Latest / INSPIRE STORY / #049_ The Secret to Living Longer?

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#049_ The Secret to Living Longer? · INSPIRE STORY

0:01
Speaker 1: Get your NAD levels up. You can do that with
0:04
Speaker 1: being a little bit hungry. You can also do that
0:06
Speaker 1: by restricting the total amount of protein that you bring
0:10
Speaker 1: on board. So eating a lot of steak would be
0:12
Speaker 1: about the worst thing you could do. Never exposing your
0:15
Speaker 1: body to any changes in temperature probably another thing. Basically,
0:19
Speaker 1: everything that makes your body happy and sedentary and unstressed
0:24
Speaker 1: is bad for you. And the reason is that you're
0:26
Speaker 1: not engaging your survival circuits. But now we can kick
0:30
Speaker 1: those survival genes into action by putting our bodies under
0:32
Speaker 1: a bit of stress hormesis or eating plants with those
0:36
Speaker 1: molecules that signal stress. We call that xenochromesis. And that
0:42
Speaker 1: is right now, with the exception of some clinical trial
0:45
Speaker 1: proof that exercise and dieting is really the best thing
0:48
Speaker 1: we can do for our bodies. Exercise is a treatment
0:53
Speaker 1: for the body that actually puts the entire system in
0:56
Speaker 1: a state of defense, and so it's less about getting
1:00
Speaker 1: the blood to flow and more about getting your tissues
1:04
Speaker 1: to act younger. And that's really the huge benefit that
1:07
Speaker 1: you get from exercise.
1:09
Speaker 2: That's David Sinclair and this is the Ritual Podcast. The
1:25
Speaker 2: Ritual Podcast. Here's a couple uncontroversial facts. Everybody grows old
1:34
Speaker 2: and everybody dies. But is this actually set in stone?
1:39
Speaker 2: Does it have to be this way? What if we
1:42
Speaker 2: thought about aging as a disease, as a curable disease,
1:47
Speaker 2: and what would you do? And what would the world
1:49
Speaker 2: look like if we could suddenly live to be two
1:52
Speaker 2: hundred plus years. My name is Rich Roll, I'm your host.
1:56
Speaker 2: This is my podcast, and this is but a few
2:00
Speaker 2: of the topics we explore today with one of the
2:03
Speaker 2: world's leading scientific authorities on longevity, aging, and how to
2:07
Speaker 2: slow its effects. David Sinclair is a professor in the
2:11
Speaker 2: Department of Genetics at Harvard Medical School. He's co director
2:15
Speaker 2: of the Paul F. Glenn Center for the Biological Mechanisms
2:18
Speaker 2: of Aging. He obtained his PhD in molecular genetics at
2:22
Speaker 2: the University of New South Wales, Sydney in nineteen ninety five,
2:25
Speaker 2: and worked as a postdoctoral researcher at MIT, where, among
2:30
Speaker 2: other things, he co discovered the cause of aging for yeast.
2:34
Speaker 2: David is the co founder of several biotech companies. He's
2:38
Speaker 2: also the co founder and co chief editor of the
2:40
Speaker 2: journal Aging. His work has been featured in a variety
2:44
Speaker 2: of books, documentaries, and media, including Sixty Minutes, Nightline and Nova.
2:50
Speaker 2: He's also an inventor with thirty five patents to his name,
2:54
Speaker 2: has been lauded as one of the top one hundred
2:56
Speaker 2: Australian innovators, and he made Time Magazines Life of the
3:00
Speaker 2: one hundred most Influential People in the World. Finally, he
3:04
Speaker 2: is the author of a new upcoming book entitled Lifespan,
3:08
Speaker 2: The Revolutionary Science of Why We Age and Why We
3:11
Speaker 2: Don't Have To, which comes out September tenth and is
3:14
Speaker 2: currently available for pre order. Check the link in the
3:17
Speaker 2: show notes to check that out. If you enjoyed my
3:20
Speaker 2: episode with doctor Walter Longo, a fellow brilliant warrior in
3:24
Speaker 2: the longevity space, we mentioned him a few times today
3:27
Speaker 2: that was episode three sixty seven, or if you happen
3:30
Speaker 2: to hear David on Joe Rogan's podcast a few months ago,
3:33
Speaker 2: which was great, by the way, then I'm fairly confident
3:37
Speaker 2: that you're going to love this one. So this is
3:41
Speaker 2: a mind blowing conversation on everything aging longevity, the scientific
3:47
Speaker 2: mechanisms that contribute to biological degeneration, and the hard work
3:53
Speaker 2: that David and others are devoting to both better understanding
3:57
Speaker 2: these mechanisms as well as learning how to prevent and
4:00
Speaker 2: even reverse them. I want to say upfront, it's not
4:04
Speaker 2: just about living as many years as possible, but more
4:08
Speaker 2: about how to live as vibrantly and as energetically as
4:12
Speaker 2: possible for as long as possible. That's really the goal here.
4:15
Speaker 2: I should also say that this one gets pretty deep
4:18
Speaker 2: in the weeds scientifically, which is of course perfect for
4:21
Speaker 2: the geeks among us, but it's also grounded in practical
4:25
Speaker 2: takeaways for everybody. In addition to being a lovely guy,
4:29
Speaker 2: David is a true pioneer. It is an honor and
4:34
Speaker 2: it is a privilege to share this brilliant man's work
4:38
Speaker 2: and wisdom with you today. So without further ado, I
4:42
Speaker 2: give you doctor David Sinclair. Good to have you here,
4:48
Speaker 2: thank you for doing this, Thanks for having me on.
4:51
Speaker 2: I'm excited to talk to you. This is a subject
4:56
Speaker 2: of personal interest, of course, and I think interest of everybody,
5:01
Speaker 2: and the work that you're doing is really not only
5:03
Speaker 2: fascinating but obviously revolutionary or potentially revolutionary. So first off,
5:09
Speaker 2: thank you for the work that you're doing, and I
5:13
Speaker 2: look forward to exploring this with you. I think a
5:16
Speaker 2: good place to start would be just hearing a little
5:21
Speaker 2: bit about what got you interested in this field to
5:24
Speaker 2: begin with, Like why longevity, why aging? Anti aging?
5:30
Speaker 1: Yeah, sure, I think we're all the same. When we're
5:33
Speaker 1: about the age of four or five, we realized that
5:37
Speaker 1: we're not going to be around forever. And even scarier
5:40
Speaker 1: for a young kid, your parents are going to die,
5:42
Speaker 1: and your grandparents are going to die, and your pen
5:43
Speaker 1: and cat's going to die. So I remember going through
5:46
Speaker 1: that very vividly. My grandmother, who essentially raised me, was
5:50
Speaker 1: a very honest person, and she would just tell it
5:52
Speaker 1: as it is, and she said to me as a
5:54
Speaker 1: four year old, yeah, yeah, I'm not going to be around.
5:57
Speaker 1: Your parents are going to die, your cat's going to die,
5:59
Speaker 1: You're going to die. That's a bit of a shock
6:01
Speaker 1: to a four year old who, you know, who probably
6:03
Speaker 1: still believed in Santa Clause at four. It was brutal
6:07
Speaker 1: and that may be the turning point in my life.
6:10
Speaker 1: But what most kids do, and it's been well studied,
6:13
Speaker 1: is that they bury that thought. It's just too sad
6:17
Speaker 1: and it's distracting to dwell on that every day of
6:20
Speaker 1: your life. So we actually we typically forget about it
6:23
Speaker 1: by the age of six or seven, and then it
6:26
Speaker 1: doesn't emerge till we get into our late forties early
6:29
Speaker 1: fifties and we think, okay, maybe there is no such
6:32
Speaker 1: thing as immortality. But up until then, most people don't
6:35
Speaker 1: even think about it.
6:37
Speaker 2: I feel like we still don't really think about it.
6:39
Speaker 2: We certainly don't talk about it. And death is almost
6:43
Speaker 2: a verboat and subject, and our exposure to the reality
6:46
Speaker 2: of death and aging in its most latent, mature forms
6:52
Speaker 2: is something we do our best to whitewash and remove
6:55
Speaker 2: from our field of vision.
6:57
Speaker 1: Yeah, I agree with that, and it really takes a
6:59
Speaker 1: lot of courage to be able to think deeply and
7:02
Speaker 1: ponder your loved one's mortality and your own, and so
7:08
Speaker 1: I also I don't think about it too much myself,
7:11
Speaker 1: though I probably do think about it more than most.
7:14
Speaker 1: But seriously, I think if all of us right now
7:17
Speaker 1: would consider what they have right now and losing all
7:21
Speaker 1: of that and most likely not seeing most of these
7:24
Speaker 1: people ever again, if any of them, I mean, that's
7:27
Speaker 1: a pretty sad thing, and I don't mean to depress everybody,
7:30
Speaker 1: but that's something really worth appreciating. That we are here
7:35
Speaker 1: right now, most of us are healthy, but that will
7:37
Speaker 1: not last.
7:40
Speaker 2: Yeah. I feel like we all intellectually understand that to
7:44
Speaker 2: be the case. But I think there's something innately human
7:49
Speaker 2: about being in denial of that truth in order to
7:53
Speaker 2: kind of get through the day. Like on some level,
7:56
Speaker 2: I have this signal in the back of my mind going, yeah,
7:58
Speaker 2: I know it's going to happen, but yeah, I might
8:01
Speaker 2: just evade that somehow. I think I'm going to get
8:03
Speaker 2: around that.
8:04
Speaker 1: Yeah, Well, that's what we do. That's why we survive
8:06
Speaker 1: as human beings. It's a pretty cruel thing to have
8:10
Speaker 1: a species that's conscious of its own mortality. It's not
8:13
Speaker 1: a happy thing. And most animals, actually, as far as
8:16
Speaker 1: we know, all animals except us, go through life not
8:19
Speaker 1: knowing that they're going to die and that their family
8:22
Speaker 1: is going to die. But we are burdened with that
8:25
Speaker 1: but as a coping mechanism, and I believe that it's
8:28
Speaker 1: probably evolutionary wide into our genome that we don't think
8:32
Speaker 1: about that, because people who did always worry about dying,
8:35
Speaker 1: that their tribes probably died out thousands of years ago.
8:38
Speaker 2: Right. Well, it can be paralyzing too. And you talk
8:42
Speaker 2: about this and that you were nice enough to send
8:44
Speaker 2: me the introduction to your new book that's coming out
8:46
Speaker 2: at the end of the year, and you talk about
8:50
Speaker 2: your grandmother and the impact that she's had on you
8:53
Speaker 2: and her sort of lifestyle antidote to this, those of
9:00
Speaker 2: living her life in accordance with the ticking clock. Right,
9:03
Speaker 2: that she wanted to live this joyous I mean, she
9:06
Speaker 2: sounded like amazing, Right, She's living this joyous, childlike existence,
9:11
Speaker 2: you know, until her body could no longer keep up
9:14
Speaker 2: with her spirit.
9:15
Speaker 1: Right. Well, as a young kid, she was still in
9:17
Speaker 1: her forties. She had my father when she was fourteen fifteen,
9:21
Speaker 1: and so that allowed her to be very young as
9:25
Speaker 1: a grandmother, but she was also mentally young. She was vivacious.
9:30
Speaker 1: She's one of those people where you know that she's
9:33
Speaker 1: got so much energy she can't contain it. So's she
9:37
Speaker 1: came from hungry. She escaped Hungry after nineteen fifty six
9:41
Speaker 1: when Russia cracked down on a revolution, when as far
9:45
Speaker 1: away from Europe as she could, which was Australia. Sydney
9:47
Speaker 1: is where she settled and where I grew up, and
9:50
Speaker 1: there she felt free. She was oppressed for most of
9:53
Speaker 1: her life, with rape and pillage, going on and she
9:56
Speaker 1: got to Australia and everyone had enough to eat, and
9:59
Speaker 1: they had money, and they had sunshine, and she just
10:02
Speaker 1: loved life. And so she was one of the first people.
10:06
Speaker 1: I hear her wear a bikini in Australia and she
10:07
Speaker 1: got taken off bonde Beach in the nine fifties wearing
10:11
Speaker 1: one of those.
10:11
Speaker 2: It's incredible to hear that, knowing what I know, knowing
10:14
Speaker 2: what Bondai Beach represents, that she was like the first
10:18
Speaker 2: person to wear a bikini on that beach and got
10:20
Speaker 2: chastise exrectly. Yeah.
10:21
Speaker 1: Yeah, these days you get chastise for wearing a top.
10:24
Speaker 2: Yeah, if you're a woman.
10:26
Speaker 1: But yeah, she went lived in New Guinea with the
10:28
Speaker 1: natives for a while and hung out there by herself.
10:32
Speaker 1: My father had to go get her because she was
10:34
Speaker 1: probably drinking a fair amount. She says she tasted human
10:38
Speaker 1: flesh up there with the cannibal. So that's a pretty
10:41
Speaker 1: big thing for a woman to do that in the
10:43
Speaker 1: nineteen sixties. So she was great. She raised me to
10:47
Speaker 1: just love life, to always stay young, and she says,
10:49
Speaker 1: grown ups ruin everything. Stay young.
10:52
Speaker 2: Yeah, she had this mantra of this a milm poem
10:55
Speaker 2: right about maintaining your six year old self throughout your life.
11:00
Speaker 1: That's right now. We are six, and she would read
11:02
Speaker 1: that to my brother and me, and she would just say,
11:08
Speaker 1: make the most of your life, stay young, don't listen
11:12
Speaker 1: to the naysayers. Adults are mostly naysayers, and leave the mark.
11:17
Speaker 1: Do what's good for humanity. She was a humanist at heart,
11:22
Speaker 1: even towards the end of her life, a declared humanist.
11:25
Speaker 1: And so her goal and my goal is the same,
11:28
Speaker 1: which is nothing matters except making the world a better
11:32
Speaker 1: place after you've been here.
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Speaker 2: Profound, especially given that so much of the work that
11:38
Speaker 2: you do is at the cutting edge, and it's impossible
11:43
Speaker 2: that that's not going to ruffle feathers and create you know,
11:46
Speaker 2: a cadre of naysayers who are trying to take it
11:49
Speaker 2: down a peg.
11:51
Speaker 1: Well, yeah, I mean, it hasn't been an easy career,
11:53
Speaker 1: even from the outset, as Volta Longo on your show
11:57
Speaker 1: rightly said, it was rough. In the old days, aging
12:00
Speaker 1: wasn't even considered a true science. But like most careers,
12:04
Speaker 1: if you try to push the envelope and say things
12:06
Speaker 1: that others have never said before, you will have people
12:08
Speaker 1: who try to pull you down, but it's you know,
12:12
Speaker 1: I'm pretty stubborn and I keep my eye on the goal,
12:15
Speaker 1: which is to help humanity, So these daily fights and
12:19
Speaker 1: things don't really get me down so much.
12:21
Speaker 2: Right, So, your grandmother has this profound impact on you,
12:25
Speaker 2: and you're a young, enterprising university student in New South Wales,
12:31
Speaker 2: and from what I gather, there was sort of one
12:34
Speaker 2: particular lecture that kind of turned things for you, that
12:39
Speaker 2: got you out here to the United States.
12:42
Speaker 1: Well there was. Prior to hearing the lecture I was.
12:46
Speaker 1: I remember sitting playing cards with my friends, and I
12:49
Speaker 1: didn't try that hard in college or in school, mostly
12:54
Speaker 1: with playing cards and drinking heavily. But I do remember
12:57
Speaker 1: one moment's telling them all, do you realize we're probably
13:01
Speaker 1: the last generation to live quote unquote a natural lifespan,
13:05
Speaker 1: and others who are downstream of us, our descendants are
13:09
Speaker 1: going to live a lot healthier and longer lives than us,
13:12
Speaker 1: And we've been born one generation too early. Do you
13:14
Speaker 1: realize how sad that is? And they just went, yeah,
13:17
Speaker 1: deal with cards, David shut up. But that stuck with me,
13:21
Speaker 1: and so when I heard the lecture from Lenny Garenti,
13:23
Speaker 1: who was an MIT professor still Is. He came and
13:27
Speaker 1: he talked about a project that had just started up
13:30
Speaker 1: in his lab over in Boston to study yeast aging,
13:35
Speaker 1: same yeast that's in bread and beer. And I was
13:38
Speaker 1: studying yeast for my PhD. So I knew yeast intimately
13:41
Speaker 1: that were my friends. I would look at them on
13:43
Speaker 1: the microscope and what he told me was they age.
13:46
Speaker 1: And I didn't know that. Most people don't know that yet.
13:48
Speaker 1: Cells get old, they get fat, they get slower, they
13:50
Speaker 1: get sterile.
13:50
Speaker 2: I didn't know that.
13:52
Speaker 1: Yeah, they're little creatures. They're a lot smaller than we are,
13:56
Speaker 1: but they have the same struggles through life. They have
13:58
Speaker 1: to find mates, they breed, And so I thought that
14:02
Speaker 1: was a wonderful way to start studying aging, because if
14:05
Speaker 1: we can't figure it out for yeast, we've got no
14:07
Speaker 1: hope figuring it out for humans.
14:08
Speaker 2: Sure, So that begins this lifelong journey, this exploration into
14:15
Speaker 2: aging and longevity. So before we embark on that, let's
14:20
Speaker 2: define our terms. I mean, what is aging from your perspective.
14:25
Speaker 1: Well, I've come to the conclusion that aging is a condition.
14:32
Speaker 1: I will be bold and say it should be declared
14:34
Speaker 1: a disease, and that often strikes people most people as ludicrous.
14:40
Speaker 1: But let's do do some thought experiments here, one being
14:46
Speaker 1: if I was to tell you rich that I just
14:49
Speaker 1: found your real birth certificate, okay, and you say, well,
14:52
Speaker 1: what is it now? I'm telling you unfortunately, you're a
14:55
Speaker 1: hundred years old. Are you going to want to die tomorrow?
14:58
Speaker 1: You're healthy, you're fit. So the point there is nobody
15:04
Speaker 1: who's healthy and vigorous and enjoys their daily life and
15:08
Speaker 1: enjoys their family wants to die. So often I ask
15:11
Speaker 1: people about how long do they want to live, and
15:13
Speaker 1: the typical answer is I don't want to live beyond
15:16
Speaker 1: eighty God forbid one hundred. And that's because they don't
15:19
Speaker 1: think of people who are old as being anything worth
15:24
Speaker 1: going on, right, So that's one aspect on the aging
15:27
Speaker 1: as a disease. If you go to the Mirk Manual
15:30
Speaker 1: of Geriatrics, which is the bible of this field, the
15:33
Speaker 1: definition of a disease versus aging is very simple. It's
15:38
Speaker 1: a fifty percent cut off. If something bad happens to
15:41
Speaker 1: your body and you're in a minority in the population,
15:44
Speaker 1: that's a disease something worth treating. But if it happens
15:48
Speaker 1: to fifty one percent. Then hey, that's natural, that's just aging.
15:51
Speaker 1: We should just deal with it. That's what God gave us.
15:54
Speaker 1: And that's ridiculous. You know, if you're off by a
15:56
Speaker 1: fraction of a percent, it's aging.
15:57
Speaker 2: Well, by that argument, diabetes and hearts disease are just
16:01
Speaker 2: conditions of life. Given how many people are succumbing to
16:05
Speaker 2: these diseases.
16:06
Speaker 1: Heart disease is about forty percent, so that's borderline. Right,
16:09
Speaker 1: if it was fifty one percent, you might just say, hey,
16:11
Speaker 1: too bad, that's aging.
16:13
Speaker 2: H yeah, well disease, right, it is a you know,
16:17
Speaker 2: a disease is a condition in which your body is
16:20
Speaker 2: out of balance, in which there is a lack of
16:22
Speaker 2: equilibrium and processes are not you know, functioning properly. So
16:27
Speaker 2: by that argument, it makes perfect sense that you would
16:29
Speaker 2: qualify as such.
16:30
Speaker 1: Well, we can call it whatever we want. You know,
16:32
Speaker 1: it's our world. We can create it ourselves. And there's
16:35
Speaker 1: so there's no law that says aging is not a disease,
16:39
Speaker 1: just as there isn't a law that says it is
16:40
Speaker 1: a disease. But what do we choose to call it
16:43
Speaker 1: really determines how we go after it, how we classify it,
16:48
Speaker 1: and classifications have a big impact on regulation. And right now,
16:53
Speaker 1: there's no country in the world that considers aging a
16:55
Speaker 1: condition that can be treated. So even if a doctor
16:58
Speaker 1: had a pill that could treat aging, that doctor could could,
17:03
Speaker 1: but but it'd have to be off label prescribe a
17:05
Speaker 1: medicine to help you. That's crazy, that's really crazy. That
17:09
Speaker 1: probably the best thing a doctor could do for you
17:11
Speaker 1: is to give you a medicine that would prevent pretty
17:14
Speaker 1: much all chronic old age diseases. But right now that's
17:17
Speaker 1: not possible because of the regulation.
17:19
Speaker 2: But we don't die of old age. We die of
17:23
Speaker 2: diseases that are precipitated by declining well being, Right, I mean,
17:31
Speaker 2: how does that? How do you think about that? All?
17:33
Speaker 1: Right? Well, so let's take cancer for example, that if
17:37
Speaker 1: you smoke, it increases your chance of getting lung cancer
17:40
Speaker 1: by about fivefold, and all we worry about that, we
17:43
Speaker 1: try to, we spend billions of dollars on trying to
17:46
Speaker 1: treat cancer and prevent smoking. Getting to the age of
17:49
Speaker 1: sixty increases your chance of cancer by one thousandfold. Okay,
17:54
Speaker 1: aging is the root cause of by far? What is
17:58
Speaker 1: the magnitude of all of these diseases that we eventually get,
18:01
Speaker 1: they're not separate things. Aging is what caused these How
18:04
Speaker 1: many people do you know that get heart disease Alzheimers
18:07
Speaker 1: in their twenties? Very few. The reason is because the
18:09
Speaker 1: body is young enough to fend its fend off these diseases.
