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Dr. 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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depending on how bright or dim a given environment is.
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With Roca eyeglasses and sunglasses,
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you always see things with the utmost clarity.
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In addition, they're very lightweight
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and they won't slip off your face.
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In fact, they were designed to be worn while biking
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or running and in various activities,
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but they also have a terrific aesthetic
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so you could wear them to dinner or work.
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I wear readers at night and when I drive
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and I wear the sunglasses for most of the day.
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If you'd like to try Roca sunglasses or eyeglasses,
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you can go to roca.com, that's R-O-K-A.com
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Again, that's Roca, R-O-K-A.com
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and enter the code Huberman at checkout.
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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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I've long been a believer in getting regular blood work done
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for the simple reason that many of the factors
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you can also get a clear picture
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of what your biological age is
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and compare that to your chronological age.
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And obviously your biological age is the important one
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because it predicts how long you will live
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and it's the one that you can control.
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The great thing about Inside Tracker
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but it also offers clear directives to lifestyle factors,
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nutritional factors, and supplementation
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to get 25% off any of Inside Tracker's plans.
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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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00:06:15.860
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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Each serving of Magic Spoon has zero grams of sugar,
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So it really matches that low carb, keto-ish approach.
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There's only 140 calories per serving
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and they have a variety of flavors,
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cocoa, fruity, peanut butter, frosted.
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I particularly like frosted because it tastes like donuts.
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I try not to eat donuts, but I do love the frosted.
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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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If you want to try Magic Spoon,
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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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typically you do.
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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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It was horrible.
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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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Yeah, isn't it?
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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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It was horrible.
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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
link |
00:13:15.740
or a compact disc.
link |
00:13:16.580
For the younger people, we used to use these things.
link |
00:13:18.260
I recall.
link |
00:13:19.080
Yep.
link |
00:13:19.920
And then the epigenome is the reader that says,
link |
00:13:21.600
okay, in this cell, we need to play that set of songs.
link |
00:13:25.700
And in this other cell,
link |
00:13:26.540
we have to play a different set of songs.
link |
00:13:28.340
But over time, aging is the equivalent
link |
00:13:30.020
of scratching the CD and the DVD
link |
00:13:32.260
so that you're not playing the right songs.
link |
00:13:34.520
And cells, when they don't hear the right songs,
link |
00:13:37.640
they get messed up and they don't function well.
link |
00:13:40.180
And that is what I'm saying is the main driver of aging.
link |
00:13:43.360
And these other hallmarks
link |
00:13:45.060
are largely manifestations of that process.
link |
00:13:47.580
Can we go a little deeper into what these scratches are?
link |
00:13:52.140
Is it the way that the DNA are packed into a cell?
link |
00:13:57.020
Is it the way that they're spaced?
link |
00:14:00.860
What are the scratches that you're referring to?
link |
00:14:04.700
So DNA is six foot long.
link |
00:14:06.660
If you join your chromosomes together,
link |
00:14:07.820
you get about six foot per cell.
link |
00:14:09.880
So there's enough to go to the moon
link |
00:14:11.080
and back eight times in your body.
link |
00:14:12.740
And it has to be wrapped up to exist inside us.
link |
00:14:16.140
But it's not just wrapped up willy-nilly.
link |
00:14:18.260
It's not just a bundle of string.
link |
00:14:20.340
It's wrapped up very carefully in ways
link |
00:14:22.140
that dictates which genes are switched on and off.
link |
00:14:25.360
And when we're developing in the embryo,
link |
00:14:27.740
the cell marks the DNA with chemicals that says,
link |
00:14:30.800
okay, this gene is for a nerve cell.
link |
00:14:32.780
You, you cell, will stay a nerve cell
link |
00:14:35.380
for the next hundred years, if you're lucky.
link |
00:14:37.620
Don't turn into a skin cell.
link |
00:14:38.900
That would be bad.
link |
00:14:40.540
And those chemicals,
link |
00:14:42.660
there are many different types of chemicals,
link |
00:14:43.920
but one's called methylation.
link |
00:14:45.500
Those little methyls will mark which songs get played
link |
00:14:48.860
for the rest of your life.
link |
00:14:50.360
And there are other marks that change daily.
link |
00:14:52.740
But in total, what we're saying is that
link |
00:14:54.820
the body controls the genome through the ability
link |
00:14:58.340
to mark the DNA and then compact some parts of it,
link |
00:15:03.360
silence those genes, don't read those genes,
link |
00:15:05.980
and open others, keep others open that should stay open.
link |
00:15:09.820
And that pattern of genes that are silent and open,
link |
00:15:13.620
silent open, is what dictates the cell's type,
link |
00:15:16.980
the cell's function.
link |
00:15:18.340
And then the scratches are the disruption of that.
link |
00:15:21.140
So genes that were once silent,
link |
00:15:24.180
and you could say it's a gene that is involved in skin,
link |
00:15:28.540
it's starting to come on in the brain,
link |
00:15:29.940
shouldn't be there, but we see this happen,
link |
00:15:32.060
and vice versa, the gene might get shut off
link |
00:15:33.940
over time during aging.
link |
00:15:35.500
Cells over time lose these structures,
link |
00:15:38.460
lose their identity,
link |
00:15:39.480
they forget what they're supposed to do,
link |
00:15:41.700
and we get diseases.
link |
00:15:43.300
We call that aging, and we can measure that.
link |
00:15:46.100
In fact, we can measure it in such a way
link |
00:15:47.780
that we can predict when somebody's going to die
link |
00:15:49.980
based on the changes in those chemicals.
link |
00:15:53.400
Are these changes the same sorts of changes
link |
00:15:55.740
that underlie the outward body surface manifestations
link |
00:16:00.580
of aging that most of us are familiar with?
link |
00:16:02.340
Graying of the hair, wrinkling of the skin,
link |
00:16:04.400
drooping of the face.
link |
00:16:09.020
Walking around New York lately, it's amazing to me,
link |
00:16:11.940
there are certain people that seem to walk
link |
00:16:14.100
looking down at the sidewalk
link |
00:16:15.500
because their spine is essentially in a C-shape, right?
link |
00:16:19.740
A hallmark, if you will,
link |
00:16:21.260
of aging that most of us are familiar with.
link |
00:16:23.760
Are these same sorts of DNA scratches associated with that,
link |
00:16:26.860
or are we talking about people
link |
00:16:27.940
that potentially are going to look older,
link |
00:16:30.200
but simply live longer?
link |
00:16:32.160
Well, it's actually, you are as old as you look
link |
00:16:34.940
if you want to generalize.
link |
00:16:36.720
So let's start with centenarian families.
link |
00:16:39.260
These are families that tend to live over 100.
link |
00:16:42.020
When they're 70, they still look 50 or less.
link |
00:16:45.020
So it is a good indicator.
link |
00:16:47.540
It's not perfect because you can,
link |
00:16:48.980
like me, grow up in Australia
link |
00:16:50.740
and accelerate the aging of your skin,
link |
00:16:54.020
but in general, how you look.
link |
00:16:55.560
No one's ever died from gray hair,
link |
00:16:57.460
but overall, you can get a sense
link |
00:16:59.360
just from the ability of skin to hold itself up,
link |
00:17:02.540
how thin it is, the number of wrinkles.
link |
00:17:04.640
That is actually, a great paper just came out
link |
00:17:07.440
that said that an AI system looking at the face
link |
00:17:10.060
could very accurately predict someone's age.
link |
00:17:12.240
Very interesting.
link |
00:17:13.700
So I started off in developmental neurobiology.
link |
00:17:16.920
So one of the things that I learned early on
link |
00:17:19.500
that I still believe wholeheartedly
link |
00:17:22.620
is that development doesn't stop at age 12 or 15,
link |
00:17:27.760
or even 25, that your entire life
link |
00:17:30.700
is one long developmental arc, right?
link |
00:17:35.100
So in thinking about different portions
link |
00:17:37.220
of that developmental arc,
link |
00:17:38.760
the early portion of infancy and especially puberty
link |
00:17:43.260
seem like especially rapid stages of aging.
link |
00:17:47.060
And I know we normally look at babies and children
link |
00:17:49.740
and kids in puberty and we think,
link |
00:17:50.880
oh, they're so vital, they're so young.
link |
00:17:53.860
And yet the way you describe these changes in the epigenome
link |
00:17:58.140
and the way you have framed aging as a disease
link |
00:18:01.060
leads me to ask, are periods of immense vitality,
link |
00:18:07.700
the same periods when we're aging faster?
link |
00:18:11.340
Yes, yes, and this is something I've never talked about,
link |
00:18:15.060
at least not publicly, so this is a really good question.
link |
00:18:18.100
So those chemicals we can measure,
link |
00:18:20.260
it's also known as the Horvath clock,
link |
00:18:21.700
it's the biological clock,
link |
00:18:22.900
it's separate from your chronological age.
link |
00:18:25.300
So actually what I didn't mention is that
link |
00:18:27.140
when the AI looked at the faces of those people,
link |
00:18:29.580
they could predict their biological age, their internal age.
link |
00:18:33.460
So your skin represents the age of your organs as well.
link |
00:18:36.820
And the people that look after themselves,
link |
00:18:38.540
we can talk about how to do that later,
link |
00:18:40.500
but there are some people that are 10, 20 years younger
link |
00:18:42.860
than other people biologically.
link |
00:18:46.100
And it turns out if you measure that clock from birth
link |
00:18:48.460
or even before birth, if you look at animals,
link |
00:18:50.860
there's a massive increase in age
link |
00:18:53.380
based on that clock early in life.
link |
00:18:55.940
So you're right, so that's a really important point
link |
00:18:58.460
that you have accelerated aging
link |
00:19:00.460
during the first few years of life,
link |
00:19:02.100
and then it goes linear towards the rest of your life.
link |
00:19:05.500
But there's another interesting thing you brought up,
link |
00:19:06.980
which is that we're finding that the genes
link |
00:19:08.740
that get messed up, that get scratched,
link |
00:19:11.060
that are leading to aging
link |
00:19:13.060
are those early developmental genes.
link |
00:19:15.500
They come on late in life and just mess up the system,
link |
00:19:19.020
and they seem to be particularly susceptible
link |
00:19:20.820
to those scratches.
link |
00:19:22.500
So what's causing the scratches?
link |
00:19:24.260
Well, we know of a couple of things in my lab,
link |
00:19:25.900
we figured out one is broken chromosomes, DNA damage,
link |
00:19:30.140
particularly cuts to the DNA breaks.
link |
00:19:32.300
So if you have an X-ray or a cosmic ray,
link |
00:19:35.340
or even if you go out in the sun
link |
00:19:36.700
and you'll get your broken chromosomes,
link |
00:19:38.820
that accelerates the unwinding
link |
00:19:41.460
of those beautiful DNA loops that I mentioned.
link |
00:19:46.380
We can actually do this to a mouse.
link |
00:19:47.860
We can accelerate that process,
link |
00:19:50.140
and we get an old mouse, 50% older,
link |
00:19:52.500
and it has this bent spine kyphosis,
link |
00:19:54.660
it has gray hair, its organs are old.
link |
00:19:56.820
So we now can control aging in the forwards direction.
link |
00:19:59.940
The other thing that accelerates aging
link |
00:20:01.540
is massive cell damage or stress.
link |
00:20:05.180
So we pinched nerves,
link |
00:20:07.260
and we saw that their aging process
link |
00:20:09.100
was accelerated as well.
link |
00:20:10.580
Incredible.
link |
00:20:11.420
Yeah, this is more of an anecdotal phenomenon.
link |
00:20:15.060
It is an anecdotal phenomenon,
link |
00:20:16.780
but this experience of in junior high school,
link |
00:20:20.260
you know, going home for a summer and you come back,
link |
00:20:23.420
high school in the US usually starts eighth or ninth grade
link |
00:20:26.100
or grade eight or grade nine for your Canadians.
link |
00:20:29.780
And then some of the kids,
link |
00:20:32.580
like they grew beards over the summer,
link |
00:20:34.620
or they completely matured quickly over the summer.
link |
00:20:37.780
Do you think there's any reason to believe
link |
00:20:39.540
that rates of entry into and through puberty
link |
00:20:44.060
can predict overall rates of aging?
link |
00:20:47.260
In other words, if a kid is a slow burner, right?
link |
00:20:52.260
They basically acquire the traits of puberty
link |
00:20:57.020
slowly over many years.
link |
00:20:59.020
Can we make some course prediction
link |
00:21:01.820
that they are going to live a long time
link |
00:21:03.740
versus a kid that goes home for the summer
link |
00:21:05.740
and comes back a completely different organism
link |
00:21:08.380
or appearing to be a completely different organism?
link |
00:21:10.780
Like they basically age very quickly in the summer.
link |
00:21:12.700
Does that mean they're aging very quickly overall?
link |
00:21:14.900
Well, yeah, I don't want to scare anybody.
link |
00:21:16.780
Sure.
link |
00:21:17.620
There are studies that show that
link |
00:21:21.540
the slower you take to develop,
link |
00:21:23.460
it also is predictive of having a longer, healthier life.
link |
00:21:27.540
And it may have something to do with growth hormone.
link |
00:21:30.100
We know that growth hormone is pro-aging.
link |
00:21:33.780
Anyone who's taking growth hormone, pay attention.
link |
00:21:37.260
We notice, look at someone who's taking growth hormone.
link |
00:21:39.820
They often will acquire these characteristics of vitality,
link |
00:21:42.940
like improved smoothness of skin,
link |
00:21:44.780
but their whole body shape changes.
link |
00:21:47.060
Yeah, I mean, you'll feel better for a short amount of time.
link |
00:21:50.260
You'll build up muscle, you'll feel great,
link |
00:21:52.100
but it's like burning your candle at both ends.
link |
00:21:54.660
Ultimately, if you want to live longer,
link |
00:21:56.660
you want less of that.
link |
00:21:57.700
And the animals that have been generated
link |
00:22:00.620
and mutants that have low growth hormone,
link |
00:22:03.140
sometimes these are dwarfs,
link |
00:22:05.540
they live the longest by far.
link |
00:22:07.660
A guy in my lab, Michael Bonkowski,
link |
00:22:10.020
he had the longest lived mouse.
link |
00:22:11.820
A mouse typically lives about two and a bit years.
link |
00:22:14.340
He had a mouse that lived five years
link |
00:22:16.420
and he gave it caloric restrictions for fasting
link |
00:22:18.980
combined with one of these dwarf mutations,
link |
00:22:20.820
low growth hormone.
link |
00:22:22.180
I think he called it Yoda.
link |
00:22:23.900
But you look at who lives the longest,
link |
00:22:27.580
it's the really small people.
link |
00:22:30.460
This is a bit anecdotal,
link |
00:22:31.460
but it sounds like it might be true
link |
00:22:34.380
is that the people who played the Munchkins
link |
00:22:36.140
in the Wizard of Oz,
link |
00:22:37.300
many of them went on to live into their 90s and beyond.
link |
00:22:39.940
Really? Yeah.
link |
00:22:41.780
Amazing.
link |
00:22:42.620
Oh, there are some Laurent dwarfs as well.
link |
00:22:44.980
There are dwarf mutations in South America
link |
00:22:49.180
and they seem to be protected
link |
00:22:50.380
against many of the diseases of aging.
link |
00:22:52.220
You barely ever see heart disease
link |
00:22:53.620
or cancer in these families.
link |
00:22:55.380
So I, having owned a very large dog breed,
link |
00:22:58.580
a Bulldog Mastiff who lived a long life
link |
00:23:01.660
for a bulldog, 11 years,
link |
00:23:03.140
but there are many dogs that will live 12, 16 years
link |
00:23:07.540
that are smaller dogs.
link |
00:23:08.860
Can we say that there's a direct relationship
link |
00:23:10.860
between body size and longevity
link |
00:23:13.180
or duration of life?
link |
00:23:16.260
Well, there is,
link |
00:23:17.580
but that doesn't mean that you're a slave
link |
00:23:19.260
to your early epigenome,
link |
00:23:21.660
nor to your genome.
link |
00:23:23.260
The good news is that the epigenome can change.
link |
00:23:26.260
Those loops and structures can be modified
link |
00:23:29.180
by how you live your life.
link |
00:23:30.860
And so if you're born tall and I wasn't,
link |
00:23:33.580
and I wished at the time I did grow,
link |
00:23:37.500
but no matter what size you are,
link |
00:23:38.860
you can have a bigger impact on your life
link |
00:23:41.020
than anything your genes give you.
link |
00:23:42.940
80% is epigenetic, not genetic.
link |
00:23:45.900
So let's talk about some of the things that people can do.
link |
00:23:48.220
And I've kind of batched these into categories
link |
00:23:51.380
rather than just diving right into actionable protocols.
link |
00:23:56.580
So the first one relates to food, blood sugar, insulin.
link |
00:24:02.980
This is something I hear a lot about
link |
00:24:04.580
that fasting is good for us,
link |
00:24:07.180
but rarely do I hear why it's good for us.
link |
00:24:10.980
One of the reasons I'm excited to talk to you today
link |
00:24:12.860
is because I want to drill into the details of this,
link |
00:24:15.660
because I think understanding the mechanism
link |
00:24:17.580
will allow people to make better choices
link |
00:24:19.860
and not simply to just decide
link |
00:24:22.260
whether or not they're going to fast or not fast
link |
00:24:24.060
or how long they're going to fast,
link |
00:24:25.620
I think should be dictated
link |
00:24:26.500
by some understanding of the mechanism.
link |
00:24:28.460
So why is it that having elevated blood sugar,
link |
00:24:32.900
glucose, and insulin ages us more quickly?
link |
00:24:36.620
And or why is it that having periods of time each day
link |
00:24:40.820
or perhaps longer can extend our lifespan?
link |
00:24:45.180
Well, let's start with what I think was a big mistake
link |
00:24:48.340
was the idea that people should never be hungry.
link |
00:24:52.140
We live in a world now
link |
00:24:53.100
where there's at least three meals a day,
link |
00:24:55.460
and then we've got companies selling bars
link |
00:24:57.780
and snacks in between.
link |
00:24:59.860
So the feeling of hunger,
link |
00:25:01.220
some people never experience hunger in their whole lives.
link |
00:25:03.860
It's really, really bad for them.
link |
00:25:07.340
It was based, I believe, on the 20th century view
link |
00:25:10.700
that you don't want to stress out the pancreas
link |
00:25:13.020
and you try to keep insulin levels pretty steady
link |
00:25:16.540
and not have this fluctuation.
link |
00:25:19.380
What we actually found, my colleagues and I,
link |
00:25:23.420
across this field of longevity
link |
00:25:25.780
is that when you look at, first of all, animals,
link |
00:25:28.180
whether it's a dog or a mouse or a monkey,
link |
00:25:31.420
the ones that live the longest, by far, 30% longer
link |
00:25:35.740
and stay healthy are the ones that don't eat all the time.
link |
00:25:40.100
It actually was first discovered
link |
00:25:41.380
back in the early 20th century, but people ignored it.
link |
00:25:44.500
And then it was rediscovered in the 1930s.
link |
00:25:47.020
Clive McKay did caloric restriction.
link |
00:25:49.220
He put cellulose in the food of rats
link |
00:25:51.980
so they couldn't get as many calories even though they ate,
link |
00:25:54.620
and those rats lived 30% longer.
link |
00:25:57.140
But then it went away, and then it came back in the 2000s
link |
00:26:00.700
in a big way when a couple of things happened.
link |
00:26:02.700
One is that my lab and others showed
link |
00:26:05.580
that there are longevity genes in the body
link |
00:26:08.860
that come on and protect us from aging and disease.
link |
00:26:11.980
The group of genes that I work on are called sirtuins.
link |
00:26:13.940
There's seven of them.
link |
00:26:15.420
And we showed in 2005 in a science paper
link |
00:26:18.620
that if you have low levels of insulin
link |
00:26:22.340
and another molecule called insulin-like growth factor,
link |
00:26:25.780
those low levels turn on the longevity genes.
link |
00:26:28.820
One of them that's really important is called SIRT1.
link |
00:26:32.140
But by having high levels of insulin all day,
link |
00:26:35.340
being fed means your longevity genes are not switched on.
link |
00:26:39.220
So you're falling apart.
link |
00:26:40.300
Your epigenome, your information
link |
00:26:42.500
that keeps your cells functioning over time
link |
00:26:44.140
just degrades quickly.
link |
00:26:45.180
Your clock is ticking faster by always being fed.
link |
00:26:50.700
The other thing that I think might be happening
link |
00:26:53.260
by always having food around
link |
00:26:55.860
is that it's not allowing the cell to have periods of rest
link |
00:27:00.300
and reestablish the epigenome.
link |
00:27:03.300
And so it also is accelerating in that direction.
link |
00:27:07.660
There's plenty of other reasons as well
link |
00:27:09.060
that are not as profound,
link |
00:27:10.060
such as having low levels of glucose in your body
link |
00:27:14.260
will trigger your major muscles in your brain
link |
00:27:17.020
to become more sensitive to insulin
link |
00:27:19.660
and suck the glucose out of your bloodstream,
link |
00:27:21.660
which is very good.
link |
00:27:22.740
You don't want to have glucose flowing around too much.
link |
00:27:25.540
And that will ward off type 2 diabetes.
link |
00:27:27.900
So hunger, of course, is associated with low blood glucose
link |
00:27:32.260
and low insulin.
