I brought two top Silicon Valley entrepreneurs working on extending lifespans on the Newcomer podcast this week.
One of them is trying to help people live longer. The other, their dogs.
James Peyer, the CEO of Cambrian Bio, is acquiring majority stakes in drugs that could combat a particular illness while showing promise for broader use among healthy humans. Meanwhile, Celine Halioua, the CEO of Loyal, is developing drugs to make dogs live longer.
Fundamentally life extension, or longevity, is about finding drugs and treatments that can be given to healthy humans to help them live longer, healthier lives. Instead of just treating illnesses, entrepreneurs in the space want to find ways to stave off aging in already healthy people.
The space has long been a fascination of mine. In February 2022, I profiled Elad Gil’s investments in an array of companies looking to make healthy humans live longer, healthier lives.
The HBO show Silicon Valley helped popularize the idea that Silicon Valley elites were pumping their veins with younger people’s blood. (I’ve yet to get anyone to confess to me that they’re buying plasma.)
To the chagrin of this week’s guests, one tech mogul desperate to avoid death has received a lot of the attention recently. That’s Braintree founder Bryan Johnson.
Time magazine just profiled Johnson under the headline “The Man Who Thinks He Can Live Forever.”
Johnson, 46, is a centimillionaire tech entrepreneur who has spent most of the last three years in pursuit of a singular goal: don’t die. During that time, he’s spent more than $4 million developing a life-extension system called Blueprint, in which he outsources every decision involving his body to a team of doctors, who use data to develop a strict health regimen to reduce what Johnson calls his “biological age.” That system includes downing 111 pills every day, wearing a baseball cap that shoots red light into his scalp, collecting his own stool samples, and sleeping with a tiny jet pack attached to his penis to monitor his nighttime erections. Johnson thinks of any act that accelerates aging—like eating a cookie, or getting less than eight hours of sleep—as an “act of violence.”
Even as Johnson is getting a lot of attention for his self-experimentation, there’s a growing view that there could be something credible behind Silicon Valley’s interest in life extension. The Economist just wrote that “slowing human ageing is now the subject of serious research.”
Many in mainstream science and medicine look at all this slightly askance. That is understandable. It is an area which attracts chancers and charlatans as well as those with more decent motives, and its history is littered with “breakthroughs” that have led more or less nowhere. America’s Food and Drug Administration does not recognise “old age” as a disease state, and thus as a suitable target for therapy. Nevertheless, evidence has been accumulating that such research might have something to offer.
Some established drugs really do seem to extend life, at least in mice. That offers both the possibility that they might do so in people and some insight into the processes involved. The ever-greater ease with which genes can be edited helps such investigations, as does access to large amounts of gene-sequence data. The ability to produce personalised stem cells, which stay forever young, has opened up new therapeutic options. And new diagnostic tools are now offering scientists means to calculate the “biological ages” of bodies and organs and compare them with actual calendar ages. In principle this allows longevity studies to achieve convincing results in less than a lifetime.
I dug in with Halioua and Peyer about where they saw the most opportunities, how their own companies were progressing, and why they thought Johnson’s publicity campaign was doing a disservice to companies working on longevity.
The duo helped break down the space, discussing which types of companies they think are innovators, which efforts are more speculative moonshots, and which ones are simply snake oil.
Give it a listen.
Get full access to Newcomer at www.newcomer.co/subscribe
00:00:01
Hey, it's Eric Newcomer. Welcome to the Newcomer podcast,
00:00:04
Probably my favorite episode ever.
00:00:06
This week a conversation with James Pyer, the CEO of Cambrian
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Bio, and Celine Haliwa, the CEO of Loyal.
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James is trying to help humans live forever, and Celine is
00:00:20
trying to help your dog live as long as possible.
00:00:23
We get into life extension and longevity, Silicon Valley's
00:00:28
chase to fight off death. You've probably read about tech
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mogul Brian Johnson. He was just profiled in time,
00:00:36
who's desperately trying to figure out ways to optimize his
00:00:38
life to drag it out as long as possible.
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Celine and James are skeptical of that effort.