18:13
Speaker 1: So my approach to this is that if we can
18:16
Speaker 1: figure out why we get old and how to reprogram
18:19
Speaker 1: the body, the cells in the body to be young again,
18:23
Speaker 1: we won't get those diseases. And even if we have
18:25
Speaker 1: these those diseases, the body can heal itself like we
18:28
Speaker 1: were twenty again.
18:30
Speaker 2: Okay, so then when we age, what is actually happening
18:34
Speaker 2: on a cellular level.
18:37
Speaker 1: All right, So let's go back just fifty years to
18:41
Speaker 1: set the stage of where we are now, because it's
18:43
Speaker 1: pretty exciting times fifty years ago. Well, let's go back
18:47
Speaker 1: to the nineteen fifties. Everyone was excited about radiation or
18:51
Speaker 1: scared probably is better way to put it. And there
18:54
Speaker 1: are a lot of theories that will put out. So's
18:57
Speaker 1: Leo Zillard. Peter Mettawa came up with these theories about
19:00
Speaker 1: the mutation hypothesis that we lose our genetic information. Mutations
19:06
Speaker 1: occur and they accumulate during our lifetime, and that's what
19:09
Speaker 1: causes aging, and mutations largely occur by radiation that we're
19:13
Speaker 1: exposed to.
19:14
Speaker 2: It's like a breakdown in the structure of the DNA.
19:19
Speaker 1: Right right, so you lose the information in the genome.
19:23
Speaker 1: But what'spened. Two things have happened just in my lifetime.
19:27
Speaker 1: First of all, that idea that mutations themselves cause aging
19:32
Speaker 1: has been largely disproved. You can make mice that have
19:37
Speaker 1: loads of mutations, you can knock out their ability to
19:40
Speaker 1: repair these things, and they don't get old. They live
19:43
Speaker 1: a normal, healthy lifespan. That's just one example of a
19:46
Speaker 1: whole litany of examples of why that theory from the
19:50
Speaker 1: nineteen fifties is, in my view, most likely to be
19:54
Speaker 1: not as prominent, if not just downright wrong. The big
20:01
Speaker 1: thing that happened early in my career in the nineteen
20:04
Speaker 1: nineties was the discovery that there are control genes that
20:09
Speaker 1: control our bodies health and longevity, and so single genes
20:13
Speaker 1: control health. So it's not as complicated as we once thought.
20:17
Speaker 1: You can make one mutation and an organism, whether it's
20:20
Speaker 1: a yeast in the case of my work in vaulters.
20:24
Speaker 1: Cynthia Kenyan's done worms. These organisms live a lot longer,
20:28
Speaker 1: ostensibly by mimicking fasting, caloristriction, and exercise. And that was
20:34
Speaker 1: a big deal. That was a paradigm shift in thinking.
20:36
Speaker 1: There was a lot of debate and argument. We're all
20:38
Speaker 1: over that now we all agree.
20:39
Speaker 2: So essentially, it's just so I understand there are specific
20:44
Speaker 2: control genes that you can identify, and when you just
20:47
Speaker 2: tweak those, it has that downstream impact that you're seeking.
20:51
Speaker 1: Right, So the analogy would be, you've got your body
20:54
Speaker 1: is a car, it wears out. But what we didn't
20:57
Speaker 1: realize until the nineteen nineties would but there were bodies
21:00
Speaker 1: repair people who go in and they constantly fix you.
21:04
Speaker 1: It's just that as you get older, they become decrepit
21:06
Speaker 1: themselves and they don't work very hard. And we've now
21:09
Speaker 1: got these genetic and increasingly pharmacological ways and dietary ways
21:13
Speaker 1: of getting them out of bed earlier in the morning
21:16
Speaker 1: and fixing your body. But then the next big change
21:19
Speaker 1: that happened was that we asked the question, well, what
21:21
Speaker 1: are these longevity repaired genes actually doing downstream to keep
21:26
Speaker 1: the body healthy? In other words, wide as calorie restriction
21:29
Speaker 1: works so well, and we in the aging field have
21:32
Speaker 1: come up with eight or nine what we call the
21:37
Speaker 1: hallmarks of aging, the underlying causes of aging, from chilomere
21:42
Speaker 1: last mitochondrial, decayed proteins, misfolding. But I think there's actually
21:47
Speaker 1: one of those pieces of the pie, one of those
21:50
Speaker 1: eight or nine, that's above all of them, that rules
21:54
Speaker 1: them all. And this is what I think is that
21:56
Speaker 1: the basis of what I'm calling the information theory of
21:59
Speaker 1: aging and how we came across that. It's a pretty
22:03
Speaker 1: interesting story that goes all the way back to my
22:05
Speaker 1: original days at MIT in the nineties. Well do you tell,
22:09
Speaker 1: we'll do so that when I got to the to
22:12
Speaker 1: MIT what I wanted to figure out, and don't forget,
22:16
Speaker 1: I was in a dream team of people, so I'm
22:18
Speaker 1: certainly not taking credit for most of this, but one
22:22
Speaker 1: of the things I was personally excited about was trying
22:24
Speaker 1: to figure out why don't you cells live for error
22:26
Speaker 1: because they're small, they're pretty simple. And what we and
22:30
Speaker 1: the team for sure deserves credit for finding was that
22:33
Speaker 1: there's a set of genes in YE cells and also
22:36
Speaker 1: in our bodies as well, but at the time we
22:38
Speaker 1: didn't know it that sense the environment. So when a
22:43
Speaker 1: Y cell is hungry, or it has too much temperature change.
22:46
Speaker 1: You make it hot, you make it really cold, or
22:49
Speaker 1: you subtract out some amino acids, it will live longer.
22:53
Speaker 1: And that is because it's activating a set of genes
22:56
Speaker 1: called the sertuins, and they are called curtoins because their
22:59
Speaker 1: first yeast gene was called SIR two. Now what's key
23:03
Speaker 1: to this whole information theory is that SIR two is
23:07
Speaker 1: an acronym stands for silent information regulator number two. The
23:13
Speaker 1: number two doesn't matter, but the silent information regulator is
23:16
Speaker 1: a really big deal, and we didn't understand it at first.
23:20
Speaker 1: So just a little bit about genetics. Silent information is
23:25
Speaker 1: essentially a gene that switched off and stays off, and
23:29
Speaker 1: in yeast, that's the genes that control whether it's yeast
23:33
Speaker 1: cell is a male or female. So SIR too, that
23:35
Speaker 1: gene was known already to yease biologists in the nineteen
23:40
Speaker 1: eighties to silence genes to keep them off. And what
23:45
Speaker 1: the lab that I was in Guarenti's lab discovered is
23:48
Speaker 1: that if you mutate these surgenes two and three, so
23:52
Speaker 1: four genes, the yeat cells live longer. We didn't know
23:57
Speaker 1: that a silent silencing gene would have anything to do
24:01
Speaker 1: with longevity. We thought that we'd find an antioxidant gene
24:04
Speaker 1: or something like that, or a mutation fixer, but out
24:08
Speaker 1: came this silencing what we now known is know as
24:11
Speaker 1: an epigenetic regulator, and that was that blew everyone away.
24:15
Speaker 1: But it was very confusing. Why would a gene regulator
24:19
Speaker 1: have any impact on longevity? But what I think now
24:22
Speaker 1: is that the major cause of aging is a loss
24:25
Speaker 1: not of the genetic information, but the epigenetic information of
24:29
Speaker 1: the body.
24:30
Speaker 2: So explain the difference between genetics and epigenetics.
24:34
Speaker 1: Right, So genetics is really easy. It's just the ATCG
24:38
Speaker 1: code in the DNA strand, it's digital information. Instead of
24:42
Speaker 1: being zeros and ones, it's four letters chemical letters. And
24:46
Speaker 1: that genome is split up into various little sections that
24:51
Speaker 1: we call genes that typically make proteins and they take
24:55
Speaker 1: care of us. But what we haven't really talked much
24:59
Speaker 1: about in the public is the epigenome because in part
25:02
Speaker 1: because it was much harder to study. We've only just
25:04
Speaker 1: got the tools now to read the whole epigenome. But
25:07
Speaker 1: really put, simply, if we could take a journey inside
25:10
Speaker 1: the cell and then delve into the nucleus where all
25:12
Speaker 1: the DNA is. We wouldn't see it just flopping around.
25:15
Speaker 1: The DNA strand is very tightly packaged in other proteins
25:20
Speaker 1: called histones, and those histones can be tightly bundled up
25:24
Speaker 1: with the DNA. Basically, DNA wraps twice around a histone
25:27
Speaker 1: and then moves on to another one like a bead
25:29
Speaker 1: on a string, and those histones come together very tightly
25:34
Speaker 1: to silence genes. So that's what the surtouins do. They
25:38
Speaker 1: bundle up the genes so that they get switched off
25:41
Speaker 1: or the histones might be spread out, and they allow
25:44
Speaker 1: the cell to read the gene. And that's how a
25:47
Speaker 1: cell says, oh, these genes should be on when we're young,
25:50
Speaker 1: and that cell should be a neuron and that cell
25:53
Speaker 1: should be a liver. And that's what we call the epigenome.
25:56
Speaker 1: It's the system that controls how the DNA packaged and
26:01
Speaker 1: says to the cell, these genes should be on and
26:03
Speaker 1: these genes should be off.
26:05
Speaker 2: Essentially, the expression of the gene, whether it is expressed
26:10
Speaker 2: or not expressed, right, But a function of epigenetics.
26:13
Speaker 1: It's really that's true, but I put it in different
26:17
Speaker 1: terms than other scientists that I know of, because DNA
26:21
Speaker 1: is digital. The epigenome, if you look at it, is
26:24
Speaker 1: actually analog, and analog information is extremely subject to noise
26:29
Speaker 1: over time. The main reason we switch to digital, and
26:33
Speaker 1: so the epigenome the problem is that it's it has
26:36
Speaker 1: to be analog because even in the first life forms
26:38
Speaker 1: that had an epigenome, they need to change their gene
26:42
Speaker 1: expression in response to what we eat, so the time
26:45
Speaker 1: of day, whereas the genome doesn't change essentially, and so
26:50
Speaker 1: this analog system had to exist. But being analog means
26:52
Speaker 1: that it's very hard to copy. It's also very hard
26:55
Speaker 1: to maintain in a pristine state over a period of
27:00
Speaker 1: two weeks for ye cell or eighty years for human
27:03
Speaker 1: And so I'm fairly convinced, given the work we've done
27:06
Speaker 1: over the last ten years, a lot of it unpublished,
27:08
Speaker 1: that the reason we age is that it's the analog
27:12
Speaker 1: information in the body that's lost over time, not the
27:14
Speaker 1: digital in the same way that a compact disc has
27:17
Speaker 1: digital information, and if you scratch it up, you lose
27:20
Speaker 1: the ability to read the right songs at the right time.
27:22
Speaker 2: Right. That's super interesting. How does that square with this
27:27
Speaker 2: definition of epigenetics that's out there, that's a little bit
27:30
Speaker 2: more kind of woo woo ephemeral. This idea that you
27:36
Speaker 2: had a great grandfather and he suffered a certain trauma
27:41
Speaker 2: and that is expressed in your psychological behavior in twenty nineteen.
27:47
Speaker 2: Isn't that part of the epigenetic conversation?
27:50
Speaker 1: It is, It absolutely isn't. So the epigenome, I think,
27:53
Speaker 1: is even more interesting than the genome, which gets all
27:55
Speaker 1: the attention. So the epigenome doesn't just tell your cell
27:59
Speaker 1: how to exist throughout your life and whether it should
28:03
Speaker 1: stay a liver cell or a neuron, but it also
28:06
Speaker 1: you can pass epigenetic information from one generation to another.
28:10
Speaker 1: So if a YE cell was stressed during its lifetime,
28:14
Speaker 1: its daughter will also be and that happens to us
28:18
Speaker 1: as well. We've done some experiments in my Sydney lab
28:22
Speaker 1: at the University of New South Wales where we stress
28:26
Speaker 1: the mother or we make her fat, or we make
28:29
Speaker 1: her hungry, and the offspring in the case of the
28:33
Speaker 1: fat mother are prone to diabetes because of the epigenetic transferabality.
28:38
Speaker 1: But the good news is that we've now because we
28:40
Speaker 1: know this and how to control the epigenome somewhat. We
28:43
Speaker 1: can now treat those offspring and prevent them from getting diabetes.
28:47
Speaker 2: That's wild.
28:49
Speaker 1: So controlling the epigenome, polishing that compact disc, getting the
28:53
Speaker 1: body to reset the epigenume to being healthy and young
28:56
Speaker 1: is what I'm focusing intensely on right now.
28:59
Speaker 2: And to extend that metaphor, keeping that compact disc super polished,
29:07
Speaker 2: making you know, making sure the integrity of the analog aspect,
29:10
Speaker 2: that epigenetic aspect of of you know, the aging mechanism
29:15
Speaker 2: is running properly, involves this, Sir two, right, Like, I'm
29:21
Speaker 2: let's get back to that, because that's where I'm starting
29:23
Speaker 2: to like yet quite understand what you're saying.
29:26
Speaker 1: Okay, So sir too is sitting on these genes, bundling
29:30
Speaker 1: them up and making sure that they stay off. So
29:34
Speaker 1: let's say you're a nerve cell, pristine young nerve cell.
29:37
Speaker 1: You're in a fifteen year old or twenty year old
29:40
Speaker 1: young kid. Your surtoins particularly three main ones or seven
29:46
Speaker 1: of them, three of them are doing this. They say, Okay,
29:50
Speaker 1: all of the neuron cells you don't want to express
29:54
Speaker 1: a liver cell, so let's keep that quiet for the
29:56
Speaker 1: rest of your life. That's what these aurtoins do. But
30:00
Speaker 1: the problem is we find is if that the sirtuins
30:03
Speaker 1: have other roles besides keeping genes silent, they actually are
30:07
Speaker 1: very important, particularly number one and six. They are involved
30:12
Speaker 1: in repairing damaged DNA as well. And the worst type
30:16
Speaker 1: of DNA damage that they have to repair, the most
30:19
Speaker 1: fatal for the cell, potentially fatal, is a broken chromosome
30:23
Speaker 1: what we call a DNA double strand break. And in yeast,
30:27
Speaker 1: when I was back at MIT, we had a paper
30:30
Speaker 1: in the journal Cell that said that these curtouins they
30:33
Speaker 1: moved to DNA breaks when they're needed, move away from
30:37
Speaker 1: the genes that they should be silencing. These genes come
30:40
Speaker 1: on temporarily, probably as a stress response, and then they
30:45
Speaker 1: have to repair the break and then they hopefully go
30:48
Speaker 1: back to where they came from. The problem is we
30:51
Speaker 1: found in yeast, and we are finding this also in mammals,
30:54
Speaker 1: is that they don't always find their way back to
30:56
Speaker 1: where they started, and so you over time lose the
31:01
Speaker 1: youthful gene expression thanks to the mislocalization of the sirtuins
31:06
Speaker 1: and other proteins, not just surturons, but they're are bellweather
31:09
Speaker 1: of this this CD scratching, So.
31:11
Speaker 2: They're sort of like ambulances or you know, the California
31:17
Speaker 2: Highway construction crew who's been dispatched to a certain you know,
31:21
Speaker 2: pothole or problem. They fix it, but over time they
31:25
Speaker 2: start to the radios don't work on the way home
31:27
Speaker 2: and they get lost. Is that it?
31:29
Speaker 1: Yeah, I kind of put that better myself, right, And
31:33
Speaker 1: the worst part about it is that it's a positive
31:36
Speaker 1: feedback in the sense that now you've got some these
31:40
Speaker 1: pothole workers who've lost their way and you're not fixing
31:44
Speaker 1: the potholes as well. Ah, and you get more and
31:46
Speaker 1: more potholes, which distracts these workers even more. And this
31:50
Speaker 1: is why after age forty, particularly after age fifty, you
31:54
Speaker 1: get this massive decline in health. And we have actually
31:59
Speaker 1: engineered ye cell and a mouse in a way that
32:02
Speaker 1: we can distract those surve proteins and see them age
32:06
Speaker 1: more rapidly, essentially create some few extra potholes and distract
32:11
Speaker 1: those workers, and we actually do see that aging goes faster.
32:15
Speaker 1: But the good news is interesting for the mice. Anyone
32:18
Speaker 1: who's worried about our animals, we have ways of reversing that.
32:22
Speaker 2: Now, and one of the things that you've discovered in
32:27
Speaker 2: the search to try to create greater functionality here is
32:34
Speaker 2: the impact of something called NAD on this process, right.
32:39
Speaker 1: Exactly, So the sirtuins turn out to be enzymes and
32:44
Speaker 1: very special enzymes. What think of them as the crew
32:49
Speaker 1: that's directing the pothole repairs and or you know, like
32:52
Speaker 1: I said, the body shop repair people. They literally modify
32:57
Speaker 1: other proteins to do a better job at repairing the body.
33:01
Speaker 1: And by modifying that they remove chemical groups called acetyls,
33:06
Speaker 1: and in doing that they can actually have a much
33:10
Speaker 1: bigger impact on the body than just one enzyme alone.
33:13
Speaker 1: They control hundreds of other repair enzymes. But they only work,
33:17
Speaker 1: they can only remove that little acetyl piece off other
33:21
Speaker 1: proteins if they have NAD. Around technical terms, we call
33:26
Speaker 1: it a co substrate. But that just basically means if
33:28
Speaker 1: you don't have NAD, the certoin enzymes, they can't silence genes,
33:32
Speaker 1: they can't repair DNA. And by the way, without NAD,
33:35
Speaker 1: you're dead in a matter of minutes.
33:37
Speaker 2: Or le's like the key sustenance for the certoins exactly.
33:42
Speaker 1: But NED is a pretty boring molecule at least it
33:44
Speaker 1: was until certoins were discovered. It's needed for basic biochemical
33:49
Speaker 1: reactions in the body, and you can find it in textbooks.
33:52
Speaker 1: If you studied biology in college, you would have read
33:55
Speaker 1: about NAD. And before we came along, people have really
33:59
Speaker 1: forgot and about ANAD. They said, it's a house giving molecule.
34:02
Speaker 1: We we know everything we need to know about ANAD,
34:05
Speaker 1: and then along come the surtoons and it's wow. NAD
34:08
Speaker 1: isn't just there to keep us to do chemical reactions.
34:12
Speaker 1: It's sensing how much food we eat, preferably less, how
34:17
Speaker 1: much we exercise preferably more, and even things like hot
34:20
Speaker 1: and cold, and in the E cells. Turns out, if
34:23
Speaker 1: you stress thosey cells a little bit with those treatments,
34:27
Speaker 1: you turn on the ability to make more NAD for
34:30
Speaker 1: the stratoins to do a better job. And so now
34:32
Speaker 1: you can have the curtuins keeping those genes silent and
34:36
Speaker 1: also repairing the DNA and finding their way back home
34:39
Speaker 1: much more easily. So NAD is the best way we
34:42
Speaker 1: know of to keep those sortoins active and able to
34:45
Speaker 1: cope with that repair and silencing process.
34:48
Speaker 2: And as we age, do we develop a deficiency of NAD, Yeah,
34:54
Speaker 2: we do.
34:55
Speaker 1: That's the sad thing is that when you measure ANAD
34:58
Speaker 1: in animals and also in human we have about half
35:01
Speaker 1: the levels we once did once you reach some almost fifty. Now.
35:05
Speaker 1: I haven't measured my ANAD levels, but I would say
35:08
Speaker 1: it's probably, based on the study, is about half of
35:10
Speaker 1: what it was when I was twenty, which is a
35:12
Speaker 1: scary thought. This is a molecule. It's needed for life.
35:15
Speaker 1: We now know it's a molecule needed for the surtuins.
35:17
Speaker 1: We've also found that many diseases are associated, if not caused,
35:21
Speaker 1: by low NAD levels, and so I think one of
35:25
Speaker 1: the approaches that we're taking has a lot of promise,
35:29
Speaker 1: which is to give the body extra precursors to NAD,
35:33
Speaker 1: to raise those levels back up to youthful levels and
35:35
Speaker 1: let the curtuins do their work.
35:37
Speaker 2: And this is the n NM.
35:39
Speaker 1: Man, that's nimn n a men. Don't confuse it with
35:43
Speaker 1: M and m's that they're not as good for you.
35:45
Speaker 2: Probably it's tasty.
35:47
Speaker 1: It's actually I have tasted it an men and it's
35:50
Speaker 1: pretty sweet. It's not a bad molecule. So often people
35:54
Speaker 1: wonder what is NIMN It stands for a nicotinamide mono nucleotide. Actually,
36:00
Speaker 1: the nuclear tide part of it, interestingly, is related to DNA.
36:03
Speaker 1: It's one of the early molecules that formed on the
36:05
Speaker 1: planet when we first had life. But anyway, and a
36:09
Speaker 1: man is taken up by the cells, you can eat it,
36:11
Speaker 1: you can give it to mice in their water supply.
36:14
Speaker 1: It goes into the body very rapidly and the body
36:17
Speaker 1: turns it into NAD in one step, and that step
36:21
Speaker 1: is what gets activated by stress. So go back to yeast.
