself, but to other creatures.
link |
And there's a way of doing this
link |
that's completely painless to the person.
link |
Oh, there are a few.
link |
It's a tiny, tiny needle too.
link |
But the great thing about this
link |
is that it's a one-time treatment.
link |
Those genes go into the back of the eye
link |
and stay there forever.
link |
And you can just turn them on whenever you want.
link |
So what we've found is you can turn them on in the mice,
link |
they get their vision back,
link |
and then you turn it off again.
link |
And so far, many months out,
link |
the benefit has remained.
link |
But if it does decline,
link |
we'll just turn it back on and reset the system,
link |
So one day, what's exciting
link |
is that we could potentially do this
link |
across the entire body
link |
and just take this antibiotic every five years
link |
and go back time and time again.
link |
In thinking about the body
link |
and what's going on under the hood,
link |
I'm amazed still that there isn't
link |
a simple, affordable technology
link |
that would allow me to just look into my body
link |
and see whether or not there are any tumors growing anywhere.
link |
I mean, it's not that hard to look into the body.
link |
I mean, that the technology exists.
link |
Why hasn't anybody created an at-home
link |
or pseudo at-home solution,
link |
like a clinic where you can go and pay 50 bucks or 100 bucks
link |
and see if you have any tumors growing in your body?
link |
Yeah, it's still expensive.
link |
You can get your doctor to try to get you in.
link |
There's some companies that offer blood tests
link |
that look at circulating DNA that'll measure it.
link |
We're getting there.
link |
We're still probably five to 10 years away
link |
from being really cheap.
link |
You can do things like a colon cancer test at home.
link |
I think it's a hundred and something dollars.
link |
You ship off your shit, excuse my language,
link |
and they measure it.
link |
And they tell you if you've got colon cancer
link |
with high probability.
link |
I did that during the pandemic
link |
because I didn't want to get a colonoscopy.
link |
Is it more accurate or as accurate as a colonoscopy?
link |
I believe it's close to being as accurate.
link |
The downside is that during a colonoscopy,
link |
they can pinch off the polyps that are looking dangerous,
link |
whereas this obviously isn't that.
link |
But it's certainly easier to do.
link |
And my father, who's Australian,
link |
tells me that it's free for Australians.
link |
They get this test routinely.
link |
I want to return to the topic that I took us away from,
link |
so I apologize, which is behavioral protocols.
link |
Do you regularly do the cold shower thing,
link |
ice baths, cold water swims?
link |
Are you into that whole biz?
link |
Well, you do know that I've done it at least once
link |
because we did it together.
link |
Not the same bath, just to be very clear.
link |
Same sauna, different ice baths.
link |
The idea of Sinclair and Huberman
link |
taking an ice bath together is,
link |
it might warm some people's hearts,
link |
but just to be very clear,
link |
same ice bath, different times.
link |
Thank you for clarifying.
link |
I don't do them regularly.
link |
I do try to sleep cool.
link |
I sleep better anyway.
link |
I try to dress without a lot of warm clothes.
link |
I'm here in a t-shirt and it's middle of summer,
link |
but in winter, I'll try to wear a t-shirt too.
link |
So you're challenging your system to thermoregulate.
link |
I've got this hypothesis with Ray Cronus.
link |
We published what's called the metabolic winter hypothesis,
link |
which is, tens of thousands of years ago,
link |
we were either hungry or cold or both.
link |
And we rarely experienced that now.
link |
And so we try to give ourselves the metabolic winter.
link |
And part of the problem, I think,
link |
with the obesity epidemic is that we're never cold.
link |
And cold, when you're cold, you have to burn energy.
link |
It may be only slightly.
link |
But over the whole night, if you're a little bit cool,
link |
you'll actually expend more energy.
link |
So I try to do that.
link |
But I'm not a big fan of cold showers.
link |
The sauna, I don't have access to my gym as much as I did.
link |
But I do wanna get back into it.
link |
I used to do it regularly with my son
link |
and I posted on Instagram once
link |
that he could stay in there for 15 minutes
link |
and I could only stay in for about three.
link |
Anyway, long story short,
link |
I try to compensate with changes in my diet and exercise
link |
until I get back into it.
link |
You reminded me of something that I meant to ask earlier,
link |
that obesity reduces NAD levels and accelerates aging.
link |
I mean, okay, so again, this is the scientist in us.
link |
So someone's carrying a lot of excess adipose tissues,
link |
subcutaneous and visceral fat.