link |
00:27:34.100
Do you think there's anything
link |
00:27:35.180
about the subjective experience of hunger itself
link |
00:27:38.060
that could be beneficial for longevity?
link |
00:27:40.260
Yeah, I do.
link |
00:27:43.900
Though you get used to the feeling of not eating.
link |
00:27:46.740
So I'm kind of screwed that way.
link |
00:27:49.180
It's like cold water.
link |
00:27:50.100
You eventually adapt.
link |
00:27:51.420
You get used to it, unfortunately.
link |
00:27:53.980
But there are some studies that are being done
link |
00:27:55.820
at the National Institutes of Health
link |
00:27:57.460
that are able to simulate the effect of hunger,
link |
00:28:00.780
but still provide the calories.
link |
00:28:02.420
And it's looking like there's a small component
link |
00:28:04.700
that's due to hunger.
link |
00:28:05.980
But most of it, actually,
link |
00:28:07.420
is because you've got these periods of not being fed
link |
00:28:10.300
and then the body turns on these defensive genes.
link |
00:28:13.940
There's a really interesting experiment
link |
00:28:15.300
that was published maybe a couple of years ago
link |
00:28:17.220
by Rafael de Carbo down at the NIH.
link |
00:28:20.060
What he did was he took over 10,000 mice
link |
00:28:22.060
and gave them different combinations
link |
00:28:24.140
of fat, carbohydrate, protein.
link |
00:28:26.740
And he was trying to figure out what was the best combination.
link |
00:28:29.980
And then he also cleverly had a group,
link |
00:28:32.700
well, two groups, one that was fed all the time,
link |
00:28:35.060
or ate as much as they wanted,
link |
00:28:37.260
and the other group was only given food for an hour a day.
link |
00:28:40.500
And it turns out they ate
link |
00:28:41.340
roughly the same amount of calories.
link |
00:28:43.060
Because, of course, in an hour,
link |
00:28:44.380
they're stuffing their faces.
link |
00:28:46.700
It turns out it didn't matter what diet he gave them.
link |
00:28:49.780
It was only the group that ate within that window
link |
00:28:51.620
that lived longer and dramatically longer.
link |
00:28:53.940
So my conclusion is,
link |
00:28:56.020
and mice are very similar to us metabolically,
link |
00:28:58.020
I think that tells us that it's not as important
link |
00:29:00.460
what you eat, it's when you eat during the day.
link |
00:29:02.860
What is the protocol that people can extrapolate from that?
link |
00:29:07.980
Or maybe I should just ask you,
link |
00:29:09.100
what is your protocol for when to eat
link |
00:29:12.340
and when to avoid food?
link |
00:29:14.100
Do you fast, do you ever fast longer than 24 hours?
link |
00:29:18.580
What do you do?
link |
00:29:19.500
And what do you think is a good jumping off place
link |
00:29:21.660
if people want to explore this as a protocol?
link |
00:29:23.940
Well, if there's one thing I could say,
link |
00:29:26.060
if I would say definitely try to skip a meal a day,
link |
00:29:29.700
that's the best thing.
link |
00:29:30.740
Does it matter which meal?
link |
00:29:32.060
Or are they essentially equivalent?
link |
00:29:33.140
Well, as long as it's at the end
link |
00:29:35.020
or the beginning of the day,
link |
00:29:36.180
because then you add that to the sleep period
link |
00:29:38.660
where you're hopefully not eating.
link |
00:29:40.260
I think that that's an excellent point.
link |
00:29:41.700
I realize it's a simple one,
link |
00:29:43.020
but I think it's an excellent one
link |
00:29:44.020
because I think one of the things
link |
00:29:45.460
that people struggle with the most
link |
00:29:46.660
is knowing when and how to initiate
link |
00:29:49.620
this so-called intermittent fasting.
link |
00:29:51.820
And the middle of the day obviously
link |
00:29:53.540
is not tacked to the sleep cycle in the same way.
link |
00:29:55.500
So it's much harder as well for many people.
link |
00:29:58.980
Yeah. Yeah.
link |
00:29:59.900
Well, I'll tell you what I do.
link |
00:30:01.580
I skip breakfast.
link |
00:30:02.740
I have a tiny bit of yogurt or olive oil
link |
00:30:04.940
because the supplements I have need to be dissolved in it.
link |
00:30:08.260
And then I go throughout the whole day
link |
00:30:09.700
as I'm doing right now here with this glass of water here.
link |
00:30:13.820
I'm just keeping myself filled with liquids.
link |
00:30:15.860
And so I don't feel hungry.
link |
00:30:18.980
Beware that the first two to three weeks
link |
00:30:21.020
when you try that, you will feel hungry.
link |
00:30:22.820
And you also have a habit of wanting to chew on something.
link |
00:30:26.180
There's a lot of physical parts to it,
link |
00:30:28.260
but try to make it through the first three weeks
link |
00:30:30.180
and do without breakfast or do without dinner.
link |
00:30:33.220
And you'll get through it.
link |
00:30:34.860
And I did that for most of my life actually,
link |
00:30:38.300
mainly because I wasn't hungry in the morning.
link |
00:30:40.700
Some people are very hungry in the morning
link |
00:30:42.420
and they may want to consider skipping dinner instead.
link |
00:30:45.180
But I will go throughout the whole day.
link |
00:30:47.100
I don't get the crashes of the high glucose
link |
00:30:49.980
and the low glucose.
link |
00:30:51.780
Anyone who goes, oh man, it's three o'clock.
link |
00:30:53.740
I'm gonna need a sleep.
link |
00:30:55.100
If you do what I do, you will not experience that anymore.
link |
00:30:58.420
Because what my body does is it regulates
link |
00:31:01.460
blood sugar levels naturally.
link |
00:31:02.820
My liver is putting out glucose when it needs to
link |
00:31:05.020
and it's very steady and gives me pure focus
link |
00:31:07.620
throughout the day.
link |
00:31:08.460
And I don't even have to think about lunch.
link |
00:31:10.020
I'm just powering through.
link |
00:31:11.660
At dinner, I love food as much as anybody.
link |
00:31:14.500
So I will eat a regular, pretty healthy meal.
link |
00:31:18.900
I'll try to eat mostly vegetables.
link |
00:31:20.540
I can eat some fish, some shrimp.
link |
00:31:23.300
I rarely will eat a steak.
link |
00:31:25.900
In fact, my microbiome is so adapted to my diet.
link |
00:31:29.220
Now, if I eat a steak, it will not get digested very well.
link |
00:31:31.980
I'll feel terrible.
link |
00:31:33.740
If I don't eat a steak, I feel terrible.
link |
00:31:36.180
Well, we...
link |
00:31:37.020
Argentine lineage.
link |
00:31:37.980
Well, we can talk about that.
link |
00:31:39.700
Well, everybody's different.
link |
00:31:40.900
I mean, that's the other thing.
link |
00:31:41.860
What works for me may not be perfect for you.
link |
00:31:43.820
And we do have to measure things to know what's working.
link |
00:31:47.620
I rarely eat dessert.
link |
00:31:48.740
I gave up dessert and sugar when I turned 40.
link |
00:31:53.060
And occasionally, I'll steal a bit of dessert
link |
00:31:55.500
because it doesn't hurt if you steal it, right?
link |
00:31:57.780
But other than that, I avoid sugar,
link |
00:32:00.380
which includes simple carbohydrates, bread I try to avoid.
link |
00:32:04.940
I've actually noticed, this is just a side note.
link |
00:32:07.980
I used to get buildup of plaque pretty easily.
link |
00:32:10.180
And every time I went to the dentist,
link |
00:32:11.260
they'd have to scrape it off.
link |
00:32:12.180
And I even bought tools to scrape it off
link |
00:32:13.540
because it was driving me nuts.
link |
00:32:15.700
I don't get plaque anymore.
link |
00:32:16.940
And I think it's because of my diet.
link |
00:32:18.900
I don't have those sugars in my mouth
link |
00:32:20.340
that the bacteria feed on
link |
00:32:21.340
and then form the biofilm on the teeth.
link |
00:32:24.060
Much better breath, by the way.
link |
00:32:27.020
That's a benefit.
link |
00:32:28.380
So, do you ever fast longer than this?
link |
00:32:31.500
It sounds like if you go to bed,
link |
00:32:35.180
well, you tend to stay up late, I know,
link |
00:32:36.780
because I get texts from you at like two in the morning,
link |
00:32:40.580
my time, which means you're out very late
link |
00:32:42.540
and up early as well.
link |
00:32:43.820
But assuming that people go to sleep
link |
00:32:45.980
sometime around 11, 30, or 12, plus or minus an hour,
link |
00:32:50.220
and wake up sometime around 7 a.m.,
link |
00:32:52.180
plus or minus 90 minutes,
link |
00:32:55.900
you're eating more or less on a,
link |
00:32:57.660
it sounds like some like 20 hours of fasting,
link |
00:33:00.940
four hours of eating, or 16 hours of fasting,
link |
00:33:03.220
eight hours of food intake, et cetera.
link |
00:33:05.980
But do you ever do longer fasts,
link |
00:33:07.860
like 48 hours or 72 hours or week-long fasts?
link |
00:33:11.420
Occasionally I do.
link |
00:33:13.500
So my typical day,
link |
00:33:14.340
I would only eat within a two-hour window,
link |
00:33:16.340
just usually I'm either eating out or-
link |
00:33:18.860
So you're 22 too?
link |
00:33:20.180
Yeah, yeah, but I love, well-
link |
00:33:23.060
And if you exercise, do you feel like,
link |
00:33:24.980
then you just power through and maintain that fasted state?
link |
00:33:27.820
Absolutely, I can exercise.
link |
00:33:29.260
And now my body's so used to it,
link |
00:33:30.660
I don't feel like I need food after exercising.
link |
00:33:32.780
I used to.
link |
00:33:35.540
But have I gone longer?
link |
00:33:36.460
Yes, but not very often.
link |
00:33:37.980
I find it quite difficult to go more than 24 hours.
link |
00:33:42.180
But when I do it, maybe it's once a month,
link |
00:33:43.900
I'll go for two days.
link |
00:33:46.220
After two, and actually even better,
link |
00:33:48.100
if you go for three days without eating,
link |
00:33:49.980
it kicks in even greater longevity benefits.
link |
00:33:55.060
So there's a system called the autophagy system,
link |
00:33:57.780
which digests old and misfolded proteins in the body.
link |
00:34:01.620
And there's a natural cleansing
link |
00:34:02.900
that happens when you're hungry.
link |
00:34:04.820
Macro-autophagy, its name is.
link |
00:34:06.740
But a good friend of mine, Anna Maria Cuervo
link |
00:34:09.220
at Albert Einstein College of Medicine,
link |
00:34:11.140
discovered a deep cleanse called the chaperone-mediated
link |
00:34:14.300
autophagy, which kicks in day two, day three,
link |
00:34:18.020
which really gets rid of the deep proteins.
link |
00:34:21.620
And what excites me is she just put out a big paper
link |
00:34:24.500
that said, if you trigger this process in an old mouse,
link |
00:34:28.860
it lives 35% longer.
link |
00:34:31.140
Wow.
link |
00:34:31.980
Yeah, so it's a big deal.
link |
00:34:32.940
If I could go longer, I would.
link |
00:34:34.580
But I just find that with my lifestyle,
link |
00:34:36.420
and I'm going always day 110%, I need to eat
link |
00:34:41.220
at least once a day, unfortunately.
link |
00:34:42.940
One more practical question
link |
00:34:44.100
than a mechanistic question related to this.
link |
00:34:46.060
The practical question is when you are fasting,
link |
00:34:48.980
regardless of how long,
link |
00:34:50.460
I know you're ingesting fluids like water
link |
00:34:52.500
and presumably some caffeine.
link |
00:34:54.260
I heard you had several or more espresso today,
link |
00:34:59.620
which is impressive.
link |
00:35:01.540
But are you also ingesting electrolytes?
link |
00:35:04.820
Like I know some people get lightheaded,
link |
00:35:06.500
they start to feel shaky when they fast,
link |
00:35:08.820
and that the addition of sodium to their water
link |
00:35:11.500
or potassium, magnesium is something
link |
00:35:14.220
that's becoming a little more in vogue now.
link |
00:35:16.060
Is that something that you do
link |
00:35:17.140
or that you see a need for people to do?
link |
00:35:19.420
Well, it makes sense, but I haven't had a need to do it.
link |
00:35:23.540
So I don't, I just, I drink tea during the day
link |
00:35:26.020
and coffee when I'm first awake and I don't get the shakes.
link |
00:35:29.500
So, you know, I don't fix what's not broken.
link |
00:35:31.820
And I do add things to my protocol
link |
00:35:34.260
that I think will improve me
link |
00:35:36.180
and avoid those things, of course, that won't.
link |
00:35:39.620
But yeah, because I don't have a need for it, I don't try it.
link |
00:35:42.260
But it does make sense,
link |
00:35:43.100
especially if you've had a big night the night before,
link |
00:35:46.100
you probably want to supplement with that.
link |
00:35:48.020
But I think there's fair amount of good stuff
link |
00:35:51.020
in tea and coffee as it is.
link |
00:35:53.380
Okay, so then the mechanistic question is,
link |
00:35:57.340
you've told us that there's ample evidence
link |
00:35:59.900
that keeping your blood sugar low for a period of time,
link |
00:36:02.860
each 24 hours, can help trigger some of these
link |
00:36:06.140
pro-longevity anti-aging mechanisms
link |
00:36:10.340
and that extending them out two or three days
link |
00:36:12.940
can trigger yet additional mechanisms
link |
00:36:15.660
of gobbling up of dead cells and things of that sort.
link |
00:36:21.220
How is it that blood glucose triggers these mechanisms?
link |
00:36:24.780
Because we've said, okay,
link |
00:36:25.620
remove glucose and things get better.
link |
00:36:28.140
You've talked before, maybe we could talk more now
link |
00:36:32.060
about some of the underlying cellular
link |
00:36:33.620
and genetic mechanisms, things like the sirtuins,
link |
00:36:36.020
but how are glucose and the sirtuins
link |
00:36:37.900
actually tethered to one another mechanistically?
link |
00:36:40.860
Yeah, there's a really good question.
link |
00:36:43.100
That proves you're a scientist or world leading on.
link |
00:36:47.220
So what we now know is that these longevity pathways,
link |
00:36:51.420
we call them, these longevity genes talk to each other.
link |
00:36:54.140
And we used to say,
link |
00:36:54.980
oh, my longevity gene's more important than yours.
link |
00:36:56.780
It was ridiculous, because they're all talking to each other.
link |
00:36:58.980
You pull one lever and the other one moves.
link |
00:37:01.420
And the way to think of it is that there are systems set up
link |
00:37:03.420
to detect what you're eating.
link |
00:37:05.340
So the sirtuins will mainly respond to sugar and insulin.
link |
00:37:10.780
And then there's this other system called mTOR,
link |
00:37:13.780
which is sensing how much protein
link |
00:37:16.060
or amino acids are coming into your body.
link |
00:37:18.420
And they talk to each other.
link |
00:37:19.340
We can pull one and affect the other and vice versa.
link |
00:37:22.380
But together, when you're fasting,
link |
00:37:24.380
you'll get the sirtuin activation, which is good for you.
link |
00:37:28.620
And you'll also, through lack of amino acids,
link |
00:37:31.500
particularly three of them, leucine, isoleucine, valine,
link |
00:37:34.980
the body will downregulate mTOR.
link |
00:37:37.220
And it's that up sirtuin, down mTOR
link |
00:37:39.940
that is hugely beneficial
link |
00:37:41.260
and turns on all of the body's defenses,
link |
00:37:44.180
the chewing up the old proteins,
link |
00:37:46.340
improving insulin sensitivity, giving us more energy,
link |
00:37:49.020
repairing cells, all of that.
link |
00:37:51.380
And so these two pathways,
link |
00:37:52.660
I think are the most important for longevity.
link |
00:37:55.020
So interesting.
link |
00:37:55.860
You mentioned leucine.
link |
00:37:57.660
Within the resistance training,
link |
00:38:00.580
slash bodybuilding, slash fitness community,
link |
00:38:02.700
leucine gets a lot of attention
link |
00:38:04.260
because there are longstanding debates
link |
00:38:06.340
about how much protein one needs per day
link |
00:38:08.620
and how much one can assimilate at each meal.
link |
00:38:10.500
It makes for many YouTube videos and not much else, frankly.
link |
00:38:15.500
However, it's clear that because of leucine's effects
link |
00:38:18.780
on the mTOR pathway, that there are many people,
link |
00:38:22.340
not just people in these particular fitness communities
link |
00:38:24.780
that are actively trying to ingest more leucine
link |
00:38:28.020
on a regular basis
link |
00:38:29.620
in order to maximize their wellness and fitness
link |
00:38:33.180
and in some cases muscle growth, but also just wellness.
link |
00:38:36.540
But what I interpret your last statement to mean
link |
00:38:39.500
is that leucine, because it triggers cellular growth,
link |
00:38:42.780
is actually pro-aging in some sense.
link |
00:38:46.340
Is that right?
link |
00:38:47.820
Well, it could be.
link |
00:38:48.900
That's what the evidence suggests.
link |
00:38:50.260
And again, it goes back to the debate, should you supplement
link |
00:38:53.100
with growth hormone or testosterone,
link |
00:38:56.380
all of these activities will give you immediate benefits.
link |
00:38:59.940
You'll bulk up more, you'll feel better immediately.
link |
00:39:04.180
But based on the research,
link |
00:39:05.980
it's at the expense of long-term health.
link |
00:39:08.380
So my view of longevity, the way I treat my body,
link |
00:39:12.140
is I don't burn both candles.
link |
00:39:14.980
I have one end of the candle lit.
link |
00:39:16.740
I'm very careful, I don't blow on it.
link |
00:39:18.780
But I also do enough exercise
link |
00:39:20.460
that I'm building up my muscle, but I'm not huge.
link |
00:39:23.460
Anyone who's seen me knows
link |
00:39:25.500
that I'm not a professional bodybuilder.
link |
00:39:28.260
But I tried to actually, here's the key,
link |
00:39:30.660
and I haven't said this publicly that I can remember.
link |
00:39:33.340
I pulse things so that I get periods of fasting
link |
00:39:36.620
and then I eat, then I take a supplement,
link |
00:39:40.420
then I fast, then I exercise.
link |
00:39:42.940
And I'm taking the supplements and eating
link |
00:39:45.860
in the right timing to allow me
link |
00:39:48.900
to build up muscle sometimes.
link |
00:39:50.900
Because you can't just expect to take something constantly
link |
00:39:55.300
and do something constantly for it to work.
link |
00:39:57.540
And that's why it's taken me about 15 years
link |
00:39:59.620
to develop my protocol.
link |
00:40:00.900
And there's a lot of subtlety to it.
link |
00:40:02.860
Yeah, it sounds like a very rational protocol.
link |
00:40:04.940
Does the name Ori Hofmeckler mean anything to you?
link |
00:40:07.740
No.
link |
00:40:08.580
Okay.
link |
00:40:09.420
Just briefly, I discovered Ori Hofmeckler
link |
00:40:12.300
about 15 years ago.
link |
00:40:14.580
He was in Israeli special forces.
link |
00:40:16.780
He's now got to be close to 70.
link |
00:40:19.060
Forgive me, Ori, if that number is inflated.
link |
00:40:23.380
He wrote a book called The Warrior Diet,
link |
00:40:26.060
which got very little attention at the time.
link |
00:40:28.300
But what he said was,
link |
00:40:29.940
when he was in Israeli special forces,
link |
00:40:31.820
they rarely ate more than once per day
link |
00:40:34.260
and sometimes once every second or third day.
link |
00:40:36.700
And this is a guy who maintains
link |
00:40:38.420
an incredible physical stature.
link |
00:40:41.380
You know, he's very lean, very strong,
link |
00:40:43.660
and very vital at, you know,
link |
00:40:46.860
I wouldn't say an advanced age,
link |
00:40:48.040
but he's getting up there
link |
00:40:49.060
and he just seems to be getting better and better.
link |
00:40:51.500
Ori Hofmeckler was the person
link |
00:40:53.300
who essentially founded, if you will,
link |
00:40:55.780
although our ancestors founded, to be completely fair,
link |
00:40:59.360
the so-called intermittent fasting diet.
link |
00:41:03.420
He called it The Warrior Diet
link |
00:41:04.740
and this book didn't get much attention.
link |
00:41:06.120
But one of the things that you just said
link |
00:41:08.700
really reminded me of Ori.
link |
00:41:10.420
I sat down with him.
link |
00:41:11.260
I actually went to his home and sat down with him
link |
00:41:12.860
and he said, fasting is wonderful,
link |
00:41:15.260
but these pulses where you nourish the body
link |
00:41:18.140
or even slightly overnourish the body,
link |
00:41:20.880
provided they aren't too frequent,
link |
00:41:23.180
have a tremendous effect on vitality.
link |
00:41:25.940
And so I want to use that as kind of a segue
link |
00:41:28.120
to address this issue of vitality versus longevity,
link |
00:41:33.140
because here you're telling me,
link |
00:41:35.440
and certainly the evidence supports that, you know,
link |
00:41:38.620
growth hormone will make you feel better and younger,
link |
00:41:40.580
taking testosterone or estrogen, we should probably say.