36:24
Speaker 1: For example, when we shock the yeast with the lack
36:28
Speaker 1: of glucose sugar, or give them a bit of heat,
36:31
Speaker 1: or take away amino acids, they will make more NAD
36:34
Speaker 1: by converting this intermediate into NAD. And we think that's
36:39
Speaker 1: true for the body as well. For our bodies when
36:41
Speaker 1: we exercise, if we go hungry, we see more NAD
36:44
Speaker 1: produced still over time.
36:46
Speaker 2: And this is a product of hormesis, stressing the body
36:52
Speaker 2: to create a favorable downstream result exactly.
36:57
Speaker 1: So hormesis is that the crux of why exercise and
37:01
Speaker 1: dieting is good for you, why calorie restriction makes animals
37:04
Speaker 1: live longer, And we didn't know that until the early
37:06
Speaker 1: two thousands, but all of this came together and then
37:09
Speaker 1: we figured out a FA yeast this entire pathway, and
37:13
Speaker 1: then we've been working on testing whether that hypothesis in
37:18
Speaker 1: or at least that factor yeast is true in US
37:20
Speaker 1: as well, and so far it looks like it's surprisingly
37:23
Speaker 1: similar to what we learned there.
37:25
Speaker 2: Right, So you've developed this NMN. I guess you would
37:31
Speaker 2: call it a supplement. Yeah, supplement product is something that
37:34
Speaker 2: you take. Your skin looks amazing, there's not a gray
37:37
Speaker 2: hair on your head. You're fifty, right, looking very youthful,
37:42
Speaker 2: a good ambassador of the work that you do. And
37:47
Speaker 2: this is very interesting. So by supplementing this, you are
37:53
Speaker 2: basically taking out an insurance policy that allows your curtuins
37:58
Speaker 2: to function they that they're supposed to do without this
38:02
Speaker 2: degrading impact over time. Is that an accurate assessment of
38:07
Speaker 2: the idea here?
38:08
Speaker 1: Yes, you've got it. And so I don't know whether
38:13
Speaker 1: these molecules that I take are going to be helpful,
38:18
Speaker 1: but I do know that they're not hurting me, as
38:20
Speaker 1: you said, and if I'm around you know, and all
38:24
Speaker 1: my colleagues are old, we'll know something is happening. But
38:29
Speaker 1: what's important, I think for your listeners to know is
38:33
Speaker 1: I am trying to get these molecules at least tested,
38:36
Speaker 1: if not proven, hopefully to work in people. And so
38:40
Speaker 1: that requires a lot of time and money and effort.
38:43
Speaker 1: And so there are ongoing clinical trials. One of them's
38:48
Speaker 1: run out of Harvard University at the Brigham and Women's Hospital,
38:52
Speaker 1: and we're early stage. We've just done the safety studies,
38:55
Speaker 1: but later this year we should have a readout of
38:57
Speaker 1: what we call efficacy, which would be whether what we
39:00
Speaker 1: see in the mice some of it is recapitulated in
39:05
Speaker 1: older patients as well. And eventually I want this to
39:08
Speaker 1: be a drug that will treat diseases as well.
39:11
Speaker 2: Right. So yeah, so FDA approved the farmer route, not
39:15
Speaker 2: the supplement route. Right.
39:18
Speaker 1: It's very hard to straddle both. Actually, I think it's
39:22
Speaker 1: impossible to straddle both, and so I've chosen to take
39:26
Speaker 1: the farmer route because I want to be able to
39:28
Speaker 1: have something that is proven to work, is safe, and
39:33
Speaker 1: I just think that for me is the better path
39:37
Speaker 1: for me. I want to be someone that is not conflicted,
39:41
Speaker 1: is not trying to promote anything. I never sell products
39:44
Speaker 1: or try to endorse anything. And so people can come
39:47
Speaker 1: to me and or I can give lectures freely and
39:50
Speaker 1: people can know that I have no hidden agenda.
39:53
Speaker 2: But you have your hands in all kinds of companies
39:56
Speaker 2: out there. You're very enterprising entrepreneurial scientists.
40:01
Speaker 1: Well, I do, but there's nothing you can buy from me.
40:03
Speaker 1: So there's nothing I'm going to gain really immediately. But
40:05
Speaker 1: I do. I do entrepreneurial activities not because I'm I
40:12
Speaker 1: just I'm interested in the short term gain. I want
40:16
Speaker 1: to leave a legacy, and so I've had my eye
40:18
Speaker 1: on that goal since I was in my twenties. And
40:20
Speaker 1: that goal is to leave a mark. And I'm not
40:23
Speaker 1: just satisfied with publishing papers in these journals. I want
40:26
Speaker 1: to have a medicine, if not hopefully a few of them,
40:29
Speaker 1: that will save hundreds, if not hundreds of thousands of lives.
40:36
Speaker 2: Thinking, you know, forward towards that creates a lot of
40:42
Speaker 2: interesting thought experiments around what would actually happen should your
40:47
Speaker 2: mission come to fruition? Right, So is your mission to
40:54
Speaker 2: end aging as we know it? Like, what is the
40:57
Speaker 2: specific goal that you're striving towards here?
41:02
Speaker 1: Well, I'm not trying to end aging. I don't believe
41:06
Speaker 1: that there's going to be immortality. But I do believe
41:09
Speaker 1: that the way we've been going about medicine for the
41:12
Speaker 1: last couple of one hundred years can be improved. The
41:15
Speaker 1: way we've been going about it has been take one
41:18
Speaker 1: disease at a time and study it and ignore aging,
41:23
Speaker 1: and hopefully make a medicine to treat that. And so
41:25
Speaker 1: we've been very successful as a species making medicines that
41:28
Speaker 1: prevent and treat heart disease, for example. But what that
41:32
Speaker 1: got us heah, we get an extra couple of years
41:34
Speaker 1: of life, and that's all because other disease are still
41:37
Speaker 1: coming along right behind. But we end up spending those
41:40
Speaker 1: years with other chronic diseases, and we're actually spending longer
41:44
Speaker 1: times of our lives in a six state than we
41:46
Speaker 1: used to. And that's really to me. It's something you
41:51
Speaker 1: wouldn't even wish on your worst enemies, is to extend
41:54
Speaker 1: life but not extend health.
41:56
Speaker 2: Right, if we were to, if you were to identify
42:00
Speaker 2: like the sort of ultimate age that we could perpetuate,
42:04
Speaker 2: I mean, what is that is that thirty five? Is
42:06
Speaker 2: it twenty five? Is it forty six? Like? Is there
42:10
Speaker 2: a chronological period of time where you think the human
42:14
Speaker 2: mechanism is functioning at its peak, and that's where we
42:17
Speaker 2: could we should just sort of lock it in.
42:20
Speaker 1: Yeah. Yeah, Well I don't know. I'm fifty and i
42:23
Speaker 1: feel like I'm still twenty, so I'm not seeing any decay.
42:26
Speaker 1: So any age between twenty and forty fifty is fine
42:29
Speaker 1: with me.
42:30
Speaker 2: Ah.
42:31
Speaker 1: I mean, clearly, the athletes lose their ability to perform
42:35
Speaker 1: it at that level. But I'm a mental athlete and
42:38
Speaker 1: my brain is far better than it was even a
42:41
Speaker 1: year ago, So I definitely don't want to go back
42:44
Speaker 1: in time. Put it that way. But what's interesting about
42:49
Speaker 1: athletes is we're finding that because we know a lot more,
42:51
Speaker 1: they know a lot more about how to keep their
42:53
Speaker 1: body young, part through what they eat, how they live.
42:58
Speaker 1: We're seeing these athletes also actors. Take Tom Cruise, I'm
43:01
Speaker 1: looking a lot and acting a lot younger physically as
43:04
Speaker 1: well than what we had just a twenty thirty years ago,
43:07
Speaker 1: previous generation.
43:08
Speaker 2: Yeah, are you working with Tom Cruise behind the scenes?
43:11
Speaker 2: Not Tom Cruise, No, no, but somebody else, somebody else here.
43:14
Speaker 2: You don't want to.
43:15
Speaker 1: Say, Well, there are plenty people I get to meet. Yeah,
43:20
Speaker 1: it's a fun job.
43:21
Speaker 2: I put it that way, right, right, right, Well, all
43:23
Speaker 2: these billionaires who are injecting themselves with young people's blood,
43:27
Speaker 2: there's certainly a lot of interest in youth and longevity
43:31
Speaker 2: amongst the well healed. So I'm sure you've got, you know,
43:36
Speaker 2: a rolodex of fascinating people that are trying to get
43:40
Speaker 2: your time.
43:42
Speaker 1: It's true, and I help as much as I can,
43:46
Speaker 1: and often I'm asked, well, David, you're working on these medicines,
43:51
Speaker 1: and how come only super rich people get access to you, which,
43:57
Speaker 1: first of all, that's not true. I reply to every
43:59
Speaker 1: email that I can. But also it's similar to the
44:02
Speaker 1: right brothers that the phase that we're in now with
44:05
Speaker 1: aging in that we know that we can build a glider.
44:09
Speaker 1: It's flying. We've seen that, we know how to do this.
44:11
Speaker 1: It's just a question of strapping on an engine and
44:15
Speaker 1: taking off and flying around. And we're building that. But
44:18
Speaker 1: that takes entrepreneurs, it takes investment, and certainly the two thousand,
44:24
Speaker 1: so that the early nineteen hundreds required millions of dollars
44:28
Speaker 1: of investment. And who were the first people that were
44:31
Speaker 1: flying was probably wealthy people, people who knew others. And
44:36
Speaker 1: it's not so much elitism It's just that's how all
44:39
Speaker 1: technology rolls out, and so I see this as going
44:44
Speaker 1: as rapidly as possible to be, and my mission to
44:47
Speaker 1: roll this out to everybody on the planet and not
44:49
Speaker 1: just wealthy nations. I've pledged to make the drugs that
44:53
Speaker 1: I'm making available to everybody on the planet as soon
44:56
Speaker 1: as possible.
44:57
Speaker 2: Well, it is true that people are looking, you know,
45:00
Speaker 2: more youthful in their later years, and we're seeing athletes
45:05
Speaker 2: who are performing at a very high level at ages
45:08
Speaker 2: that people would have thought was impossible, you know, fifteen
45:12
Speaker 2: years ago. And that's super interesting. And I would imagine
45:15
Speaker 2: that's a function of a multitude of factors, including you know,
45:18
Speaker 2: people have to these athletes have to make There has
45:21
Speaker 2: to be a way for them to make a living
45:22
Speaker 2: so that they can continue to do this. But one
45:24
Speaker 2: of the things that was super interesting about the studies
45:27
Speaker 2: that you've done on mice with nad n MN was
45:32
Speaker 2: the increased blood flow that was created that led these
45:37
Speaker 2: mice to have like this something like a sixty to
45:40
Speaker 2: eighty percent boost in their ability to like be on
45:43
Speaker 2: a treadmill and and produce you know, an athletic output.
45:50
Speaker 2: I mean, I read that I was like, wow, like,
45:52
Speaker 2: what's the athletic implications of that? Is this doping or
45:55
Speaker 2: is this like cool? Like what's happening here?
46:00
Speaker 1: Well, it's certainly cool science. Whether or not it's it
46:04
Speaker 1: should be considered doping or not, I'm not really sure.
46:07
Speaker 1: Because we're talking about boosting a natural molecule. It's in
46:10
Speaker 1: your body anyway.
46:11
Speaker 2: It's increasing blood flow, right, it's like it's improving like
46:15
Speaker 2: your vascular delivery system.
46:18
Speaker 1: It is, so let me explain how that works. What
46:21
Speaker 1: we discovered was that the surtuins, let's go back to
46:26
Speaker 1: those guys again, in the lining of your blood vessels.
46:29
Speaker 1: They're not very active as you get older, and one
46:32
Speaker 1: of the main reasons that you don't respond well to exercise.
46:35
Speaker 1: You know, if you're seventy or eighty, maybe even younger
46:37
Speaker 1: and you exercise, you still aren't a super athlete because
46:40
Speaker 1: they're what we think is the major reason. One of
46:43
Speaker 1: the main reasons is that the lining of your blood vessels,
46:46
Speaker 1: the surtuins thirty one is the main gene isn't doesn't
46:51
Speaker 1: have enough nad around. And what was remarkable was that
46:54
Speaker 1: we could treat mice with the Centermen molecule just give
46:58
Speaker 1: it to them in their water supply, raise the NAD
47:01
Speaker 1: levels back up to young levels in the blood vessels.
47:03
Speaker 1: And now we had old mice that first of all,
47:06
Speaker 1: they acted as though physically they'd been training, but they
47:10
Speaker 1: hadn't been. But also if we gave the men and
47:13
Speaker 1: men on top of exercise, they became super athletes beyond
47:17
Speaker 1: what exercise alone could get them. That's wild and it's
47:21
Speaker 1: super cool as well, because one of the major causes
47:25
Speaker 1: of disability and frailty as we get older, even into
47:28
Speaker 1: our sixties and seventies, why do we feel tired when
47:31
Speaker 1: we were older, is because we don't have enough of
47:33
Speaker 1: this blood flow, and very few people have ever thought
47:36
Speaker 1: to figure out why that is. And so that's why
47:39
Speaker 1: we jumped on that, And so imagine it's great for
47:43
Speaker 1: young people as well. I think it could keep people
47:46
Speaker 1: in tip top shape, especially people who cannot exercise as
47:49
Speaker 1: much as they want, like myself who types for a living.
47:53
Speaker 1: But more importantly, far more important than people like me,
47:55
Speaker 1: is those people who are already frail, people who are
47:58
Speaker 1: in bed or who are we cannot really walk very far.
48:03
Speaker 1: We give them potentially these nead boosters, as we call them,
48:06
Speaker 1: let's call it the MiB six two six, which is
48:08
Speaker 1: the drug form of what we're developing. Give it to
48:11
Speaker 1: them for a few weeks and they hopefully what I
48:14
Speaker 1: hope is we'll see is they have the energy, they
48:16
Speaker 1: have the new blood flow, they can start to walk again.
48:19
Speaker 1: And that's a virtuals a virtuous cycle, a positive feedback
48:23
Speaker 1: in a good way so that they get out of bed,
48:26
Speaker 1: they walk, they get more exercise, and get back into mobility,
48:29
Speaker 1: because it's the lack of mobility that ends up killing you.
48:32
Speaker 2: Yeah, yeah, And what are the implications on arthrosclerosis is
48:37
Speaker 2: it can it reverse arterial damage and create greater plasticity,
48:41
Speaker 2: Like how does that work?
48:43
Speaker 1: We haven't just an entement on that, but others have
48:46
Speaker 1: and we find that this one sort two and is
48:50
Speaker 1: extremely important for protecting the the cudiovascular system from plaque
48:57
Speaker 1: as well as keeping it youthful. And so there's a
48:59
Speaker 1: study by Doug Seals at the University of Colorado just
49:03
Speaker 1: to mention a much an independent study. They gave enemen
49:07
Speaker 1: to old mice and similar to the way we saw
49:11
Speaker 1: new blood vessels growing, they saw that the existing blood
49:14
Speaker 1: vessels had had much better plasticity and resilience as well,
49:19
Speaker 1: and so the hope is that if we can get
49:21
Speaker 1: these molecules to be super potent and targeted to the
49:25
Speaker 1: right part of the body, we'll have all of those effects.
49:29
Speaker 2: And does this also have implications for mitochondrial decline because
49:35
Speaker 2: isn't that another key aspect of aging?
49:39
Speaker 1: Well, it does. And just to preface that, often what
49:44
Speaker 1: I'm saying sounds too good to be true, because every
49:48
Speaker 1: time people ask me that, yeah, it does that, it
49:51
Speaker 1: cures this, it is that. Well, first of all, we're
49:53
Speaker 1: still in mice. We don't know if it works in humans,
49:55
Speaker 1: but we're going to figure that out in the next
49:57
Speaker 1: year or so. But yeah, you asked me about my Andrea.
50:00
Speaker 1: We've published. These are all cell and science papers, so
50:05
Speaker 1: these are top studies. These aren't just off the right
50:07
Speaker 1: kind of stuff, so a lot of work has gone
50:09
Speaker 1: into them. What we showed in mitochondria was that raising
50:13
Speaker 1: the levels of NAD in cells fixed what was a
50:17
Speaker 1: really curious defect that happens as the mice got older.
50:21
Speaker 1: So what was that. What we found is that the
50:25
Speaker 1: organelles the different parts of the cell that have different genomes,
50:29
Speaker 1: So we have the nuclear genome or chromosomes, but we
50:31
Speaker 1: also have mitochondrial DNA inside those of mitochondria. We found
50:35
Speaker 1: that those two genomes were not communicating as the mice
50:37
Speaker 1: got older, and so we called it genome asynchrony. And
50:42
Speaker 1: it's essentially, if you want to put it into some
50:44
Speaker 1: sort of an analogy, a metaphor, it's as though when
50:48
Speaker 1: you're young and you're a young couple, the people get along,
50:52
Speaker 1: they're in this small apartment. They communicate well, but by
50:54
Speaker 1: the end of it, they can't stand each other. They're
50:56
Speaker 1: not communicating. We see that with the mitochondria.
50:59
Speaker 2: Staring at their pe at dinner not talking to each other.
51:02
Speaker 1: Yeah, I mean, imagine how bad that is for our bodies.
51:04
Speaker 1: And so we figured out why that occurs and traced
51:08
Speaker 1: it all the way back to the lack of NAD.
51:10
Speaker 1: So by replacing the or replenishing the NAD, the mitochondria
51:15
Speaker 1: started communicating the nucleus. The mighty chondria said to the nucleus, hey,
51:19
Speaker 1: give us some protein like you used to when we
51:21
Speaker 1: were young. And that completely restored the function of those
51:24
Speaker 1: mitochondria in the muscle. And so we called that reversal
51:28
Speaker 1: of aspects of aging. In fact, those muscles that we
51:31
Speaker 1: looked at in those mice. Those mice were two years
51:33
Speaker 1: old and within just a I think it was two
51:36
Speaker 1: weeks of treatment, they were just like a young mouse.
51:41
Speaker 2: Wow, implications are insane or something like this? I mean,
51:46
Speaker 2: that's amazing. Are there any negative consequences of this? I
51:51
Speaker 2: just feel like there's a there's often a hubris in
51:55
Speaker 2: humans with this sort of thing, and our reductionist scientific
51:58
Speaker 2: method to zero in on one thing and we see
52:01
Speaker 2: this positive implication and we are blind to, you know,
52:05
Speaker 2: all these other aspects of what goes on, because it's
52:09
Speaker 2: a holistic machine. You know, there's a lot going on.
52:12
Speaker 2: Just you know, there's a lot of dominoes that are
52:14
Speaker 2: stacked up against each other here.
52:17
Speaker 1: That's right. And part of the problem I think with
52:20
Speaker 1: medicine and why pharmaceutical industries had trouble making drugs with
52:26
Speaker 1: outside effects is that they are first of all, that
52:29
Speaker 1: they're using synthetic molecules that the body has never seen,
52:32
Speaker 1: in part to pattern protection and super charged molecules. But
52:37
Speaker 1: also the problem is that they're intervening in aspects of
52:42
Speaker 1: the body that normally don't change, and it'd be like
52:47
Speaker 1: revving up a mini Cooper's engine, but not making sure
52:52
Speaker 1: that they have the right gearbox and tires to deal
52:54
Speaker 1: with it. And so the approaches we take we try
52:57
Speaker 1: to change those parts of the body's body that changes
53:00
Speaker 1: naturally when we exercise or when we diet. And that's
53:02
Speaker 1: why philosophically, I'm less concerned about side effects, because they're
53:07
Speaker 1: really just replacing what we've lost with age, similar to
53:10
Speaker 1: the NAD levels. But are the side effects, well, we
53:13
Speaker 1: haven't seen any. We've just been giving an amen to
53:15
Speaker 1: mice for the last year or so. We haven't finished
53:20
Speaker 1: the study, and thank you to all of the people
53:23
Speaker 1: online who crowdsourced fund funded that study, but we're already
53:27
Speaker 1: seeing a lifespan extension in those mice, and so that's exciting.
53:31
Speaker 1: And every time you see a lifespan extension in the mice,
53:34
Speaker 1: it's hard to argue that we're hurting them. Now, maybe
53:37
Speaker 1: there's something going on, but maybe they're depressed or something.
53:40
Speaker 1: But other than that, they are otherwise perfectly healthy. Now, again,
53:45
Speaker 1: these are mice. We haven't treated humans, so that's why
53:47
Speaker 1: we're doing these safety studies. I don't stay up at
53:51
Speaker 1: night worrying about the side effects, given what I've seen
53:54
Speaker 1: over the last year. In many years, in many labs
53:57
Speaker 1: across the world, there have beens of animals treated with
54:01
Speaker 1: these molecules. Nothing that rings alarm bells. But if you
54:07
Speaker 1: wanted to push me right, Rich says David, You've got
54:10
Speaker 1: to come up with one thing that you could see
54:12
Speaker 1: might be negative. It would be blood vessel growth. If
54:17
Speaker 1: you have a tumor already that needs a good blood supply,
54:20
Speaker 1: and we grow more blood vessels, that would not be good.
54:24
Speaker 1: And so that's actually why we've done a couple of
54:26
Speaker 1: studies in mouse in mouse cancer models and given them
54:29
Speaker 1: an amen. And the good news for the listeners is
54:32
Speaker 1: that we've not seen any deteriorational acceleration of those cancers,
54:39
Speaker 1: and in one case we saw that the tumors grew
54:42
Speaker 1: much more slowly than without the nimen. But that doesn't
54:47
Speaker 1: really mean that it's perfectly safe. So it's one of
54:51
Speaker 1: the reasons why I'm doing these clinical trials is that,
54:54
Speaker 1: first of all, I want to be the first person
54:56
Speaker 1: to know if it's unsafe. My family definitely wants to
54:59
Speaker 1: know that, but I want to be able to sleep
55:02
Speaker 1: soundly knowing that I'm not doing any harm to anybody.