link |
But why should that reduce NAD in any ways
link |
that are independent of effects on glucose and insulin?
link |
Is there something direct about white adipose tissue?
link |
And the reason I ask this
link |
is not simply to dig into mechanism alone,
link |
but I think there are really interesting data now
link |
that fat actually gets neural innervation.
link |
I mean, it's not just stored fuel.
link |
It's stored fuel that's acting as an endocrine organ,
link |
So yeah, why would being fat make people age faster?
link |
Yeah, that's a question that is so obvious,
link |
but so few people ask it.
link |
That's what makes you a good scientist.
link |
And so that we don't know,
link |
but I'll give you my best answer,
link |
which is that obesity comes along with a lot of problems
link |
that include a lot of senescent cells in fat.
link |
If you stain old fat for senescent cells, it lights up.
link |
And when you kill off those cells,
link |
at least in mice and maybe in humans,
link |
it looks like the fat is less toxic to the body
link |
because those senescent cells in the fat
link |
are secreting these inflammatory molecules
link |
that will accelerate aging as we now know.
link |
You talk about the sirtuins and NAD.
link |
So if we just look philosophically at why this would be,
link |
the sirtuins only like to come on or get activated
link |
when the body is under adversity.
link |
And if a cell is surrounded by fat or contains a lot of fat,
link |
it's going to think times are good,
link |
doesn't need to switch on.
link |
So that's the evolutionary argument.
link |
Mechanistically, we don't know,
link |
but it could have something to do
link |
with the response to glucose,
link |
which then responds to the sirtuin gene.
link |
But that hasn't been worked out very well.
link |
And is there any evidence
link |
that leptin, this hormone from fat,
link |
can actually interact with the sirtuin pathway?
link |
I don't recall seeing that.
link |
Maybe I could do a sabbatical in your lab
link |
and that'd be a fun one.
link |
Because leptin during development
link |
is what triggers the permission
link |
for the hypothalamus to enter puberty, right?
link |
This is why kids that eat a lot
link |
when they're young and get overweight
link |
will also start to undergo puberty more quickly,
link |
although they have reproductive issues later.
link |
Well, yeah, we should study the hypothalamus together
link |
because the hypothalamus can control the aging of the body.
link |
The most interesting part of the brain.
link |
If you turn on the SIRT1 gene,
link |
the sirtuin gene that we work on in the hypothalamus,
link |
it actually will extend lifespan.
link |
Also, it's been shown by Dongxin Cai
link |
at Albert Einstein College of Medicine
link |
that if you inhibit inflammation
link |
in the hypothalamus in a mouse,
link |
it will increase or maintain the expression
link |
of what's called GnRH,
link |
which is the hormone that he found actually controls
link |
longevity in the mouse in part.
link |
And so keeping inflammation down in the hypothalamus
link |
is sufficient to extend the lifespan of animals.
link |
And I reviewed that paper for Nature about seven years ago.
link |
And that was the first demonstration
link |
that the hypothalamus is one of the leading regulators
link |
of the body's age.
link |
I find this fascinating.
link |
GnRH, for those of you that don't know,
link |
actually comes from neurons in the hypothalamus
link |
that then literally reach down into the pituitary
link |
and trigger the release of all the things
link |
that control fertility,
link |
luteinizing hormone, follicle stimulating hormone, et cetera.
link |
It's such a powerful set of neurons,
link |
and it's never really been clear
link |
what at a behavioral level triggers the release of GnRH.
link |
There's all the stories about pheromones
link |
and timers and puberty, et cetera,
link |
but environmental conditions and dietary conditions
link |
and behaviors that can control GnRH release,
link |
I think is an incredible area for exploration.
link |
I'd love to do that sabbatical, by the way.
link |
I have a couple seemingly random questions,
link |
but I can't help but ask because one thing I like to do
link |
is forage the internet for practices
link |
that at least more than a few people are doing
link |
and then wonder whether or not there's any basis for it.
link |
You mentioned methylation as a detrimental process,
link |
the way it disrupts the epigenome,
link |
the CD reader, so to speak.
link |
There are people out there who are ingesting methylene blue.
link |
And when I was a kid,
link |
I used methylene blue to clean my fish tank.
link |
And I love fish tanks.
link |
I know you're into aquaria also.
link |
A different podcast episode, talk about aquaria,
link |
but why in the world would people ingest methylene blue?