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Spoilers. We get into what's credible, the
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moon shots and the snake oil in the life extension and longevity
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space. If you're curious about Silicon
00:00:56
Valley's effort to live forever, you want to fend off death.
00:01:00
This is a great dive and with sort of serious players in this
00:01:05
space about the effort to find drugs that will keep people and
00:01:12
our pets living longer. Give it a listen.
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Celine and James, thank you for joining the podcast.
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Welcome. Nice being here, Eric.
00:01:20
Yeah. Thanks for having us life
00:01:22
extension longevity, like things everybody wants for themselves
00:01:26
and to know how they can live longer and it's a fun space to
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talk about. So really, really excited for
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this episode. I mean, I I think just start
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off, can you each give the sort of 1st 30 seconds how you came
00:01:43
to the longevity space? Next 30 seconds, just like at
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the high level, we'll dig into it more like what your company
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does, so people know who we're talking to.
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Celine, do you wanna start us off?
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Yeah, so I got interested in aging and longevity kind of
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indirectly. I was working, so my undergrad's
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in neuroscience and I have an incomplete PhD in health
00:02:04
economics. And while I was doing research
00:02:06
in Neuro, we were working in a Parkinson's lab.
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And Parkinson's, A neuro time disorder that is predominantly
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caused by a loss of a certain type of neuron, that is.
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Infamously difficult to treat with modern therapies.
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And I remember sitting in this lab thinking, why are we waiting
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until there's decades of damage and decades of neuronal loss?
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So start trying to treat the patient instead of trying to
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understand what led to them having this loss of brain
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function. And so that kind of Long story
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short, led me into the aging field, which the way I think
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about aging drugs is preventative medicines for
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multiple age-related diseases at the same time.
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So not nearly as sexy as. Of 20 year lifespans,
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immortality, saving Johnson's Johnson, things like that.
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Sorry, I had to. We'll get into him.
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We'll get into him. We'll get into that I'm sure.
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And now I run a company called Loyal.
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We're developing what we hope to be the first FDA approved drugs
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explicitly designed to extend the lifespan and health span.
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And we're specifically working on dogs, dogs.
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So yeah, that's, yeah, that's the take away.
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You're starting with dog. It's easier, we'll get into it,
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but it's easier to extend the lifespan of dogs than humans
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because of regulation, right. I mean, it's sort of regulatory.
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It's honestly just a like a logistics thing or anything
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else, right? Like a dog.
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Well, like one of the core ideas is that big dogs live very short
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lives. You know, a great day might live
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678 years while Chihuahua lives 18 years.
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You can see aging and you can see lifespan in a dog in a much
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shorter period of time than you can or a person.
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If I give you guys a lifespan extension drug, I'm not gonna
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know if it works or not for a really long time.
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Good luck like getting some VC to fund that, not the less the
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clinical studies. My wife's family has a black lab
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named Moon Unit that I've gotten very attached to and.
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Well, we're working on it. Yeah, exactly.
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Chop, chop. The realization that I, you
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know, you're getting attached to a big dog halfway through their
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life is sort of like, Oh no, what am I doing like?
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Anyway, I have a senior Roddy who I'm in love with.
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And yeah, yeah. So anyhow, that's what I'm up
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to. All right, James, what about
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you? How did you get into this space?
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So my story starts in the late 90s when.
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The the aging space was really act like academically in its
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infancy in a lot of ways. And we had just kind of
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discovered that there were these things inside of each of our
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cells called telomeres that shortened every time a cell
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divided. And a couple of books got
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published in the late 90s when I was a student that said, hey, if
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we can extend, like prevent the telomeres from shortening and
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keep them long, then cells should be able to live forever.
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And then sure enough, like right after that, we were able to take
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normal human cells and let them divide an infinite number of
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times by keeping their telomeres long.
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And then that led to this explosion of, Oh my God, is this
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the answer for aging. And it turned out not to be the
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case, but it kind of sent me down this path.
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Similar to Celine's story of like, this could be the core.
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Not telomeres specifically, but like the study of why our cells
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and our organs stop working as we get it.
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Old that could be the key to keeping people healthy, the key
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to preventing diseases from from happening in the 1st place.
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Around the same time, my grandfather was diagnosed with
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cancer, which kind of went from zero to 60.