55:06
Speaker 2: Me being a non scientist. I've been operating under this
55:11
Speaker 2: idea that, you know, part of aging is a result
55:14
Speaker 2: of free radical damage, and that we should be eating
55:18
Speaker 2: a lot of antioxidants to combat this free radical damage.
55:22
Speaker 2: And when you were talking to Joe, you were sort
55:24
Speaker 2: of dispelling some aspect of that conventional wisdom. So can
55:29
Speaker 2: you explain that a little bit.
55:32
Speaker 1: Yeah, so free radicals are part of the story, but
55:36
Speaker 1: really it looks like just a minor part of it.
55:39
Speaker 1: So free radicals will will cause DNA damage, we know that,
55:44
Speaker 1: and it'll cause those DNA breaks that scratch the CD
55:48
Speaker 1: so that I'm not saying that they're not completely that
55:52
Speaker 1: they're irrelevant, but.
55:54
Speaker 2: I'mostly cell oxidation.
55:55
Speaker 1: Cell oxidation, you don't want it. But let's go back
55:59
Speaker 1: to that our analogy. I think we've in terms of
56:02
Speaker 1: the free radical idea. It's as though we've said, hey,
56:06
Speaker 1: you know what, the windscreen wiper blades are old, let's
56:08
Speaker 1: replace those. Let's fix those windscreen wipers, not realizing that
56:11
Speaker 1: that's the least of our problems. We got other things
56:13
Speaker 1: that we could do to keep our bodies healthy. And
56:17
Speaker 1: so that and you know, there's a lot of studies
56:20
Speaker 1: in the world now that have where people have tried
56:23
Speaker 1: to use antioxidants and failed to extend lifespan in animals.
56:27
Speaker 1: There are some success stories, but you can also think
56:30
Speaker 1: of other reasons why those molecules, those quote unquote antixidants
56:34
Speaker 1: have actually worked. And one reason that I think is
56:38
Speaker 1: plausible is that those antioxidants that typically come from the
56:42
Speaker 1: plant world are engaging the bodies surtoins and other survival
56:47
Speaker 1: longevity mechanisms, so that they're not only mopping up free radicals,
56:51
Speaker 1: but they're engaging our survival systems as well.
56:55
Speaker 2: And as veratrol would be one of those.
56:58
Speaker 1: Right, So that's what got me started thinking about this.
57:00
Speaker 1: But if you look into the science of this and
57:03
Speaker 1: the literature, pretty much every molecule that we take in
57:08
Speaker 1: from plants that has medicinal properties, let's say ECGC from
57:13
Speaker 1: t what else. Aspirin is also a good example. These
57:18
Speaker 1: molecules have so many different effects on different parts of
57:20
Speaker 1: the cell, different pathways, and so they might activate AMPK
57:24
Speaker 1: while they're inhibiting imtour while they're activating surratoons. That cannot
57:28
Speaker 1: be a coincidence that these plant molecules have all the
57:32
Speaker 1: right impact on these longevity pathways. It's as though we've
57:37
Speaker 1: I would say, the only explanation, no, take it back.
57:40
Speaker 1: The main explanation I think is that we've evolved to
57:42
Speaker 1: sense the plant's stress conditions so that we hunker down
57:46
Speaker 1: when we're going to run out of food. There is
57:48
Speaker 1: one other explanation that is that these molecules in plants
57:51
Speaker 1: we make something quite similar, but we just don't know
57:53
Speaker 1: what they are yet, So they might be a human
57:55
Speaker 1: resivitual that we haven't found yet.
57:57
Speaker 2: Right, right, and so basic the resveratrol, which is an antioxidant,
58:03
Speaker 2: is also a plant's stress response to you know, some
58:10
Speaker 2: external event, right, in order to defend itself and make
58:14
Speaker 2: it itself stronger. And by taking that in we're having
58:17
Speaker 2: a similar impact on our own cell structure.
58:21
Speaker 1: That's exactly right. And so we've found pockets in proteins
58:25
Speaker 1: that sense how much resvitrol is in the body. One,
58:28
Speaker 1: this certuin that I've been talking about, has a pocket
58:31
Speaker 1: that resvertrol sticks in and it activates it. We know
58:36
Speaker 1: that at great detail down at the atomic level. But
58:39
Speaker 1: these other molecules also happen to bind at the right
58:41
Speaker 1: place on these proteins. So it's exactly what you said,
58:44
Speaker 1: which is that when the plant is stressed, it's making
58:47
Speaker 1: its own molecules like rosvitrol to survive. Plants have certuins,
58:51
Speaker 1: sirtoins are found even in bacteria. And I don't think
58:55
Speaker 1: the plants are trying to make us healthy, but we
58:58
Speaker 1: use them as a way to make our selves healthy.
59:00
Speaker 1: And we've learned over the last few thousand years or
59:02
Speaker 1: maybe longer, that if you eat these types of foods
59:06
Speaker 1: at this time of year and you bottle it and
59:08
Speaker 1: keep it dark and put some alcohol in there, it'll
59:10
Speaker 1: preserve those molecules and you'll get some health benefits as well,
59:13
Speaker 1: and you might get tipsy as well. But we've had
59:16
Speaker 1: to do that empirically rather than knowing exactly how it's
59:19
Speaker 1: been working right.
59:21
Speaker 2: And it's it's problematic as well because it's not as
59:24
Speaker 2: binary as we would imagine. There were all those beta
59:27
Speaker 2: carotene studies like if you you know, if you take base,
59:30
Speaker 2: you know, super dose with this, it will combat all
59:35
Speaker 2: these things and make you healthier in all these different ways.
59:37
Speaker 2: But whether it was a bioavailability issue or you know,
59:41
Speaker 2: it's like when we extract these healthy you know, aspects
59:45
Speaker 2: of a plant and take them in a singular dose,
59:48
Speaker 2: it doesn't quite have the impact that it does when
59:51
Speaker 2: it's in the complex matrix of the plant food itself.
59:56
Speaker 1: You've hit on something that I think about a lot,
59:58
Speaker 1: which is so we've been just taking the plane resivitual molecule,
1:00:02
Speaker 1: but when you drink it in red wine or you
1:00:04
Speaker 1: take it in its natural form, all of these molecules
1:00:07
Speaker 1: are coming with a cocktail that's probably finely tuned our
1:00:11
Speaker 1: bodies are finely tuned to. And also what we find
1:00:14
Speaker 1: is these combination of molecules are actually synergistic. So for example,
1:00:19
Speaker 1: if you take corusitin crossettans people call it at the
1:00:23
Speaker 1: same time with resvitroal, they will both last longer in
1:00:26
Speaker 1: the body. And by separating these out, which we like
1:00:29
Speaker 1: to do as reduction as scientists, we're losing some of that.
1:00:33
Speaker 1: And also the other problem is that if you're just
1:00:35
Speaker 1: using a plain chemical like corossetin, these are fairly insoluble,
1:00:39
Speaker 1: so most of it doesn't even get absorbed. It's only
1:00:42
Speaker 1: when it's in its natural state, when it's combined with
1:00:45
Speaker 1: sugars and in many cases fats, that's important to help
1:00:49
Speaker 1: the uptake and that's why often when people ask me
1:00:53
Speaker 1: how it's resvitual, would you need to take to have
1:00:55
Speaker 1: an impact? I have to be careful because sure, if
1:00:58
Speaker 1: you take it in its pure form, you need hundreds
1:01:00
Speaker 1: of glasses of red wine, if you drink a few
1:01:03
Speaker 1: glasses of red wine for a decade, Not that I'm
1:01:05
Speaker 1: advocating that, but there are some signs that combination of
1:01:09
Speaker 1: molecules with the alcohol that helps the absorption could be
1:01:12
Speaker 1: way better, way better delivery vehicle than just eating a
1:01:17
Speaker 1: spoonful of rust powder, which is like brick dust.
1:01:20
Speaker 2: Right right right, Other than red wine, what are good
1:01:22
Speaker 2: sources of that of resartual?
1:01:25
Speaker 1: Very little is in the food supply. Unfortunately it's a
1:01:29
Speaker 1: little bit of nuts and of course grapes, but it's
1:01:32
Speaker 1: very hard to get the quantities besides in red.
1:01:35
Speaker 2: Wine and buying it in powder form. I mean, how
1:01:38
Speaker 2: much of that is just paying for expensive urine versus
1:01:42
Speaker 2: real impact.
1:01:43
Speaker 1: Well, so I don't really know that, but I do
1:01:49
Speaker 1: know that if you take it with fatty food, so
1:01:53
Speaker 1: I take it with yogurt or something that at least
1:01:55
Speaker 1: will help absorb it, that it's very helpful and part.
1:01:59
Speaker 2: Of the AD's with the absorption.
1:02:02
Speaker 1: Oh yeah, So We've saw levels in mice and humans
1:02:05
Speaker 1: that were five to tenfold higher with some fat included.
1:02:09
Speaker 1: And actually we had much better results in the mouse
1:02:11
Speaker 1: studies when we gave them resivitual in a fatty diet.
1:02:16
Speaker 2: And what is what is it about res viratral that
1:02:19
Speaker 2: makes it superior to say something like turmeric, which is
1:02:23
Speaker 2: also a powerful antioxidant. Are they qualitatively different or are
1:02:28
Speaker 2: they you know, can you switch these things out for
1:02:31
Speaker 2: each other?
1:02:32
Speaker 1: I don't know the answer to that. I've actually spent
1:02:35
Speaker 1: less time studying resivirtual the last decade because I'm more
1:02:38
Speaker 1: interested in some of these other thing well, and now
1:02:42
Speaker 1: we're beyond that as well. That's certainly exciting. It's heading
1:02:46
Speaker 1: in past the clinic hopefully trying to figure out what
1:02:51
Speaker 1: the scratches are in the cd IS is. That is
1:02:54
Speaker 1: a major focus of my lab right now. And so
1:02:57
Speaker 1: I think that what the future looks like is that
1:02:59
Speaker 1: we hopefully we'll be able to take some of these
1:03:02
Speaker 1: longevity stimulators, and a man is just one of them.
1:03:05
Speaker 1: Of course, there's synalytics, which story the zombie cells we've got,
1:03:10
Speaker 1: but we've got met foreman, which seems to be beneficial,
1:03:13
Speaker 1: So I don't want to, you know, basically annoy all
1:03:16
Speaker 1: my colleagues who have spent decades showing that their pathways
1:03:18
Speaker 1: are important too, but that these are mostly preventative. What
1:03:24
Speaker 1: really we want to do is get you out to
1:03:28
Speaker 1: ninety one hundred hundred and ten healthy. But eventually things
1:03:31
Speaker 1: will wear out, things will still decay even with these treatments.
1:03:34
Speaker 1: They're not that good even with healthy lifestyle. So the
1:03:38
Speaker 1: new work in my lab is what do you do
1:03:41
Speaker 1: when you need a new kidney, a new liver, or
1:03:44
Speaker 1: you lose your eye sight? Can we tell those organs
1:03:47
Speaker 1: to be young again? And literally make it young again?
1:03:50
Speaker 2: The difference between prevention and reversal, right, basically right?
1:03:55
Speaker 1: You know, it's interesting Rich that I think I was
1:03:58
Speaker 1: one of the first people, crazy people, to use the
1:04:01
Speaker 1: word age reversal in this field. It was a shame
1:04:05
Speaker 1: on you.
1:04:05
Speaker 2: It was not well received. I imagine it was.
1:04:07
Speaker 1: About five years ago. Now it's fairly common. It's funny.
1:04:10
Speaker 1: It takes a while, but you used to be able
1:04:13
Speaker 1: to say delaying aspects of aging, and that was the limit.
1:04:17
Speaker 1: But it's clear from work that we've published and work
1:04:20
Speaker 1: that we haven't yet published, but reversing aging is really
1:04:23
Speaker 1: easily doable. We do it all the time in my lab.
1:04:27
Speaker 1: I mean similar to, you know, once you know how
1:04:30
Speaker 1: something works, the answer is pretty simple. Best analogy is,
1:04:34
Speaker 1: you know, Joseph Lister said, hey, let's wash our hands
1:04:36
Speaker 1: before we cut off a person's leg or deliver a baby,
1:04:40
Speaker 1: and save millions of lives, probably right now, a billion lives,
1:04:45
Speaker 1: you know, for goodness sakes, we solve this with soap.
1:04:48
Speaker 1: The same with aging. Once you know how simple the
1:04:50
Speaker 1: process is, it's not that hard to fix.
1:04:53
Speaker 2: Well, we all are familiar with this concept of biological
1:04:59
Speaker 2: age versus you know, what's the other one, like experiential age,
1:05:05
Speaker 2: like you know, how we look and feel isn't necessarily
1:05:08
Speaker 2: wed to our date of birth. So on some level
1:05:13
Speaker 2: we have a fluid understanding or conceptualization of aging. Some
1:05:18
Speaker 2: people look older and comport themselves like an older person
1:05:23
Speaker 2: than somebody else who's exactly that same age. So clearly
1:05:26
Speaker 2: there's something happening here that goes beyond just pure genetic
1:05:31
Speaker 2: blueprint that we can influence through diet, lifestyle and some
1:05:35
Speaker 2: of these other factors that you're exploring now.
1:05:38
Speaker 1: Yeah, so less than Hulff, by some estimates, only twenty
1:05:42
Speaker 1: five percent is determined by your genetic makeup and the
1:05:45
Speaker 1: rest is how you live and your epigenome control, which
1:05:48
Speaker 1: is great, means we have much more control over our
1:05:50
Speaker 1: lives than we thought we did. And we see that
1:05:54
Speaker 1: now that the impact of diet is just incredible.
1:05:57
Speaker 2: What is the biggest thing that we have control over?
1:06:01
Speaker 2: What are the most important things?
1:06:02
Speaker 1: Sure? Well, if there was one thing that I could say,
1:06:06
Speaker 1: if there's one thing you could do, it would be
1:06:08
Speaker 1: eat less. That's the main thing. And I know you've
1:06:11
Speaker 1: had plenty of people.
1:06:12
Speaker 2: Right, We've had Valter Longo, who's you know, discussed this
1:06:16
Speaker 2: at length with his intermittent fasting and his fasting, mimicking
1:06:19
Speaker 2: diet and all of that, And I know this is
1:06:20
Speaker 2: something that you practice and are on board with as well.
1:06:23
Speaker 2: So what is going on with either calorie restriction or
1:06:28
Speaker 2: the way that we time our intake of food that
1:06:31
Speaker 2: has implications on aging or it's reversal.
1:06:35
Speaker 1: Yeah, So calorie restriction is the most robust way to
1:06:38
Speaker 1: prevent cancer, heart disease, or pretty much all diseases. It's
1:06:41
Speaker 1: been known for since nineteen sixteen and then a very
1:06:44
Speaker 1: classic study in the nineteen thirties by McCain colleagues. So
1:06:49
Speaker 1: we all agree that calor restriction or intimate and fasting
1:06:53
Speaker 1: these days works. The question is how. And what we've
1:06:57
Speaker 1: found is that some of the pathways that we study
1:07:00
Speaker 1: in the aging field, sertuins are a major part. M
1:07:04
Speaker 1: tour is the other which Volta has talked about on
1:07:07
Speaker 1: the show. These are pathways that respond particularly to how
1:07:10
Speaker 1: much we're eating, and if we eat a lot of food,
1:07:14
Speaker 1: they stop defending our body or telling proteins to defend us.
1:07:17
Speaker 1: And if we less, what happens is they get kicked
1:07:22
Speaker 1: into action and they do a whole range of things
1:07:24
Speaker 1: that protect us from disease and even can reverse aspects
1:07:27
Speaker 1: of eating. And so just to focus for a little
1:07:30
Speaker 1: bit on the sertuins because we're on that theme. When
1:07:34
Speaker 1: you are hungry, your NAD levels go up, and so
1:07:38
Speaker 1: now your situins are quite active and repairing the body,
1:07:42
Speaker 1: and they can make sure that the body doesn't lose
1:07:44
Speaker 1: its epigenomic stability, in other words, keep those scratches from
1:07:49
Speaker 1: accumulating over time. And the longer you do fasting over
1:07:53
Speaker 1: your lifetime, the slower those scratches will accumulate, and so
1:07:58
Speaker 1: we size as well. Raises nad levels, and your listeners
1:08:03
Speaker 1: might be wondering why would exercise and diet turn on
1:08:07
Speaker 1: these pathways in the first place. Well, what we think
1:08:10
Speaker 1: is going on is that in early life, in the
1:08:13
Speaker 1: primordial ponds, there were picture earlier Earth. There's Earth's covenant ocean,
1:08:18
Speaker 1: there's these islands, and there's little pools, and we think
1:08:21
Speaker 1: that's where life formed. This is the cutting edge science
1:08:23
Speaker 1: right now. In those pools are little strands of RNA
1:08:26
Speaker 1: that have come together from chemicals from meteorites. First cells
1:08:31
Speaker 1: are forming. Those first cells need to be able to
1:08:33
Speaker 1: control those genes on and off. So when do you
1:08:37
Speaker 1: want genes on and off? Well, responding to stress. So
1:08:41
Speaker 1: if there's a cosmic ray coming and hitting and smashing
1:08:45
Speaker 1: that genome of that little organism, it needs to have
1:08:49
Speaker 1: a system to defend itself, to hunger down, survive, and
1:08:53
Speaker 1: then repopulate that pond when all the other organisms have
1:08:56
Speaker 1: otherwise die off. It's extremely ancient genes that we have
1:09:01
Speaker 1: inherited from those forebears of ours. But now we can
1:09:04
Speaker 1: kick those survival genes into action by putting our bodies
1:09:07
Speaker 1: under a bit of stress hormesis or eating plants with
1:09:10
Speaker 1: those molecules that signal stress. We call that zeno hormesis zeno,
1:09:16
Speaker 1: meaning between species. And that is right now, with the
1:09:20
Speaker 1: exception of some clinical trial proof that exercise and dieting
1:09:25
Speaker 1: is really the best thing we can do for our bodies.
1:09:27
Speaker 2: Wow, is there when it comes to fasting? Is there
1:09:34
Speaker 2: any indication, like I'm trying to get a sense of
1:09:37
Speaker 2: can you do it too much? Are people who are
1:09:39
Speaker 2: doing these thirty day water fasts are they getting any
1:09:42
Speaker 2: additional benefit beyond somebody who's doing Vaulter's fasting mimicking diet
1:09:48
Speaker 2: which actually involves eating you know, meals throughout the day.
1:09:52
Speaker 2: Or do we still have a lot to learn here?
1:09:55
Speaker 1: Well, yeah, we always have a lot to learn, but
1:09:56
Speaker 1: we know a heck of a lot more than we
1:09:58
Speaker 1: did a few years ago. What we've found in mice
1:10:01
Speaker 1: as a field is that. And just a study that
1:10:04
Speaker 1: came out about a month ago from Raphael Dicabo's lab
1:10:07
Speaker 1: at NIH found that it's not so much what you eat,
1:10:10
Speaker 1: but when you eat that's so important for those animals
1:10:13
Speaker 1: and probably for us as well. That doesn't mean that
1:10:16
Speaker 1: we can just eat whatever we want and go hungry.
1:10:18
Speaker 1: I think it's a combination of the two things, and
1:10:20
Speaker 1: that's what I do with my own body as best
1:10:23
Speaker 1: I can. But primarily you need to be hungry a
1:10:26
Speaker 1: little bit, preferably every day, but at least a couple
1:10:30
Speaker 1: of days a week.
1:10:31
Speaker 2: I think that hunger creates that stress response that kickstus
1:10:36
Speaker 2: Sertoin's doing what you want.
1:10:37
Speaker 1: It does the body shop prepare people actually get your
1:10:41
Speaker 1: NAD levels up, and you can do that with being
1:10:45
Speaker 1: a little bit hungry. You can also do that by
1:10:48
Speaker 1: restricting the total amount of protein that you bring on board.
1:10:51
Speaker 1: So eating a lot of steak would be about the
1:10:54
Speaker 1: worst thing you could do. Never exposing your body to
1:10:58
Speaker 1: any changes in temperature probably another thing. Basically, everything that
1:11:02
Speaker 1: makes your body happy and sedentary and unstressed is bad
1:11:07
Speaker 1: for you. And the reason is that you're not engaging
1:11:10
Speaker 1: your survival circuits.
1:11:13
Speaker 2: And how does that square with studies that are coming
1:11:17
Speaker 2: out about sauna therapy or cold water therapy. I mean,
1:11:21
Speaker 2: these are other stressors, right that I'm sure are having
1:11:25
Speaker 2: cellular implications.
1:11:28
Speaker 1: Well, they are, but we don't know a lot. I'm
1:11:31
Speaker 1: unaware of any rigorous studies of cold therapy or even saunas,
1:11:36
Speaker 1: but we do know from anecdotal and historical records that
1:11:44
Speaker 1: even the Romans knew or thought they knew that heat
1:11:47
Speaker 1: and cold was good for you, and a lot of
1:11:50
Speaker 1: northern countries swear by it at least once a week.
1:11:53
Speaker 1: You want to go into that sauna and then jump
1:11:55
Speaker 1: into a cold pool. Now, I don't know if that works.
1:11:57
Speaker 1: I don't think anybody really know if it knows if
1:12:01
Speaker 1: it works. But what I can tell you is that
1:12:03
Speaker 1: it does fit with the hormesis idea that we studied
1:12:08
Speaker 1: yeast years ago. And what I found was that when
1:12:11
Speaker 1: you raise the temperature of a y cell, it will
1:12:15
Speaker 1: turn on the sortun pathway, it'll make mon ad give
1:12:18
Speaker 1: it a bit of what we call a heat shock.