link |
Meaning, is their logic correct
link |
and or is that a dangerous practice?
link |
I'm not sure I'd want to ingest methylene blue.
link |
Sounds like a bad thing to do.
link |
It stains your body.
link |
You've seen these people turn blue.
link |
Yeah, there was someone in my lab as a postdoc
link |
was using it to study a completely different process
link |
related to the blood brain barrier
link |
and used to inject into animals and they would turn blue.
link |
But then again, people ingest colloid silver.
link |
You know, they'll put in there.
link |
There's this, please, people don't do this.
link |
Or if you do, just don't tell me because I won't like it.
link |
They, people put it in their eyes
link |
and some people actually stain their skin.
link |
They actually become kind of a,
link |
this silver, purple, brown color if they do it excessively.
link |
I mean, there's a lot of crazy stuff out there,
link |
but what do you think they're thinking
link |
with this methylene blue thing
link |
or should we just get them to a good psychiatrist?
link |
I don't know for sure.
link |
I think methylene blue was found to extend the lifespan
link |
of some lower organism and that's where it came from.
link |
My recollection with the-
link |
This is on lower organisms.
link |
Yes, smaller organisms.
link |
I think, doesn't, do you remember, Andrew,
link |
does it interrupt or interfere with mitochondrial activity
link |
and that's why we're doing it.
link |
Yeah, we need to look this up and post it.
link |
We'll get to the bottom of this.
link |
But those methyls, let's talk about those.
link |
Those methyls have to be placed
link |
on the right part of the genome.
link |
They get attached to the right genes and the wrong genes.
link |
And if you have a lot of methylation,
link |
it's going to mess up the epigenome.
link |
Smoking will do that, lack of exercise, all that good stuff.
link |
So what you actually want to do is you want to measure it
link |
and make sure what you're doing with your body is working.
link |
How do you know that if you do this
link |
or that is actually helping?
link |
And so you can test your age.
link |
I could take a swab from your mouth
link |
and tell you how old you are biologically,
link |
and then we could work on trying to bring that down.
link |
And actually, there are anecdotes now
link |
that people are reversing their age by a decade or more
link |
just by doing some of the things that we've talked about
link |
and some other cutting-edge stuff
link |
that I'm going to write about.
link |
But yeah, but you have to measure stuff.
link |
I didn't want to forget to bring that up.
link |
I'm measuring stuff all the time.
link |
I have blood tests like you.
link |
I've got this monitor that's stuck to my chest right now
link |
that's measuring myself 1,000 times a second.
link |
And I measure my biological age.
link |
What's it measuring 1,000 times a second?
link |
A huge host of things?
link |
So this little device is stuck here,
link |
and it's for two weeks.
link |
You just recharge it or send it back and get a new one.
link |
It's got body temperature movement, heart rate variability.
link |
It's an FDA-approved device.
link |
It's not one of these recreational things.
link |
It also listens to my voice.
link |
Eventually, it'll tell me if I need a psychiatrist
link |
or if I'm depressed.
link |
It will tell me how I sleep, obviously.
link |
But when you put all that data together
link |
and it's individualized and anonymized,
link |
it can now tell my doctor in real time
link |
if I've got a cold that needs an antibiotic
link |
or it's just a virus,
link |
if I am suffering from COVID-19,
link |
or even if I'm going to have a heart attack next week.
link |
And so these little devices
link |
are going to be with us all the time
link |
instead of going to your doctor once a year,
link |
which is ludicrous.
link |
I have to ask you about X-rays
link |
because every time I go through the scanner at the airport,
link |
I think Sinclair would never do this.
link |
And the argument I heard you give about this before
link |
was a really excellent one,
link |
which is that it's a low level amount of radiation
link |
going through at the airport,
link |
but the argument is always,
link |
well, it's just as much as on the plane.
link |
And your argument, your counterargument, I should say,
link |
was, well, then why would I want to do both, right?
link |
So when you go to the airport,
link |
assuming you're not running late
link |
and you have to go through the standard line,
link |
what do you say to them?
link |
Do you say, I'm David Sinclair,
link |
and then they shuttle you to your own line?
link |
You do say, I don't like this thing.
link |
Do you have to give them a reason?
link |
You can say, I don't want this,
link |
and they'll get annoyed
link |
because it's hard for them to pat you down,
link |
but you get a pat down and you're done.
link |
As long as you're not in a hurry, it's fine.
link |
If you want to pay for the TSA Pre in America
link |
or the way to get around those scanners, you can do that.