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And he was, you know, treated, failed treatment and was gone
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within a year and a half of his diagnosis.
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And I just saw how to Celine's point about Parkinson's.
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Like how? Futile.
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It was to wait for decades of molecular damage, right?
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Decades of a disease to build up bit by bit.
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Cancer I think, is a great example of this where it has to
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go through one mutation, big expansion bottleneck, expansion
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bottleneck before ever even thinking about how do we treat
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this, how do we stop this from happening.
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And for the past 20 years I've been either as a researcher or
00:06:06
for the last almost 10 as a kind of.
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Investor, company, builder and now executive in this space have
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been trying to ask the question how do we take these discoveries
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from the academic world and understanding how our bodies age
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and turn those into medicines with the thesis that's almost
00:06:25
100% aligned with with Celine that like this is not about.
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You know, longevity or even health span.
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That the the best and highest use of these breakthroughs in
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our understanding is to create a new generation of preventative
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medicines. That if you Fast forward 50
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years, people are going to look at this research now and kind of
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equate it with what happened in the first half of the 20th
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century with vaccines and antibiotics.
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These were the biggest killers of humanity.
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And now we've figured out ways of understanding how they work
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and how to get there before the disease like robs us of our
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ability to to deal with them by becoming so complex and so, so
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damaging. Cambrian is is kind of a unique
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company that I run. So, so we partner with academics
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who have made breakthroughs in aging research all over the
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world, who have figured out ways to create a drug that can target
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a different aspect of aging. And then we bring that into
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Cambrian and move that forward into human clinical trials.
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So we don't have any dog FDA stuff pending.
00:07:27
Our strategy is slightly different which is we find a
00:07:30
drug that has the potential to slow these aging processes to
00:07:34
prevent disease, to extend health span.
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But we say, all right, well, this could be a great cancer
00:07:39
drug. It could be a great.
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Drug for heart disease. It could be a great drug even
00:07:43
for like a rare orphan genetic disease.
00:07:45
So let's start there and after we show safety and efficacy,
00:07:49
then you can do something closer and closer to prevention.
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The idea is you're picking drugs that you think would sort of be
00:07:56
useful to the general person or that have some reason why they
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would be preventative. That's right.
00:08:02
And so we can get into some aspects of this, but it looks
00:08:04
actually like we're going to be able to start our first
00:08:06
preventative trial in human patients as early as the end of
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next year. So you guys are both sort of
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hinted at this, but just defining the space longevity,
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life extension from what you're saying like there's a sort of
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innocuous way to phrase it, which is just sort of
00:08:20
preventative medicine, right? Or am I wrong?
00:08:24
Is saying that like a core idea here is that most drugs are
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meant to treat people where something's like clearly wrong
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and there are somewhere outside of the human baseline.
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And a key idea here is that even if you're at the human baseline
00:08:39
or over performing, are there drugs we should give you earlier
00:08:43
in your life that that give you a better outcome?
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Is that the right way to think about it?
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Would you quibble with anything or add anything there?
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What I've found has been kind of the aha moment when I'm trying
00:08:55
to It's a lot of my job fundraising and also activating
00:08:58
and educating pet parents and vets is explaining what is this
00:09:02
aging thesis. And the way I think about it is
00:09:05
that as we get chronologically older, the cells that make up
00:09:12
our body accumulate damage. They, you know, accumulate
00:09:16
mistakes, etc. And these are inherently things
00:09:20
that occur overtime. And a disease that's associated
00:09:23
with this damage or decaying or loss of resiliency, a loss of
00:09:27
function, depends on where it's happening, right.
00:09:29
So if it's happening in your brain, it might lead to our
00:09:31
dementia or an urgent disorder. If it's happening in your joint,
00:09:34
it might lead to osteoarthritis, it's happening in your immune
00:09:36
system, it might lead to cancer. And these things are classically
00:09:39
thought of as completely unrelated diseases, right?
00:09:42
Having osteoarthritis considered mechanistically very different
00:09:45
from having Parkinson's and at the end stage.