1:12:20
Speaker 1: We do know that if we cool our bodies down
1:12:23
Speaker 1: we shiver a little bit, it will build brown fat,
1:12:26
Speaker 1: which has a lot of health giving properties as well
1:12:29
Speaker 1: boost those mitochondria, which is always a good thing. So
1:12:33
Speaker 1: that fits with the science. So that's why, besides the
1:12:35
Speaker 1: fact that it feels really good and invigorating, I think
1:12:37
Speaker 1: it's also going to turn out to be healthy as well.
1:12:40
Speaker 2: Yeah, I think there are some studies that are happening
1:12:42
Speaker 2: around sauna on vascular health and things like that. I'm
1:12:46
Speaker 2: not steeped in it, but I know there's certain things
1:12:49
Speaker 2: that are.
1:12:49
Speaker 1: Yeah, there are some studies. I agree with you. There's one.
1:12:53
Speaker 1: I think it was a few thousand finish businessmen who
1:12:55
Speaker 1: regularly takes on as and they had protection against heart disease.
1:12:58
Speaker 1: Apparently it's early days, but rich you asked me earlier
1:13:02
Speaker 1: and I haven't addressed yet what's too much? And I
1:13:05
Speaker 1: definitely think you can do too much of anything. And
1:13:09
Speaker 1: we call you know in homesis there's this U shaped
1:13:11
Speaker 1: curve inverted you so that you just have to find
1:13:14
Speaker 1: the optimal. And that's really tricky, not only because it's
1:13:19
Speaker 1: hard to know if you're overdoing it. We don't know
1:13:21
Speaker 1: what those parameters are. We barely know what the biomarkers
1:13:24
Speaker 1: are if you were to measure them in your blood,
1:13:26
Speaker 1: but also because it's different for everybody, that your optimum
1:13:31
Speaker 1: might be different from my optimum, and it's certainly different
1:13:36
Speaker 1: for men and women and people have different ages. So'
1:13:38
Speaker 1: alta Longo mentioned that you might want to restrict your
1:13:40
Speaker 1: protein when you're young, but when you're older that come
1:13:43
Speaker 1: back to bite you. So there's a lot of variables
1:13:46
Speaker 1: here and it's extremely difficult for us to test one
1:13:50
Speaker 1: human group, let alone all of the different variables.
1:13:53
Speaker 2: Well, the way I do it is I just overdo everything.
1:14:00
Speaker 1: All as they may, right, So that makes plan yeah right,
1:14:04
Speaker 1: this is the Zuckerberg way. It's fail fast. Sure, but
1:14:08
Speaker 1: you know, I really think that that overdoing it on
1:14:10
Speaker 1: your physical body, So running over doing it with running,
1:14:15
Speaker 1: for example, playing some very high impact sports. We just
1:14:19
Speaker 1: know already that those are people who tend to have
1:14:23
Speaker 1: to have their joints replaced in their fifties.
1:14:26
Speaker 2: My joints are pretty good right now, but yeah, back's
1:14:29
Speaker 2: a little creaky, you know, ankles are a little stiff
1:14:32
Speaker 2: when I wake up in the morning. You know, it's
1:14:34
Speaker 2: like going out and crushing it and putting in giant
1:14:37
Speaker 2: miles all the time. I mean, you know, this is
1:14:39
Speaker 2: not a recipe for you know, maximum longevity. I'm aware
1:14:43
Speaker 2: of that, but it also makes me feel great, like
1:14:46
Speaker 2: I you know, there's countervailent, counterbalancing, you know, aspects to
1:14:50
Speaker 2: all of these.
1:14:51
Speaker 1: Do you measure your biomarkers? Do you know what it's doing?
1:14:55
Speaker 2: Probably not as precisely as as you would. I've had
1:14:58
Speaker 2: blood work done and my blood work is fine. In fact,
1:15:02
Speaker 2: I'm getting it done again quite soon. But it's been good.
1:15:07
Speaker 2: I tend to get a dreanal fatigue. That's like the
1:15:09
Speaker 2: main thing that I have to worry about, because it's
1:15:12
Speaker 2: just a work hard, play hard person in general.
1:15:14
Speaker 1: Yeah, well, if you over do it, you can also
1:15:16
Speaker 1: be susceptible to infections getting holds pretty badly.
1:15:19
Speaker 2: I never get sick. I don't have that problem.
1:15:22
Speaker 1: That's a great sign. One thing that's in common with
1:15:25
Speaker 1: all of the people that live a long time into
1:15:27
Speaker 1: the hundreds is that they say when I was younger,
1:15:30
Speaker 1: throughout most of my life, I never got sick.
1:15:33
Speaker 2: All right, Well, I got that going for me. But
1:15:35
Speaker 2: I will tell you this. My grandfather died of a
1:15:40
Speaker 2: heart attack at age fifty four and fifty two, and
1:15:43
Speaker 2: I've been plant based for fifteen years and an athlete
1:15:46
Speaker 2: and all of this sort of thing. But it started
1:15:49
Speaker 2: to really occupy a lot of mental space because I
1:15:53
Speaker 2: very much share his genetic blueprint, and you know, we
1:15:56
Speaker 2: look alike, We've made similar decisions in our lives, We've
1:15:59
Speaker 2: lived our lives very similarly. And it definitely has me,
1:16:04
Speaker 2: you know, a little more freaked out than maybe it
1:16:06
Speaker 2: should because of that genetic predisposition, the heart disease that
1:16:12
Speaker 2: runs in my family, and things to countervail, you know,
1:16:17
Speaker 2: to live my life in contradiction to that. I know
1:16:20
Speaker 2: it's it's sort of looming there, and so what should
1:16:25
Speaker 2: I be doing?
1:16:26
Speaker 1: Well, do you know what genome you have? I should
1:16:29
Speaker 1: have that test that I have. You haven't tested your genome.
1:16:32
Speaker 1: So we have to hook you up with one of
1:16:34
Speaker 1: my good friends at Stanford. You're at Stanford's. I know that.
1:16:36
Speaker 1: So it's a apropos that you go see my good
1:16:39
Speaker 1: friend Carlos Bustamante, who's the dean of ys out there.
1:16:44
Speaker 1: He's the guy. He's done some pretty important genomes historical
1:16:48
Speaker 1: So Kennewick man that kind of thing, right, He will
1:16:51
Speaker 1: help you interpret your genome. You can have it done
1:16:55
Speaker 1: at some of the commercial places if you want. That's
1:16:58
Speaker 1: what most people do. It's pretty informative. I found it's
1:17:02
Speaker 1: not just for fun. I found that I carry some
1:17:05
Speaker 1: pretty bad genes and I'm modifying my life based on those.
1:17:10
Speaker 1: And actually, to bring it home, my wife has predisposition
1:17:14
Speaker 1: based on her genome for ulcer of colidis, and she
1:17:18
Speaker 1: actually ended up quitting her job and doing what she
1:17:21
Speaker 1: always wanted to do because she figured that she was
1:17:24
Speaker 1: going to have a shorter health span than most people.
1:17:27
Speaker 1: And she's modified her life and her diet and so far,
1:17:29
Speaker 1: so good. She's I wouldn't say how old she is,
1:17:33
Speaker 1: that wouldn't be polite, but at the same age that
1:17:36
Speaker 1: she is now, her mother was suffering from a malster
1:17:39
Speaker 1: of colidis and now has no bowel and it's not
1:17:41
Speaker 1: very great for her. So I think that the genome
1:17:45
Speaker 1: is important to know. I know some people say that
1:17:47
Speaker 1: I just don't want to know.
1:17:49
Speaker 2: There's definitely part of me that because there's a that
1:17:53
Speaker 2: sets in motion a series of decisions that you make
1:17:55
Speaker 2: about your life based upon something that may or may
1:17:59
Speaker 2: not come to pay So I definitely have concerns about that.
1:18:04
Speaker 1: Well, let me tell you a story about myself. I
1:18:08
Speaker 1: had my genome done. I did it at twenty three
1:18:10
Speaker 1: and meter and then I had it done full genome,
1:18:13
Speaker 1: and I found out that I carried susceptibility gene to
1:18:17
Speaker 1: emphysema CRPD, and that my lungs are not very good
1:18:20
Speaker 1: at clearing out toxins from smoking. Now I've never smoked.
1:18:24
Speaker 1: I'm a militant against smoking, in part because my mother
1:18:29
Speaker 1: died from smoking. And guess which parent I inherited that
1:18:32
Speaker 1: gene mutation from.
1:18:34
Speaker 2: From your mother?
1:18:34
Speaker 1: It was my poor mother. If my mother had the
1:18:37
Speaker 1: information that she had after her lung was removed and
1:18:40
Speaker 1: eventually died from, she probably would have quit smoking earlier
1:18:45
Speaker 1: rather than waiting until she had one lung. So you
1:18:47
Speaker 1: can really be empowered by this information, and I try
1:18:49
Speaker 1: to avoid dust. I try to avoid second ant smoke
1:18:52
Speaker 1: for that reason.
1:18:54
Speaker 2: Going back to something you said earlier, you said it's
1:18:57
Speaker 2: important to keep your men acid your protein intake low.
1:19:03
Speaker 2: So explain why that's important.
1:19:07
Speaker 1: Well, it comes down to an enzyme complex called m
1:19:12
Speaker 1: tor and it's called target of rappermisin, so rappermcin is
1:19:17
Speaker 1: a It all started back on Easter Island. We had Segal,
1:19:23
Speaker 1: which is he was a scientist who went to Easter
1:19:26
Speaker 1: Island or Rappannui, which is why it's called rapper mice.
1:19:29
Speaker 1: And he found bacteria that had this peculiar molecule called rappermisin,
1:19:34
Speaker 1: and his lab was at Columbia University, and eventually he
1:19:38
Speaker 1: ran out of money and he was told just throw
1:19:40
Speaker 1: away all your stuff in your freezers, and he decided
1:19:43
Speaker 1: not to, and thank goodness he didn't, because in his
1:19:46
Speaker 1: freezer was the organism that gave rise to this rappermcin molecule,
1:19:51
Speaker 1: which is now used to treat a whole variety of ailments,
1:19:55
Speaker 1: mostly immune disorders, but possibly even aging. And the reason
1:19:59
Speaker 1: that or excited about wrappermcin or at least molecules like
1:20:02
Speaker 1: rappermisin to treat aging is that if you disable m
1:20:07
Speaker 1: tour or you give rappimcin, which is essentially the same effect,
1:20:11
Speaker 1: what you do is you trick the body into thinking
1:20:14
Speaker 1: that it's got a deficiency in amino acids. So mtur
1:20:18
Speaker 1: has been around very long time, similar to sirtuins, but
1:20:21
Speaker 1: its job is to sense how much meat or the
1:20:24
Speaker 1: amino acids of protein is coming into the cell and
1:20:28
Speaker 1: the body. So if you eat a lot of meat,
1:20:31
Speaker 1: what you're doing is you're telling the m tor system
1:20:34
Speaker 1: times are great, lots of protein, don't worry, go reproduce, grow,
1:20:40
Speaker 1: build new tissue. But at the expense of hunkering down
1:20:44
Speaker 1: and repairing things. And so if you're always eating meat
1:20:48
Speaker 1: and always eating a lot and a lot of protein,
1:20:50
Speaker 1: your m tore system won't bother to defend you because
1:20:53
Speaker 1: it will always be on and the on for MTUR
1:20:57
Speaker 1: is actually the anti longevity. It's the growth and reproduction
1:21:01
Speaker 1: path versus the hunker down survive mode.
1:21:05
Speaker 2: Right. So longevity dictates that you want to be doing
1:21:09
Speaker 2: what's necessary to signal your body to enter into that
1:21:13
Speaker 2: reparative mode, right, And that's at odds with when you're
1:21:19
Speaker 2: younger you want performance gains. If you're an athlete, you
1:21:22
Speaker 2: want to build you know, big muscles and all of
1:21:24
Speaker 2: these things that that's all fine, but you can't have both.
1:21:30
Speaker 1: It's very hard, I would say. And people who are
1:21:35
Speaker 1: who grow fast a have to be extra cautious because
1:21:40
Speaker 1: their bodies, especially when they're young, are spending more of
1:21:44
Speaker 1: their energy on growing than hunkering down. And this is
1:21:50
Speaker 1: just a fact, but it's probably depressing to some people that,
1:21:54
Speaker 1: at least in dogs, and it looks also like in
1:21:57
Speaker 1: humans that if you've got a highly active growth system
1:22:00
Speaker 1: a lot of growth hormone, it will work against you
1:22:04
Speaker 1: later in life.
1:22:05
Speaker 2: Yeah.
1:22:05
Speaker 1: Yeah, but you know, again, a lot of it's in
1:22:07
Speaker 1: the control of our environment. If you're if you're a
1:22:11
Speaker 1: told person, I'm not, but if you're super tall, I
1:22:13
Speaker 1: think it's even more important to make sure that you're
1:22:17
Speaker 1: what you eat and how you fast and how you
1:22:20
Speaker 1: exercise is optimal if you want to live the maximum
1:22:22
Speaker 1: potential lifespan.
1:22:24
Speaker 2: I have a lot of friends who get testosterone therapy
1:22:29
Speaker 2: and can get you know, HGH and all of these
1:22:32
Speaker 2: sort of things, and the ideas it's boosting their you know,
1:22:37
Speaker 2: virility and their energy levels and all of that. But
1:22:40
Speaker 2: I can't help but wonder what the implications are on
1:22:43
Speaker 2: their long term wellness and well being and longevity. Like
1:22:47
Speaker 2: there's a there's an evolutionary rationale why these things decline
1:22:52
Speaker 2: over age, Right.
1:22:54
Speaker 1: Well, you could say the same about an ad that
1:22:57
Speaker 1: it declines and it's not good to boost it. So
1:22:59
Speaker 1: I think think that that's dangerous to use that argument
1:23:03
Speaker 1: that just because something goes down, it it's meant to.
1:23:07
Speaker 1: But there have been millions of dollars poured into clinical
1:23:10
Speaker 1: studies with tusoscerone with no benefit to health span and
1:23:15
Speaker 1: I believe lifespan as well, And so in our field
1:23:18
Speaker 1: we actually regard those studies as somewhat of a failure
1:23:22
Speaker 1: to deliver it. And so I think that the evidence
1:23:25
Speaker 1: is there that it will give you testosterone probably gives
1:23:28
Speaker 1: you great benefits if you're exercising you can build up
1:23:30
Speaker 1: more muscle, you're more quote unquote virile. But in the
1:23:34
Speaker 1: long run, it doesn't help you and probably hurts.
1:23:38
Speaker 2: You because it's signaling your body that it doesn't need
1:23:42
Speaker 2: to produce it on its own, or because it's stimulating
1:23:46
Speaker 2: growth in areas that you don't want growth.
1:23:50
Speaker 1: That would be my explanation. I don't know for sure,
1:23:52
Speaker 1: but I think just telling the body grow, build muscle
1:23:55
Speaker 1: all the time is basically sending the wrong message for
1:23:58
Speaker 1: a long lifespan.
1:24:01
Speaker 2: What about exercise. What's happening when we exercise and how
1:24:05
Speaker 2: is that impacting aging longevity?
1:24:10
Speaker 1: Well, first of all, let me tell you what exercise isn't.
1:24:14
Speaker 1: It's not just making your blood floor around your pipes
1:24:16
Speaker 1: and cleaning them out. That's what I was led to
1:24:19
Speaker 1: believe in the nineteen seventies. What's actually gons on majorly
1:24:23
Speaker 1: is two things. One is it's activating these longevity pathways
1:24:27
Speaker 1: in your bloodstream, and I've mentioned earlier that the sratoons
1:24:31
Speaker 1: are a major part of that. But it's also having
1:24:36
Speaker 1: highly anti inflammatory effects and it's able to change the
1:24:42
Speaker 1: way our bodies actually respond to the environment. Exercise is
1:24:52
Speaker 1: treatment for the body that actually puts the entire system
1:24:56
Speaker 1: in a state of defense, and so it's less about
1:25:00
Speaker 1: about getting the blood to flow and more about getting
1:25:03
Speaker 1: your tissues to act younger. And that's really the huge
1:25:07
Speaker 1: benefit you get from exercise.
1:25:09
Speaker 2: So why can't we diet and exercise ourselves into immortality.
1:25:16
Speaker 1: Yeah, that's a good question, because I think that these
1:25:20
Speaker 1: defense pathways are not perfect. They don't know how to
1:25:25
Speaker 1: fully reverse the scratches, polish off the scratches on the CD.
1:25:30
Speaker 1: Sure they can slow them down, but as we lose
1:25:33
Speaker 1: our epigenetic information, our ability to read the right genes
1:25:37
Speaker 1: at the right time, that's beyond the expectations of the
1:25:42
Speaker 1: cratoons and mTOR. We need something more potent to really
1:25:46
Speaker 1: reset the body's clock. Now, the body's clock, we actually
1:25:49
Speaker 1: understand a lot more about that. Now we can read
1:25:52
Speaker 1: that clock in our blood and in our tissues, and
1:25:55
Speaker 1: it's at the level of the genome and the changes
1:25:58
Speaker 1: to the genome. We've been working on ways to actually reset,
1:26:02
Speaker 1: literally reset that clock, and that would be the way
1:26:06
Speaker 1: to not just live an extra five or ten years
1:26:09
Speaker 1: in a healthy way, but potentially take a ninety hundred
1:26:13
Speaker 1: year old and make them feel decades younger. Pretty quickly.
1:26:17
Speaker 2: Wow, So what are the big questions that you're wrestling
1:26:21
Speaker 2: with right now that you're trying to get answered, and
1:26:25
Speaker 2: what would be the studies that you would like to
1:26:28
Speaker 2: see conducted, the research you know in your perfect world
1:26:32
Speaker 2: that would help you make the breakthroughs that you know you're.
1:26:36
Speaker 1: Attempting to make in this well the hot area now
1:26:43
Speaker 1: as the NAD boosters move into drug development and so
1:26:46
Speaker 1: that's that's on its way. What's coming down the line
1:26:49
Speaker 1: that isn't well known is called cellular reprogramming. This is
1:26:55
Speaker 1: truly resetting that epigenome. It is it's essentially telling the
1:27:01
Speaker 1: cell can you go and find the information that once
1:27:05
Speaker 1: existed when you were young and ignore all the other
1:27:09
Speaker 1: information that's accumulated over time. We call this epigenetic noise
1:27:14
Speaker 1: in my lab. It's a term that we've had to
1:27:16
Speaker 1: coin because we've run out of vocabulary. So epigenetic noise,
1:27:21
Speaker 1: as I mentioned, is caused by mostly DNA breaks and
1:27:23
Speaker 1: other things that occur to us. But how do you
1:27:26
Speaker 1: say to the cell your DNA should be wrapped up
1:27:29
Speaker 1: in that those histone proteins this way and just to
1:27:34
Speaker 1: ignore all those other changes that have occurred. So we
1:27:36
Speaker 1: think we've found a way, at least early days. I
1:27:42
Speaker 1: don't know if you and your listeners are familiar with
1:27:45
Speaker 1: the fluripotent stem cell technology where you can take a
1:27:47
Speaker 1: skin cell and turn it into a stem cell.
1:27:51
Speaker 2: Now, explain that.
1:27:53
Speaker 1: Yeah, So there's a famous scientist called Chinya Yamanaka, and
1:27:58
Speaker 1: he won the Nobel Prize nineteen sorry, twenty twelve, and
1:28:02
Speaker 1: what he found was that by turning on four genes
1:28:06
Speaker 1: in cells, and they can be hair cells, skin cells,
1:28:10
Speaker 1: liver cells, he can take an adult cell and make
1:28:12
Speaker 1: it super young again, so that it now is what
1:28:16
Speaker 1: we call a pluriprot and stem cell. We call them
1:28:19
Speaker 1: ips for short. Those can be made into any other
1:28:22
Speaker 1: cell type, such as an egg or a liver cell.
1:28:28
Speaker 2: WHOA, So you could literally take any human cell, pull
1:28:32
Speaker 2: a strand of hair track to cell, activate those four
1:28:36
Speaker 2: genes and end up with this stem cell.
1:28:39
Speaker 1: Well, not only can you, we all do it now.
1:28:43
Speaker 1: It's commonplace. Every graduate student typically works on this stuff,
1:28:48
Speaker 1: so it's commonplace. But the trick is how do you
1:28:52
Speaker 1: use that technology for human health? And we're just learning
1:28:55
Speaker 1: how to do that now. But what's crazy is so
1:28:57
Speaker 1: I could take your skin cell and I could make
1:29:00
Speaker 1: a sperm out of it, I could make an egg
1:29:02
Speaker 1: out of it, and I could make a new U
1:29:04
Speaker 1: that way. It's crazy stuff, but that's crazy what's doable.
1:29:07
Speaker 1: But getting back to aging, what does that mean. Well,
1:29:10
Speaker 1: what we decided to do, with some other colleagues who
1:29:13
Speaker 1: are also in this field, is about four of us
1:29:17
Speaker 1: turn on those yamen archifactors as we call them, those
1:29:19
Speaker 1: reset genes, not in a cell in the dish, but
1:29:23
Speaker 1: in an animal and maybe one day a human, because
1:29:27
Speaker 1: maybe we could use them to partially reset the age
1:29:30
Speaker 1: of a cell. We don't want to go all the
1:29:32
Speaker 1: way back to beginnings. We don't want to turn us
1:29:34
Speaker 1: into all into a stem cell. That would be the
1:29:37
Speaker 1: end of us, would be a giantterotoma or a giant
1:29:39
Speaker 1: cancer tumor. But if we could just do a little bit,
1:29:43
Speaker 1: just pulse the body so that it goes back to
1:29:46
Speaker 1: its earlier age, that would be the big bank that
1:29:51
Speaker 1: in biology.