link |
So I travel a lot, so it's worth it anyway.
link |
But I just go through the metal detector.
link |
I don't get scanned.
link |
And the metal detector doesn't have the same problem.
link |
And what about x-rays at the dentist?
link |
Well, you know, one x-ray is not going to kill you.
link |
Two is not going to kill you.
link |
But I'd rather- Three will kill you.
link |
No, I'm just kidding.
link |
I try to limit it because it's cumulative.
link |
And I went for six years without having a dental x-ray.
link |
And then my last visit, I just gave up.
link |
I was tired of arguing with my dentist.
link |
So they gave me one,
link |
but they've got lead coats on
link |
and they put lead all over your body.
link |
That's telling you something right there.
link |
And funnily enough, my teeth hadn't changed.
link |
Now, you could balance that by saying,
link |
well, one x-ray, two x-rays, three x-rays
link |
is worth it if I have cavities.
link |
You want to know what's in there.
link |
But doing it regularly, for me,
link |
I don't think was worth it
link |
because my teeth were in perfect health
link |
and have always been.
link |
Don't have any cavities.
link |
Didn't have braces.
link |
Don't stop scanning me.
link |
I mean, I know you have to pay for the machine,
link |
but do I have a choice?
link |
So stop pressuring me.
link |
You know, who shared your sentiments about x-rays
link |
and the dentist in general,
link |
my apologies to the dentists out there,
link |
was the great physicist, Richard Feynman.
link |
This is a story about him
link |
that's not especially well-known,
link |
but he had very serious health concerns about x-rays
link |
because he understood the physics
link |
and he understood enough biology
link |
that he was actually quite vocal
link |
about his dislike of dental technology and its dangers.
link |
And he talked about some of that.
link |
People can find that on the internet if they like.
link |
Speaking of people who are like Feynman,
link |
who've been engaged in public discourse about science,
link |
one of the things that I appreciate about you,
link |
in fact, the way that you and I
link |
initially came to know one another
link |
is through your public health education efforts.
link |
So obviously we're doing this podcast.
link |
You've done the Joe Rogan podcast, Lex Friedman's podcast.
link |
Excuse me, Lex, I'm still adjusting that.
link |
Lex Friedman podcast and many other podcasts.
link |
You've written an amazing book.
link |
What are you thinking these days
link |
in terms of what the world needs
link |
in terms of education from scientists,
link |
education from MDs, education in general
link |
as it relates to these things?
link |
Because I think if nothing else,
link |
2020 revealed to us that there's a gap.
link |
There's a gap in understanding
link |
and that the scientists too are guilty
link |
of not knowing what to do with all the information
link |
that's out there on PubMed or elsewhere.
link |
Just what are you thinking for yourself?
link |
And in general, I'd like to just know
link |
what do you think the world needs there?
link |
Maybe we can recruit some more public educators.
link |
Yeah, well, we've gone from a time
link |
when you and I were in college and young professors
link |
where the only way to get our voice out to the public
link |
was either through a newspaper
link |
or a very short radio interview,
link |
which for me was extremely frustrating
link |
because particularly the newspapers and my topic
link |
every time was twisted into something
link |
that was not just embarrassing,
link |
but Harvard University used to bring me into the back office
link |
and slap my wrist. Frankenstein.
link |
How did you say such a thing?
link |
We're all gonna live 200, I didn't say that.
link |
So we're now also in a world
link |
where we're overwhelmed with information
link |
and most of it is wrong
link |
and anyone can pretend to be an expert.
link |
So we've gone from early days to now, the future,
link |
and we're experiencing it right now
link |
thanks to guys like you, people like you,
link |
is that the experts, some experts,
link |
a small number who are brilliant and good communicators
link |
are talking directly to the public.
link |
This has never been able to be possible
link |
until this time right now.
link |
So another five years from now, and certainly by 10 years,
link |
I would hope that there are trusted sources of information
link |
of people who cannot just communicate the ideas directly,
link |
but are able to talk about things that are going on
link |
that aren't even published yet to say,
link |
here's what's really going on
link |
and this is what the future looks like.
link |
But this is somebody like yourself
link |
who spent their whole life studying a particular topic
link |
and knows what they're talking about.
link |
And this is also something
link |
that I think most people don't know,
link |
that we scientists, if we tell a lie, we burst into flames.