00:09:48
They are. They are very mechanistically
00:09:49
different. An OA drug isn't going to most
00:09:52
likely positively impact dementia, but the underlying
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drivers that led to a patient developing diseases, the
00:09:59
processes of aging, the processes of damage are
00:10:02
conserved or that's a piece of the field.
00:10:04
So if you develop a drug that targets the way a body breaks
00:10:07
down over time, it may have a positive impact on these
00:10:10
classical diseases that are today thought of as totally
00:10:13
separate and one like nice. You know anecdote to that is the
00:10:17
only lifespan extension study has been run to completion in
00:10:20
dogs. Was actually run by the dog food
00:10:22
company Purina in the late 1990s.
00:10:24
There was a cleric restriction study which is kind of the OG
00:10:27
way to extend lifespan is one of the reasons why tech grows
00:10:30
intermittent fast and they showed a tier lifespan extension
00:10:33
in Labradors. But more interestingly to this
00:10:36
thesis they showed A2 year delay in incidence of cancer and
00:10:40
osteoarthritis. Again, two single.
00:10:42
If they do what? Sorry, what's the?
00:10:44
Caloric restriction. So these two unrelated diseases,
00:10:49
cancer and osteoarthritis. There was a delayed incidence of
00:10:52
almost two years in these dogs who are calorically restricted
00:10:56
compared to the dogs that weren't.
00:10:59
And so that suggests that these dogs are potentially aging at a
00:11:02
slower rate or aging more healthily, which is why they
00:11:05
lived longer, but also why these unrelated age-related diseases
00:11:08
developed later. In life.
00:11:09
So that's how I think about it. And we can do this
00:11:11
pharmacologically as well. So like Celine said, like the OG
00:11:15
way of extending lifespan in animals was to just reduce their
00:11:20
number of calories. And like you go into this, your
00:11:22
body goes into this like famine preservation sort of mode.
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Some processes run slower, but overall your lifespan is
00:11:30
extended and there's now more than 80 different.
00:11:35
Drugs or genes that you can tweak that not in dogs, which
00:11:38
are bigger and more complex and live longer.
00:11:40
My background is as a mouse geneticist, so so you know, I I
00:11:43
live in the world of mice more than dogs.
00:11:45
But in mice, you know their natural lifespan is only about 2
00:11:48
1/2 years. So you can run these studies in
00:11:51
mice really, really easily and with large numbers to get good
00:11:54
statistical confidence. And a drug like there's one
00:11:57
called rapamycin that a lot of people know about and talk about
00:12:01
which hits this this pathway called M Tor.
00:12:04
M Tor is one of the key pathways that is on when we're eating
00:12:07
three meals a day and gets kind of cranked down when we are not
00:12:12
eating three meals a day, right. When you eat once a day or you
00:12:14
know if you're reducing your number of calories and just by
00:12:18
giving small amounts of this drug to mice, you can increase
00:12:22
healthy lifespan by like close to 20%.
00:12:25
And you get exactly that same phenotype that Celine is talking
00:12:27
about where it's that the reason that the mice are living longer
00:12:30
and healthier is because they're.
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Memory is working better, they get less cancer, their skin is
00:12:36
in better condition, their joints are in better condition.
00:12:38
And it's all of these things happening at once, because
00:12:40
you're fiddling with something core to how cells and tissues
00:12:45
function properly, not waiting for, like trying to untangle
00:12:49
that this very, you know, disease specific, what's the
00:12:51
name of that drug? It's called rapamycin.
00:12:54
Are people taking that? So this is.
00:12:56
A triggered. This is a whole, so rapamycin is
00:13:00
actually an FDA approved drug. And the things that it is FDA
00:13:04
approved for are and it's sort of like it's got a couple of
00:13:08
variants, but it was first approved as an immunosuppressive
00:13:12
therapy for people who are getting kidney transplants
00:13:14
because large amounts of this drug actually suppress your
00:13:17
immune system. And then it was kind of approved
00:13:20
for two other things which is treating sort of mid to late
00:13:23
stage cancer patients to prevent their tumors from growing.
00:13:26
And then finally there's a specific rare disease that where
00:13:30
this this pathway is cranked up that causes epilepsy and giving
00:13:34
this can reduce the number of seizures.