1:29:52
Speaker 2: That's just straight up out of a science fiction movie.
1:29:56
Speaker 1: Well that's what a lot of us.
1:29:57
Speaker 2: Your face is lit up like a Christmas tree, though,
1:30:00
Speaker 2: like this is definitely what gets you excited.
1:30:03
Speaker 1: Well, it does, and it did sound like science fiction
1:30:06
Speaker 1: and That's why it took me a couple of years
1:30:08
Speaker 1: to convince my students to work on it, because they
1:30:10
Speaker 1: thought it was crazy and it would be impossible. But
1:30:14
Speaker 1: then there was a study that came out from the
1:30:16
Speaker 1: Sulk Institute down in San Diego, from one Colos Belmonte's lab,
1:30:21
Speaker 1: and he did that crazy experiment before we had a
1:30:23
Speaker 1: chance to do it. He gets full credit. What he
1:30:27
Speaker 1: did was he made a mouse that he could turn
1:30:30
Speaker 1: on these four yamenaca jenes in the animal once it
1:30:33
Speaker 1: was an adult, and ask what happens. And what happened
1:30:36
Speaker 1: was after two days, the mice died. Okay, that's not
1:30:40
Speaker 1: going to win you a Nobel prize.
1:30:42
Speaker 2: That's that's not a good start.
1:30:44
Speaker 1: That's a bad day for the mouse especially. But what
1:30:47
Speaker 1: he figured out was that if he switched the system
1:30:49
Speaker 1: off on that second day, the mice were fine. Well,
1:30:54
Speaker 1: they recovered, but they ended up being much healthier. And
1:30:57
Speaker 1: he did this in a what we call a pro
1:30:59
Speaker 1: jeroid mouse, but that just means a mouse that ages rapidly.
1:31:02
Speaker 1: It's the same essential mouse that you can find those
1:31:07
Speaker 1: young patients who age prematurely, the poor kids that get
1:31:11
Speaker 1: old when they're thirteen there's a mouse that is a
1:31:14
Speaker 1: model for that disease. So the Belmonte lab they turn
1:31:17
Speaker 1: on these jeens every two days out of a week,
1:31:20
Speaker 1: and then no, it's every two days, and then they
1:31:23
Speaker 1: wait another two days and they turn them on again.
1:31:26
Speaker 1: Those mice lived thirty to forty percent longer.
1:31:29
Speaker 2: Wow. So it's sort of like they're getting pulsed with it, right.
1:31:33
Speaker 1: So the argument if you want to criticize the work,
1:31:35
Speaker 1: and a lot of people have, is that they're just
1:31:38
Speaker 1: making mouse the mice sick and its form of hormesis.
1:31:42
Speaker 1: But I didn't think that was true because we've been
1:31:44
Speaker 1: working on this reset button for ages and we thought
1:31:48
Speaker 1: that was probably the secret. And one of the things
1:31:51
Speaker 1: we did was we had tried a whole bunch of
1:31:55
Speaker 1: genes for resetting and they didn't work. But now we
1:31:58
Speaker 1: saw that those yemen Archie factors could be important. And
1:32:00
Speaker 1: so what we did was we first of all, we
1:32:02
Speaker 1: wanted to figure out why are they toxic? Why is
1:32:04
Speaker 1: it hurting the animals, And so we left off one
1:32:07
Speaker 1: of the genes that was really toxic. It's called NICK,
1:32:11
Speaker 1: and NICK is already known to be a cancer causing genes,
1:32:14
Speaker 1: So that wasn't didn't take a genius. But when we
1:32:16
Speaker 1: put in three out of those four genes, it turns
1:32:19
Speaker 1: out that the mice are perfectly fine. They don't get sick.
1:32:22
Speaker 1: We've now put it into mice and they're perfectly fine.
1:32:26
Speaker 1: But what we're seeing is evidence of regeneration and age
1:32:29
Speaker 1: reversal in those old mice.
1:32:33
Speaker 2: And because you're seeing it in mice, you know, what
1:32:38
Speaker 2: does that mean in terms of human health? Like? Is
1:32:41
Speaker 2: this I mean, I granted it's not a one to
1:32:43
Speaker 2: one ratio. Because you see a thirty to forty percent
1:32:46
Speaker 2: increase in lifespan in a mouse doesn't mean that's going
1:32:49
Speaker 2: to work in humans. Like what are the similarities and
1:32:51
Speaker 2: differences when we move, you know, up the food chain
1:32:55
Speaker 2: to more complex organisms? Yeah?
1:32:57
Speaker 1: Right, so that it's fair to say that we've cured
1:33:00
Speaker 1: cancer in mice a thousand times over. It's a lot
1:33:03
Speaker 1: easier to do things in mice. For some reason, extending
1:33:06
Speaker 1: lifespan and mice may be much easier because they only
1:33:08
Speaker 1: live a few years or as we live eighty on average.
1:33:12
Speaker 1: But these fundamental mechanisms that I'm describing today are found
1:33:17
Speaker 1: in everything from a ye cell to a plant. Many animals,
1:33:21
Speaker 1: mice of course, and us. So these aren't just some
1:33:25
Speaker 1: esoteric pathway. These are fundamental mechanisms of living things. So
1:33:29
Speaker 1: as my philosophy is that as long as we don't
1:33:32
Speaker 1: do any harm, there's a very good chance that what
1:33:34
Speaker 1: we can do in a ye cell, a worm and
1:33:36
Speaker 1: a mouse will also work in a human because a
1:33:39
Speaker 1: yeas to a mouse is ninety nine point nine percent
1:33:41
Speaker 1: of the way there. It's just that little bit of
1:33:43
Speaker 1: extra difference. But if you ask a ye cell, we're
1:33:47
Speaker 1: basically a giant mouse.
1:33:50
Speaker 2: Wow. So in your lifetime, our lifetime, I guess we
1:33:54
Speaker 2: should say, I don't know what lifetime means given the
1:33:57
Speaker 2: work that you're doing. Lifetime doesn't mean what it would
1:34:00
Speaker 2: normally mean, I suppose, but rationally or realistically or reasonably,
1:34:05
Speaker 2: you know, given your aspirations, where do you think you
1:34:09
Speaker 2: will see all of this in you know, forty to
1:34:13
Speaker 2: fifty years from now, like during our typical lifespan?
1:34:17
Speaker 1: Yeah, what's a typical lifespan? It's hard to see where
1:34:20
Speaker 1: the world's going by looking backwards. In nineteen oh two,
1:34:26
Speaker 1: would we have predicted that we'd be flying dumbo jets
1:34:28
Speaker 1: and flying to the moon. I don't think going to
1:34:31
Speaker 1: the moon.
1:34:31
Speaker 2: We're pretty terrible at predicting.
1:34:33
Speaker 1: We're really badger, right, So Arthur C. Clark said it's
1:34:37
Speaker 1: a very dangerous profession that he was into predicting the future.
1:34:41
Speaker 1: But I'm happy to do it. There's nothing no harm
1:34:43
Speaker 1: in trying to see what the future looks like. And
1:34:45
Speaker 1: I have a front row seat, so you know, I'm
1:34:48
Speaker 1: partially qualified to make these guesses. So what I see
1:34:52
Speaker 1: for the future is first of all, that there are
1:34:54
Speaker 1: two futures. One is, if no aging research is successful,
1:34:57
Speaker 1: what does the world look like? And that's a well,
1:35:00
Speaker 1: it's still pretty good, but it's not great. Pretty good
1:35:03
Speaker 1: in the sense that the trajectory is that are child
1:35:05
Speaker 1: born today in the US will expect to live tow
1:35:09
Speaker 1: one hundred and four. Remember that this child is going
1:35:13
Speaker 1: to see the twenty second century. What great things will
1:35:16
Speaker 1: be available for them? Who knows. But even if so,
1:35:21
Speaker 1: even if we don't do anything, we're going to have
1:35:23
Speaker 1: longer lifespans. By the way, in Japan it's one hundred
1:35:26
Speaker 1: and seven, so it's not crazy to say that people
1:35:29
Speaker 1: will be living into their hundreds.
1:35:30
Speaker 2: Even given the exploding obesity epidemic and the increasing rates
1:35:36
Speaker 2: of heart disease and type two diabetes and all of
1:35:39
Speaker 2: these chronic lifestyle ailments that are being driven by our
1:35:43
Speaker 2: habits and our diets.
1:35:46
Speaker 1: Yeah, that's a real problem. In fact, by twenty fifty,
1:35:49
Speaker 1: half the world will be obese, can you believe? Right,
1:35:52
Speaker 1: So that's actually one of the developments that I'm working
1:35:56
Speaker 1: on developing drugs. One of the companies that I'm helping
1:35:59
Speaker 1: is working on an anti obesity drug that I'm hopeful
1:36:04
Speaker 1: will be of a large impact. But yeah, it's I
1:36:07
Speaker 1: got a drug for that. What's that?
1:36:09
Speaker 2: Move your body and change your diet? Dude?
1:36:12
Speaker 1: Yeah?
1:36:13
Speaker 2: Right. I don't mean to be insensitive to this epidemic,
1:36:19
Speaker 2: but I think there's a lot of people that just
1:36:21
Speaker 2: struggle with adopting healthy lifestyle habits.
1:36:25
Speaker 1: Correct, But even with the obesity epidemic, which is slowing
1:36:28
Speaker 1: our progress, that line extrapolates to one hundred and four.
1:36:32
Speaker 1: Now there, these are just numbers, right, These are extrapolations.
1:36:35
Speaker 1: But I think if we're successful with the mTOR inhibitors,
1:36:40
Speaker 1: the Rappa mice and analogs with met forman, if it's
1:36:43
Speaker 1: able to be widely distributed, not yet, but hopefully one day,
1:36:46
Speaker 1: if it's safe enough and what I'm working on, and
1:36:49
Speaker 1: other things that we could expect to live decades longer.
1:36:54
Speaker 1: So in the future, in fifty years from now, the
1:36:57
Speaker 1: technologies could be remarkable.
1:36:59
Speaker 2: So think of this.
1:37:02
Speaker 1: I'm pretty optimistic, but the rate of change in technology
1:37:06
Speaker 1: still makes my head spin. This reprogramming stuff, we've only
1:37:09
Speaker 1: been getting results since May of last year, and we're
1:37:13
Speaker 1: making advances in leaps and bounds. We've now reversed the
1:37:17
Speaker 1: loss of eyesight in old mice and other defects, and
1:37:22
Speaker 1: that's just the eye. If this reprogramming really works and
1:37:25
Speaker 1: it's safe, then all bets are off. Then we could
1:37:28
Speaker 1: turn back the clock by decades. It's looking like now
1:37:32
Speaker 1: it's really early, and I don't want to get everyone
1:37:35
Speaker 1: upset that, you know, I'm over speculating. The caveat is
1:37:38
Speaker 1: that it's early. But if you'd asked me three years
1:37:41
Speaker 1: ago what's the biggest breakthrough, I would have said caloric
1:37:46
Speaker 1: restriction mimetics and exercise mamtics. But this true resetting of
1:37:51
Speaker 1: the clock is something very different. It's a lot more
1:37:53
Speaker 1: powerful and potentially potentially dangerous. But there is that glimmer
1:37:57
Speaker 1: that we've finally figured out why we age and how
1:37:59
Speaker 1: to teneback, and.
1:38:01
Speaker 2: That resetting the clock really resets. It's not just lifespan,
1:38:07
Speaker 2: it's health span, right, It's not just living to one
1:38:11
Speaker 2: hundred and four, it's being vital in those later years.
1:38:14
Speaker 2: Like most people really don't want to be ninety eight
1:38:19
Speaker 2: years old and completely feeble and dependent upon people around
1:38:23
Speaker 2: them just to go to the bathroom and get dressed.
1:38:27
Speaker 1: Right. Well, most people, myself included, look at what life's
1:38:30
Speaker 1: like of a late ninety year old and you know,
1:38:33
Speaker 1: I think, God forbid, I don't want to be that age.
1:38:37
Speaker 1: And it's fair enough. But what we have to remember
1:38:40
Speaker 1: is that we're going to extend the healthy period of
1:38:43
Speaker 1: life so that when you're in your seventies, eighties, nineties,
1:38:46
Speaker 1: you don't have to worry so much about getting cancer
1:38:49
Speaker 1: and heart disease and dementia, which is a huge growing problem.
1:38:53
Speaker 1: And we hope to compress the last period of life
1:38:56
Speaker 1: when you are sick, the period of morbidity as we
1:38:58
Speaker 1: call it. And that's true in the animal studies that
1:39:02
Speaker 1: there's this what's called the Gompertz Maker mortality curve that
1:39:05
Speaker 1: we draw as scientists, and it's a curve that shows
1:39:09
Speaker 1: that for most of the time people are alive and healthy,
1:39:11
Speaker 1: and then you get this exponential drop off of people.
1:39:15
Speaker 1: And that's true for worms and yeast as well, and
1:39:18
Speaker 1: that happens really quickly. But there's this tale. Now. What
1:39:21
Speaker 1: we're trying to do is push that curve out as
1:39:24
Speaker 1: far as we can so that hopefully everybody one day
1:39:27
Speaker 1: gets to live to one hundred or whatever we choose,
1:39:29
Speaker 1: one hundred and thirty and then that period is maybe
1:39:32
Speaker 1: a week of being sick and then you die quickly
1:39:35
Speaker 1: or actually you have the choice to terminate your own
1:39:37
Speaker 1: life when you're done with it.
1:39:40
Speaker 2: It's super interesting. I mean, we've seen over the years
1:39:43
Speaker 2: as science has progressed, increases in lifespan, you know, we
1:39:49
Speaker 2: die forty and fifty and sixty. But as you mentioned,
1:39:53
Speaker 2: you know, in the introduction of your book, we haven't
1:39:55
Speaker 2: seen the ceiling change that much. You know, the oldest
1:40:00
Speaker 2: recorded person is something like one hundred and twenty two,
1:40:02
Speaker 2: and it's very unusual for anyone to live past one
1:40:05
Speaker 2: hundred and ten. That was true way back in the day,
1:40:07
Speaker 2: and it's still true today, even though we're living later.
1:40:12
Speaker 2: We're not busting through that glass ceiling on what's possible.
1:40:17
Speaker 2: Well exactly until now until but with the work that
1:40:20
Speaker 2: you're doing.
1:40:21
Speaker 1: Well, I think that's the point Richard, you're right about
1:40:23
Speaker 1: that is that if you look at the history of humanity,
1:40:26
Speaker 1: it's not a guide to the future. Again, in the
1:40:29
Speaker 1: same way that in nineteen oh two you would have
1:40:32
Speaker 1: said humans are not supposed to fly. The same thing
1:40:34
Speaker 1: we've got now technology that will, we think, change the
1:40:38
Speaker 1: way humans can live. And the people who once lived
1:40:41
Speaker 1: over one hundred if they spend their whole life with
1:40:44
Speaker 1: the right diet and the right genes, plus the technologies
1:40:48
Speaker 1: that are being developed around the world. Who says they
1:40:51
Speaker 1: couldn't go way past that point?
1:40:54
Speaker 2: How far past?
1:40:56
Speaker 1: Well? I think anyone who says they know.
1:41:01
Speaker 2: I'm not going to let me pin you down on
1:41:02
Speaker 2: a number, well.
1:41:03
Speaker 1: I'm trying not to because it upsets my colleagues when
1:41:05
Speaker 1: I put a number down. But I think this guy's
1:41:08
Speaker 1: a limit. I think we have to remember that for
1:41:11
Speaker 1: every year you're alive, you get another couple of months
1:41:13
Speaker 1: of life, and that'll continue, I think, and probably be
1:41:17
Speaker 1: even better an event. It gets pretty interesting when you
1:41:20
Speaker 1: get an extra eleven months for every year you're alive.
1:41:24
Speaker 2: Because the science is advancing so rapidly.
1:41:28
Speaker 1: Right, right, And so we've been very good at extending
1:41:31
Speaker 1: lifespan by having vaccinations and washing hands and all of
1:41:36
Speaker 1: that stuff. Now the frontier that's left is to actually
1:41:40
Speaker 1: modify the body and give it protection from aging itself.
1:41:44
Speaker 1: And that's where the biggest gains are going to come
1:41:46
Speaker 1: from in the future.
1:41:47
Speaker 2: Well, everything is changing so quickly across the board with
1:41:52
Speaker 2: technology and science right now that it's almost incumbent upon
1:41:57
Speaker 2: people who are at the vanguard or the cutting edge
1:41:59
Speaker 2: of what they do. To really also be in some
1:42:03
Speaker 2: respects a philosopher, Like how much time do you spend
1:42:07
Speaker 2: thinking about the long term implications of the work that
1:42:10
Speaker 2: you do should it come to its fruition? Right, Like,
1:42:16
Speaker 2: let's put our thought experiment hats on and envision what
1:42:20
Speaker 2: the world would look like if suddenly living to two
1:42:23
Speaker 2: hundred was normal like that? What does that mean for
1:42:27
Speaker 2: how we populate the planet and cohabitate in a sustainable fashion?
1:42:33
Speaker 2: Is that even possible? Right?
1:42:37
Speaker 1: Well, there are plenty of people who claim they know
1:42:39
Speaker 1: what the future looks like. They don't, But I'm trying
1:42:42
Speaker 1: to at least model it teaming up with economists and
1:42:45
Speaker 1: philosophers and bioethicists. I feel it's my responsibility. If I'm
1:42:50
Speaker 1: going to be part of changing the world, I need
1:42:53
Speaker 1: to get the world ready for when this is coming.
1:42:55
Speaker 1: And it's not a question of if it's a win,
1:42:57
Speaker 1: because even if I step out of this studio today
1:43:00
Speaker 1: and I'm hit by a bus, this is still going
1:43:01
Speaker 1: to happen. Okay, So how fast it happens, it's hard
1:43:06
Speaker 1: to know, but I think in the next few years
1:43:08
Speaker 1: there will be one drug that gets on the market
1:43:10
Speaker 1: that's proven to impact aging, or at least aspects of it,
1:43:14
Speaker 1: and it'll just grow. There'll be a lot more so
1:43:17
Speaker 1: in the future.
1:43:17
Speaker 2: They will be sorry to interrupt, but like, regardless of
1:43:20
Speaker 2: whether we philosophize about it and how much time and
1:43:23
Speaker 2: energy we invest in trying to think about whether this
1:43:25
Speaker 2: is a good idea or not, it is happening irrespective.
1:43:28
Speaker 1: Right, And that's why it's the way we function. Well,
1:43:31
Speaker 1: that's why you're right that a good scientist should be
1:43:34
Speaker 1: a philosopher, should be a humanist as well, and many
1:43:38
Speaker 1: of us are because we've seen what's coming and Vulture
1:43:41
Speaker 1: is a good example of all to longer. Okay, so
1:43:44
Speaker 1: what do I do? So I've been going around talking
1:43:49
Speaker 1: with politicians and with economists, with policymakers, with bioethicists, trying
1:43:55
Speaker 1: to first of all, wake the world up, because most
1:43:58
Speaker 1: of the world is still asleep that this is coming.
1:44:01
Speaker 1: But once people get woken up, I find finally over
1:44:04
Speaker 1: the last few years there is increasing awareness that this
1:44:07
Speaker 1: is going to happen. Then the question is what are
1:44:10
Speaker 1: we going to do with the world, what does it
1:44:12
Speaker 1: look like? And if it's going to go to hell?
1:44:14
Speaker 1: Excuse my language, can we prevent that? And I really
1:44:19
Speaker 1: do see our set of folk in the road that
1:44:21
Speaker 1: if we don't do anything now, this will happen, and
1:44:24
Speaker 1: if we do something, we'll live in a much better world.
1:44:28
Speaker 1: And I'm trying to push the world, push the needle,
1:44:30
Speaker 1: so we head off into that brave, great new world.
1:44:34
Speaker 1: And some of the things that we have to be
1:44:35
Speaker 1: very careful with. First of all, this population growth. There's
1:44:39
Speaker 1: the environment. There's what are people do if they're taking
1:44:44
Speaker 1: social security? Does it wreck the economy? Do their lives
1:44:48
Speaker 1: become meaningless? Are they just a burden on society? Crazy
1:44:52
Speaker 1: stuff like what happens when you have politicians that have
1:44:55
Speaker 1: been around for two hundred years and they're still making policy,
1:44:58
Speaker 1: or people on the Supreme Court, a lot of things
1:45:00
Speaker 1: will change. Yeah, yeah, and women, what about them? So
1:45:04
Speaker 1: that can we extend their period of fertility so that
1:45:08
Speaker 1: ada can have the career they always wanted to and
1:45:11
Speaker 1: be will they be around to take care of the
1:45:14
Speaker 1: great grandkids and see what happens to them? I mean
1:45:17
Speaker 1: right now, we live in a world where close to
1:45:20
Speaker 1: half of all women take time off during the critical
1:45:23
Speaker 1: period of their careers. And could that change? And not
1:45:27
Speaker 1: only that, if you have kids when you're old, especially
1:45:29
Speaker 1: men who are capable of doing that, there's this response
1:45:33
Speaker 1: that how can you have kids when you're forty or
1:45:35
Speaker 1: fifty You won't even be alive when they're in high school?
1:45:39
Speaker 1: That should change as well. We can stretch out lifespan
1:45:43
Speaker 1: and health span in a way that allows us to
1:45:45
Speaker 1: have much more say in what we do early in life,
1:45:49
Speaker 1: stay younger for longer mentally, and career wives take longer
1:45:53
Speaker 1: to find what we love to do. And even when
1:45:56
Speaker 1: we're done with a career, we'll be able in this
1:45:59
Speaker 1: new world to have second third careers, have a second chance,
1:46:03
Speaker 1: third chance at the career. People always wanted.