link |
00:41:43.100
There are, right,
link |
00:41:44.700
women who take hormone therapies later in life
link |
00:41:47.060
who take estrogen,
link |
00:41:47.940
they experience a strong increase in vitality
link |
00:41:50.540
if it's done correctly.
link |
00:41:52.180
But there is an effect of aging the body more rapidly.
link |
00:41:56.480
It's sort of a second puberty, if you will.
link |
00:41:59.380
But this idea of restriction and then pulsing,
link |
00:42:02.620
not necessarily feast and famine,
link |
00:42:04.680
but certainly famine and feast in lowercase letters,
link |
00:42:08.700
there really seems to be something about that.
link |
00:42:10.980
So at a cellular level,
link |
00:42:13.940
like we kind of go back to mTOR and the sirtuins,
link |
00:42:16.940
how do you think that the cells might be reacting
link |
00:42:20.500
to this kind of lowercase feast
link |
00:42:24.060
and uppercase famine type protocol?
link |
00:42:28.120
Right.
link |
00:42:30.020
Well, the pulsing, I think,
link |
00:42:32.620
is what you want to do is to get the cells
link |
00:42:35.020
to be perceiving adversity, okay?
link |
00:42:39.260
Because our modern life, we're sitting around,
link |
00:42:41.160
we're eating too much, we're not exercising,
link |
00:42:45.660
our cells respond.
link |
00:42:47.040
They go, hey, everything's cool, no problem.
link |
00:42:49.460
And they become relaxed
link |
00:42:51.020
and they don't turn on their defenses and we age rapidly.
link |
00:42:53.220
We can see it in the clock.
link |
00:42:54.640
People who exercise and eat less
link |
00:42:56.740
have a slower ticking clock.
link |
00:42:58.260
It's a fact.
link |
00:43:00.680
But my protocol is different than most people's
link |
00:43:03.440
because I am pulsing it.
link |
00:43:05.500
Now, first of all, let's get to why did I even think
link |
00:43:08.240
that might be possible?
link |
00:43:09.180
Because I didn't read the warrior diet.
link |
00:43:11.880
What I found in my research was that
link |
00:43:15.660
if we gave resveratrol, this red wine molecule
link |
00:43:18.220
that became well-known in the 2000s,
link |
00:43:22.100
if we gave it to mice, their whole lifespan,
link |
00:43:25.100
they were protected against a high fat diet,
link |
00:43:27.360
which we call the Western diet.
link |
00:43:29.000
They had lean organs.
link |
00:43:30.820
They lived slightly longer, but not a lot.
link |
00:43:33.820
And if we gave them a high fat diet without resveratrol,
link |
00:43:37.860
they actually lived a lot shorter.
link |
00:43:40.500
So resveratrol protected them against the high fat diet.
link |
00:43:43.380
We gave it to them on a normal diet.
link |
00:43:44.780
They just ate it when they wanted
link |
00:43:46.460
and there wasn't much effect.
link |
00:43:48.500
This is what's not known,
link |
00:43:49.700
though it's in the supplemental data of the paper
link |
00:43:51.740
that nobody ever reads.
link |
00:43:54.080
The mice that were given resveratrol every second day
link |
00:43:57.020
on a normal diet lived dramatically longer
link |
00:44:00.180
than any other group.
link |
00:44:02.540
So people out there, you know, my critics say,
link |
00:44:05.100
oh, resveratrol didn't extend the lifespan
link |
00:44:06.900
of mice on a normal diet, therefore it's not aging.
link |
00:44:10.580
It's just protecting against a high fat diet.
link |
00:44:12.720
Well, look at the supplemental data, please.
link |
00:44:15.200
If you give it to the mice every other day,
link |
00:44:17.880
we had mice living over three years.
link |
00:44:19.940
Wow, that's a long time.
link |
00:44:21.620
I have got many, many mice in my ownership
link |
00:44:25.980
in my lab at Stanford,
link |
00:44:27.020
and that's a very long life for a mouse.
link |
00:44:29.500
It was by far.
link |
00:44:30.540
And so it was a long lifespan extension.
link |
00:44:33.900
And what that told me is that probably
link |
00:44:36.980
you don't want to be taking a supplement every day.
link |
00:44:40.300
You can take it either every other day
link |
00:44:42.120
or give your body a rest.
link |
00:44:43.700
And I do the same with my meals.
link |
00:44:45.460
I rest during the day and then I give a nutritious dinner
link |
00:44:48.780
to my body and then give it a rest.
link |
00:44:50.860
Same with exercise.
link |
00:44:51.940
And then I try to time it because there are times
link |
00:44:54.100
when I'm taking the drug metformin,
link |
00:44:56.460
which mimics low energy. For those of you who don't know,
link |
00:45:00.120
metformin is a drug given to type 2 diabetics
link |
00:45:02.300
to bring down their blood sugar levels.
link |
00:45:04.400
But it's been found that looking at tens of thousands
link |
00:45:06.540
of veterans and others,
link |
00:45:08.420
that those two type 2 diabetics live longer than people
link |
00:45:10.900
that don't even get type 2 diabetes.
link |
00:45:12.380
So it's a longevity drug.
link |
00:45:14.900
Right now you have to get it from your doctor in the US
link |
00:45:17.620
and most other countries,
link |
00:45:18.820
you can just get it over the counter.
link |
00:45:21.700
And you protect it, it looks like,
link |
00:45:23.740
based on epidemiological data, cancer, heart disease,
link |
00:45:28.700
frailty, what else, dementia.
link |
00:45:33.440
So I take metformin.
link |
00:45:35.180
You take metformin and your fasting each day.
link |
00:45:37.940
So when do you take it relative to the fasting?
link |
00:45:39.940
Yeah, I always take metformin in the morning,
link |
00:45:44.020
along with the resveratrol,
link |
00:45:46.420
because for a number of reasons,
link |
00:45:48.380
but mainly because my body responds better
link |
00:45:52.740
and I've been measuring my body for 12, 13 years.
link |
00:45:56.420
But here's the thing, if I'm going to exercise that day,
link |
00:45:59.620
I will skip the metformin.
link |
00:46:02.020
And a lot of people who do pay attention
link |
00:46:04.420
to this kind of thing,
link |
00:46:06.180
think that they should stop taking metformin
link |
00:46:07.980
because they're never going to get muscle
link |
00:46:09.480
or it's going to affect their ability to build up muscle.
link |
00:46:13.180
But that's not true.
link |
00:46:15.260
What metformin does to you,
link |
00:46:16.640
it actually just reduces your ability to have stamina
link |
00:46:20.540
because it's inhibiting your body's ability
link |
00:46:22.300
to make energy.
link |
00:46:24.500
And so what happens is when you're on metformin,
link |
00:46:26.700
you do fewer reps, but guess what?
link |
00:46:29.420
Those muscles that you do build up on metformin
link |
00:46:32.460
have the same strength and have much lower inflammation
link |
00:46:35.080
and other markers of aging.
link |
00:46:37.620
You just won't have that extra 5% size of muscles.
link |
00:46:41.900
So if you want large muscles, don't take metformin
link |
00:46:44.800
and you'll be fine during your exercise.
link |
00:46:48.020
But for me, I'm not trying to get giant.
link |
00:46:50.740
I want strong muscles and I want to live longer
link |
00:46:52.860
and healthier.
link |
00:46:53.900
So I just try to time it so that I get the most reps
link |
00:46:59.100
out of my exercise regime.
link |
00:47:02.720
But sometimes in scientific literature,
link |
00:47:04.860
it's worth bringing this up.
link |
00:47:06.740
If there's a 5% difference in a graph,
link |
00:47:09.200
then either the press release or some reporter will say,
link |
00:47:13.540
oh my goodness, big difference,
link |
00:47:15.020
5% can't take metformin during exercise.
link |
00:47:17.840
That's the headline.
link |
00:47:19.020
And then you go in and it's barely significant.
link |
00:47:21.540
And the graph is distorted because they've changed the axes
link |
00:47:24.260
to make it look bigger.
link |
00:47:25.960
And now it's become a myth that metformin
link |
00:47:29.360
greatly inhibits your ability to exercise,
link |
00:47:31.260
which is not true.
link |
00:47:32.780
But in an abundance of caution,
link |
00:47:34.220
I skip my metformin on days I'm going to exercise.
link |
00:47:37.460
And not only that, I'm one of the 20% of people
link |
00:47:39.580
that has a stomach sensitivity to it.
link |
00:47:42.620
So if I'm not feeling great that day,
link |
00:47:44.340
I don't take it either.
link |
00:47:45.540
You mentioned metformin is available only by prescription
link |
00:47:48.140
from a doctor, at least in the US.
link |
00:47:50.660
Berberine, this is a substance that comes from tree bark,
link |
00:47:53.340
who I also learned about many years ago from Ori.
link |
00:47:57.220
He said, if ever I'm going to overeat
link |
00:47:59.300
like a Thanksgiving meal or something, I take berberine.
link |
00:48:02.620
Those were his words.
link |
00:48:03.820
And I tried it.
link |
00:48:04.660
And what's remarkable about berberine
link |
00:48:06.220
is that you can eat enormous quantities of food
link |
00:48:09.540
and not feel as if you've eaten enormous quantities of food.
link |
00:48:12.380
I'm not necessarily recommending people do this,
link |
00:48:14.740
but what I noticed was if I took berberine,
link |
00:48:18.740
which my understanding is it works very similarly
link |
00:48:21.180
to metformin, works on the AMPK pathway
link |
00:48:23.700
and the mTOR pathway, et cetera,
link |
00:48:26.220
that if I didn't ingest food in particular carbohydrates,
link |
00:48:29.900
I would feel a little dizzy and kind of get a headache,
link |
00:48:32.060
like almost hypoglycemic.
link |
00:48:35.300
What are your thoughts on berberine
link |
00:48:36.560
as an alternative to metformin?
link |
00:48:38.860
And are there any cautionary notes?
link |
00:48:41.060
I mean, obviously people should talk to their doctor
link |
00:48:42.780
before adding or subtracting anything from their life,
link |
00:48:45.140
including breath work or anything that comes up.
link |
00:48:49.380
But with all that set aside,
link |
00:48:52.020
what are your thoughts about berberine
link |
00:48:53.700
and timing of low blood sugar and these sorts of things?
link |
00:48:57.760
Right.
link |
00:48:58.600
Well, before I had access to metformin,
link |
00:49:00.460
I was taking berberine.
link |
00:49:01.780
It's often known as the poor man's metformin.
link |
00:49:05.260
He just called me poor.
link |
00:49:06.820
Women can take it too.
link |
00:49:08.560
So the thing with berberine, and we started it in my lab,
link |
00:49:11.420
it is effective at boosting energetics in the body,
link |
00:49:15.080
just like AMPK and metformin does.
link |
00:49:19.360
And we've actually given it to rats and mice
link |
00:49:21.700
and seen that they are very healthy,
link |
00:49:23.100
especially on a high-fat diet.
link |
00:49:25.540
So I think it's likely to be good.
link |
00:49:27.680
There are some human studies that exist,
link |
00:49:29.660
clinical trials showing that it increases
link |
00:49:31.420
insulin sensitivity.
link |
00:49:32.380
You have to take high doses.
link |
00:49:33.460
Which is a good thing, right?
link |
00:49:34.760
Yeah.
link |
00:49:35.600
I think when people hear insulin sensitivity,
link |
00:49:36.740
sometimes people think, oh, well, that's bad, right?
link |
00:49:39.140
No, but you want your cells to be insulin sensitive.
link |
00:49:41.220
You don't want a lot of blood sugar floating around
link |
00:49:43.500
that can't be sequestered into cells.
link |
00:49:45.520
Exactly.
link |
00:49:46.360
So this is anti-type 2 diabetes.
link |
00:49:49.220
And so this berberine does have wonderful effects
link |
00:49:52.940
on the metabolism of animals and in some clinical trials
link |
00:49:56.520
on dozens of people it's been tested.
link |
00:49:58.500
Now there's one cautionary tale, which just came up.
link |
00:50:01.940
Matt Kaeberlein's lab published that berberine
link |
00:50:04.500
reduced the lifespan of worms.
link |
00:50:07.380
But I'm not sure worms trump human clinical trials
link |
00:50:10.240
at this point.
link |
00:50:11.240
So I would say-
link |
00:50:12.080
Not in my opinion.
link |
00:50:12.900
But no disrespect to my C. elegans colleagues,
link |
00:50:15.300
or rather my colleagues that work on C. elegans.
link |
00:50:17.340
Yeah.
link |
00:50:18.180
Well, what I like to do is to give all the information
link |
00:50:20.220
people can decide what they want.
link |
00:50:21.980
But I would say if, based on the worm data,
link |
00:50:24.260
I wouldn't panic just yet.
link |
00:50:25.980
I think berberine has been shown
link |
00:50:27.220
to be really safe in humans.
link |
00:50:29.440
You mentioned resveratrol.
link |
00:50:31.020
I think now would be a great time to talk a little bit
link |
00:50:33.240
about protocols for resveratrol,
link |
00:50:35.020
grape seed extract, et cetera.
link |
00:50:37.380
Let's start with the obvious one
link |
00:50:38.980
that I know you get a lot.
link |
00:50:40.220
But for the record, can't I just drink red wine
link |
00:50:45.060
and get enough resveratrol, David?
link |
00:50:47.980
You can try.
link |
00:50:48.860
You need to drink about 200 glasses a day.
link |
00:50:51.580
So I-
link |
00:50:52.420
I'm sure it's been tried.
link |
00:50:54.060
There are some.
link |
00:50:55.500
And I drink a glass of red wine a day if I get the chance.
link |
00:51:00.020
But any more than that, it's a lot of calories
link |
00:51:02.220
and your liver will get fatty and it's all bad.
link |
00:51:04.140
So realistically, you can only get the thousand milligrams
link |
00:51:08.180
that I take a day from a supplement that's pure.
link |
00:51:13.260
Now, there are a lot of people selling resveratrol.
link |
00:51:14.900
If it's not light gray or white in color, throw it away.
link |
00:51:19.060
The brown stuff has gone bad or is contaminated.
link |
00:51:22.980
And the contaminated stuff, beware, it'll cause diarrhea.
link |
00:51:26.460
But regular resveratrol should not do that.
link |
00:51:28.660
So a thousand milligrams per day is what you do?
link |
00:51:31.460
Yeah, and I have for about 15 years now.
link |
00:51:34.800
And you ingest that with some fatty substance
link |
00:51:38.380
like olive oil or yogurt, is that right?
link |
00:51:40.740
Yeah, you have to.
link |
00:51:41.580
And other supplements, quercetin, curcumin,
link |
00:51:44.940
these are crunchy things.
link |
00:51:46.260
They're not going to get through your gut.
link |
00:51:48.020
And I'm not just making this up.
link |
00:51:49.540
I always base my statements on human studies.
link |
00:51:53.040
So we've done a lot of studies on resveratrol
link |
00:51:55.380
as have others since.
link |
00:51:56.780
And we know that from, we found out early,
link |
00:51:59.360
I was one of the first people to take a high dose
link |
00:52:00.980
for resveratrol.
link |
00:52:02.380
And when we included it with food,
link |
00:52:04.680
the levels in my blood went up fivefold.
link |
00:52:07.500
And so you want to have something in there.
link |
00:52:09.140
If you just drink it with water,
link |
00:52:10.120
it's not going to get through.
link |
00:52:11.680
And unfortunately, some people have done clinical trials
link |
00:52:13.980
without even thinking that they might need
link |
00:52:16.020
to dissolve it in something.
link |
00:52:17.820
So are you taking this all at once in the morning
link |
00:52:20.260
and chasing it with some olive oil?
link |
00:52:21.820
Or are you dissolving it in yogurt?
link |
00:52:24.620
What's the specific protocol?
link |
00:52:26.580
Yeah, I've been improving, perfecting what I do.
link |
00:52:31.580
For about 10 years, I would take some Greek yogurt,
link |
00:52:34.740
a couple of spoonfuls, put the resveratrol on there,
link |
00:52:37.580
mix it around, make sure it's dissolved,
link |
00:52:39.460
and put that in my mouth and swallow that.
link |
00:52:41.540
These days, what I like to do,
link |
00:52:42.740
because I've realized that olive oil,
link |
00:52:45.500
and particularly oleic acid,
link |
00:52:47.620
one of the monounsaturated fatty acids,
link |
00:52:50.220
is also an activator of the sirtuin defenses.
link |
00:52:53.860
So I'm trying to ingest more oleic acid.
link |
00:52:56.940
So I switched to olive oil.
link |
00:52:58.580
What I do is I put a couple of teaspoons of olive oil
link |
00:53:00.780
in a glass, mix around the resveratrol,
link |
00:53:04.100
and maybe some quercetin, a similar molecule,
link |
00:53:07.100
make sure it's dissolved.
link |
00:53:08.900
I put a little bit of vinegar,
link |
00:53:11.340
and if I have a basil leaf, I'll put that in,
link |
00:53:14.240
and it's like drinking some salad dressing, and it's great.
link |
00:53:17.260
Delicious.
link |
00:53:19.900
That raises a question that I want to ask
link |
00:53:22.780
before we get to NMN and NR and vitamin B3,
link |
00:53:27.780
which is, by doing that,
link |
00:53:31.020
do you think that it breaks your fast?
link |
00:53:33.260
And I want to just frame this question of breaking the fast
link |
00:53:36.420
in a more general scientific theme,
link |
00:53:38.660
and I'd love your thoughts on this.
link |
00:53:41.020
One of the questions I get asked all the time is,
link |
00:53:43.340
does ingesting blank break the fast?
link |
00:53:46.140
Does eating this or drinking this, coffee,
link |
00:53:49.300
if I walk in the room and someone else is eating a cracker,
link |
00:53:51.580
does it break my fast?
link |
00:53:53.380
People get pretty extreme with this.
link |
00:53:54.980
My sense, and please tell me if I'm wrong,
link |
00:53:57.940
but my sense is that it depends on the context
link |
00:54:00.580
of what you did the night before,
link |
00:54:02.180
whether or not you're diabetic, lots of things.
link |
00:54:04.820
So for instance, if I eat an enormous meal at midnight,
link |
00:54:07.940
go to sleep, wake up at 6 a.m.,
link |
00:54:11.260
I could imagine that black coffee
link |
00:54:14.260
or coffee with a little bit of cream
link |
00:54:15.700
might quote unquote break my fast,
link |
00:54:17.660
but the body doesn't have a breaking the fast switch.
link |
00:54:20.140
The body only speaks in the language of glucose,
link |
00:54:22.540
AMPK, mTOR, et cetera.
link |
00:54:24.820
So do you worry that ingesting these calories
link |
00:54:28.580
is going to quote unquote break your fast?
link |
00:54:30.260
And more generally, how do you think about the issue
link |
00:54:33.140
of whether or not you're fasting enough
link |
00:54:34.860
to get these positive effects?
link |
00:54:36.620
Because not everybody can manage on just water or just tea,
link |
00:54:41.700
or we should say not everybody is willing to manage
link |
00:54:44.620
on just water or just tea for a certain part of the day.
link |
00:54:47.420
Well, my first answer is not scientific, it's philosophical.
link |
00:54:50.740
If you don't enjoy life, what's the point?
link |
00:54:53.300
And so I'd like a cup of coffee in the morning,
link |
00:54:56.260
little bit of milk, spoonful of yogurt's not gonna kill me.
link |
00:55:00.780
Olive oil doesn't have protein or carbs in it, not many.
link |
00:55:04.260
And so I'm probably not affecting
link |
00:55:05.780
those longevity pathways negatively.
link |
00:55:09.460
But without that, first of all,
link |
00:55:11.580
I wouldn't enjoy my life as much.
link |
00:55:13.100
Well, the olive oil is not as great as the yogurt,
link |
00:55:15.220
but I'm trying to optimize.
link |
00:55:18.020
And there's no perfect solution to what we're doing.
link |
00:55:21.660
And we're still learning.
link |
00:55:22.700
We don't know what's optimal for me,
link |
00:55:24.780
let alone everybody else.
link |
00:55:26.500
But I'm with you, I don't believe that taking
link |
00:55:29.180
a couple of spoonfuls of something
link |
00:55:30.700
unless it's high fructose corn syrup is gonna hurt you
link |
00:55:34.340
because I've now got the rest of the day
link |
00:55:36.060
till about eight, nine p.m. of not eating anything.
link |
00:55:39.420
And I forgive myself for that.
link |
00:55:42.580
And there's a really good point here.
link |
00:55:44.540
You and I were discussing this earlier.
link |
00:55:46.500
The point about doing this is that you try to do your best.
link |
00:55:52.500
If you go from regular living to don't eat the whole day,
link |
00:55:56.940
you're gonna fail, like quitting smoking cold turkey.
link |
00:56:00.020
It's easier to chew gum and stick the patch on
link |
00:56:02.500
because your body has to get used to all sorts of habits.
link |
00:56:04.860
And it's social, it's physical,
link |
00:56:06.540
putting stuff in your mouth, chewing,
link |
00:56:08.380
not just the low blood sugar levels.
link |
00:56:10.380
And your brain will fight it.
link |
00:56:11.860
Your limbic system is gonna go, hey, do it, do it, do it.
link |
00:56:15.140
And you're gonna have to fight it.
link |
00:56:17.340
But once you get through it, you'll be better.