00:13:36
So those all three are like high doses of this and it's never
00:13:41
been widely experimented in low doses in humans.
00:13:44
Some people are self medicating but.
00:13:48
Man, we just don't know very much.
00:13:50
And the difference between the low dose and a high dose and
00:13:53
like when you jump into potential side effects versus
00:13:55
when your dose is too low and there's just going to be no
00:13:58
benefits. We have no idea in America am I
00:14:03
allowed as an individual to take a drug off label of my own
00:14:07
direction, or what sort of the freedom an individual has to
00:14:11
take a drug that's prescribed for one thing and mess around
00:14:14
with it for other reasons. So there's two levels here.
00:14:18
There's first what your doctor can do.
00:14:20
So a physician in the United States is allowed to prescribe a
00:14:26
drug off label with no restrictions.
00:14:29
If if your doc said hey Eric, like take this drug, it's for
00:14:33
breast cancer, but you know you have whatever and I want you to
00:14:37
take this. Like there is no authority that
00:14:40
can stop the doctor or you from making that decision.
00:14:44
There are two sort of like upstream ways that that happens
00:14:48
less. First is that your insurance
00:14:50
company may not pay for that drug and there are prohibitions
00:14:55
from, let's say I run the biotech company that created
00:14:58
that drug for breast cancer. I can never tell the doctor, oh
00:15:01
please. Also you know recommend it for,
00:15:05
I don't know cough or something like this, right?
00:15:08
So upstream, those are the protections we have in place.
00:15:11
But the doctor patient relationship is pretty open,
00:15:16
Yeah. Do you consider like Ozempic
00:15:21
wigovy to be life extension drugs you want?
00:15:25
To stop, You're the human guy. OK.
00:15:29
I can say intent put. Put that on my tombstone, the
00:15:33
human guy. I'll say this, my favorite
00:15:38
little anecdote about weight appetent suppressants is that
00:15:42
one of the bigger dog drug failures was a drug that was a
00:15:46
weight loss drug for dogs as approved years ago that worked
00:15:50
predominantly by suppressing the desire to eat and it was a huge
00:15:53
market failure despite the fact that dogs have a very high
00:15:56
incidence of obesity, just like humans.
00:15:58
The reason being is that people they perceive their dog wanting
00:16:02
dinner or wanting a treat as love.
00:16:05
And so when the dog suddenly isn't hounding you for dinner,
00:16:08
isn't hounding for a tree, and it's just kind of ignoring you,
00:16:10
they're like, God, my dog doesn't love me as much.
00:16:12
Like, oh, cheated. So one of the things we
00:16:14
explicitly look at in our studies is ensuring it doesn't
00:16:18
reduce desire to eat and doesn't reduce weight.
00:16:22
Because it would probably be a commercial failure, so I will
00:16:24
not be doing Ozempic for dogs. But James, I'm sure you have
00:16:28
more human biology expertise here.
00:16:31
So what I would say on the more critical side, jumping off from
00:16:34
what Celine was saying, is that Ozempic is not a drug that I
00:16:38
think is suitable for everybody, right?
00:16:41
We're not going to end up in a situation where really healthy
00:16:45
people who have a great diet and exercise are in relatively good
00:16:48
shape, but aging should go on Ozempic, right?
00:16:51
But it is a. Really damn good drug for
00:16:53
obesity, and it looks like the effects are just really powerful
00:16:58
for obesity and for type 2 diabetes.
00:17:00
Like this is worthy of its blockbuster status.
00:17:04
The main drawback that makes this from a risk reward
00:17:08
perspective, good for diabetics and people who are obese, but
00:17:13
not good for people who don't have those things.
00:17:16
Is that when you stop eating? Because that's the way that this
00:17:19
drug works, right? You.
00:17:20
You feel full even if you haven't eaten that much.
00:17:23
When you're not eating, you consume more fat for calories,
00:17:26
but you also consume muscle. So even for these people that
00:17:29
have a lot of extra fat, about 1/3 of the weight that they lose
00:17:33
is actually muscle mass. And if you look in people who
00:17:36
are older, right? So in your 20s and 30s, if you
00:17:39
lose a little bit of muscle mass while you're.