1:46:09
Speaker 2: Not to be contrarian, but at the same time, like
1:46:11
Speaker 2: I'm just envisioning myself, like, Okay, I'm going to live
1:46:14
Speaker 2: to be two hundred and be around for a long time.
1:46:18
Speaker 2: Maybe in my forties, I have a couple kids, take
1:46:21
Speaker 2: a break, you know, something happens. Then twenty years later
1:46:27
Speaker 2: I decided, like I want to have kids again. They're
1:46:30
Speaker 2: all going to live to be three hundred years old
1:46:32
Speaker 2: because the science will improve and we begin populating the
1:46:37
Speaker 2: planet with people who are going to be around a
1:46:39
Speaker 2: lot longer, who maybe having more children that they than
1:46:44
Speaker 2: they would or otherwise, yes, they're productive longer, they're contributing
1:46:50
Speaker 2: to society for a much longer period of time. But
1:46:55
Speaker 2: I have a hard time seeing my way around just
1:46:58
Speaker 2: what I think is the biggest issue initially, which is
1:47:00
Speaker 2: population control, Like how are we going to keep the
1:47:04
Speaker 2: planet from going past the ten billion mark into the
1:47:09
Speaker 2: fifteen billion mark? Like how are you game theorying around that?
1:47:14
Speaker 1: Right? Well, who says fifteen billion is a problem that
1:47:19
Speaker 1: that's a debate as well.
1:47:20
Speaker 2: Well, there's all these other problems that we would have
1:47:22
Speaker 2: to solve in order to make the planet habitable for
1:47:24
Speaker 2: that many people, right.
1:47:25
Speaker 1: And I believe that they are solvable. Now, I'm not
1:47:28
Speaker 1: hoping for overpopulation by any means, And in fact, if
1:47:32
Speaker 1: you do the numbers, the great population growth isn't that great.
1:47:34
Speaker 1: If people live longer, surprisingly low and as the world
1:47:39
Speaker 1: gets wealthier, particularly developing nations, they will have fewer kids.
1:47:42
Speaker 1: That's proven out. Let's look at the world. If we
1:47:45
Speaker 1: don't do anything about longevity, and we continue to treat
1:47:49
Speaker 1: one disease at a time, we are already heading for
1:47:52
Speaker 1: a health care crisis. Social security is going bankrupt. We've
1:47:56
Speaker 1: got healthcare occupying twenty percent and increasing GDP of this nation.
1:48:01
Speaker 1: Around the world, we're being basically dragged down economically by
1:48:05
Speaker 1: healthcare costs. The proportion of people getting older is growing
1:48:09
Speaker 1: dramatically right now. For the first time, just this year,
1:48:12
Speaker 1: we've got more people over sixty five than under five.
1:48:16
Speaker 1: So there's a gray tsunami coming. It's already here really
1:48:20
Speaker 1: that we have to deal with. So what's the best
1:48:22
Speaker 1: way to deal with that? Well, you can't just go
1:48:26
Speaker 1: around hoping that older people will die off. In fact,
1:48:29
Speaker 1: that's a huge waste of resources. These are mostly productive
1:48:34
Speaker 1: with wise people. So the solution, I think is to
1:48:38
Speaker 1: make them and keep them productive members of society. Like
1:48:41
Speaker 1: my father who's gone back and started a second career
1:48:44
Speaker 1: and helps raise the kids. They're not a big burden
1:48:46
Speaker 1: on society if they're productive and they're living alone or
1:48:50
Speaker 1: not needing any help at home, and that's a huge
1:48:54
Speaker 1: cost saving, huge.
1:48:57
Speaker 2: Train on society. They're not requiring all these healthcare costs
1:49:01
Speaker 2: and governmental assistance and they're actually being productive. And yeah, contributed.
1:49:05
Speaker 1: And so Dana Goodman, he is at the Rank Corporation,
1:49:08
Speaker 1: he calculated that of all of the medical treatments that
1:49:11
Speaker 1: are being developed from angiogenesis inhibitos of this is for
1:49:14
Speaker 1: heart disease and pacemakers cancer treatments diabetes, the one that
1:49:18
Speaker 1: gives you, by far the biggest bang for the economy
1:49:21
Speaker 1: and for your life is an anti aging as he
1:49:25
Speaker 1: called it, anti aging treatment. And to give you an
1:49:28
Speaker 1: idea of the difference to a pacemaker, advance will extend
1:49:32
Speaker 1: a human life at the cost of I think it
1:49:35
Speaker 1: was a million bucks to the US economy to do it.
1:49:40
Speaker 1: For a calabor restriction mamtic or anti aging molecule. It
1:49:43
Speaker 1: was I think seven thousand dollars for a million. So
1:49:47
Speaker 1: this is a cheap way to prevent this loss of
1:49:52
Speaker 1: the economic activity. That's money. Remember, if it's fifty trillion
1:49:58
Speaker 1: dollars in the long run that it's calculated to be
1:50:00
Speaker 1: saved by doing this. That is money that can then
1:50:03
Speaker 1: be used for helping the environment, helping safe species, help
1:50:07
Speaker 1: figuring out things like energy. Let me give you a
1:50:11
Speaker 1: really good example of why I'm really optimistic about the future.
1:50:16
Speaker 1: We humans can solve anything if we just put our
1:50:18
Speaker 1: minds to it, and that's been proven out. I mean,
1:50:21
Speaker 1: these days, I've got a supercomputer in my pocket for
1:50:23
Speaker 1: goodness sakes. In Australia, there was a coal fired power
1:50:27
Speaker 1: plant down in South Australia and there was a big
1:50:31
Speaker 1: jetty a wharf where they would just bring in coal
1:50:34
Speaker 1: day in, day out, burning coal global warming contributor. Turns out,
1:50:40
Speaker 1: it became too expensive to run that coal fired power plant,
1:50:44
Speaker 1: so they shut it down, putting thousands of people out
1:50:46
Speaker 1: of work in this little community. So a brilliant bunch
1:50:51
Speaker 1: of benure capitalists said, we've got human capital, We've got
1:50:54
Speaker 1: this wharf, we've got a lot of sunshine. It's on
1:50:57
Speaker 1: the barren South Australian coasts. What are we going to
1:50:59
Speaker 1: do with that? And they figured out, let's use the
1:51:02
Speaker 1: sun's energy to pump millions of gallons of water out
1:51:06
Speaker 1: of the ocean, purify it, put it in greenhouses. And
1:51:10
Speaker 1: these days there's thirty thousand tons of tomatoes being shipped
1:51:16
Speaker 1: out from that wharf in South Australia. And those people
1:51:20
Speaker 1: that lost their jobs, most of them got a job
1:51:23
Speaker 1: at the farm.
1:51:25
Speaker 2: I love that story. I wish we could replicate that,
1:51:29
Speaker 2: you know, across the board, in so many industries that
1:51:31
Speaker 2: are quickly becoming antiquated and environmentally, you know, hazardous, And
1:51:38
Speaker 2: there's so many problems that I'm concerned about that I
1:51:43
Speaker 2: feel like, despite our industrious nature and our best intentions,
1:51:49
Speaker 2: we just fumble over ourselves and are unable to solve.
1:51:53
Speaker 2: And that tempers the optimism that I have that I
1:51:57
Speaker 2: share with you when I see that, when I see
1:51:59
Speaker 2: problems that are right in front of us that we
1:52:01
Speaker 2: need to solve and we're seemingly incapable of doing it.
1:52:05
Speaker 2: I don't know whether because there's no political will or
1:52:08
Speaker 2: the incentives are not properly aligned to make it happen.
1:52:13
Speaker 1: I agree with you, and when I was young, I
1:52:16
Speaker 1: was pretty negative. I didn't even think humans belonged on
1:52:19
Speaker 1: the planet. We should all just kill us. We didn't
1:52:21
Speaker 1: deserve to be.
1:52:22
Speaker 2: Wow, that's dark.
1:52:24
Speaker 1: But as a goot older, I've become much more optimistic
1:52:28
Speaker 1: because I've seen what's possible when you bring armies of smart,
1:52:32
Speaker 1: dedicated people together. And that's what I see my job.
1:52:36
Speaker 1: It's one thing I've found that I'm okay at is
1:52:40
Speaker 1: finding a goal and then bringing people together to solve
1:52:42
Speaker 1: what seems to be impossible and.
1:52:45
Speaker 2: You're surrounded by tons of super smart people.
1:52:48
Speaker 1: What about the.
1:52:50
Speaker 2: Psychological implications on a young person who's presented with this
1:52:58
Speaker 2: new reality of living to be two hundred or three
1:53:01
Speaker 2: hundred years old? You know, talk about a change in
1:53:06
Speaker 2: the incentive landscape, like that person suddenly is no longer
1:53:12
Speaker 2: in a hurry to figure things out? Like how does
1:53:15
Speaker 2: that impact an individual in terms of how they make
1:53:20
Speaker 2: decisions about how they're going to make their way in
1:53:22
Speaker 2: the world When suddenly time really isn't it isn't the
1:53:26
Speaker 2: ticking clock right that your grandmother spoke about?
1:53:32
Speaker 1: Yeah, wouldn't that be great?
1:53:34
Speaker 2: I think that it's a shame or does it just
1:53:36
Speaker 2: create a bunch of lazy people? Oh? Well, I think
1:53:39
Speaker 2: that can be a drain on society.
1:53:41
Speaker 1: People will be people, right, those of us who get
1:53:43
Speaker 1: up every day with a mission will continue to do
1:53:46
Speaker 1: that no matter what age they are, and probably vice versa.
1:53:51
Speaker 1: But it does give you a different perspective. So the
1:53:54
Speaker 1: way we live our lives now, we expect to live
1:53:57
Speaker 1: to eighty and if we're healthy, beyond that. But what
1:54:01
Speaker 1: that means is that when we're ound teens, we have
1:54:03
Speaker 1: to grow up. We're in our twenties, we have to
1:54:05
Speaker 1: find a profession. In our thirties, we have to get
1:54:09
Speaker 1: good at that. In our forties, we make the most
1:54:11
Speaker 1: of it. In our fifties, we're looking at what is
1:54:14
Speaker 1: our legacy. Wouldn't it be great if we could be
1:54:17
Speaker 1: sixty or seventy and say, finally I figured it out,
1:54:21
Speaker 1: and you know what is my legacy going to be?
1:54:24
Speaker 1: And just start again or use all that wisdom to
1:54:26
Speaker 1: do something brand new. And we are entering a world
1:54:29
Speaker 1: like that. When we were kids, being sixty was old,
1:54:33
Speaker 1: seventy was I forget it. And a lot of people
1:54:35
Speaker 1: that I knew in their seventies wouldn't even know how
1:54:38
Speaker 1: to type on a computer. And I find that people
1:54:41
Speaker 1: now that are in their seventies and eighties, they're playing
1:54:43
Speaker 1: tennis and typing on Twitter. So we're living in a
1:54:46
Speaker 1: different world and just like today, you know, eighty is
1:54:49
Speaker 1: that is fifty. Essentially in the future, ninety hundred year
1:54:54
Speaker 1: olds will still be just as active as we are
1:54:56
Speaker 1: in our fifties.
1:54:58
Speaker 2: Yeah, when your your focus is in the hard science geneticist,
1:55:06
Speaker 2: but I can't help when we're having a discussion about
1:55:09
Speaker 2: longevity and aging, I can't help but think about the
1:55:14
Speaker 2: blue zones and the characteristics of these, you know, little
1:55:18
Speaker 2: pockets across planet Earth where we're finding populations of people
1:55:23
Speaker 2: that tend to live longer and be happier than others.
1:55:26
Speaker 2: And what are their shared characteristics. And of course it's
1:55:29
Speaker 2: certain diet protocols, it's having an active lifestyle that isn't
1:55:34
Speaker 2: running on the treadmill, but being kind of consistently engaged
1:55:38
Speaker 2: in some kind of low grade movement throughout the day.
1:55:43
Speaker 2: But on top of that, there's also this aspect of faith.
1:55:49
Speaker 2: Most of these communities have some kind of faith that
1:55:52
Speaker 2: congeals them, that creates, you know, a community sensibility that
1:55:57
Speaker 2: to which they collectively adhere, and also this sense of purpose.
1:56:03
Speaker 2: Like I think it's uh Jokanawans who call it the
1:56:06
Speaker 2: ekey guy right, that they're driven by something that uh
1:56:13
Speaker 2: exceeds their personal ego like that that is fueling their
1:56:18
Speaker 2: life with with meaning really that gives them a contentedness
1:56:25
Speaker 2: that makes them a healthier person and able to live longer.
1:56:29
Speaker 1: Yeah, if you don't have a mission in life, go
1:56:32
Speaker 1: get one. It'll it'll keep you happier and probably longer
1:56:36
Speaker 1: leaved as well.
1:56:39
Speaker 2: Like you, you can take all the restrol you want.
1:56:42
Speaker 2: And you know, we could talk about the genetics. But
1:56:45
Speaker 2: if you're aimless, then you don't have purpose and you're
1:56:48
Speaker 2: you know mentally, you know, not dialed in, and you're
1:56:51
Speaker 2: not taking care of yourself and you're not eating, well,
1:56:53
Speaker 2: you're missing the big picture.
1:56:55
Speaker 1: Well, this is the problem with retirement. I mean, it's
1:56:57
Speaker 1: all it's all fine to go on cruises and enjoys
1:57:00
Speaker 1: some relaxation. But once you've lost your purpose, that's when
1:57:04
Speaker 1: things go downhill. And I saw that with my father. Actually,
1:57:07
Speaker 1: so my father retired a typical age of was a
1:57:10
Speaker 1: sixty six eighty seven and spent it was about ten
1:57:14
Speaker 1: years just flailing around. You can only I think, go
1:57:18
Speaker 1: on so many cruises before you get sick of it.
1:57:20
Speaker 1: It wasn't until he started his new career, which is
1:57:24
Speaker 1: working at the university on an ethics panel for experiments
1:57:28
Speaker 1: that he poked up, and he was excited about life.
1:57:31
Speaker 1: And I've never seen him happier. Isn't that crazy that
1:57:34
Speaker 1: someone who's essentially eighty turning eighty has never been happier
1:57:38
Speaker 1: or more vigorous. That's really, I think inspiring and shows
1:57:43
Speaker 1: me what the world could be like for millions of people.
1:57:47
Speaker 2: Yeah, my wife's father was an engineer in Alaska. He
1:57:53
Speaker 2: passed away a couple of years ago, but he worked
1:57:56
Speaker 2: well into his late ages on gigantic construction projects in
1:58:04
Speaker 2: Anchorage because the community there is largely Native American and
1:58:11
Speaker 2: they have a reverence and a respect for their elders
1:58:14
Speaker 2: that is kind of lacking in most of you know,
1:58:17
Speaker 2: the rest of our culture. And they would continue to
1:58:20
Speaker 2: employ him, and he kept saying, like, I can't even
1:58:23
Speaker 2: see anymore what they're like. But they respected his experience
1:58:28
Speaker 2: and it was just like the right thing to do,
1:58:30
Speaker 2: and he did contribute, you know, in a very material
1:58:32
Speaker 2: way to advancement of these projects. So he worked essentially
1:58:37
Speaker 2: all the way to the end, and it just defies
1:58:39
Speaker 2: that whole paradigm of people. You know, this the great
1:58:43
Speaker 2: generation working towards their retirement and their four oh one
1:58:46
Speaker 2: K so that they could live out the rest of
1:58:48
Speaker 2: their lives in leisure, playing golf and hanging out at
1:58:52
Speaker 2: the club, only to discover that that's the thing that
1:58:55
Speaker 2: makes you depressed.
1:58:57
Speaker 1: Well, it really is, and so society would be so
1:59:00
Speaker 1: much better if people stayed healthy. But also we're able
1:59:03
Speaker 1: to contribute. It's getting up in the morning and knowing
1:59:05
Speaker 1: that you've got something to do. It's important. And on
1:59:09
Speaker 1: the retirement age now, I think that if you've been
1:59:12
Speaker 1: busting roads your whole life, you really deserve to have
1:59:16
Speaker 1: a second chance. So I think that as nations become wealthier,
1:59:20
Speaker 1: and we're already finding that people are talking about we
1:59:23
Speaker 1: call a living wage when people take time off work,
1:59:27
Speaker 1: I would suggest that the best thing we could do
1:59:29
Speaker 1: is people get healthier for longer and just sitting around
1:59:32
Speaker 1: being healthy, that they actually have a choice to take
1:59:36
Speaker 1: some paid time off to start a new career. So
1:59:39
Speaker 1: let's say someone who's been busting roads or you know
1:59:41
Speaker 1: that's just a catch all term for someone who didn't
1:59:43
Speaker 1: like their career, gets a few years off paid by
1:59:46
Speaker 1: the government to do what they always wanted to do.
1:59:50
Speaker 1: And it can be anything, can be building model aeroplanes
1:59:53
Speaker 1: or helping out at nursing homes. But that living wage
1:59:56
Speaker 1: would come back in huge dividends because then you'd have
1:59:59
Speaker 1: people like my other who are helping society. It doesn't
2:00:02
Speaker 1: even have to be paid work, by the way. But
2:00:04
Speaker 1: I think just getting people with the wisdom and knowledge
2:00:08
Speaker 1: that they've accumulated over a lifetime instead of just throwing
2:00:11
Speaker 1: that away into the ground and in the crematorium. Let's
2:00:15
Speaker 1: use that human capital. It's worth trillions of dollars and
2:00:18
Speaker 1: we just throw throw it away.
2:00:22
Speaker 2: Yeah, And being able to leverage the collective wisdom of
2:00:27
Speaker 2: centenarians who are mentally fit enough to pass down their
2:00:31
Speaker 2: wisdom and experience to a younger generation, and at the
2:00:34
Speaker 2: same time changing our perception of the elderly. You know,
2:00:39
Speaker 2: right now, we warehouse them, we dismiss them, We want
2:00:42
Speaker 2: to pretend they don't exist. We want them to go away,
2:00:44
Speaker 2: We don't want to hear what they have to say.
2:00:45
Speaker 2: I mean, I think there's some cultural shifts that would
2:00:48
Speaker 2: have to take place as well. Well.
2:00:51
Speaker 1: They would. I mean, who wasn't a twenty year old
2:00:53
Speaker 1: who's guilty of don't want to hang around the old fogs.
2:00:56
Speaker 2: That's not going to change.
2:00:57
Speaker 1: That is not going to change. But you know, I
2:01:00
Speaker 1: think as you get older, you realize that they're very
2:01:02
Speaker 1: special people. Anyone who's managed to survive for eighty plus
2:01:07
Speaker 1: years and what they've seen, especially people who had to
2:01:10
Speaker 1: live through World War Two, one of the worst times
2:01:12
Speaker 1: in human history, what they can tell you about the
2:01:15
Speaker 1: meaning of life. And also what I've learned in life
2:01:18
Speaker 1: is it's important to learn from mistakes, not just success.
2:01:21
Speaker 1: And everyone's had mistakes, but if you can see what
2:01:25
Speaker 1: the mistakes others have had in their lives before you
2:01:28
Speaker 1: make those same mistakes, that's really the way to avoid
2:01:32
Speaker 1: the pitfalls in life. And I've really benefited from having
2:01:36
Speaker 1: some mentors in my life. I would love to these
2:01:39
Speaker 1: days sit down with people who have these stories to
2:01:41
Speaker 1: tell about what have they learned in their life that
2:01:44
Speaker 1: they could pass on to future generations.
2:01:46
Speaker 2: Right well, in terms of passing on wisdom down the line,
2:01:52
Speaker 2: I think we should round this out with some practical
2:01:56
Speaker 2: wisdom and advice for people that are listening in terms
2:01:59
Speaker 2: of things that they can do in their daily lives
2:02:02
Speaker 2: to improve their longevity and combat aging, to increase their
2:02:08
Speaker 2: health span. What are some of the top things.
2:02:12
Speaker 1: Well, here's what I do. That's how that's how I
2:02:15
Speaker 1: convey advice. So every day I wake up having had
2:02:21
Speaker 1: a decent night sleep preferably, and I'll go have a
2:02:25
Speaker 1: yogurt that I make myself for the microbiome. Try to
2:02:28
Speaker 1: keep my microbiome in chick. I take a little bit
2:02:32
Speaker 1: of his virtuals sprinkled in that yogurt.
2:02:35
Speaker 2: Is there a particular brand or do you have some
2:02:37
Speaker 2: special Harvard Lab version that no one else can get
2:02:43
Speaker 2: except for me, because you're going to get it to
2:02:45
Speaker 2: me right.
2:02:46
Speaker 1: Well, we'll talk. I fortunately have pharmaceutical grade res virtual basement,
2:02:52
Speaker 1: so it's been that and the same with anemen.
2:02:57
Speaker 2: And is that that's not commercially available? Can people get
2:03:00
Speaker 2: that from me? Well, for you, you don't count because
2:03:03
Speaker 2: you're working in it. But for somebody who's listening, like
2:03:06
Speaker 2: they can't go to their doctor and get this prescribed
2:03:10
Speaker 2: and they can't purchase it right.
2:03:12
Speaker 1: Well, there's a lot of things sold online which I
2:03:16
Speaker 1: apologize I can't endorse or talk about. It's just I
2:03:19
Speaker 1: try to stay above that fray. But there are people
2:03:22
Speaker 1: selling things online that I'm going to use social media
2:03:26
Speaker 1: to be able to talk more about it, so stay
2:03:29
Speaker 1: tuned or release what I can. But I'm also looked out,
2:03:34
Speaker 1: looked over by a very large institution called Harvard University.