link |
00:56:19.620
But you do it in stages.
link |
00:56:21.780
Do breakfast first, then do small lunch,
link |
00:56:24.940
and then eventually cut lunch out.
link |
00:56:26.660
Don't go cold turkey because everyone knows
link |
00:56:29.300
it's a fact that if you try to do a strict diet
link |
00:56:32.580
right out of the gates, you'll almost always fail.
link |
00:56:36.180
No, I think that captures the essence of fasting rationally
link |
00:56:41.180
and a rational approach to supplementation very well.
link |
00:56:46.160
Along the lines of supplementation,
link |
00:56:47.820
what about NMN, NR, and B3 niacin?
link |
00:56:55.820
I want to know what you do.
link |
00:56:57.380
I also want to know what I should do.
link |
00:56:59.640
And I think most people want to know what they should do.
link |
00:57:02.620
I mean, these are molecules that impact the sirtuin pathway,
link |
00:57:05.820
impact the pathways that control aging
link |
00:57:08.860
or rates of aging in the epigenome.
link |
00:57:11.540
How do they do that?
link |
00:57:12.880
And how does one incorporate that
link |
00:57:14.540
into a supplementation protocol,
link |
00:57:16.940
should they choose to do that?
link |
00:57:18.160
All right.
link |
00:57:19.260
Well, disclaimer is that I don't recommend anything,
link |
00:57:21.540
but I talk about what I do.
link |
00:57:23.980
So a bit of scientific background.
link |
00:57:25.160
These sirtuin genes that we discovered,
link |
00:57:26.780
first in yeast cells when I was at MIT,
link |
00:57:29.160
and then in animals as I moved to Harvard in the 2000s.
link |
00:57:33.340
And one of my first postdocs,
link |
00:57:35.380
actually literally my first postdoc, Chaim Cohen,
link |
00:57:37.740
published a great paper just a couple of months ago
link |
00:57:41.260
and found that turning on the sirtuin 6 gene,
link |
00:57:44.940
remember the 7, number 6 gene is very potent.
link |
00:57:47.700
It extended the lifespan dramatically of mice
link |
00:57:50.020
that he engineered, both males and females, which is great.
link |
00:57:53.180
So what you want to do is,
link |
00:57:55.300
so naturally boost the activity of these sirtuins.
link |
00:57:58.580
They are genes, but they also make proteins.
link |
00:58:00.580
That's what genes typically make or encode.
link |
00:58:03.460
And then those proteins take care of the body
link |
00:58:04.960
in many different ways, as we've discussed.
link |
00:58:07.380
So how do you turn on these genes
link |
00:58:09.100
and make the proteins they make even more active?
link |
00:58:11.580
You want to rev up that system.
link |
00:58:12.600
So exercise will do it, fasting will do it.
link |
00:58:16.540
What about supplementation?
link |
00:58:17.780
Well, the first activator of the sirtuins
link |
00:58:20.020
that we discovered that acts on the enzyme
link |
00:58:22.560
to make it do a better job of cleaning up the body
link |
00:58:24.820
and protecting was resveratrol.
link |
00:58:27.500
We looked at thousands of different molecules,
link |
00:58:30.300
eventually tens of thousands.
link |
00:58:32.020
And the one that was the best was resveratrol in the dish.
link |
00:58:35.820
And then we gave it to little organisms, worms,
link |
00:58:38.340
and then flies and mice, eventually humans.
link |
00:58:41.860
And we saw that it activated that enzyme.
link |
00:58:44.060
So resveratrol is one way to activate it.
link |
00:58:46.540
You can think of it as the accelerator pedal on a car.
link |
00:58:49.340
It revs it up, but there's something else
link |
00:58:52.380
that the sirtuins need to work, and that's NAD.
link |
00:58:56.140
NAD is a really small molecule,
link |
00:58:57.900
a little chemical in the body that we need for life.
link |
00:59:00.620
It's used by the body for chemical reactions,
link |
00:59:03.340
400 different reactions in the body,
link |
00:59:04.900
and without it, you're dead within seconds.
link |
00:59:08.380
You need NAD.
link |
00:59:09.220
The problem that we've seen is that NAD levels decline
link |
00:59:13.060
as you become obese, as you get older,
link |
00:59:16.960
if you don't ever get hungry.
link |
00:59:19.380
And the body not only doesn't make enough of it,
link |
00:59:22.700
it's chewing it up as well.
link |
00:59:23.940
There's an enzyme called CD38 that Eric Verdin over at UCSF
link |
00:59:29.800
showed chews up, oh, he's now at the Buck Institute
link |
00:59:32.220
in California, chews up NAD.
link |
00:59:34.700
As you get older, so it's a double whammy.
link |
00:59:36.340
You don't make as much, you chew it up,
link |
00:59:38.500
which is really bad because what we've shown in my lab
link |
00:59:40.520
and so have others is that NAD levels are really important
link |
00:59:43.260
for keeping those sirtuin defenses at a youthful level.
link |
00:59:47.220
And you can give a lot of resveratrol,
link |
00:59:48.780
but if you don't have the fuel,
link |
00:59:50.360
you're basically accelerating a car
link |
00:59:52.500
that doesn't have enough gas.
link |
00:59:54.180
So you wanna do both, and that's what I do.
link |
00:59:55.740
I take a precursor to NAD called NMN,
link |
01:00:00.180
and the body uses that to make the NAD molecule in one step.
link |
01:00:05.140
And so I know from measuring dozens of human beings
link |
01:00:09.340
that if you take NMN for the time period that I do,
link |
01:00:13.500
I've been taking it for years,
link |
01:00:14.400
but if you take it for about two weeks,
link |
01:00:16.300
you will double, on average,
link |
01:00:18.160
double your NAD levels in the blood, okay?
link |
01:00:20.840
That's not public information.
link |
01:00:22.140
That's from clinical trials that are not yet published
link |
01:00:24.800
over the last two years.
link |
01:00:26.660
There are other ways to increase NAD levels
link |
01:00:29.160
in someone like me who's getting older, I'm 52 now.
link |
01:00:33.340
You can take NR, which is used to make NMN,
link |
01:00:36.740
which is used to make NAD.
link |
01:00:39.500
And both NMN and NR are sold by companies in the U.S.
link |
01:00:45.340
NR lacks the phosphate.
link |
01:00:49.440
Phosphate's a small chemical that the body needs.
link |
01:00:52.060
You've probably heard of the atom phosphorus.
link |
01:00:56.460
Let's go back one step.
link |
01:00:57.980
How do you make NR?
link |
01:00:59.260
NR gets made from vitamin B3 often.
link |
01:01:02.680
You can also find it in milk and other foods.
link |
01:01:05.740
But sometimes people ask me,
link |
01:01:06.860
why don't you just take vitamin B3
link |
01:01:08.540
and won't that just force the body to make NAD?
link |
01:01:12.060
And the answer is no, it doesn't work very well.
link |
01:01:14.820
We know this just by doing the experiment.
link |
01:01:17.860
But the reason I think is, is that NAD is a,
link |
01:01:21.520
I said it's a small molecule,
link |
01:01:22.660
but relative to vitamin B3, it's big.
link |
01:01:25.540
It's got those phosphates on there.
link |
01:01:27.540
It's got a sugar.
link |
01:01:30.020
It's got the vitamin B attached.
link |
01:01:33.420
So you've got all these components that come together
link |
01:01:35.660
to make this very complicated little molecule called NAD.
link |
01:01:40.140
And when you give NMN, it contains all three components
link |
01:01:43.540
that the body needs to make NAD.
link |
01:01:45.620
If you give NR, or just vitamin B3,
link |
01:01:48.340
which is an even smaller molecule,
link |
01:01:50.080
the body has to find these other components
link |
01:01:51.840
from somewhere else.
link |
01:01:53.140
So where do you get phosphate?
link |
01:01:55.140
Well, body needs it for DNA, needs it for bones.
link |
01:01:58.520
So high doses of something
link |
01:02:00.900
that requires additional phosphate
link |
01:02:03.500
makes me a little concerned.
link |
01:02:05.460
And we have compared NMN and NR head-to-head
link |
01:02:07.820
in mouse studies.
link |
01:02:09.660
For instance, NMN we've shown in a cell paper
link |
01:02:12.540
a few years ago, makes mice run further.
link |
01:02:14.740
Old mice can run 50% further
link |
01:02:16.260
because they had better blood flow, better energy.
link |
01:02:18.220
NR at the same dose did not do that.
link |
01:02:20.020
In fact, it had no effect.
link |
01:02:21.300
I see, dosage-wise, if I were elect to take NMN
link |
01:02:26.380
in supplement form to increase my NAD levels
link |
01:02:29.920
and presumably slow my aging,
link |
01:02:33.780
how much NMN should I take?
link |
01:02:35.240
What's the protocol that you do?
link |
01:02:39.100
And are the various forms that are out there,
link |
01:02:42.100
are some better or some worse?
link |
01:02:45.660
Well, I'm always happy to tell you what I do
link |
01:02:47.580
and what my father does, my 82-year-old father.
link |
01:02:50.060
We take a gram of NMN every day.
link |
01:02:52.980
So it's a gram of resveratrol and a gram of NMN.
link |
01:02:56.020
Right.
link |
01:02:56.860
Okay, 1,000 milligrams.
link |
01:02:58.020
Now, another important point,
link |
01:03:02.020
which is I'm not the same as everybody else.
link |
01:03:04.880
I have a different microbiome, age, sex, right?
link |
01:03:08.380
And so I've been measuring myself.
link |
01:03:10.420
And so I know if something's,
link |
01:03:12.500
or I think I know if something's making me better or worse
link |
01:03:14.700
based on measuring 45 different things.
link |
01:03:17.900
So I just want people to be aware
link |
01:03:20.580
that what I do may not perfectly work at all for others.
link |
01:03:25.060
But I have studied, as I said,
link |
01:03:26.820
dozens of people who take NMN at a gram,
link |
01:03:31.220
sometimes two grams.
link |
01:03:32.280
And I know by looking at all those people
link |
01:03:34.860
that without any exceptions,
link |
01:03:36.900
that if you do what I do,
link |
01:03:37.780
your NAD levels go up by about twofold or more.
link |
01:03:42.020
And so I do that every day, the 1,000 milligrams.
link |
01:03:44.480
Now, people sell it.
link |
01:03:45.820
Now, I never get into brands and all that.
link |
01:03:48.220
First of all, I don't have the time to measure products.
link |
01:03:52.100
I don't know, though I should say,
link |
01:03:54.220
I do want to say I'm working on a solution
link |
01:03:57.020
for people to know what works
link |
01:03:59.300
and what's real and what isn't, but I'm not there yet.
link |
01:04:02.340
And in the meantime, I would say,
link |
01:04:04.340
if you do want to buy this,
link |
01:04:06.540
let's say you want to buy NMN,
link |
01:04:08.120
look for a company that is well-established,
link |
01:04:10.760
that has high levels of quality control.
link |
01:04:13.900
Look for three letters, GMP,
link |
01:04:16.260
which is good manufacturing practices.
link |
01:04:19.140
And so that means they make it
link |
01:04:20.260
under a certain level of quality control.
link |
01:04:22.280
You're not going to find iron filings in there,
link |
01:04:25.500
and it probably has the stuff in it that they say it does.
link |
01:04:30.580
So that's all I can say right now.
link |
01:04:32.600
I'm working on something that's going to be much more helpful.
link |
01:04:34.960
But overall, make sure it's white, crystalline, NMN,
link |
01:04:39.580
and that to me, it tastes like burnt popcorn.
link |
01:04:42.460
You crack open the capsules and you'll take a little sample
link |
01:04:44.920
to make sure it tastes like burnt popcorn.
link |
01:04:46.780
Well, when I'm making my capsules, I'll taste it.
link |
01:04:50.460
And I do a lot of quality control on the stuff that I take.
link |
01:04:53.540
Do you take that gram all at once with the resveratrol
link |
01:04:56.060
or do you take it spread throughout the day?
link |
01:04:58.580
It's all in the morning for those things.
link |
01:05:01.540
So if I take metformin, it's NMN
link |
01:05:04.820
and the resveratrol all together.
link |
01:05:06.620
And there's a good reason for that.
link |
01:05:08.380
It's all scientific, I try to be.
link |
01:05:10.400
The levels of NAD go up in the morning
link |
01:05:13.800
in our bodies naturally.
link |
01:05:14.720
Our bodies actually have a cycle of NAD, it's not steady.
link |
01:05:17.240
It's circadian.
link |
01:05:18.080
It's circadian.
link |
01:05:18.900
In fact, NAD controls your clock.
link |
01:05:22.240
This was shown by Shin, MI, and colleagues
link |
01:05:24.240
in a nice science paper about a decade ago
link |
01:05:27.080
that if you disrupt the NAD cycle,
link |
01:05:28.880
which is controlled by the sirtuin gene that we worked on,
link |
01:05:33.000
that is what's telling your body, oh, it's time to eat,
link |
01:05:35.840
it's time to go to sleep.
link |
01:05:37.320
And if you take the NMN late at night,
link |
01:05:40.220
for example, you can disrupt your circadian rhythms.
link |
01:05:43.320
Interesting.
link |
01:05:44.160
Conversely, when I travel and I want to reset my clock
link |
01:05:47.200
to the time zone, I will take a boost of NMN in the morning
link |
01:05:52.520
and I feel great.
link |
01:05:53.880
Does this protocol for you,
link |
01:05:57.480
does it produce any immediate effects
link |
01:06:00.160
of increased energy, et cetera?
link |
01:06:01.920
You mentioned that one would, if it's right for them,
link |
01:06:05.840
would have to take it for at least two weeks
link |
01:06:08.200
to start to see the NAD levels increase.
link |
01:06:10.120
At that point, when NAD levels increase,
link |
01:06:13.560
could one possibly expect an increase
link |
01:06:16.020
in overall energy focus, et cetera?
link |
01:06:20.500
I realize we're not making promises here,
link |
01:06:21.980
but I'm just wondering whether or not the only measure
link |
01:06:24.040
of whether or not this protocol is working
link |
01:06:25.860
is whether or not you die at age blank or blank plus 20.
link |
01:06:30.920
And of course, once you're dead,
link |
01:06:33.840
you can't really know if you would have lived longer
link |
01:06:36.520
if you'd done something differently and vice versa.
link |
01:06:38.560
Sure, well, there was a study, again, by Shina Mai,
link |
01:06:41.200
my good friend at Washington University in St. Louis,
link |
01:06:43.880
that showed that it improves,
link |
01:06:46.640
remember, this insulin sensitivity, which is a good thing.
link |
01:06:50.440
But you can't know your insulin sensitivity
link |
01:06:52.120
unless you're measuring a glucose,
link |
01:06:53.800
have a glucose monitor on your arm.
link |
01:06:55.120
Do you have one on right now?
link |
01:06:56.320
No.
link |
01:06:57.720
No, I used to.
link |
01:06:58.700
I learned a lot.
link |
01:06:59.540
Yeah, last time I saw you had this thing.
link |
01:07:01.040
It looks like a small leech, not a large leech,
link |
01:07:04.200
and it was measuring your blood glucose.
link |
01:07:06.200
They're very informative
link |
01:07:07.320
because you learn what your body reacts to,
link |
01:07:09.480
and grapes were really bad.
link |
01:07:11.360
Rhonda Patrick agrees with that.
link |
01:07:14.080
But the issue was what, where were we, Andrew?
link |
01:07:19.640
The issue is whether or not
link |
01:07:20.560
you can expect any immediate effects
link |
01:07:22.840
on energy, vitality, focus, just even subjective.
link |
01:07:26.480
So what do you feel is the question?
link |
01:07:28.040
And anecdotally,
link |
01:07:29.640
because I've been taking this for a long time,
link |
01:07:31.000
if I don't take it, I start to feel 50 years old.
link |
01:07:33.120
It's horrible.
link |
01:07:33.960
I can't think straight.
link |
01:07:35.760
It may be placebo, but who knows?
link |
01:07:38.840
But what we're doing now are very careful clinical trials.
link |
01:07:41.480
We've done the safety for two years,
link |
01:07:43.320
and we're now treating elderly patients
link |
01:07:45.680
at Harvard Medical School with some wonderful colleagues.
link |
01:07:49.080
And those people are actually going to be,
link |
01:07:51.360
and currently in MRIs,
link |
01:07:53.720
so you can measure the energetics and the NAD levels
link |
01:07:57.600
in their legs as they exercise in real time.
link |
01:08:00.800
And that will tell us if what we see in the mice,
link |
01:08:03.400
this increased endurance, actually works.
link |
01:08:05.800
In the meantime, it's fun to talk about anecdotes.
link |
01:08:07.840
I have a number of athlete friends,
link |
01:08:10.480
some of which have increased their,
link |
01:08:13.680
lowered their time in marathons, for example.
link |
01:08:15.800
There's a good friend of ours in our circle
link |
01:08:18.840
that is winning marathons at age 50 now.
link |
01:08:21.800
And he attributes that to the protocol that he's on.
link |
01:08:24.560
Interesting.
link |
01:08:25.400
I haven't started taking NMN,
link |
01:08:26.840
but I'm planning to do that when my next birthday arrives,
link |
01:08:30.080
which is in a couple of months.
link |
01:08:31.360
But I do experiments on my sister and have for years,
link |
01:08:34.240
I have a sister who's three years older than I am,
link |
01:08:37.280
who is very enthusiastic about these protocols.
link |
01:08:40.120
And I'll tell you that after reading your book,
link |
01:08:43.040
I started purchasing for her
link |
01:08:44.960
and giving her an NMN supplement.
link |
01:08:47.160
And she claims, and I believe her,
link |
01:08:50.120
she has a quite sensitive system
link |
01:08:51.600
and she's very tuned into it.
link |
01:08:52.920
She feels far and away better when she takes it
link |
01:08:56.360
as opposed to when she doesn't.
link |
01:08:57.680
And I've done the control experiment of removing her supply
link |
01:09:01.200
and then giving it back to her and this kind of thing.
link |
01:09:03.360
So that's my other laboratory.
link |
01:09:06.960
This is what younger brothers do to older sisters.
link |
01:09:10.120
I have a question about something that,
link |
01:09:11.560
if it has no relevance,
link |
01:09:12.600
we can just treat it as a speed bump and then move right on.
link |
01:09:16.080
And the artificial sweeteners, these things that,
link |
01:09:18.800
or I should say non-glucose increasing sweeteners.
link |
01:09:23.040
So you've got stevia, which is a plant basically,
link |
01:09:26.080
and then you've got sucralose and aspartame
link |
01:09:29.120
and all these things.
link |
01:09:30.040
There is some evidence that I know we're both aware of,
link |
01:09:33.320
they've been published in quite reputable journals
link |
01:09:35.400
showing that they can disrupt the gut microbiome
link |
01:09:38.680
in certain cases, in particular saccharin,
link |
01:09:40.600
the one that basically nobody uses anymore.
link |
01:09:43.720
And it's questionable as to whether or not stevia
link |
01:09:45.480
has the same negative effects, et cetera.
link |
01:09:47.040
That's not what this is about.
link |
01:09:48.160
But in terms of the sensation of,
link |
01:09:51.880
or the perception of sweet taste,
link |
01:09:54.720
is that itself a possible detriment to these pro-longevity,
link |
01:09:59.720
forgive me for using the term, the pathways.
link |
01:10:04.120
If I were to drink a Diet Coke during a fast,
link |
01:10:07.040
am I somehow disrupting this?
link |
01:10:08.480
And I'm asking this question
link |
01:10:09.360
because I get asked this question a lot.
link |
01:10:11.480
Well, there may be small effects.
link |
01:10:13.640
I don't think they're worth worrying about.
link |
01:10:16.360
Joe Rogan laughed at me
link |
01:10:17.760
because I was drinking a Diet Coke
link |
01:10:18.960
during the first interview I did with him.
link |
01:10:21.320
I will drink Diet Coke.
link |
01:10:23.160
I've read the scientific literature.
link |
01:10:24.840
And again, it's this 5% thing
link |
01:10:26.600
that I think is blown out of proportion.
link |
01:10:29.120
If I was to put a number on it,
link |
01:10:31.000
I would say if eating a high sugary meal
link |
01:10:36.000
or drinking a sugar-filled soda,
link |
01:10:39.800
what is that, 30 grams of sugar,
link |
01:10:42.080
let's say that's a 10 out of 10 bad for you.
link |
01:10:45.760
A Diet Coke might be a one.
link |
01:10:48.880
And if I'm, you know, which am I gonna do?
link |
01:10:50.760
I could have a 10 or a one or go without in my life.
link |
01:10:53.960
I'll do the one on occasion.
link |
01:10:56.000
I try to avoid them because I don't like the ones as much.
link |
01:11:00.600
But you can't say that sucralose
link |
01:11:02.200
is equivalent to drinking a sugary soda.
link |
01:11:05.120
There's just no comparison.
link |
01:11:07.200
And I think, what is it, stevia.
link |
01:11:09.480
I do use stevia whenever I can
link |
01:11:11.120
because it's a naturally sourced product.
link |
01:11:14.920
And I haven't seen any good evidence yet
link |
01:11:16.760
that it's bad for you.
link |
01:11:18.520
But I think a lot of this is overblown.