link |
We absolutely cannot tell something that's untrue
link |
and to the best of our knowledge, we say it as it is
link |
because if we don't, we're beaten up
link |
or we kicked out of the university.
link |
So the people who survived to our age,
link |
and I'm a little older than you,
link |
so I've survived a bit longer.
link |
But a lot younger inside.
link |
No, but we have to measure you with my stroke test.
link |
I probably need a little help, but hopefully not too much.
link |
We'll measure that and we'll work on your eating.
link |
But this is really, really important
link |
is that finally people like you
link |
are allowed by our universities to talk to the public.
link |
I used to do it with a real threat,
link |
People would look at me,
link |
oh, he's a salesman, he's promoting this and that.
link |
It was seen as a real negative.
link |
But finally, I think we're in a world
link |
where it's not negative anymore.
link |
And the pandemic showed that we needed voices of reason,
link |
voices of fact that you could trust.
link |
And you can see the popularity of your podcast
link |
shows that the public are desperate for facts
link |
that they can trust
link |
because they don't know what to believe anymore.
link |
Well, I am being completely honest when I say this
link |
that I followed your lead.
link |
I saw you on the Joe Rogan podcast and my jaw dropped.
link |
I was like, this is amazing.
link |
Because he had other good scientists on before,
link |
but your tenured professor, Harvard genetics,
link |
department of genetics.
link |
And for those of you who don't know,
link |
there's Harvard and of course Harvard Medical School,
link |
and they're both excellent, of course,
link |
but these are the top, top tiers of academia.
link |
And I certainly understand what it takes
link |
to get there and survive there
link |
and to thrive there.
link |
It's like a game of pinball.
link |
You just get to, if you're doing really well,
link |
you get to keep playing.
link |
That's the truth in academia.
link |
And if you're not, you stop playing basically.
link |
But when I saw you explain what you were doing
link |
in a way that was accessible to people
link |
and also talking about possible protocols
link |
that they might explore for themselves
link |
to see if those were right for them,
link |
I was just dazzled and excited.
link |
And I made every effort to get in contact with you
link |
and the rest is history.
link |
But I think what's really exciting to me these days
link |
is because of 2020 and everything that's happened
link |
and it continues to happen, there's a thirst for knowledge.
link |
There's also this direct to the public route
link |
that you mentioned.
link |
And I think there's also an openness,
link |
I'd love your thoughts on this,
link |
but it seems to me that there's an openness
link |
from the general public about health practices,
link |
that there are actually things that people can do
link |
to control their stress level, to control their sleep,
link |
to control their cholesterol,
link |
if that's what they need to do, maybe they don't,
link |
and to even control their lifespan,
link |
which I think is remarkable.
link |
And I know I speak on behalf of so many people
link |
when I just, I want to say thank you.
link |
You've truly changed the course of my life.
link |
I would not be sitting here doing this
link |
were it not for your example.
link |
And I always say, Sinclair, many people have written books,
link |
many academics have written books as you have,
link |
but in terms of doing podcasts
link |
and really getting out there with your message
link |
in a way that I have to assume raised your cortisol level
link |
and heart rate just a little bit,
link |
but you did it nonetheless.
link |
You know, you were truly first man in
link |
and that deserves a nod
link |
and I have a great debt of gratitude to you for that.
link |
So thank you so much.
link |
Thanks, Andrew, you've become a good friend
link |
and I'm super proud of what you've done
link |
and what you, I know what you will do.
link |
So in addition to your book
link |
and your presence on social media,
link |
Instagram and Twitter, and appearances on podcasts,
link |
recently I've noticed that you've opened up
link |
a sort of an email slash website that people can ask,
link |
access, excuse me, to get some information
link |
about their own health and rates of aging.
link |
Tell us about that and what's being measured
link |
and what is this test that you've been working on,
link |
secretly and now soon not so secretly?
link |
Yeah, well, what I want is a credit score for the body
link |
to make it easy for people to follow their health.
link |
And there is a number,
link |
there's a biological age that you can measure.
link |
Unfortunately, the test is many hundreds of dollars
link |
right now, but in my lab,
link |
we've been able to bring that down a lot.
link |
And so I want to democratize this test
link |
so that everybody has access to a score for their health
link |
that can predict not just their future health
link |
and time of death, but to change it.
link |
And I'm building a system that will point people
link |
in the right direction and give them discounts
link |
for certain things that will improve
link |
not just their health now,
link |
but 10, 20, 30 years into the future.