2:03:38
Speaker 1: To be careful what I say and what I do,
2:03:40
Speaker 1: But I also want to be able to say with
2:03:43
Speaker 1: authority the science. So anyway, my apologies for not being
2:03:47
Speaker 1: able to say, go buy this product. I just am
2:03:49
Speaker 1: not able to say that. But I can point you
2:03:52
Speaker 1: in the right direction I think you should look for.
2:03:54
Speaker 1: If you're going to take a supplement, make sure it's
2:03:56
Speaker 1: from a reputable source. And there are some reputable company
2:04:00
Speaker 1: some of them are not.
2:04:01
Speaker 2: Sometimes it's hard to know. There's really harsh out there,
2:04:04
Speaker 2: and there's a lot of quackery.
2:04:07
Speaker 1: Yeah, so my dream rich is to have an independent
2:04:10
Speaker 1: group who does these studies and leaves me out of it.
2:04:13
Speaker 1: But maybe I can enable that group to test things
2:04:17
Speaker 1: and report on it, and that would be the ideal.
2:04:19
Speaker 1: But I got into trouble when I used to talk
2:04:21
Speaker 1: about supplements. I once said on NBC or Want a
2:04:25
Speaker 1: TV show that some of the supplements have tested don't
2:04:28
Speaker 1: have the product in it, and that got some people
2:04:31
Speaker 1: very upset, and I got dragged into a fight between
2:04:33
Speaker 1: two companies and there was a lawsuit and I lost
2:04:36
Speaker 1: a year's salary on legal costs. So that you know,
2:04:40
Speaker 1: it's a good lesson. Don't talk about supplements if you
2:04:43
Speaker 1: can help it. You know that said. Look for quality brands,
2:04:48
Speaker 1: look for purity. Don't take things that have a lot
2:04:52
Speaker 1: of mixed things in it. You just don't know what
2:04:53
Speaker 1: else you're getting in there. Look for clinical trials that
2:04:58
Speaker 1: have been tested on some products. So some products that
2:05:00
Speaker 1: raise NAD have been published in clinical studies, and so
2:05:05
Speaker 1: you can go to pub med. If you google the
2:05:08
Speaker 1: words pub me D you can find some scientific papers
2:05:12
Speaker 1: and look for so TUN's look for NAD. Look for
2:05:16
Speaker 1: either n MEN or it's similar molecule its cousin called NR.
2:05:23
Speaker 1: And actually people are wondering what's NR. It stands for
2:05:26
Speaker 1: nico tinamide ribo side. So that's as best I can
2:05:32
Speaker 1: do to help there. I try to do some exercise.
2:05:35
Speaker 1: At least once a week on the weekends of my
2:05:37
Speaker 1: son and I go to the gym for two to
2:05:41
Speaker 1: three hours. There were just once a week. Well, we
2:05:44
Speaker 1: try to do more, but I'm traveling a lot, so
2:05:47
Speaker 1: hopefully twice a week at minimum. We have a gym
2:05:50
Speaker 1: at home. Actually, I built a gym adjacent to my bedroom,
2:05:54
Speaker 1: which I can see through the windows, and for a
2:05:57
Speaker 1: while there I figured, just looking at the gym's probably helping.
2:06:00
Speaker 1: I was hoping at least okay, yeah, mentally, you know,
2:06:04
Speaker 1: if I just look at the treadmill, it's probably good.
2:06:06
Speaker 1: But no, I try to use it more and more,
2:06:08
Speaker 1: especially because I've been writing this book and I've spent hundreds,
2:06:12
Speaker 1: if not a thousand or more hours sitting down, which
2:06:15
Speaker 1: is really bad. I'm trying to make up for all
2:06:18
Speaker 1: of that. So we do that. We do high intensity
2:06:21
Speaker 1: running on treadmills, and we also do weight training with
2:06:26
Speaker 1: a trainer every for an hour. And actually, my trainer
2:06:30
Speaker 1: recently looked at my body and he said, I used
2:06:33
Speaker 1: to work out when you were young, and I said, yeah,
2:06:35
Speaker 1: I did. How do you know what he goes because
2:06:37
Speaker 1: you're all messed up. My arms are turned in word,
2:06:40
Speaker 1: my palms aren't straight. I slouched to one side, and
2:06:44
Speaker 1: so he's fixing that part of my body. But so
2:06:47
Speaker 1: I'm trying to get back into shape.
2:06:48
Speaker 2: Is there research on the differences between high intensity training
2:06:54
Speaker 2: and aerobic training in terms of longevity.
2:06:58
Speaker 1: Not in longevity much. There have been some human studies
2:07:02
Speaker 1: that have looked at biomarkers and other things like that,
2:07:06
Speaker 1: and also the relationship to frailty and what, as far
2:07:12
Speaker 1: as I can tell from leading it reading a very
2:07:14
Speaker 1: complex body of literature, is that you want to do
2:07:18
Speaker 1: some not high impact, but high intensity aerobics. Get your
2:07:22
Speaker 1: heart rate up pretty high until you're feeling some hypoxia.
2:07:28
Speaker 1: You're gasping for breath, and that hypoxic response is a
2:07:31
Speaker 1: hormontic response. It will stimulate your body to fight back.
2:07:36
Speaker 1: So get your heart rate up. They say as little
2:07:38
Speaker 1: as five minutes is sufficient. I don't know. I go
2:07:42
Speaker 1: a little bit further. I don't see any harm in
2:07:44
Speaker 1: doing that. So you know, ten to fifteen minutes of panting,
2:07:47
Speaker 1: but then I slow down and then I do a
2:07:49
Speaker 1: bit of jogging as well. But it's that really what
2:07:52
Speaker 1: you just want to do a bit of jogging, a
2:07:55
Speaker 1: bit of sprinting, bit of jogging, a bit of sprinting.
2:07:57
Speaker 1: But it doesn't seem to have to last for that.
2:07:59
Speaker 2: Long to be good, just to get that stimulus response.
2:08:03
Speaker 1: Yeah, yeah, because your body has an epigenetic memory of
2:08:06
Speaker 1: those exercises and so it lasts for days.
2:08:10
Speaker 2: And what about training twenty five to thirty hours a
2:08:14
Speaker 2: week for ultra distance triathlons and marathons. Yeah, it's I mean,
2:08:19
Speaker 2: it's not digging my early grave.
2:08:21
Speaker 1: I don't think so. I've seen data on bicyclists. This
2:08:25
Speaker 1: is not the same thing. But bicyclists who I think
2:08:30
Speaker 1: that they were riding over eighty miles a week, their
2:08:36
Speaker 1: chance of getting a heart disease was reduced by forty
2:08:40
Speaker 1: in old age and massive number. And so I think that,
2:08:46
Speaker 1: you know, if you're not wearing body parts out, certainly
2:08:48
Speaker 1: your organs are going to be younger for longer.
2:08:50
Speaker 2: Yeah, although there aren't there some there's some research out there.
2:08:53
Speaker 2: There's some research out there that says long term, like
2:08:57
Speaker 2: super you know a lot of aerobic exercise ultra marathoners,
2:09:03
Speaker 2: marathoners have scarring in their heart tissue, and there's some
2:09:07
Speaker 2: cardiac implications that don't look so great for that. I'm
2:09:10
Speaker 2: always getting tweets from people all the time telling me
2:09:13
Speaker 2: that I'm harming myself.
2:09:16
Speaker 1: Well, I think you're going to live longer than someone
2:09:18
Speaker 1: who sits on the couch and eats potato chips all
2:09:20
Speaker 1: the time. So I can't speak for the fibrosis and
2:09:24
Speaker 1: the heart other than to say, we're also working on
2:09:27
Speaker 1: that where I have a synalytics company with some real
2:09:31
Speaker 1: experts in the field, like Manuel Serrano in Spain who
2:09:35
Speaker 1: clone the sinescence genp. Sixteen, and so we're trying to
2:09:40
Speaker 1: figure out how to fix problems like that that accumulate
2:09:42
Speaker 1: over time.
2:09:43
Speaker 2: Right, Okay, so exercise, what about what's your specific for
2:09:49
Speaker 2: fasting protocol look like?
2:09:50
Speaker 1: Then I don't have one. I do try to eat
2:09:53
Speaker 1: smaller meals. I try to not overeat, and I try
2:09:56
Speaker 1: to skip meals, which is pretty easy because I'm not
2:09:59
Speaker 1: hung when I wake up other than that little yogurt
2:10:02
Speaker 1: which is just for re virtual solubility. And then I'm
2:10:06
Speaker 1: so busy i usually skip lunch, so I'm practically eating one,
2:10:11
Speaker 1: maybe two meals a day by default. I'm never able
2:10:15
Speaker 1: to literally go a whole day without eating. For some reason,
2:10:18
Speaker 1: it's just too hard. I'd like to. I think that
2:10:20
Speaker 1: would be a great thing. I know Peter Atia does
2:10:23
Speaker 1: it really well and others, but I'm unable to. I
2:10:27
Speaker 1: think I've got to feel my brain. Without my brain,
2:10:30
Speaker 1: I've got no job, so that's.
2:10:31
Speaker 2: All to be able to think straight. I think better
2:10:34
Speaker 2: when I haven't eaten. You know, you get the brain
2:10:37
Speaker 2: fog after the lunch and the lull and the energy.
2:10:40
Speaker 2: Sometimes it's better to be without food in terms of
2:10:44
Speaker 2: focus for me personally.
2:10:45
Speaker 1: Yeah, I agree with that one hundred percent. But then
2:10:47
Speaker 1: you get to a point after diminishing twenty four hours,
2:10:51
Speaker 1: then it starts to go down.
2:10:53
Speaker 2: So you're not super hardcore about these kinds of practices.
2:10:58
Speaker 1: No, I probably should be better about it. But as
2:11:01
Speaker 1: I've said, I'm not so worried about my longevity. I mean,
2:11:05
Speaker 1: I'm hoping not to die in the next few years
2:11:07
Speaker 1: because I've got some work to do. I try to
2:11:09
Speaker 1: be a role model for others, but I'm not obsessive
2:11:12
Speaker 1: about it. I do have some bad genes that I inherited,
2:11:15
Speaker 1: so I'm trying to live at least eighty to ninety years.
2:11:20
Speaker 1: I'd like to live longer. I'd love to be able
2:11:21
Speaker 1: to continue working and doing good. I'd like to see
2:11:24
Speaker 1: where the world goes with all of this research. I'd
2:11:27
Speaker 1: like to figure out what we have in our pockets
2:11:28
Speaker 1: besides computers twenty years from now. But to your point,
2:11:33
Speaker 1: I do what I can within reason. Most of my
2:11:36
Speaker 1: mental energy and dedication is devoted to this cause, which
2:11:41
Speaker 1: is finding cures for diseases, improving people's lives, getting the
2:11:46
Speaker 1: word out that this is coming and this is important
2:11:49
Speaker 1: for the world to know about. One last question sleep.
2:11:55
Speaker 1: If so much of what we've talked about is trying
2:11:58
Speaker 1: to get the body to get into its reparative state,
2:12:04
Speaker 1: isn't sleep the ultimate example of that? Is this not
2:12:08
Speaker 1: something that we should be really trying to enhance and
2:12:11
Speaker 1: focus on if we're concerned about longevity. Yeah, Well, first
2:12:17
Speaker 1: of all, the longevity genes that I work on are
2:12:19
Speaker 1: central to the circadian rhythm, which is the sleep wake cycle.
2:12:23
Speaker 1: And if you're out of whack and you don't get
2:12:24
Speaker 1: enough sleep, that we think has negative effects on the
2:12:28
Speaker 1: curtoins and NAD levels. NAD levels will precisely cycle with
2:12:33
Speaker 1: the day. Just before you wake up or before you
2:12:36
Speaker 1: have breakfast, your NAD levels will start to spike and
2:12:42
Speaker 1: get you ready for the meal. So if you start
2:12:45
Speaker 1: to miss sleep and you get your if you have
2:12:46
Speaker 1: a lot of jet lag like I do, it's not good.
2:12:48
Speaker 1: We know that mice, when you mutate their body clock,
2:12:52
Speaker 1: they get signs of premature aging. And in fact, if
2:12:54
Speaker 1: you prevent a rat from sleeping, it'll pretty quickly develop diabetes.
2:13:00
Speaker 1: It's really important to maintain a good cycle and reset
2:13:04
Speaker 1: your body clock if you're traveling. And then the other
2:13:07
Speaker 1: problem is that without a proper sleep, you're not clearing
2:13:14
Speaker 1: out a lot of the toxins that accumulate in your brain.
2:13:17
Speaker 1: And we just recently as a scientific world, has realized
2:13:21
Speaker 1: that as you're sleeping and dreaming, one of the things
2:13:24
Speaker 1: that's happening is that those canals in your brain are
2:13:27
Speaker 1: getting rid of what's built up during the day. And
2:13:29
Speaker 1: if you wake up early and you haven't had enough sleep,
2:13:31
Speaker 1: your brain is still clogged with that stuff, and so
2:13:35
Speaker 1: you can't think well during the day, which is lethal
2:13:37
Speaker 1: to someone like me who's supposed to be at peak
2:13:40
Speaker 1: performance mentally. So let me tell you about what I do,
2:13:44
Speaker 1: because I've missed out on sleep for more than a
2:13:47
Speaker 1: couple of decades. I'm an insomniac actually, and with kids,
2:13:52
Speaker 1: it didn't help that at all. So what I managed
2:13:56
Speaker 1: to do was to calm myself down at night. I
2:14:00
Speaker 1: do a little bit of meditation, avoid the screens, the
2:14:04
Speaker 1: blue light. I wear those light blucking glasses. If I'm traveling,
2:14:10
Speaker 1: I'll take a little bit of a sleeping pill, which
2:14:15
Speaker 1: I need to just calm down. But I don't eat
2:14:16
Speaker 1: the whole thing. I just nibble on the pill and
2:14:18
Speaker 1: that's enough to calm me down. So I finally get
2:14:21
Speaker 1: to sleep because my brain is so active it would
2:14:23
Speaker 1: keep going all night and then waking up in the morning.
2:14:26
Speaker 1: I find that that combination of the rostral and Animen
2:14:29
Speaker 1: and a little bit of coffee really kickstarts the day
2:14:32
Speaker 1: and I'm ready to go. And by the way, please
2:14:36
Speaker 1: don't criticize me colleagues for saying this, because it's an
2:14:39
Speaker 1: end of one as we call it. But I find
2:14:42
Speaker 1: that jet lag is ameliorated. It's a lot less when
2:14:46
Speaker 1: I travel and I use the Animen to reset that
2:14:49
Speaker 1: body clock, which we now know, at least in mice,
2:14:53
Speaker 1: that cycle of nad through the day is probably what's
2:14:57
Speaker 1: driving jet lag as well.
2:14:58
Speaker 2: If so, it helps you over the gel.
2:15:00
Speaker 1: Now, well, I find it does for me, and I
2:15:02
Speaker 1: travel a lot, and I've experiment a lot on myself
2:15:05
Speaker 1: with these things, and that's one thing that I am
2:15:10
Speaker 1: pretty sure is true, is that the ani men helps
2:15:13
Speaker 1: with that gel.
2:15:16
Speaker 2: When's the book coming out? Well, it's what's do you
2:15:20
Speaker 2: have a title for it?
2:15:21
Speaker 1: Yeah, it's called Lifespan. O Lifespan Okay, cool, Yeah, so
2:15:26
Speaker 1: we'll we're I'm just finishing it up. It's an illustrated book.
2:15:30
Speaker 1: It's got some beautiful drawings, illustrations from one of the
2:15:34
Speaker 1: best illustrators in the country. And some of these concepts,
2:15:38
Speaker 1: like the epigenome and the compact disc, they're beautiful when
2:15:42
Speaker 1: they're drawn out on the page. And so Katie Delphia
2:15:46
Speaker 1: has been working for a year on this book as well.
2:15:50
Speaker 1: And I had a co author, Matt Laplant, who has
2:15:53
Speaker 1: written a book about the epigenome. So the three of
2:15:55
Speaker 1: us have created what I think is a unique book.
2:15:58
Speaker 1: Unique it's science based, but it covers everything from the
2:16:01
Speaker 1: beginnings of life on the planet to human history and
2:16:04
Speaker 1: life in London in the eighteen thirties. What we can learn,
2:16:07
Speaker 1: what I give the readers a front row seat on
2:16:10
Speaker 1: what the cutting edge of technology is today, what's just
2:16:13
Speaker 1: around the corner because I can see it already, and
2:16:15
Speaker 1: what does life look like in the future for our families,
2:16:19
Speaker 1: for our family members, including our four legged ones, and
2:16:22
Speaker 1: project into the far future of what the future is
2:16:25
Speaker 1: going to be like if we don't succeed, and if.
2:16:27
Speaker 2: We do, it's going to be interesting either way.
2:16:33
Speaker 1: It is, but we've got to stick around to see it.
2:16:35
Speaker 2: Yeah, yeah, yeah, Well I really look forward to the book.
2:16:39
Speaker 2: Please send it to me when it's already and hopefully
2:16:43
Speaker 2: I can entice you to come back and talk to
2:16:45
Speaker 2: me a little bit more when.
2:16:46
Speaker 1: The book comes out. Sounds good, Rich, thanks for having
2:16:49
Speaker 1: me on.
2:16:49
Speaker 2: Thank you so much for the work that you're doing.
2:16:52
Speaker 2: It's inspiring, it's fascinating. We really are creating a world
2:16:58
Speaker 2: beyond anything we could have imagined as young people. And
2:17:02
Speaker 2: you know, it's a privilege and an honor for me
2:17:04
Speaker 2: to speak to somebody who's really at the cutting edge
2:17:05
Speaker 2: of all of that. So thank you for your time
2:17:07
Speaker 2: and best of luck with all of this. Man doing
2:17:10
Speaker 2: amazing work.
2:17:11
Speaker 1: Oh thanks, I appreciate it.
2:17:12
Speaker 2: Cool. So if people want to connect with you or
2:17:15
Speaker 2: learn more about your world and what you do, what's
2:17:17
Speaker 2: the best place for them to go.
2:17:20
Speaker 1: So I'm active on Twitter and I talk about some
2:17:25
Speaker 1: of the research in my lab where you've got the
2:17:26
Speaker 1: immortal jellyfish. Going to just tweet out a new transgend
2:17:30
Speaker 1: jellyfish we made last week, so that'll be the way.
2:17:34
Speaker 1: So that my Twitter handle is David A. Sinclear and
2:17:38
Speaker 1: so we're going to launch a book website soon, but
2:17:40
Speaker 1: I'll let everyone know when that's ready.
2:17:43
Speaker 2: Cool. Good talking to you.
2:17:45
Speaker 1: Thanks che feel good, I always feel good.
2:17:49
Speaker 2: I'm good. I want to always feel good. We'll talk more,
2:17:52
Speaker 2: all right, Thanks man, Peace mind officially loan. This conversation,
2:18:02
Speaker 2: which incidentally transpired a couple months ago, really deeply and
2:18:06
Speaker 2: profoundly impacted how I think about my personal longevity, my aging.
2:18:11
Speaker 2: It's shaped some new daily habits that I've been ascribing to,
2:18:15
Speaker 2: including daily intake of resveratrol, which we talked about during
2:18:19
Speaker 2: the podcast. For those interested in that product, I'll put
2:18:22
Speaker 2: a link up into the show notes, and I really
2:18:25
Speaker 2: hope you guys enjoyed it. Please do me a favor.
2:18:27
Speaker 2: Let David know what you thought about today's conversation. You
2:18:29
Speaker 2: can find him on Twitter at David A. Sinclair, And
2:18:34
Speaker 2: don't forget to pre order his new book, Lifespan, The
2:18:36
Speaker 2: Revolutionary Science of Why We Age and Why We Don't
2:18:39
Speaker 2: Have To, which hits bookstores on September tenth. If you'd
2:18:43
Speaker 2: like to support the work we do here on the podcast,
2:18:45
Speaker 2: just tell your friends about the show, share your favorite
2:18:48
Speaker 2: episode on social media. You can subscribe to the show.
2:18:51
Speaker 2: That's probably the most important of all of these things.
2:18:54
Speaker 2: If you hit that subscribe button on Apple Podcasts, on Spotify,
2:18:57
Speaker 2: on YouTube, super helpful, leave review on Apple Podcasts, and
2:19:01
Speaker 2: you can support us on Patreon at rich role dot com,
2:19:04
Speaker 2: forward slash donate. I want to thank everybody help put
2:19:07
Speaker 2: on the show today. Jason Camiolo for audio engineering, production,
2:19:10
Speaker 2: show notes, interstitial music, Blake Curtis and Margo Lubin, who
2:19:14
Speaker 2: traditionally video and edit the video version of the podcast,
2:19:18
Speaker 2: although this one was audio only. Jessica Miranda for her
2:19:22
Speaker 2: beautiful graphics, and DK David Kahn hashtag DK goals for
2:19:27
Speaker 2: advertiser relationships. The music as always by Anlemma. Thank you
2:19:31
Speaker 2: for the love you guys. I will see you back
2:19:33
Speaker 2: here in a couple days with another special edition, hotly
2:19:37
Speaker 2: anticipated edition of Coach's Corner with Chris Houth my coach
2:19:41
Speaker 2: Chris Health. Until then, take care of yourselves, embrace life.
2:19:46
Speaker 2: It's not necessarily the length of time we spend here
2:19:50
Speaker 2: on the planet, but the quality of that time, so
2:19:53
Speaker 2: be mindful about it, appreciate it, be grateful, and give
2:19:57
Speaker 2: back Peace plans, pipes,