link |
01:11:20.800
And a lot of it's the media trying to give equal weight
link |
01:11:24.200
to stories, as you know, as a scientist,
link |
01:11:27.080
it can be frustrating when something's a 10
link |
01:11:29.600
and something's a one and they're equated.
link |
01:11:33.240
How do I say this respectfully?
link |
01:11:34.480
I think if science journalists were required
link |
01:11:37.560
to post their credentials alongside their name,
link |
01:11:42.400
people would take the articles
link |
01:11:44.400
with an additional grain of salt, right?
link |
01:11:46.640
I mean, in other words,
link |
01:11:47.480
that I think that the science media
link |
01:11:49.080
is mainly generated around two specific goals.
link |
01:11:52.280
One is to make people very, very afraid
link |
01:11:55.160
or get people very, very excited.
link |
01:11:56.800
And oftentimes the get people excited part
link |
01:11:59.160
is sponsored content.
link |
01:12:00.320
And I think that's overlooked.
link |
01:12:01.800
In any case, thank you for that.
link |
01:12:04.080
I want to talk about iron and iron load.
link |
01:12:07.560
We were talking earlier about ferritin
link |
01:12:09.840
and of course women mend straight.
link |
01:12:13.200
And so their iron needs are greater
link |
01:12:16.400
than people, men that don't mend straight
link |
01:12:19.000
or women that don't mend straight.
link |
01:12:20.760
I don't think we can get right down
link |
01:12:22.960
into how much iron somebody needs
link |
01:12:24.840
because it'll vary person to person.
link |
01:12:26.400
But I was surprised to learn that iron
link |
01:12:29.600
is actually going to accelerate the aging process
link |
01:12:33.640
in various contexts.
link |
01:12:36.000
Well, this is a new finding out of Spain.
link |
01:12:39.840
Manuel Serrano's lab has found that excess iron
link |
01:12:43.960
will increase the number of senescent cells in the body.
link |
01:12:47.760
And senescent cells are these zombie cells
link |
01:12:49.840
that accumulate as you get older
link |
01:12:51.520
and they sit there and they cause inflammation mainly
link |
01:12:54.400
and also can cause cancer.
link |
01:12:56.320
And it's found that if you get rid of these cells
link |
01:12:58.640
or never accumulate them, you stay younger in animals.
link |
01:13:02.880
And there's some really interesting studies
link |
01:13:05.360
out of Mayo Clinic in humans as well.
link |
01:13:08.480
So iron is a pro-senescent metal.
link |
01:13:13.680
And so what I think is that if you're taking excess iron
link |
01:13:17.120
as a supplement, you're probably accelerating
link |
01:13:19.600
your aging process.
link |
01:13:21.080
The other thing that I found really interesting
link |
01:13:22.800
is I've looked at hundreds of thousands of people's
link |
01:13:25.720
metabolism and their blood biomarkers.
link |
01:13:29.200
I was one of the first people in Inside Tracker
link |
01:13:32.240
as a board member and I'm still a scientific lead guy.
link |
01:13:37.480
So I can look anonymously at hundreds of thousands
link |
01:13:39.880
of people's blood work.
link |
01:13:41.320
And we also know how fit they are, how old they are.
link |
01:13:45.760
Some of them are marathon runners,
link |
01:13:47.000
some of them are CrossFit.
link |
01:13:49.840
And there's a signature of health that actually
link |
01:13:52.680
is different than your average person.
link |
01:13:54.920
Now, I'm not gonna say bad things about MDs
link |
01:13:58.040
because a lot of my best friends are MDs
link |
01:14:00.320
and I work with them at Harvard Medical School.
link |
01:14:03.360
The issue though is that with MD training,
link |
01:14:07.960
there's a scale of what's normal.
link |
01:14:09.920
And if you're out of that normal range,
link |
01:14:11.960
something must be wrong.
link |
01:14:12.960
That's the paradigm that they work under.
link |
01:14:15.240
But first of all, everybody's different
link |
01:14:17.280
and you wanna know their baseline and track people
link |
01:14:18.920
over years to know what's normal for them.
link |
01:14:21.720
And what I find, for example,
link |
01:14:23.080
is people who are really healthy and live the way I do
link |
01:14:26.600
and have a diet that's fairly vegetarian but not strict
link |
01:14:32.440
still have slightly low hemoglobin levels,
link |
01:14:35.240
slightly low iron, slightly low ferritin,
link |
01:14:38.080
but we have super amounts of energy.
link |
01:14:39.600
We're not anemic and we're getting along with great in life.
link |
01:14:43.720
But a doctor who just looks at that might say,
link |
01:14:46.200
oh, we need to give you more iron, right?
link |
01:14:48.560
So what I'm getting at is an example of
link |
01:14:51.120
we need to personalize medicine
link |
01:14:53.320
and look at people over the long run
link |
01:14:55.560
to know what works for them and what's healthy for them,
link |
01:15:00.120
and not just work towards the average human
link |
01:15:02.040
but work towards what's optimal for human.
link |
01:15:04.720
I love that answer.
link |
01:15:06.360
You mentioned tracking and tracking over time,
link |
01:15:08.440
and this is a really interesting area
link |
01:15:10.840
that I know you have been focused on for a long time.
link |
01:15:13.960
I've been getting blood work done about every six months,
link |
01:15:17.080
frankly, since I was in college.
link |
01:15:18.920
I like data and I got interested in supplementation
link |
01:15:22.240
and exercise because it made me feel better,
link |
01:15:24.260
but I also want to know what was going on under the hood.
link |
01:15:27.000
So you get numbers back.
link |
01:15:28.780
You get this hormone, that hormone,
link |
01:15:30.340
this blood glucose measure, et cetera.
link |
01:15:33.800
How do you make sense of the data?
link |
01:15:35.800
I mean, what Inside Tracker is doing aside,
link |
01:15:38.240
how do you personally make sense of the data
link |
01:15:40.320
in ways that might differ from the way
link |
01:15:42.640
that a standard MD might look at one of these charts?
link |
01:15:45.120
Because the standard practice is to say,
link |
01:15:46.920
is it red, yellow, or green, right?
link |
01:15:49.320
Is it basically too high or too low?
link |
01:15:52.200
Is it somewhere close to the margins or are you okay?
link |
01:15:56.200
Are you in these ranges?
link |
01:15:57.900
Are there any things that you pay attention to
link |
01:16:00.280
that you think are particularly interesting
link |
01:16:02.800
for people to just take note of?
link |
01:16:04.280
I mean, we're not asking you
link |
01:16:05.240
to go against anybody's physician,
link |
01:16:06.920
but what sorts of things should people
link |
01:16:11.600
start to educate themselves about
link |
01:16:13.060
in terms of what these molecules are on their charts
link |
01:16:15.520
if they choose to get them and what do you look at?
link |
01:16:17.720
Yeah, well, there's a lot there.
link |
01:16:20.660
The first is that you should be tracking things
link |
01:16:23.840
because one measurement isn't enough.
link |
01:16:25.400
These things vary and over time,
link |
01:16:27.000
and if you can have a decade or more of data,
link |
01:16:29.440
it's super informative as you know well know, as you know.
link |
01:16:34.440
So the physician, interestingly, my physician,
link |
01:16:37.840
let's take him as an example.
link |
01:16:40.400
So he sees me, he says, how are you feeling?
link |
01:16:44.920
I'm feeling great, okay, see you next year.
link |
01:16:47.160
That's craziness.
link |
01:16:48.200
Anyway, so I say, okay, stop.
link |
01:16:49.800
Let's talk a little bit about-
link |
01:16:51.640
Let me educate you.
link |
01:16:52.640
That's what David tells his physician.
link |
01:16:54.440
I imagine that the like 12-year-old David Sinclair
link |
01:16:56.960
says to his physician, listen,
link |
01:16:58.560
let's have a different discussion.
link |
01:16:59.960
Is that how it works?
link |
01:17:00.800
It is.
link |
01:17:01.640
It is, he finds me pretty annoying as does my dentist.
link |
01:17:06.160
But so I said, stop, hang on, I've got this data.
link |
01:17:09.760
I've got the inside tracker data.
link |
01:17:11.120
So I pull that up on the screen
link |
01:17:13.080
and I'm showing him the changes in my cholesterol,
link |
01:17:16.960
in my CRP, which is inflammatory marker, as you know,
link |
01:17:20.960
and we're going through it
link |
01:17:21.800
and you can see things change over time
link |
01:17:23.360
and I've corrected them as they go slightly
link |
01:17:25.680
out of the optimal range for me,
link |
01:17:27.760
which is different than what he would do, of course.
link |
01:17:30.040
But what was funny is that he says, this is great.
link |
01:17:33.160
I love this data, but I'm not allowed to get this
link |
01:17:36.320
because of course the insurance companies won't pay for it.
link |
01:17:39.920
So again, you can pay out of pocket.
link |
01:17:41.920
It's not super expensive.
link |
01:17:43.160
I would say if you save a bit of money on a coffee,
link |
01:17:48.360
you can afford this kind of stuff.
link |
01:17:50.360
But the main point is that doctors do like this data.
link |
01:17:53.600
It's just that they're unable to spend the money
link |
01:17:55.880
on every one of their patients to get it.
link |
01:17:58.120
Is there a code word that someone can use
link |
01:18:00.320
with their physician that will trigger
link |
01:18:01.920
a comprehensive blood test?
link |
01:18:03.520
I keep trying to figure out what's the code
link |
01:18:06.000
that one needs to ask or tell their doctor,
link |
01:18:08.420
like I'm feeling blank so that they get a full blood panel.
link |
01:18:12.080
Well, do you have to be hemorrhaging
link |
01:18:13.660
from the gut or something?
link |
01:18:16.040
Well, I usually use the WTH method, which is what the hell?
link |
01:18:19.880
And then he says, okay, we'll do it.
link |
01:18:22.400
Cause I think a lot of people out there are thinking,
link |
01:18:24.100
look, I'd love to have blood work repeatedly over time,
link |
01:18:26.800
but that's hard to get for financial reasons.
link |
01:18:29.360
But also a lot of people just don't know
link |
01:18:30.520
how to approach the conversation.
link |
01:18:32.640
And this is one of the things
link |
01:18:33.480
that I hope that we can educate people on,
link |
01:18:36.000
that they deserve to know what's going on inside their body
link |
01:18:39.400
and that it makes a doctor's visit worthwhile
link |
01:18:42.440
and that you don't have to feign illness in order to do it.
link |
01:18:46.040
Right, yeah, and a lot of people do.
link |
01:18:47.880
So I would say if you can afford these tests,
link |
01:18:49.960
there are an increasing number of companies
link |
01:18:52.000
that offer these tests.
link |
01:18:54.000
Insight Tracker is one of them.
link |
01:18:55.920
And you just do it a couple of times a year at a minimum,
link |
01:18:59.700
and then you can share that with your doctor.
link |
01:19:01.800
If you can't afford that, then I would say to your doctor,
link |
01:19:05.040
here are the main ones that Andrew and David do.
link |
01:19:09.440
Yeah, and we must.
link |
01:19:10.440
And there's an email that is something like a phone number,
link |
01:19:13.880
rather it's 555-5555.
link |
01:19:16.600
I think if they have any complaints,
link |
01:19:17.880
they can just call that number.
link |
01:19:19.940
David will pick up on East Coast business hours
link |
01:19:22.840
and I'll pick up outside of those hours.
link |
01:19:24.920
But there were some main ones.
link |
01:19:25.760
I would say your blood sugar levels,
link |
01:19:27.880
you want to do your HbA1c,
link |
01:19:29.200
which is your average glucose levels over the month.
link |
01:19:32.240
There's CRP, which I mentioned for inflammation.
link |
01:19:35.040
Let's talk about C-reactive protein for a second,
link |
01:19:36.960
because I think it's been shown to be an early marker
link |
01:19:40.680
of macular degeneration, of heart disease,
link |
01:19:43.480
of a variety of different things.
link |
01:19:45.320
CRP is something that we don't hear enough about, I think.
link |
01:19:48.920
Maybe, what do you know about CRP that I don't?
link |
01:19:51.640
I'm guessing a lot, but.
link |
01:19:53.280
Oh, it was originally picked up as something
link |
01:19:55.400
that was associated with heart disease
link |
01:19:56.980
in the Framingham study, I believe.
link |
01:19:59.380
It is the best marker for cardiovascular inflammation
link |
01:20:03.480
and is also, we use it as a predictor of longevity.
link |
01:20:07.240
And its levels go up with mortality.
link |
01:20:11.720
And so this is an association,
link |
01:20:13.580
but there's enough data that I would say,
link |
01:20:15.760
if you have high levels of CRP,
link |
01:20:17.560
you need to get your levels down quickly.
link |
01:20:20.400
And the levels usually go up with age
link |
01:20:23.320
and with levels of inflammation.
link |
01:20:24.520
So the ways to get it down would be to switch the diet,
link |
01:20:28.000
eat less, try to eat more vegetables.
link |
01:20:30.240
You'll find it will come down.
link |
01:20:31.560
There are also drugs that can do it.
link |
01:20:33.680
Anti-inflammatories can do it as well.
link |
01:20:37.220
But CRP is, it's actually HCRP.
link |
01:20:40.000
There's a high-sensitive or HSCRP.
link |
01:20:41.880
Your doctor will know.
link |
01:20:43.240
Get one of those readings,
link |
01:20:44.240
because if you've got normal blood sugar levels,
link |
01:20:47.200
your doctor, or fasting blood sugar levels,
link |
01:20:50.260
your doctor might say you're fine.
link |
01:20:51.960
But a lot of people have normal blood sugar,
link |
01:20:54.000
but have high CRP, which is just as bad for you long-term
link |
01:20:58.720
and can predict a future heart attack.
link |
01:21:01.040
On the lines of heart attack,
link |
01:21:02.320
I want your thoughts on cholesterol,
link |
01:21:05.080
and serum cholesterol, and dietary cholesterol.
link |
01:21:07.600
I cannot, for the life of me,
link |
01:21:09.880
get my arms around this literature.
link |
01:21:12.040
And even if I ignore all the essentially nonsense
link |
01:21:16.040
that's out there in various social media groups
link |
01:21:19.200
that saying cholesterol is the worst thing in the world,
link |
01:21:22.680
or cholesterol is not, or dietary cholesterol
link |
01:21:26.060
has nothing to do with serum cholesterol
link |
01:21:28.540
and nothing to do with longevity,
link |
01:21:29.800
I can't seem to sort through the very basic data
link |
01:21:34.880
that essentially ask,
link |
01:21:38.300
is having high levels of LDL going to kill me earlier?
link |
01:21:43.060
Should I be striving to always reduce LDL and increase HDL?
link |
01:21:47.200
Is that a reasonable goal?
link |
01:21:48.640
And if so, is dietary cholesterol
link |
01:21:52.040
the primary determinant of that?
link |
01:21:53.520
And just as a final point about this,
link |
01:21:56.640
I am aware of quite good data that shows that anorexics,
link |
01:21:59.800
people that essentially eat no food
link |
01:22:01.520
unless you force them to,
link |
01:22:04.480
can often have very high LDL.
link |
01:22:06.880
So their dietary cholesterol is essentially zero,
link |
01:22:10.360
and so they're manufacturing a lot of their own.
link |
01:22:12.240
So realize this isn't your primary area of expertise,
link |
01:22:15.840
but you're a smart guy.
link |
01:22:17.440
You think about this kind of stuff a lot.
link |
01:22:19.720
What do you think is going on
link |
01:22:20.880
with the cholesterol literature,
link |
01:22:22.100
and will we ever get to the bottom of this
link |
01:22:24.620
as a scientific and medical community?
link |
01:22:26.420
Because to me, it is rather perplexing.
link |
01:22:30.120
It is, but you can get through the politics.
link |
01:22:34.600
I know a fair bit about cholesterol
link |
01:22:35.920
because it's in my family history,
link |
01:22:39.040
and I was headed for an early death.
link |
01:22:41.600
My grandmother had a stroke at 30.
link |
01:22:43.400
That's how bad I am in terms of my genetics.
link |
01:22:46.800
So I went on a statin,
link |
01:22:47.980
and I know there's a lot of people
link |
01:22:49.240
who say that statins long-term are bad.
link |
01:22:51.360
It's associated with Alzheimer's disease.
link |
01:22:57.380
I've been taking a statin since I was 29,
link |
01:23:00.380
and that's because I forced my same doctor
link |
01:23:02.720
to give me the statin.
link |
01:23:04.280
The conversation was something like this.
link |
01:23:06.040
You're too young to be on a statin.
link |
01:23:08.320
I said, what, you want me to have a heart attack
link |
01:23:10.160
before you give me something?
link |
01:23:11.360
Give it to me now.
link |
01:23:12.200
So 29, I've been on a statin,
link |
01:23:13.920
and my cholesterol was way up beyond 300,
link |
01:23:16.760
which is a massive, massive.
link |
01:23:18.080
Basically, my blood was creamy to look at.
link |
01:23:20.560
So I've now got my cholesterol down to low, low levels
link |
01:23:24.580
to what would it be?
link |
01:23:26.440
You could check on my inside tracker,
link |
01:23:28.100
but so my ratio of HDL to LDL,
link |
01:23:30.440
which you want to be less than five, is now two,
link |
01:23:33.040
and the LDL is below 100.
link |
01:23:35.280
So it's all good.
link |
01:23:36.240
And I've measured my cardiovascular health with an MRI.
link |
01:23:39.280
I've got a movie of my heart beating.
link |
01:23:41.300
I've still got a heart of a 20-year-old.
link |
01:23:43.360
So that's working.
link |
01:23:45.360
I'm willing to forego the risk
link |
01:23:46.760
that the statin is causing problems later
link |
01:23:48.640
because of my family history.
link |
01:23:50.420
But other people, I would say,
link |
01:23:53.640
be aware that statins aren't perfect drugs.
link |
01:23:57.000
There are some interesting new ones.
link |
01:23:58.400
There's one called the PSK-9 inhibitor,
link |
01:24:00.780
which is, I think, fortnightly, every two weeks, injection.
link |
01:24:04.360
That blocks the release of LDL from the liver.
link |
01:24:09.120
And then that seems to be great for lowering cholesterol,
link |
01:24:13.220
but also has other benefits that might be pro-longevity.
link |
01:24:17.360
And there were some people that I was just talking to
link |
01:24:20.360
are on the cutting edge of this,
link |
01:24:21.840
and their doctors are trying them on this drug
link |
01:24:23.920
instead of the statin.
link |
01:24:25.760
So you could talk to your doctor about that.
link |
01:24:28.260
Do you avoid dietary cholesterol for that reason also?
link |
01:24:32.760
Red meat, butter.
link |
01:24:34.040
I mean, I happen to love butter.
link |
01:24:35.280
I love red meat.
link |
01:24:36.980
I realize there's some people who don't.
link |
01:24:39.720
My cholesterol is a little bit high,
link |
01:24:40.920
but I'm working to bring that down a bit,
link |
01:24:43.440
although not by altering my food intake yet.
link |
01:24:48.000
But what do you think is the relationship
link |
01:24:49.360
between dietary cholesterol and serum cholesterol?
link |
01:24:51.720
And what's going on with the liver?
link |
01:24:53.480
Why are anorexics, why is their serum cholesterol so high
link |
01:24:57.520
when they're eating nothing?
link |
01:24:58.720
Well, there've been a number of papers over the years
link |
01:25:00.640
that have been ignored.
link |
01:25:02.040
And our friend, Peter Atiyah,
link |
01:25:04.000
brought to my attention recently a new study
link |
01:25:07.080
that I think definitively said
link |
01:25:09.140
that dietary cholesterol has almost zero impact
link |
01:25:12.480
on blood cholesterol levels.
link |
01:25:13.840
Good.
link |
01:25:14.680
Yeah, so I'm annoyed,
link |
01:25:17.240
because I've been avoiding eggs and butter
link |
01:25:19.280
for most of my life, and I didn't have to.
link |
01:25:22.180
So I had eggs plenty of time, at least in your case.
link |
01:25:26.280
Yeah, yeah, so that's the thing.
link |
01:25:28.680
You can eat these foods that were once banned,
link |
01:25:31.720
because it's very difficult to take cholesterol up
link |
01:25:34.640
into the body from the gut,
link |
01:25:36.160
and most of it's being synthesized in the body.
link |
01:25:39.280
Wow, I'm just pausing there for a second,
link |
01:25:41.160
because I think that it's what we've been told,
link |
01:25:45.920
six meals a day, eat a lot of grains and fruits
link |
01:25:49.840
and this kind of thing, avoid cholesterol.
link |
01:25:55.280
I mean, basically everything we learned in the 80s and 90s
link |
01:25:58.880
and early 2000s is getting flipped on its head now.
link |
01:26:01.940
But, and I think this is a very strong caveat
link |
01:26:07.840
that's important to mention, amino acids,
link |
01:26:12.560
in particular the amino acids
link |
01:26:14.000
that come from animal products, right?
link |
01:26:17.200
Seem to have some pro-aging effect on them, right?
link |
01:26:21.240
At least the way that I've heard you describe your diet.
link |
01:26:24.720
And I'm somebody who enjoys meat, I like it.
link |
01:26:27.840
But, so I'm by no means a vegan at all.
link |
01:26:31.160
But I've heard you say you eat mostly plants,
link |
01:26:36.000
but a little bit of fish or chicken
link |
01:26:38.160
or something of that sort, or eggs or,
link |
01:26:40.640
but is that specifically to avoid
link |
01:26:43.520
excessive amino acid intake?