00:17:42
Cutting off a lot of extra adipose tissue, you can then hit
00:17:45
the gym and rebuild that muscle mass.
00:17:47
But like, once a person is about 60 or so, like, rebuilding that
00:17:52
lost muscle is really hard and it increases your risk of all
00:17:57
sorts of other things, right? It basically makes people more
00:17:59
frail, so they're more likely to fall, more likely to get
00:18:02
orthopedic or sports type injuries if they lose a bunch of
00:18:05
muscle. And so talking our own book
00:18:08
here, a little bit similar to what Celine's talking about in
00:18:10
her dogs, The drug that Cambrian has that is furthest along, it's
00:18:14
actually already treating human patients is a drug that also
00:18:19
targets. It's kind of like the flip side
00:18:20
of the Ozempic GLP, one coin where Ozempic makes you eat
00:18:25
less. But what if, instead, your body
00:18:27
thought it was exercising more? And so the same kind of group of
00:18:30
people that have been studying aging biology have known that
00:18:33
exercise is one of the best things we can do for aging since
00:18:36
forever. And the main way that our body
00:18:38
gets the positive benefits of exercise translated into
00:18:42
increased muscle mass and more calorie consumption is by
00:18:44
activating A pathway called AMPK.
00:18:47
And Cambrian has the first drug that activates AMPK safely that
00:18:53
has already started human trials.
00:18:55
And what we see is just like. In in obesity studies, you see
00:18:58
the same sort of thing where like you can put mice on a high
00:19:00
fat diet and they lose weight even if they're eating more than
00:19:06
than mice off the drug. How much?
00:19:07
That's more in that trial. So it's been in about 100 people
00:19:11
so far. And then the study that we're
00:19:13
doing will have about another 50 people treated over the next
00:19:15
year. And do you own that drug
00:19:17
outright or is it sort of a minority stake or how does that
00:19:20
actually work? So the way that Cambrian works
00:19:23
is we own a majority stake in every drug in our pipeline
00:19:28
underneath us, but we don't own 100%.
00:19:31
We kind of share that upside, usually with specific scientists
00:19:35
that have. Kind of been working on those,
00:19:38
those products, sometimes other investors as well that have been
00:19:41
working on these products since before we got involved.
00:19:44
So we're not like a private equity group that's coming in
00:19:47
and acquiring things. We're coming in and we're taking
00:19:50
a controlling stake, but leaving upside for other people that
00:19:53
aren't want to ride this train along with us.
00:19:56
It's a cool business model. While we're talking around
00:19:58
books, yeah, what's the drug that you have this farthest
00:20:00
along? For dogs.
00:20:02
Yeah. So one thing I wanted to quickly
00:20:03
note and then I'll answer your question is what James is saying
00:20:06
about safety is super key. It's like actually one of our
00:20:09
key philosophies when I started the company is the drug might
00:20:12
not work, but it shouldn't do any harm.
00:20:14
The way to think about the safety of an aging drug is, and
00:20:17
I believe there's a quote from an ex FDA individual is that it
00:20:21
needs to be basically as safe as water.
00:20:23
And the reason being is because if I'm giving you a drug today
00:20:26
to prevent something you may or may not get in the future and it
00:20:28
kills you tomorrow or maims you tomorrow.
00:20:31
That risk reward, it's not acceptable.
00:20:33
Or even having increased risk of something bad happening to you
00:20:36
like increased frailty is not acceptable.
00:20:39
So that's one of the challenges of the field and one of the
00:20:41
reasons like James and I are working on relatively simple
00:20:44
drugs, so to speak. There's a lot of companies that
00:20:46
are doing these like really sexy, you know, epigenetic
00:20:49
reprogramming, gene therapy, da, da, da.
00:20:51
And like my work might not work. We'll see.
00:20:53
But at least I can't speak for James.
00:20:55
I'm pretty sure you're mostly doing boring molecules.
00:20:57
I'm only doing boring molecules. And that's because safety is so
00:21:02
important and you just don't want to introduce variables when
00:21:05
you don't know how something will behave in the body.
00:21:08
I think that's also been key and this is an interpretation.