link |
And we can measure that and very cheaply keep measuring it
link |
to know that you're on the right track.
link |
Because if you don't measure something,
link |
you can't optimize it.
link |
And so this is the biological age test.
link |
We've developed it.
link |
It's a simple mouth swab.
link |
We're rolling it out.
link |
We're building the system right now.
link |
And there is a signup sheet
link |
because a lot of people want to get in line.
link |
Go to drsinclair.com.
link |
You can get on that and you'll be one of the first people
link |
in the world to get this test and see what we're doing.
link |
Will people be celebrating their biological age birthdays?
link |
In other words, if I'm minus, like if I could imagine,
link |
so I'm 45 right now, soon to be 46.
link |
But if I were to be so lucky
link |
is to get my biological age to 35 within 12 months,
link |
maybe can help me do that.
link |
Do I get to celebrate a negative birthday?
link |
And my plan is that those people
link |
who take their age back a year or more,
link |
we think we can go back 20 years eventually,
link |
they'll get a birthday card from me
link |
and it's a negative birthday card.
link |
And probably very little actual birthday cake
link |
being ingested, but who cares?
link |
Because you're living that much longer.
link |
Well, it's full of stevia, that'll be fine.
link |
And thank you for talking to us today.
link |
I realized I took us down deep into the guts of mechanism
link |
and as well, talking about global protocols,
link |
everything from what one can do and take if they choose,
link |
that's right for them,
link |
to how to think about this whole process
link |
that we talk about when we talk about lifespan,
link |
as always incredibly illuminating.
link |
Thank you for joining me for my conversation
link |
with Dr. David Sinclair.
link |
If you're enjoying and or learning from this podcast,
link |
please subscribe to our YouTube channel.
link |
In addition, please subscribe on Apple and or Spotify
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and on YouTube, you can leave us comments
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and you can leave us suggestions for future podcast guests
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that you would like us to feature.
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In addition on Apple,
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you can leave us up to a five-star review
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and you can leave us a comment.
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Please also check out the sponsors mentioned
link |
at the beginning of this episode.
link |
That's the best way to support this podcast.
link |
Also, I teach science and science-related tools
link |
on Instagram, it's Huberman Lab on Instagram.
link |
I also have a Twitter, which is also Huberman Lab.
link |
So be sure to check those out.
link |
A lot of the material covers things similar to the podcast,
link |
but oftentimes I'll cover unique material
link |
not featured at all on the podcast.
link |
So that's Huberman Lab on Instagram and on Twitter.
link |
In addition, we have a Patreon,
link |
it's patreon.com slash Andrew Huberman,
link |
and there you can support the podcast
link |
at any level that you like.
link |
Today and in many other previous episodes
link |
of the Huberman Lab podcast, we discuss supplements.
link |
While supplements aren't necessary or right for everybody,
link |
many people derive tremendous benefit from supplements.
link |
For that reason, we've partnered with Thorne, T-H-O-R-N-E,
link |
because Thorne supplements are the absolute highest quality
link |
and the absolute highest precision,
link |
meaning what you see listed on the bottle
link |
is what's actually in the bottle,
link |
which is not the case for many supplement companies
link |
Thorne is one of the partners of the Mayo Clinic
link |
and all the major sports teams,
link |
and so they really are very trusted,
link |
very highest quality.
link |
If you want to see the supplements that I personally take,
link |
you can go to thorne.com slash the letter U slash Huberman,
link |
and there you'll see the supplements that I take.
link |
You can get 20% off any of those supplements,
link |
and if you navigate deeper into the Thorne site
link |
through that portal, you'll also get 20% off
link |
any of the other supplements that Thorne makes.
link |
So again, it's thorne.com slash the letter U slash Huberman
link |
to get 20% off any of the supplements that Thorne makes.
link |
Also take note that the Lifespan podcast
link |
featuring Dr. David Sinclair as a host
link |
launches Wednesday, January 5th.
link |
You can find the first episode here
link |
on the Huberman Lab podcast channel.
link |
They also have their own independent channel.
link |
You can find the link to that channel in the show notes,
link |
so please go there, subscribe on YouTube,
link |
also on Apple and Spotify.
link |
I've seen these episodes.
link |
They are phenomenal,
link |
and you're going to learn a tremendous amount about aging
link |
and how to slow and reverse aging
link |
from the world expert himself, Dr. David Sinclair.
link |
And last, but certainly not least,
link |
thank you for your interest in science.