link |
01:26:45.160
Or is it something specific about plants
link |
01:26:46.960
that excites you with respect to,
link |
01:26:50.100
I mean, vegetables are delicious too, but what is it?
link |
01:26:52.680
Is it something great about plants
link |
01:26:54.040
or is it something bad about, when I think of meat,
link |
01:26:56.440
I guess the biologist in me thinks amino acids, right?
link |
01:26:59.400
I don't think top sirloin, I think amino acid.
link |
01:27:01.760
No, I think top sirloin as I'm eating it,
link |
01:27:03.300
but really what they are are amino acids, including leucine.
link |
01:27:07.220
Yeah, well, there are two good things about plants
link |
01:27:10.680
and neither of them is taste for me.
link |
01:27:13.800
I would eat steak all the time if I could.
link |
01:27:15.660
I did when I was a kid, I'm an Australian.
link |
01:27:18.480
But plants have two benefits.
link |
01:27:19.740
One is that they're highly nutritious
link |
01:27:22.800
and they'll give you a lot of the vitamins
link |
01:27:26.500
and nutrients that I need.
link |
01:27:28.060
I don't take a multivitamin, I don't wanna
link |
01:27:30.200
have the excess iron in my body.
link |
01:27:32.200
So there's that high density nutrition.
link |
01:27:34.160
So those dark leaves, if it's a spinach salad, great.
link |
01:27:39.360
Second is that there is what's called
link |
01:27:41.360
xenohormatic molecules in plants.
link |
01:27:44.360
That term xenohormesis is a term that I came up with
link |
01:27:48.480
with my friend Conrad Howitz, which means
link |
01:27:52.800
stressed plants make molecules that benefit your health.
link |
01:27:56.220
I'll break it down.
link |
01:27:57.120
Xeno means between species and hormesis is the term
link |
01:28:00.360
whatever doesn't kill you makes you stronger
link |
01:28:02.340
and live longer.
link |
01:28:03.900
And the idea is that when plants are stressed out,
link |
01:28:07.600
think of a grapevine that's dried out
link |
01:28:09.600
and they're starting to harvest the grapes,
link |
01:28:11.200
which is typically how it's done.
link |
01:28:13.160
They are full with resveratrol because resveratrol
link |
01:28:15.800
is a plant defense molecule that I think is made
link |
01:28:19.220
to activate those sirtuin genes in a plant.
link |
01:28:21.480
So plants have sirtuins just like we do.
link |
01:28:24.200
But by purifying or at least concentrating
link |
01:28:27.000
in a light proof bottle and keeping it out of the air,
link |
01:28:30.920
we stabilize this xenohormatic molecule,
link |
01:28:33.600
or it's a cocktail, not just one, there's others in wine.
link |
01:28:36.900
We then ingest those and get the benefits
link |
01:28:39.680
of activating our own defenses
link |
01:28:41.200
because our food was getting stressed out.
link |
01:28:43.560
And by stressed, I don't mean psychologically stressed,
link |
01:28:45.580
I mean biologically stressed.
link |
01:28:47.480
And so I try to eat plants that have gone through
link |
01:28:50.680
a bit of stress, they might be brightly colored,
link |
01:28:53.120
they've had too much sun or got nibbled on by a caterpillar.
link |
01:28:57.320
So you go to places where it's organic or it's fresh,
link |
01:28:59.840
local, and those are the plants that aren't perfect
link |
01:29:01.860
and they probably have high concentrations
link |
01:29:03.200
of these molecules.
link |
01:29:04.040
And in addition, I also buy the supplements
link |
01:29:06.640
to make sure I'm getting enough of those as well.
link |
01:29:08.640
Which supplements mimic that?
link |
01:29:09.920
Well, so resveratrol will,
link |
01:29:11.080
there's another one called chrysotin,
link |
01:29:12.840
or chrysotin, some people call it,
link |
01:29:14.600
which you find in trace amounts in apples and onions.
link |
01:29:18.480
And we also showed back in 2003
link |
01:29:20.720
that it activates sirtuins as well,
link |
01:29:23.080
but others have, 20 years later,
link |
01:29:25.240
found that it kills senescent cells
link |
01:29:28.360
or helps kill senescent cells.
link |
01:29:30.560
So it's a double whammy with that molecule.
link |
01:29:33.360
And are you actively picking out the peaches
link |
01:29:35.440
that look like they were nibbled on by a caterpillar?
link |
01:29:38.560
No, but I don't worry if they've been banged up a bit.
link |
01:29:43.200
What's the story with antioxidants?
link |
01:29:45.120
Are they of any value whatsoever?
link |
01:29:46.800
Because the way that you described them at the beginning
link |
01:29:50.160
and what I've heard recently is that
link |
01:29:52.120
they are not all the rage for anti-aging.
link |
01:29:57.280
What are they doing that's useful?
link |
01:29:58.680
Should we be seeking out antioxidants anyway
link |
01:30:02.040
for other cellular health purposes?
link |
01:30:04.440
Well, yeah, antioxidants are not going to hurt you
link |
01:30:06.560
unless you take mega doses.
link |
01:30:08.200
We do need some oxidants for our immune system.
link |
01:30:11.960
And there's even what's called mitohormesis,
link |
01:30:14.040
which is your mitochondria power packs
link |
01:30:16.080
need to have a little bit of these free radicals
link |
01:30:18.400
to be able to function.
link |
01:30:19.720
So you don't want to overdose on these antioxidants,
link |
01:30:23.520
vitamin C, vitamin E, don't overdo it.
link |
01:30:26.800
You don't take a multivitamin, correct?
link |
01:30:28.520
Right.
link |
01:30:29.800
I think I'm going to stop after this conversation
link |
01:30:31.840
because I've always just taken one
link |
01:30:33.080
for the kind of insurance purpose,
link |
01:30:34.640
which is a stupid purpose, not actual insurance,
link |
01:30:38.480
but just thinking, oh, you know,
link |
01:30:39.760
I'll top off on my ACBD.
link |
01:30:42.920
Right, and I'll pee out what I don't need.
link |
01:30:45.160
Right, but that never bothered me.
link |
01:30:46.640
The whole expensive pee thing never got,
link |
01:30:48.440
that argument never got me
link |
01:30:50.600
because a good vitamin is not that expensive.
link |
01:30:54.840
I just figured better safe than sorry,
link |
01:30:56.400
but it may be that it's detrimental.
link |
01:30:58.840
Well, it can in the case of iron,
link |
01:31:00.760
as we discussed, and the antioxidants.
link |
01:31:02.680
So when I came into the aging field in the early 1990s,
link |
01:31:07.640
it was all about antioxidants.
link |
01:31:09.120
And we thought that enzymes by the name of catalase
link |
01:31:12.520
and superoxide dismutase
link |
01:31:13.880
were going to be the key to longevity.
link |
01:31:16.480
It turns out that it's largely been a failure
link |
01:31:18.920
that giving animals and humans antioxidants
link |
01:31:23.800
haven't had the longevity benefits that we dreamed of.
link |
01:31:27.480
And the main reason is that there's a lot more going on
link |
01:31:31.440
than just free radical damage.
link |
01:31:33.920
The epigenome gets disrupted.
link |
01:31:35.720
We've got these proteins misfolding.
link |
01:31:38.920
So the problem really has been that we didn't realize
link |
01:31:42.080
that you need to turn on the body's natural defenses
link |
01:31:45.560
against that plus a whole host of other things
link |
01:31:47.880
to get the true benefits.
link |
01:31:50.120
But I'm not going to say it's a problem
link |
01:31:51.360
taking an antioxidant drink.
link |
01:31:53.920
Pomegranate juice for one is full of good stuff,
link |
01:31:56.000
including xenochromatic molecules.
link |
01:31:58.520
But resveratrol is a good case in point,
link |
01:32:00.880
which is when I worked on resveratrol
link |
01:32:03.360
as a longevity molecule,
link |
01:32:05.080
first we showed it in yeast and worms and flies and mice.
link |
01:32:09.280
Before that, it was thought that resveratrol
link |
01:32:11.640
was good for your heart in red wine,
link |
01:32:13.760
when you drink red wine, because it's an antioxidant.
link |
01:32:16.720
So then we showed that it extended the lifespan
link |
01:32:18.880
of yeast cells through this genetic pathway, the sirtuins.
link |
01:32:24.960
And we then tested whether resveratrol,
link |
01:32:28.400
if we changed one atom to make it not an antioxidant,
link |
01:32:31.880
guess what?
link |
01:32:32.720
It still worked fine.
link |
01:32:33.640
So it wasn't its antioxidant activity
link |
01:32:35.480
that was extending lifespan.
link |
01:32:36.560
It was its ability to turn on the yeast's defenses
link |
01:32:38.960
against aging.
link |
01:32:40.120
Conversely, when we gave the yeast antioxidants,
link |
01:32:42.720
they lived shorter.
link |
01:32:44.480
So yeah, that was the beginning of my transformation
link |
01:32:46.840
into thinking, turn on the body's defenses,
link |
01:32:49.000
don't give it the antioxidants.
link |
01:32:50.760
This is an opportunity for me to say
link |
01:32:53.160
something that I've been wanting to say for a long time,
link |
01:32:55.640
which is that what's so wonderful about science
link |
01:32:58.600
is that because the goal is mechanism,
link |
01:33:01.480
you can really start to understand, as you just described,
link |
01:33:05.920
what actually mediates a process
link |
01:33:07.840
is very different than what modulates a process.
link |
01:33:10.000
I mean, if a fire alarm goes off in the building right now,
link |
01:33:12.160
it's going to modulate our attention.
link |
01:33:13.960
That doesn't mean that it controls our attention.
link |
01:33:16.440
It's not mechanistically relevant.
link |
01:33:18.320
And so I think this thing about antioxidants
link |
01:33:20.160
is one of these cases, it sounds like,
link |
01:33:22.440
where it's in the right ballpark,
link |
01:33:24.840
but until one really unveils the mechanism as you have,
link |
01:33:27.720
you can be, one can or a field can be badly wrong
link |
01:33:32.920
for a very long period of time.
link |
01:33:35.440
It sounds like the sirtuins,
link |
01:33:37.200
and really getting down to the guts of the machinery
link |
01:33:39.920
of what causes cells to age is really what it's about.
link |
01:33:43.400
Zooming way out, what are the behavioral tools
link |
01:33:48.000
that one can start to think about
link |
01:33:49.720
in terms of ways to modulate these,
link |
01:33:52.440
basically the way that DNA is being expressed
link |
01:33:55.120
and functioning?
link |
01:33:56.480
I've heard you talk before about hormesis of other sorts,
link |
01:34:00.680
cold exposure, we talked about fasting.
link |
01:34:03.440
We talked about exercise in broad terms,
link |
01:34:05.560
but what about any evidence, if it exists,
link |
01:34:10.760
as to whether or not aerobic training
link |
01:34:13.320
versus weight training, these sorts of things.
link |
01:34:16.040
In other words, what are the sorts of things
link |
01:34:17.600
that people can do to improve the sirtuin pathway?
link |
01:34:21.320
And I realize that they're caveats.
link |
01:34:23.240
We can't go directly from a behavior to sirtuins,
link |
01:34:25.440
but in the general theme, what can people do?
link |
01:34:28.400
What do you do?
link |
01:34:29.320
Right.
link |
01:34:30.160
Well, we know that aerobic exercise in mice and rats
link |
01:34:33.640
raises their NAD levels and their levels of sirt,
link |
01:34:37.000
one of the genes goes up to actually number one
link |
01:34:39.880
and number three.
link |
01:34:41.160
What we don't know yet is what type of exercise
link |
01:34:44.920
is optimal to get them to change.
link |
01:34:47.560
We will learn, we're doing work.
link |
01:34:49.200
Now it's revealed that we're doing work
link |
01:34:50.800
with the military in the US
link |
01:34:52.560
to try and understand that kind of thing.
link |
01:34:55.000
And I'll always tell you and the public
link |
01:34:57.160
when I don't know something, I'm not gonna extrapolate.
link |
01:35:01.240
But what do I do?
link |
01:35:02.080
I base my exercise on the scientific literature,
link |
01:35:05.080
which has shown that maintaining muscle mass
link |
01:35:08.760
is very important for a number of reasons.
link |
01:35:10.880
The two main ones are,
link |
01:35:12.720
you wanna maintain your hormone levels.
link |
01:35:14.240
I'm an older male losing my testosterone
link |
01:35:17.040
and muscle mass over time.
link |
01:35:18.880
And by exercising, I will maintain that and have.
link |
01:35:23.160
In fact, I probably haven't had a body like this
link |
01:35:26.040
since I was 20.
link |
01:35:26.880
So that's one of the benefits of having this lifestyle.
link |
01:35:30.280
Sorry to interrupt you, we did an episode on hormones
link |
01:35:33.520
and there are data in humans that show
link |
01:35:35.480
that there are some males in their 80s and 90s
link |
01:35:39.920
where their testosterone is equivalent
link |
01:35:41.840
to the average of 25 and 30 year olds.
link |
01:35:44.600
I can get you that information.
link |
01:35:45.840
It is really impressive studies.
link |
01:35:49.400
Unfortunately, they didn't include a lot of information
link |
01:35:51.200
about the lifestyle factors, et cetera.
link |
01:35:52.840
But this idea that testosterone goes down with age,
link |
01:35:56.800
it might be the trend
link |
01:35:59.640
but it's not necessarily a prerequisite.
link |
01:36:03.880
Right, I believe in naturally increasing
link |
01:36:06.600
and maintaining these hormone levels.
link |
01:36:08.040
And I've been measuring them for a long time.
link |
01:36:10.720
And I could see for me,
link |
01:36:11.800
my testosterone levels were steadily,
link |
01:36:14.120
levels were going down.
link |
01:36:15.160
And then you got tenure and they went back up again.
link |
01:36:18.120
No, I actually became complacent and it was the worst.
link |
01:36:23.440
Actually, my age changed in the wrong direction after that
link |
01:36:26.680
because I was relaxed and not worried about the future.
link |
01:36:31.760
But then I got serious.
link |
01:36:32.640
And I actually, according to the inside tracker algorithm,
link |
01:36:35.200
got my age down from 58 to 31 in a matter of months.
link |
01:36:40.720
That was a big drop.
link |
01:36:41.840
And I've been getting steadily younger
link |
01:36:43.440
over the last 10 years,
link |
01:36:44.640
according to that measurement, the blood tests.
link |
01:36:46.520
What about estrogen?
link |
01:36:47.400
Because women are different in the sense that they do,
link |
01:36:51.800
the number of eggs and the ovaries change over time, right?
link |
01:36:56.040
Do you think that they can maintain estrogen levels
link |
01:36:58.880
in over longer periods of time
link |
01:37:01.640
using some of these same protocols?
link |
01:37:03.320
Well, yeah, I get into trouble from a certain university
link |
01:37:06.600
when I talk about this too much.
link |
01:37:08.920
About estrogen?
link |
01:37:10.240
Just about fertility and long story.
link |
01:37:16.760
I don't want to get too much into the anecdotes,
link |
01:37:18.760
but I'll tell you the science,
link |
01:37:19.760
which is that if you take a mouse
link |
01:37:24.520
and put it on fasting or caloric restriction
link |
01:37:27.680
for up until the point where it should be infertile,
link |
01:37:31.760
so that's about it at a year of age,
link |
01:37:33.440
a mouse gets infertile, a female mouse.
link |
01:37:35.160
Due to fasting or due to simply to aging?
link |
01:37:38.120
Due to aging, due to aging.
link |
01:37:39.920
The fasting, it's not an extreme fast,
link |
01:37:42.800
it's just less calories.
link |
01:37:44.720
Then you put them back on a regular food
link |
01:37:47.320
and they become fertile again
link |
01:37:49.200
for many, many months afterwards.
link |
01:37:51.520
So the effect on slowing down aging
link |
01:37:55.040
is also on the reproductive system.
link |
01:37:56.960
Interesting.
link |
01:37:58.000
And so I wouldn't say to any woman,
link |
01:38:00.200
I wouldn't think that they should become super skinny
link |
01:38:02.600
to try and preserve fertility.
link |
01:38:04.120
That's not what I'm saying.
link |
01:38:05.440
But these pathways that we work on,
link |
01:38:07.160
these sirtuins, are known to delay infertility
link |
01:38:10.360
in female animals.
link |
01:38:12.080
Case in point, I'm one of the lead authors on a paper
link |
01:38:15.080
where we used NMN.
link |
01:38:16.640
Remember, this is the gas, the fuel,
link |
01:38:18.680
the petrol for the sirtuins.
link |
01:38:20.400
We gave old mice, one group of mice was 16 months old.
link |
01:38:26.600
Remember, they came infertile at 12,
link |
01:38:29.640
gave them NMN, and I think it was only six weeks later,
link |
01:38:34.120
they had offspring.
link |
01:38:36.800
They became fertile again,
link |
01:38:38.040
which goes against biology, a textbook biology,
link |
01:38:41.320
which is that female mammals run out of eggs.
link |
01:38:44.760
Turns out that's not true.
link |
01:38:46.760
You can rejuvenate the female reproductive system
link |
01:38:49.680
and even get them to come out of mouse support,
link |
01:38:52.520
as we call it.
link |
01:38:53.920
So that's a whole new paradigm in biology as well.
link |
01:38:56.560
That's super interesting.
link |
01:38:57.720
Sorry to interrupt you,
link |
01:38:58.560
but I'm reminded of a set of studies that were done
link |
01:39:01.720
by your former colleagues, because they're no longer there,
link |
01:39:04.360
David Hubel and Torrance Wiesel,
link |
01:39:05.760
my scientific great-grandparents, won the Nobel Prize
link |
01:39:07.960
for discovering what are called critical periods,
link |
01:39:10.920
this phase of early development
link |
01:39:12.240
when the brain is extremely plastic.
link |
01:39:15.000
And a big part of their work was to show
link |
01:39:17.200
that after a certain point,
link |
01:39:18.360
the critical period shuts down,
link |
01:39:19.800
essentially the brain can't change or not nearly as much.
link |
01:39:23.600
And then people came along later
link |
01:39:24.760
and showed that you could open up
link |
01:39:26.000
these critical periods again, but very briefly,
link |
01:39:28.600
and it takes a very specific stimulus, essentially,
link |
01:39:33.080
high degrees of focus, et cetera.
link |
01:39:35.280
However, there's a well-known phenomenon in this literature
link |
01:39:39.280
where if you take an animal, and to some degree,
link |
01:39:43.360
this has been shown in humans as well,
link |
01:39:45.760
and you let them pass through the critical period,
link |
01:39:48.000
but then you essentially sensory deprive them.
link |
01:39:51.040
You take away experience, you close both eyes.
link |
01:39:54.280
You essentially reopen the critical period.
link |
01:39:57.120
So it seems like, and I couldn't help but mention this,
link |
01:39:59.440
that there's this parallel between what we're talking about
link |
01:40:01.800
here with fertility and neuroplasticity,
link |
01:40:03.600
where, yes, there's a timer where certain things
link |
01:40:06.480
are available to the organism early in life,
link |
01:40:09.120
and then they tend to taper off.
link |
01:40:10.680
It's not an open and shut, but they taper off.
link |
01:40:12.800
But then a deprivation can actually reactivate
link |
01:40:16.240
the availability of that process.
link |
01:40:19.280
Forgive me, I just couldn't help but mention it,
link |
01:40:20.800
but to me, both of those things are associated with youth,
link |
01:40:24.480
fertility and neuroplasticity.
link |
01:40:26.240
And so I think that it'd be so interesting,
link |
01:40:28.560
I'd love to collaborate with you on this
link |
01:40:29.920
to explore how neuroplasticity might actually be regulated
link |
01:40:32.880
by these things like the sirtuins.
link |
01:40:35.440
Right, and the sirtuins do control memory
link |
01:40:38.720
in neurons as well.
link |
01:40:39.840
So what I think is really interesting is that
link |
01:40:42.440
what we're learning from the research is that
link |
01:40:45.600
from work that you and your colleagues have done
link |
01:40:47.800
and in my lab as well,
link |
01:40:49.360
is that the body has remarkable powers of healing
link |
01:40:52.440
and recovering from illness and injury.
link |
01:40:56.440
And what we once thought was a one-way street
link |
01:40:58.480
and you just can't repair,
link |
01:41:00.720
you can't get over these diseases,
link |
01:41:02.880
you can reset the system.
link |
01:41:04.200
And the body can really get rejuvenated
link |
01:41:06.120
in ways that in the future will wonder
link |
01:41:08.040
why didn't we work on this earlier?
link |
01:41:11.040
The future of humanity is more like
link |
01:41:12.960
us walking around like Deadpool.
link |
01:41:14.680
We'll probably be cleaner and we won't smell as badly,
link |
01:41:17.720
but Deadpool, if you don't know,
link |
01:41:20.720
can get injured and just recover.
link |
01:41:22.160
It's very hard to injure this guy.
link |
01:41:25.280
And we're gonna be the same.
link |
01:41:26.320
There are many species, you cut off the limb,
link |
01:41:28.480
the limb grows back.
link |
01:41:29.320
Salamanders, yeah.
link |
01:41:30.920
We are now learning how to tap into that system.
link |
01:41:33.600
And in part, what we're doing is reversing the age
link |
01:41:36.360
of those cells and telling them
link |
01:41:38.360
how to read the genes correctly again,
link |
01:41:40.800
reversing the age of that epigenome.
link |
01:41:43.480
And when you do that, the cells,
link |
01:41:45.160
the brain, for instance, the skin,
link |
01:41:47.920
we did the optic nerve.
link |
01:41:49.760
Now let's talk about those results for a second.
link |
01:41:51.440
Then I want to make sure that we return
link |
01:41:52.680
to some of these behavioral protocols.
link |
01:41:54.360
You had this amazing paper at the end of last year,
link |
01:41:56.440
cover article, full article in Nature,
link |
01:41:59.760
showing that essentially a small menu
link |
01:42:02.880
of transcription factors,
link |
01:42:05.080
which control gene expression, et cetera,
link |
01:42:08.520
could essentially reverse the age of neurons in the eye
link |
01:42:11.960
and rescue those cells against damage,
link |
01:42:15.920
essentially allow blind mice to see again
link |
01:42:18.760
and offset degeneration of these retinal cells.
link |
01:42:21.560
Incredible paper and such a boon to the field.
link |
01:42:26.960
Where does that stand now
link |
01:42:28.520
in terms of human clinical trials?
link |
01:42:30.080
I mean, what are you envisioning
link |
01:42:32.640
in terms of the trajectory of those data
link |
01:42:35.240
from mice into humans someday?
link |
01:42:38.640
Right, well, to get to the point immediately,
link |
01:42:43.480
we're going to be testing the treatment on monkeys,
link |
01:42:49.120
just for safety reasons.
link |
01:42:50.800
And then the first patient should be done
link |
01:42:53.920
sometime in 2022, early 2023,
link |
01:42:56.280
and we're going to try to recover blindness.
link |
01:42:58.560
This involves making an injection
link |
01:43:00.320
of a virus into the eye, right?
link |
01:43:02.680
Right now, there's no way that I am aware of
link |
01:43:05.280
to manipulate these transcription factors
link |
01:43:07.000
through a pill or some other.
link |
01:43:08.720
That's what we're working on in my lab at Harvard right now.
link |
01:43:11.760
So it will be-
link |
01:43:12.600
Pill-based modulation of transcription factors.
link |
01:43:14.440
It will be a proper pill
link |
01:43:15.280
and the whole body gets rejuvenated by 20 years.
link |
01:43:16.960
That's what we're aiming for.
link |
01:43:18.440
Now we do it with gene therapy in the eye and other places.
link |
01:43:23.080
So in the eye, yes, it's single injection.
link |
01:43:25.720
The genes go into the retina
link |
01:43:27.360
and we can turn it on with a drug called doxycycline.
link |
01:43:31.200
And we do that in the mice for four to eight weeks.
link |
01:43:34.640
Then the eye gets younger.
link |
01:43:36.120
We can measure that because we can measure the clock.
link |
01:43:38.880
And then the vision comes back in those mice.
link |
01:43:41.760
And I don't see any reason why it shouldn't work in people
link |
01:43:44.840
because it's the same structures and mechanisms
link |
01:43:47.480
that are on in the human as well.
link |
01:43:49.840
Now these-
link |
01:43:50.680
And it's one injection.
link |
01:43:51.520
As you mentioned, injections into the eye,
link |
01:43:53.560
obviously nobody should do this
link |
01:43:55.040
outside of an ophthalmology clinic.
link |
01:43:58.000
And they're definitely by an ophthalmologist.
link |
01:44:00.040
But the injections into the eye are painless
link |
01:44:03.640
if done correctly by the right person.
link |
01:44:05.440
It sounds dreadful, but it's actually,
link |
01:44:07.360
I've seen it done hundreds of times.
link |
01:44:09.240
I've done it thousands of times,
link |
01:44:11.360
and it's not to myself, but to other creatures.
link |
01:44:14.720
And there's a way of doing this
link |
01:44:15.840
that's completely painless to the person.
link |
01:44:17.560
Oh, there are a few.
link |
01:44:18.400
It's a tiny, tiny needle too.
link |
01:44:20.240
But the great thing about this
link |
01:44:21.280
is that it's a one-time treatment.
link |
01:44:22.800
Those genes go into the back of the eye
link |
01:44:24.240
and stay there forever.
link |
01:44:27.440
And you can just turn them on whenever you want.
link |
01:44:29.840
So what we've found is you can turn them on in the mice,
link |
01:44:32.360
they get their vision back,
link |
01:44:33.720
and then you turn it off again.
link |
01:44:35.440
And so far, many months out,
link |
01:44:37.480
the benefit has remained.
link |
01:44:39.520
But if it does decline,
link |
01:44:41.280
we'll just turn it back on and reset the system,
link |
01:44:43.600
rinse and repeat.
link |
01:44:45.120
So one day, what's exciting
link |
01:44:46.360
is that we could potentially do this
link |
01:44:47.760
across the entire body
link |
01:44:50.360
and just take this antibiotic every five years
link |
01:44:53.480
and go back time and time again.
link |
01:44:56.560
In thinking about the body
link |
01:44:57.600
and what's going on under the hood,
link |
01:44:58.880
I'm amazed still that there isn't
link |
01:45:01.760
a simple, affordable technology
link |
01:45:03.920
that would allow me to just look into my body
link |
01:45:05.760
and see whether or not there are any tumors growing anywhere.
link |
01:45:08.240
I mean, it's not that hard to look into the body.
link |
01:45:10.760
I mean, that the technology exists.
link |
01:45:12.160
Why hasn't anybody created an at-home
link |
01:45:14.600
or pseudo at-home solution,
link |
01:45:16.680
like a clinic where you can go and pay 50 bucks or 100 bucks
link |
01:45:19.720
and see if you have any tumors growing in your body?
link |
01:45:21.360
Yeah, it's still expensive.
link |
01:45:22.920
You can get your doctor to try to get you in.
link |
01:45:26.360
There's some companies that offer blood tests
link |
01:45:28.360
that look at circulating DNA that'll measure it.
link |
01:45:31.560
We're getting there.
link |
01:45:32.400
We're still probably five to 10 years away
link |
01:45:34.040
from being really cheap.
link |
01:45:36.600
You can do things like a colon cancer test at home.
link |
01:45:40.480
I think it's a hundred and something dollars.
link |
01:45:42.680
You ship off your shit, excuse my language,
link |
01:45:46.160
and they measure it.
link |
01:45:47.640
And they tell you if you've got colon cancer
link |
01:45:50.400
with high probability.
link |
01:45:52.000
I did that during the pandemic
link |
01:45:54.000
because I didn't want to get a colonoscopy.
link |
01:45:56.240
Is it more accurate or as accurate as a colonoscopy?
link |
01:45:58.880
I believe it's close to being as accurate.
link |
01:46:01.000
The downside is that during a colonoscopy,
link |
01:46:03.240
they can pinch off the polyps that are looking dangerous,
link |
01:46:06.560
whereas this obviously isn't that.
link |
01:46:08.760
But it's certainly easier to do.
link |
01:46:10.440
And my father, who's Australian,
link |
01:46:12.920
tells me that it's free for Australians.
link |
01:46:14.840
They get this test routinely.
link |
01:46:18.160
Interesting.
link |
01:46:19.920
I want to return to the topic that I took us away from,
link |
01:46:22.680
so I apologize, which is behavioral protocols.
link |
01:46:25.760
Do you regularly do the cold shower thing,
link |
01:46:28.320
ice baths, cold water swims?
link |
01:46:29.960
Are you into that whole biz?
link |
01:46:34.320
Well, you do know that I've done it at least once
link |
01:46:37.040
because we did it together.
link |
01:46:38.000
That's right.
link |
01:46:38.840
Not the same bath, just to be very clear.
link |
01:46:40.760
Same sauna, different ice baths.
link |
01:46:42.760
The idea of Sinclair and Huberman
link |
01:46:44.520
taking an ice bath together is,
link |
01:46:46.360
it might warm some people's hearts,
link |
01:46:48.040
but just to be very clear,
link |
01:46:50.480
same ice bath, different times.
link |
01:46:53.720
Yeah.
link |
01:46:54.560
Thank you for clarifying.
link |
01:46:56.160
I don't do them regularly.
link |
01:46:57.800
I do try to sleep cool.
link |
01:47:02.160
I sleep better anyway.
link |
01:47:03.760
I try to dress without a lot of warm clothes.
link |
01:47:06.960
I'm here in a t-shirt and it's middle of summer,
link |
01:47:09.160
but in winter, I'll try to wear a t-shirt too.
link |
01:47:11.800
So you're challenging your system to thermoregulate.
link |
01:47:14.600
Right, right.
link |
01:47:15.680
I've got this hypothesis with Ray Cronus.
link |
01:47:18.640
We published what's called the metabolic winter hypothesis,
link |
01:47:21.200
which is, tens of thousands of years ago,
link |
01:47:24.440
we were either hungry or cold or both.
link |
01:47:26.760
And we rarely experienced that now.
link |
01:47:28.760
And so we try to give ourselves the metabolic winter.
link |
01:47:32.320
And part of the problem, I think,
link |
01:47:33.440
with the obesity epidemic is that we're never cold.
link |
01:47:36.680
And cold, when you're cold, you have to burn energy.
link |
01:47:38.640
It may be only slightly.
link |
01:47:40.280
But over the whole night, if you're a little bit cool,
link |
01:47:42.560
you'll actually expend more energy.
link |
01:47:43.960
So I try to do that.
link |
01:47:45.440
But I'm not a big fan of cold showers.
link |
01:47:48.040
The sauna, I don't have access to my gym as much as I did.
link |
01:47:51.720
But I do wanna get back into it.
link |
01:47:52.960
I used to do it regularly with my son
link |
01:47:55.480
and I posted on Instagram once
link |
01:47:57.240
that he could stay in there for 15 minutes
link |
01:47:58.800
and I could only stay in for about three.
link |
01:48:01.480
Anyway, long story short,
link |
01:48:02.640
I try to compensate with changes in my diet and exercise
link |
01:48:05.680
until I get back into it.
link |
01:48:07.120
You reminded me of something that I meant to ask earlier,
link |
01:48:10.040
that obesity reduces NAD levels and accelerates aging.
link |
01:48:15.040
How?
link |
01:48:15.880
I mean, okay, so again, this is the scientist in us.
link |
01:48:20.880
So someone's carrying a lot of excess adipose tissues,
link |
01:48:24.040
subcutaneous and visceral fat.
link |
01:48:28.400
But why should that reduce NAD in any ways
link |
01:48:31.840
that are independent of effects on glucose and insulin?
link |
01:48:34.760
Is there something direct about white adipose tissue?
link |
01:48:38.200
And the reason I ask this
link |
01:48:40.320
is not simply to dig into mechanism alone,
link |
01:48:43.160
but I think there are really interesting data now
link |
01:48:45.080
that fat actually gets neural innervation.
link |
01:48:47.440
I mean, it's not just stored fuel.
link |
01:48:51.760
It's stored fuel that's acting as an endocrine organ,
link |
01:48:54.920
essentially.
link |
01:48:55.760
So yeah, why would being fat make people age faster?
link |
01:49:01.360
Yeah, that's a question that is so obvious,
link |
01:49:04.640
but so few people ask it.
link |
01:49:06.200
That's what makes you a good scientist.
link |
01:49:08.560
And so that we don't know,
link |
01:49:09.760
but I'll give you my best answer,
link |
01:49:11.360
which is that obesity comes along with a lot of problems
link |
01:49:15.720
that include a lot of senescent cells in fat.
link |
01:49:20.040
If you stain old fat for senescent cells, it lights up.
link |
01:49:24.320
And when you kill off those cells,
link |
01:49:26.520
at least in mice and maybe in humans,
link |
01:49:28.440
it looks like the fat is less toxic to the body
link |
01:49:32.120
because those senescent cells in the fat
link |
01:49:33.680
are secreting these inflammatory molecules
link |
01:49:35.960
that will accelerate aging as we now know.
link |
01:49:40.000
You talk about the sirtuins and NAD.
link |
01:49:43.600
So if we just look philosophically at why this would be,
link |
01:49:47.720
the sirtuins only like to come on or get activated
link |
01:49:51.480
when the body is under adversity.
link |
01:49:55.080
And if a cell is surrounded by fat or contains a lot of fat,
link |
01:49:59.760
it's going to think times are good,
link |
01:50:01.160
doesn't need to switch on.
link |
01:50:02.200
So that's the evolutionary argument.
link |
01:50:05.080
Mechanistically, we don't know,
link |
01:50:07.280
but it could have something to do
link |
01:50:08.520
with the response to glucose,
link |
01:50:10.360
which then responds to the sirtuin gene.
link |
01:50:13.360
But that hasn't been worked out very well.
link |
01:50:15.160
And is there any evidence
link |
01:50:16.320
that leptin, this hormone from fat,
link |
01:50:17.960
can actually interact with the sirtuin pathway?
link |
01:50:22.200
I don't recall seeing that.
link |
01:50:23.640
Maybe I could do a sabbatical in your lab
link |
01:50:25.240
and that'd be a fun one.
link |
01:50:26.920
Definitely.
link |
01:50:27.760
Because leptin during development
link |
01:50:29.200
is what triggers the permission
link |
01:50:31.160
for the hypothalamus to enter puberty, right?
link |
01:50:33.840
Yes.
link |
01:50:34.680
This is why kids that eat a lot
link |
01:50:36.080
when they're young and get overweight
link |
01:50:37.480
will also start to undergo puberty more quickly,
link |
01:50:40.360
although they have reproductive issues later.
link |
01:50:44.160
Well, yeah, we should study the hypothalamus together
link |
01:50:46.120
because the hypothalamus can control the aging of the body.
link |
01:50:50.200
The most interesting part of the brain.
link |
01:50:52.280
For sure.
link |
01:50:53.120
Yeah, absolutely.
link |
01:50:53.960
If you turn on the SIRT1 gene,
link |
01:50:55.520
the sirtuin gene that we work on in the hypothalamus,
link |
01:50:57.920
it actually will extend lifespan.
link |
01:50:59.800
Also, it's been shown by Dongxin Cai
link |
01:51:02.320
at Albert Einstein College of Medicine
link |
01:51:04.040
that if you inhibit inflammation
link |
01:51:06.080
in the hypothalamus in a mouse,
link |
01:51:08.160
it will increase or maintain the expression
link |
01:51:11.880
of what's called GnRH,
link |
01:51:13.360
which is the hormone that he found actually controls
link |
01:51:16.560
longevity in the mouse in part.
link |
01:51:18.560
And so keeping inflammation down in the hypothalamus
link |
01:51:21.240
is sufficient to extend the lifespan of animals.
link |
01:51:23.880
And I reviewed that paper for Nature about seven years ago.
link |
01:51:27.760
And that was the first demonstration
link |
01:51:29.240
that the hypothalamus is one of the leading regulators
link |
01:51:32.360
of the body's age.
link |
01:51:33.440
I find this fascinating.
link |
01:51:34.440
GnRH, for those of you that don't know,
link |
01:51:37.120
actually comes from neurons in the hypothalamus
link |
01:51:39.240
that then literally reach down into the pituitary
link |
01:51:42.280
and trigger the release of all the things
link |
01:51:43.640
that control fertility,
link |
01:51:45.240
luteinizing hormone, follicle stimulating hormone, et cetera.
link |
01:51:48.640
It's such a powerful set of neurons,
link |
01:51:50.160
and it's never really been clear
link |
01:51:51.960
what at a behavioral level triggers the release of GnRH.
link |
01:51:55.760
There's all the stories about pheromones
link |
01:51:57.520
and timers and puberty, et cetera,
link |
01:51:59.320
but environmental conditions and dietary conditions
link |
01:52:02.440
and behaviors that can control GnRH release,
link |
01:52:05.040
I think is an incredible area for exploration.
link |
01:52:10.040
I'd love to do that sabbatical, by the way.
link |
01:52:12.480
I have a couple seemingly random questions,
link |
01:52:16.200
but I can't help but ask because one thing I like to do
link |
01:52:18.520
is forage the internet for practices
link |
01:52:21.320
that at least more than a few people are doing
link |
01:52:23.640
and then wonder whether or not there's any basis for it.
link |
01:52:27.760
You mentioned methylation as a detrimental process,
link |
01:52:31.520
the way it disrupts the epigenome,
link |
01:52:33.840
the CD reader, so to speak.
link |
01:52:36.540
There are people out there who are ingesting methylene blue.
link |
01:52:40.320
And when I was a kid,
link |
01:52:41.560
I used methylene blue to clean my fish tank.
link |
01:52:44.580
And I love fish tanks.
link |
01:52:45.840
I know you're into aquaria also.
link |
01:52:48.560
A different podcast episode, talk about aquaria,
link |
01:52:50.940
but why in the world would people ingest methylene blue?
link |
01:52:56.040
Meaning, is their logic correct
link |
01:52:58.320
and or is that a dangerous practice?
link |
01:53:01.160
I'm not sure I'd want to ingest methylene blue.
link |
01:53:04.160
Sounds like a bad thing to do.
link |
01:53:06.440
It stains your body.
link |
01:53:07.640
You've seen these people turn blue.
link |
01:53:09.720
Yeah, there was someone in my lab as a postdoc
link |
01:53:13.400
was using it to study a completely different process
link |
01:53:16.380
related to the blood brain barrier
link |
01:53:17.560
and used to inject into animals and they would turn blue.
link |
01:53:20.480
But then again, people ingest colloid silver.
link |
01:53:22.960
You know, they'll put in there.
link |
01:53:23.800
There's this, please, people don't do this.
link |
01:53:25.840
Or if you do, just don't tell me because I won't like it.
link |
01:53:29.920
They, people put it in their eyes
link |
01:53:32.220
and some people actually stain their skin.
link |
01:53:34.520
They actually become kind of a,
link |
01:53:35.880
this silver, purple, brown color if they do it excessively.
link |
01:53:39.640
I mean, there's a lot of crazy stuff out there,
link |
01:53:42.040
but what do you think they're thinking
link |
01:53:44.360
with this methylene blue thing
link |
01:53:45.600
or should we just get them to a good psychiatrist?
link |
01:53:50.140
I don't know for sure.
link |
01:53:51.740
I think methylene blue was found to extend the lifespan
link |
01:53:53.880
of some lower organism and that's where it came from.
link |
01:53:56.760
My recollection with the-
link |
01:53:58.200
This is on lower organisms.
link |
01:53:59.800
Yes, smaller organisms.
link |
01:54:02.400
I think, doesn't, do you remember, Andrew,
link |
01:54:04.360
does it interrupt or interfere with mitochondrial activity
link |
01:54:07.680
and that's why we're doing it.
link |
01:54:09.740
Yeah, we need to look this up and post it.
link |
01:54:13.020
We'll get to the bottom of this.
link |
01:54:14.440
But those methyls, let's talk about those.
link |
01:54:17.400
Those methyls have to be placed
link |
01:54:18.760
on the right part of the genome.
link |
01:54:21.240
They get attached to the right genes and the wrong genes.
link |
01:54:23.320
And if you have a lot of methylation,
link |
01:54:26.080
it's going to mess up the epigenome.
link |
01:54:28.680
Smoking will do that, lack of exercise, all that good stuff.
link |
01:54:32.320
So what you actually want to do is you want to measure it
link |
01:54:34.820
and make sure what you're doing with your body is working.
link |
01:54:38.240
How do you know that if you do this
link |
01:54:40.000
or that is actually helping?
link |
01:54:41.960
And so you can test your age.
link |
01:54:43.640
I could take a swab from your mouth
link |
01:54:45.800
and tell you how old you are biologically,
link |
01:54:48.160
and then we could work on trying to bring that down.
link |
01:54:50.400
And actually, there are anecdotes now
link |
01:54:53.440
that people are reversing their age by a decade or more
link |
01:54:56.240
just by doing some of the things that we've talked about
link |
01:55:00.300
and some other cutting-edge stuff
link |
01:55:02.200
that I'm going to write about.
link |
01:55:05.460
But yeah, but you have to measure stuff.
link |
01:55:07.280
I didn't want to forget to bring that up.
link |
01:55:10.580
I'm measuring stuff all the time.
link |
01:55:11.920
I have blood tests like you.
link |
01:55:14.080
I've got this monitor that's stuck to my chest right now
link |
01:55:16.480
that's measuring myself 1,000 times a second.
link |
01:55:18.940
And I measure my biological age.
link |
01:55:20.640
What's it measuring 1,000 times a second?
link |
01:55:22.840
A huge host of things?
link |
01:55:24.020
Yeah, yeah, yeah.
link |
01:55:24.860
So this little device is stuck here,
link |
01:55:26.640
and it's for two weeks.
link |
01:55:27.860
You just recharge it or send it back and get a new one.
link |
01:55:30.760
It's got body temperature movement, heart rate variability.
link |
01:55:34.600
It's an FDA-approved device.
link |
01:55:36.300
It's not a toy.
link |
01:55:37.140
It's not one of these recreational things.
link |
01:55:40.520
It also listens to my voice.
link |
01:55:42.440
Eventually, it'll tell me if I need a psychiatrist
link |
01:55:44.720
or if I'm depressed.
link |
01:55:47.380
It will tell me how I sleep, obviously.
link |
01:55:49.640
But when you put all that data together
link |
01:55:51.040
and it's individualized and anonymized,
link |
01:55:53.220
it can now tell my doctor in real time
link |
01:55:56.880
if I've got a cold that needs an antibiotic
link |
01:55:59.320
or it's just a virus,
link |
01:56:01.100
if I am suffering from COVID-19,
link |
01:56:06.520
or even if I'm going to have a heart attack next week.
link |
01:56:09.780
And so these little devices
link |
01:56:11.000
are going to be with us all the time
link |
01:56:13.320
instead of going to your doctor once a year,
link |
01:56:14.880
which is ludicrous.
link |
01:56:17.480
I have to ask you about X-rays
link |
01:56:19.860
because every time I go through the scanner at the airport,
link |
01:56:22.260
I think Sinclair would never do this.
link |
01:56:24.820
And the argument I heard you give about this before
link |
01:56:27.860
was a really excellent one,
link |
01:56:29.080
which is that it's a low level amount of radiation
link |
01:56:33.800
going through at the airport,
link |
01:56:35.160
but the argument is always,
link |
01:56:37.000
well, it's just as much as on the plane.
link |
01:56:38.700
And your argument, your counterargument, I should say,
link |
01:56:41.640
was, well, then why would I want to do both, right?
link |
01:56:45.080
So when you go to the airport,
link |
01:56:47.160
assuming you're not running late
link |
01:56:48.560
and you have to go through the standard line,
link |
01:56:50.600
what do you say to them?
link |
01:56:52.560
Do you say, I'm David Sinclair,
link |
01:56:54.160
and then they shuttle you to your own line?
link |
01:56:56.840
What do you say?
link |
01:56:57.680
You do say, I don't like this thing.
link |
01:56:59.400
Do you have to give them a reason?
link |
01:57:01.580
No, you don't.
link |
01:57:02.420
You can say, I don't want this,
link |
01:57:04.440
and they'll get annoyed
link |
01:57:05.360
because it's hard for them to pat you down,
link |
01:57:08.260
but you get a pat down and you're done.
link |
01:57:09.760
As long as you're not in a hurry, it's fine.
link |
01:57:12.480
If you want to pay for the TSA Pre in America
link |
01:57:14.840
or the way to get around those scanners, you can do that.
link |
01:57:17.320
So I travel a lot, so it's worth it anyway.
link |
01:57:20.080
But I just go through the metal detector.
link |
01:57:21.660
I don't get scanned.
link |
01:57:22.880
And the metal detector doesn't have the same problem.
link |
01:57:26.440
And what about x-rays at the dentist?
link |
01:57:28.400
Yeah.
link |
01:57:29.240
Well, you know, one x-ray is not going to kill you.
link |
01:57:31.200
Two is not going to kill you.
link |
01:57:32.360
But I'd rather- Three will kill you.
link |
01:57:33.680
No, I'm just kidding.
link |
01:57:35.300
I try to limit it because it's cumulative.
link |
01:57:38.040
And I went for six years without having a dental x-ray.
link |
01:57:42.840
And then my last visit, I just gave up.
link |
01:57:45.080
I was tired of arguing with my dentist.
link |
01:57:47.400
So they gave me one,
link |
01:57:48.260
but they've got lead coats on
link |
01:57:50.080
and they put lead all over your body.
link |
01:57:52.360
That's telling you something right there.
link |
01:57:55.640
And funnily enough, my teeth hadn't changed.
link |
01:57:58.440
Now, you could balance that by saying,
link |
01:58:00.260
well, one x-ray, two x-rays, three x-rays
link |
01:58:02.440
is worth it if I have cavities.
link |
01:58:04.640
And that's true.
link |
01:58:05.480
You want to know what's in there.
link |
01:58:07.260
But doing it regularly, for me,
link |
01:58:10.320
I don't think was worth it
link |
01:58:11.600
because my teeth were in perfect health
link |
01:58:13.160
and have always been.
link |
01:58:14.680
Don't have any cavities.
link |
01:58:16.220
Didn't have braces.
link |
01:58:17.060
They're fine.
link |
01:58:17.880
Don't stop scanning me.
link |
01:58:18.840
I mean, I know you have to pay for the machine,
link |
01:58:20.600
but do I have a choice?
link |
01:58:22.440
Yes.
link |
01:58:23.280
So stop pressuring me.
link |
01:58:24.800
You know, who shared your sentiments about x-rays
link |
01:58:26.920
and the dentist in general,
link |
01:58:28.600
my apologies to the dentists out there,
link |
01:58:30.720
was the great physicist, Richard Feynman.
link |
01:58:33.800
This is a story about him
link |
01:58:34.960
that's not especially well-known,
link |
01:58:36.480
but he had very serious health concerns about x-rays
link |
01:58:42.160
because he understood the physics
link |
01:58:44.160
and he understood enough biology
link |
01:58:45.560
that he was actually quite vocal
link |
01:58:47.880
about his dislike of dental technology and its dangers.
link |
01:58:52.720
And he talked about some of that.
link |
01:58:54.520
People can find that on the internet if they like.
link |
01:58:58.600
Speaking of people who are like Feynman,
link |
01:59:02.680
who've been engaged in public discourse about science,
link |
01:59:06.140
one of the things that I appreciate about you,
link |
01:59:07.920
in fact, the way that you and I
link |
01:59:10.040
initially came to know one another
link |
01:59:11.980
is through your public health education efforts.
link |
01:59:15.840
So obviously we're doing this podcast.
link |
01:59:19.320
You've done the Joe Rogan podcast, Lex Friedman's podcast.
link |
01:59:22.960
Excuse me, Lex, I'm still adjusting that.
link |
01:59:24.660
Lex Friedman podcast and many other podcasts.
link |
01:59:28.860
You've written an amazing book.
link |
01:59:31.400
What are you thinking these days
link |
01:59:33.140
in terms of what the world needs
link |
01:59:35.760
in terms of education from scientists,
link |
01:59:39.480
education from MDs, education in general
link |
01:59:43.160
as it relates to these things?
link |
01:59:44.320
Because I think if nothing else,
link |
01:59:47.240
2020 revealed to us that there's a gap.
link |
01:59:50.640
There's a gap in understanding
link |
01:59:52.480
and that the scientists too are guilty
link |
01:59:54.360
of not knowing what to do with all the information
link |
01:59:57.960
that's out there on PubMed or elsewhere.
link |
01:59:59.920
Just what are you thinking for yourself?
link |
02:00:03.240
And in general, I'd like to just know
link |
02:00:04.880
what do you think the world needs there?
link |
02:00:06.360
Maybe we can recruit some more public educators.
link |
02:00:09.680
Yeah, well, we've gone from a time
link |
02:00:12.880
when you and I were in college and young professors
link |
02:00:16.780
where the only way to get our voice out to the public
link |
02:00:20.000
was either through a newspaper
link |
02:00:22.100
or a very short radio interview,
link |
02:00:24.740
which for me was extremely frustrating
link |
02:00:27.800
because particularly the newspapers and my topic
link |
02:00:31.060
every time was twisted into something
link |
02:00:32.760
that was not just embarrassing,
link |
02:00:34.520
but Harvard University used to bring me into the back office
link |
02:00:37.360
and slap my wrist. Frankenstein.
link |
02:00:39.040
How did you say such a thing?
link |
02:00:40.560
We're all gonna live 200, I didn't say that.
link |
02:00:42.940
So we're now also in a world
link |
02:00:45.600
where we're overwhelmed with information
link |
02:00:47.640
and most of it is wrong
link |
02:00:49.800
and anyone can pretend to be an expert.
link |
02:00:53.160
So we've gone from early days to now, the future,
link |
02:00:56.760
and we're experiencing it right now
link |
02:00:58.800
thanks to guys like you, people like you,
link |
02:01:01.320
is that the experts, some experts,
link |
02:01:03.160
a small number who are brilliant and good communicators
link |
02:01:07.520
are talking directly to the public.
link |
02:01:09.360
This has never been able to be possible
link |
02:01:12.160
until this time right now.
link |
02:01:15.480
So another five years from now, and certainly by 10 years,
link |
02:01:19.520
I would hope that there are trusted sources of information
link |
02:01:23.160
of people who cannot just communicate the ideas directly,
link |
02:01:28.280
but are able to talk about things that are going on
link |
02:01:31.720
that aren't even published yet to say,
link |
02:01:33.720
here's what's really going on
link |
02:01:35.660
and this is what the future looks like.
link |
02:01:37.960
But this is somebody like yourself
link |
02:01:39.560
who spent their whole life studying a particular topic
link |
02:01:42.920
and knows what they're talking about.
link |
02:01:45.320
And this is also something
link |
02:01:46.880
that I think most people don't know,
link |
02:01:49.480
that we scientists, if we tell a lie, we burst into flames.
link |
02:01:53.260
We absolutely cannot tell something that's untrue
link |
02:01:56.920
and to the best of our knowledge, we say it as it is
link |
02:01:59.840
because if we don't, we're beaten up
link |
02:02:02.440
or we kicked out of the university.
link |
02:02:04.440
So the people who survived to our age,
link |
02:02:06.720
and I'm a little older than you,
link |
02:02:07.780
so I've survived a bit longer.
link |
02:02:09.380
But a lot younger inside.
link |
02:02:11.080
No, but we have to measure you with my stroke test.
link |
02:02:13.680
I probably need a little help, but hopefully not too much.
link |
02:02:15.880
We'll measure that and we'll work on your eating.
link |
02:02:19.460
But this is really, really important
link |
02:02:21.240
is that finally people like you
link |
02:02:23.720
are allowed by our universities to talk to the public.
link |
02:02:26.920
I used to do it with a real threat,
link |
02:02:29.720
to my survival.
link |
02:02:30.640
People would look at me,
link |
02:02:31.520
oh, he's a salesman, he's promoting this and that.
link |
02:02:33.680
It was seen as a real negative.
link |
02:02:35.400
But finally, I think we're in a world
link |
02:02:36.680
where it's not negative anymore.
link |
02:02:38.560
And the pandemic showed that we needed voices of reason,
link |
02:02:42.300
voices of fact that you could trust.
link |
02:02:45.420
And you can see the popularity of your podcast
link |
02:02:48.480
shows that the public are desperate for facts
link |
02:02:52.060
that they can trust
link |
02:02:52.900
because they don't know what to believe anymore.
link |
02:02:55.680
Well, I am being completely honest when I say this
link |
02:02:59.460
that I followed your lead.
link |
02:03:01.240
I saw you on the Joe Rogan podcast and my jaw dropped.
link |
02:03:04.680
I was like, this is amazing.
link |
02:03:07.240
Because he had other good scientists on before,
link |
02:03:10.000
but your tenured professor, Harvard genetics,
link |
02:03:13.020
department of genetics.
link |
02:03:14.660
And for those of you who don't know,
link |
02:03:17.720
there's Harvard and of course Harvard Medical School,
link |
02:03:20.400
and they're both excellent, of course,
link |
02:03:23.580
but these are the top, top tiers of academia.
link |
02:03:26.360
And I certainly understand what it takes
link |
02:03:27.880
to get there and survive there
link |
02:03:29.240
and to thrive there.
link |
02:03:30.680
It's like a game of pinball.
link |
02:03:32.320
You never win.
link |
02:03:33.160
You just get to, if you're doing really well,
link |
02:03:35.680
you get to keep playing.
link |
02:03:36.600
That's the truth in academia.
link |
02:03:38.600
And if you're not, you stop playing basically.
link |
02:03:42.080
But when I saw you explain what you were doing
link |
02:03:45.040
in a way that was accessible to people
link |
02:03:47.000
and also talking about possible protocols
link |
02:03:49.640
that they might explore for themselves
link |
02:03:51.280
to see if those were right for them,
link |
02:03:53.840
I was just dazzled and excited.
link |
02:03:57.080
And I made every effort to get in contact with you
link |
02:03:59.400
and the rest is history.
link |
02:04:02.240
But I think what's really exciting to me these days
link |
02:04:05.620
is because of 2020 and everything that's happened
link |
02:04:08.320
and it continues to happen, there's a thirst for knowledge.
link |
02:04:12.240
There's also this direct to the public route
link |
02:04:15.380
that you mentioned.
link |
02:04:16.640
And I think there's also an openness,
link |
02:04:20.880
I'd love your thoughts on this,
link |
02:04:21.720
but it seems to me that there's an openness
link |
02:04:24.500
from the general public about health practices,
link |
02:04:28.800
that there are actually things that people can do
link |
02:04:30.720
to control their stress level, to control their sleep,
link |
02:04:34.480
to control their cholesterol,
link |
02:04:36.460
if that's what they need to do, maybe they don't,
link |
02:04:39.020
and to even control their lifespan,
link |
02:04:41.800
which I think is remarkable.
link |
02:04:43.780
And I know I speak on behalf of so many people
link |
02:04:47.040
when I just, I want to say thank you.
link |
02:04:48.640
You've truly changed the course of my life.
link |
02:04:51.300
I would not be sitting here doing this
link |
02:04:53.240
were it not for your example.
link |
02:04:55.320
And I always say, Sinclair, many people have written books,
link |
02:04:58.720
many academics have written books as you have,
link |
02:05:01.160
but in terms of doing podcasts
link |
02:05:02.720
and really getting out there with your message
link |
02:05:04.380
in a way that I have to assume raised your cortisol level
link |
02:05:07.100
and heart rate just a little bit,
link |
02:05:09.740
but you did it nonetheless.
link |
02:05:12.580
You know, you were truly first man in
link |
02:05:14.680
and that deserves a nod
link |
02:05:17.220
and I have a great debt of gratitude to you for that.
link |
02:05:19.840
So thank you so much.
link |
02:05:20.960
Thanks, Andrew, you've become a good friend
link |
02:05:23.300
and I'm super proud of what you've done
link |
02:05:25.240
and what you, I know what you will do.
link |
02:05:27.280
So in addition to your book
link |
02:05:29.040
and your presence on social media,
link |
02:05:31.220
Instagram and Twitter, and appearances on podcasts,
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02:05:34.640
recently I've noticed that you've opened up
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02:05:37.800
a sort of an email slash website that people can ask,
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02:05:41.600
access, excuse me, to get some information
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02:05:44.680
about their own health and rates of aging.
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02:05:46.780
Tell us about that and what's being measured
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02:05:49.440
and what is this test that you've been working on,
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02:05:53.160
secretly and now soon not so secretly?
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02:05:56.520
Yeah, well, what I want is a credit score for the body
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02:06:00.440
to make it easy for people to follow their health.
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02:06:03.680
And there is a number,
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02:06:05.040
there's a biological age that you can measure.
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02:06:06.960
Unfortunately, the test is many hundreds of dollars
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02:06:08.960
right now, but in my lab,
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02:06:10.980
we've been able to bring that down a lot.
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02:06:13.800
And so I want to democratize this test
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02:06:15.460
so that everybody has access to a score for their health
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02:06:18.120
that can predict not just their future health
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02:06:22.080
and time of death, but to change it.
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02:06:24.800
And I'm building a system that will point people
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02:06:27.680
in the right direction and give them discounts
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02:06:29.520
for certain things that will improve
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02:06:31.840
not just their health now,
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02:06:33.600
but 10, 20, 30 years into the future.
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02:06:35.720
And we can measure that and very cheaply keep measuring it
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02:06:38.660
to know that you're on the right track.
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02:06:40.420
Because if you don't measure something,
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02:06:41.480
you can't optimize it.
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02:06:43.040
And so this is the biological age test.
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02:06:44.640
We've developed it.
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02:06:45.480
It's a simple mouth swab.
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02:06:47.640
We're rolling it out.
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02:06:49.080
We're building the system right now.
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02:06:51.000
And there is a signup sheet
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02:06:52.040
because a lot of people want to get in line.
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02:06:54.280
Go to drsinclair.com.
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02:06:56.000
You can get on that and you'll be one of the first people
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02:06:58.760
in the world to get this test and see what we're doing.
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02:07:01.280
Oh, fantastic.
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02:07:03.200
Will people be celebrating their biological age birthdays?
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02:07:08.000
In other words, if I'm minus, like if I could imagine,
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02:07:10.640
so I'm 45 right now, soon to be 46.
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02:07:12.620
But if I were to be so lucky
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02:07:14.400
is to get my biological age to 35 within 12 months,
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02:07:19.160
maybe can help me do that.
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02:07:20.400
Do I get to celebrate a negative birthday?
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02:07:23.960
Absolutely.
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02:07:24.800
And my plan is that those people
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02:07:26.200
who take their age back a year or more,
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02:07:29.380
we think we can go back 20 years eventually,
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02:07:31.880
they'll get a birthday card from me
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02:07:33.280
and it's a negative birthday card.
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02:07:35.800
I love it.
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02:07:36.700
And probably very little actual birthday cake
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02:07:39.520
being ingested, but who cares?
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02:07:41.360
Because you're living that much longer.
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02:07:42.840
Well, it's full of stevia, that'll be fine.
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02:07:45.120
And thank you for talking to us today.
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02:07:47.560
I realized I took us down deep into the guts of mechanism
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02:07:52.520
and as well, talking about global protocols,
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02:07:55.960
everything from what one can do and take if they choose,
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02:07:59.240
that's right for them,
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02:08:01.160
to how to think about this whole process
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02:08:03.160
that we talk about when we talk about lifespan,
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02:08:06.840
as always incredibly illuminating.
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02:08:10.040
Thank you, David.
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02:08:11.120
Thanks, Andrew.
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02:08:12.600
Thank you for joining me for my conversation
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02:08:14.560
with Dr. David Sinclair.
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02:08:16.360
If you're enjoying and or learning from this podcast,
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02:08:18.960
please subscribe to our YouTube channel.
link |
02:08:21.000
In addition, please subscribe on Apple and or Spotify
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02:08:24.440
and on YouTube, you can leave us comments
link |
02:08:26.480
and you can leave us suggestions for future podcast guests
link |
02:08:29.200
that you would like us to feature.
link |
02:08:31.040
In addition on Apple,
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02:08:32.060
you can leave us up to a five-star review
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02:08:33.640
and you can leave us a comment.
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02:08:35.560
Please also check out the sponsors mentioned
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02:08:37.360
at the beginning of this episode.
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02:08:38.500
That's the best way to support this podcast.
link |
02:08:41.120
Also, I teach science and science-related tools
link |
02:08:43.600
on Instagram, it's Huberman Lab on Instagram.
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02:08:46.160
I also have a Twitter, which is also Huberman Lab.
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02:08:48.720
So be sure to check those out.
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02:08:50.080
A lot of the material covers things similar to the podcast,
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02:08:52.920
but oftentimes I'll cover unique material
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02:08:54.840
not featured at all on the podcast.
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02:08:56.820
So that's Huberman Lab on Instagram and on Twitter.
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02:09:00.040
In addition, we have a Patreon,
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02:09:01.640
it's patreon.com slash Andrew Huberman,
link |
02:09:04.280
and there you can support the podcast
link |
02:09:06.400
at any level that you like.
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02:09:08.020
Today and in many other previous episodes
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02:09:10.260
of the Huberman Lab podcast, we discuss supplements.
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02:09:12.920
While supplements aren't necessary or right for everybody,
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02:09:16.120
many people derive tremendous benefit from supplements.
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02:09:18.880
For that reason, we've partnered with Thorne, T-H-O-R-N-E,
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02:09:22.120
because Thorne supplements are the absolute highest quality
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02:09:25.040
and the absolute highest precision,
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02:09:27.140
meaning what you see listed on the bottle
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02:09:29.000
is what's actually in the bottle,
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02:09:30.320
which is not the case for many supplement companies
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02:09:32.880
out there.
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02:09:33.720
Thorne is one of the partners of the Mayo Clinic
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02:09:36.120
and all the major sports teams,
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02:09:37.400
and so they really are very trusted,
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02:09:39.440
very highest quality.
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02:09:40.700
If you want to see the supplements that I personally take,
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02:09:42.960
you can go to thorne.com slash the letter U slash Huberman,
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02:09:46.800
and there you'll see the supplements that I take.
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02:09:48.440
You can get 20% off any of those supplements,
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02:09:50.940
and if you navigate deeper into the Thorne site
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02:09:53.080
through that portal, you'll also get 20% off
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02:09:55.280
any of the other supplements that Thorne makes.
link |
02:09:57.160
So again, it's thorne.com slash the letter U slash Huberman
link |
02:10:02.400
to get 20% off any of the supplements that Thorne makes.
link |
02:10:05.600
Also take note that the Lifespan podcast
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02:10:07.840
featuring Dr. David Sinclair as a host
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02:10:10.080
launches Wednesday, January 5th.
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02:10:11.920
You can find the first episode here
link |
02:10:13.560
on the Huberman Lab podcast channel.
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02:10:15.400
They also have their own independent channel.
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02:10:17.760
You can find the link to that channel in the show notes,
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02:10:19.860
so please go there, subscribe on YouTube,
link |
02:10:21.640
also on Apple and Spotify.
link |
02:10:23.520
I've seen these episodes.
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02:10:24.760
They are phenomenal,
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02:10:25.760
and you're going to learn a tremendous amount about aging
link |
02:10:28.600
and how to slow and reverse aging
link |
02:10:30.560
from the world expert himself, Dr. David Sinclair.
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02:10:33.840
And last, but certainly not least,
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02:10:35.960
thank you for your interest in science.