00:21:11
They haven't hit this to me explicitly, but I think that's
00:21:13
been key to a lot of our success with the regulatory bodies is
00:21:17
demonstrating safety far and beyond what is required of us
00:21:22
legally. To answer your question on talk
00:21:25
in our talk in our book, I was trying to think.
00:21:27
Have like a metaphor. Like a dog.
00:21:29
Our furthest along drug is a daily drug for old dog lifespan
00:21:33
extension. So for dogs of almost any size,
00:21:36
any breed, for already showing signs of aging and you know, if
00:21:40
everything goes well, we're running towards it being on the
00:21:43
market in 2025. Really 2025.
00:21:46
So lots of work. I know, I know.
00:21:48
It's so cool. Lots of work.
00:21:50
You you've passed some trial or is it the same with dogs we have
00:21:54
trials or? Yeah.
00:21:57
So we've completed the safety studies awaiting FDA feedback,
00:22:00
but it looked really nice. We've completed the efficacy
00:22:04
work, awaiting feedback from the FDA.
00:22:06
And then the thing that kind of determines our go to market
00:22:08
timeline is actually manufacturing.
00:22:11
And manufacturing is like a pain in the ass.
00:22:12
It's hard, don't get me wrong, but it's a great problem to have
00:22:17
because it's completely physically possible to
00:22:19
manufacture a beef flavored pill at scale.
00:22:22
It's really just like how operationally competent are we
00:22:24
ever gonna pick the right supply chain partners, We're gonna
00:22:27
manage them correctly or we're gonna see around corners.
00:22:29
So you know if we're wrong and like we're quarter delayed or
00:22:32
something. It's not a binary existential
00:22:34
thing. Assuming the FDA agrees was the
00:22:36
technical packages that we believe are very strong showing
00:22:39
that the drug does what we think it does, what's the mechanism
00:22:43
for this drug? Yeah.
00:22:44
So kind of what James was talking about earlier with
00:22:46
caloric restriction when we started the company, we wanted
00:22:49
to take his little biological risk.
00:22:51
As possible, right? Like it is almost certainly true
00:22:53
that you can extend a dog's lifespan with a drug because
00:22:56
we've done it and everything from you know yeast to mice all
00:22:59
the way up and there's correlation data and people.
00:23:01
So it'd be weird if that wasn't possible also in dogs.
00:23:05
The question then what is the highest probability and also
00:23:07
safest thing that we could use in dogs to show that a drug can
00:23:10
be approved for lifespan extension.
00:23:12
And so as I mentioned earlier, the only lifespan extension
00:23:15
study that I'm aware of that's been run to completion and dogs
00:23:17
is at Purina lifespan extension study, which is using chlor
00:23:20
restriction. And so the drug emulates the
00:23:23
benefit or the molecular impact that has had on the dogs when
00:23:27
they chlorically restrict specifically working on
00:23:30
metabolic fitness and also fat tissue function and the
00:23:33
age-related decline of fat tissue function.
00:23:37
Cool. I mean we've sort of touched on
00:23:39
sort of different parts of life extension you both have invested
00:23:43
also and sort of see the space just sort of like a framework of
00:23:46
sort of the different categories of longevity that we're sort of
00:23:51
seen from what you're saying you're like okay, we're like
00:23:54
simple molecule to sort of the most like far out there which
00:23:58
you said like epigenetic or just give me this sort of roadmap of
00:24:02
the different buckets of this that are happening right now.
00:24:06
I can take a shot at that one. Yeah, I know that's like the
00:24:09
bucketing the world. That's like frameworks.
00:24:11
Yeah, yeah. And he's the real investor.
00:24:13
I just late investor. I did, I was at Longevity Fund
00:24:17
and I like invest a little bit personally, but I'm a much
00:24:20
better founder than I am investor.
00:24:22
So the way that I look at this space, I'm gonna give a title to
00:24:28
three different buckets. I'm gonna call them innovations,
00:24:32
Moon Shots, and Snake Oil. And I think spicy.
00:24:37
I love it. Come with the spice, James.
00:24:39
Like innovations, Moon shot? Reading on this podcast and
00:24:42
snake oil. Yeah, hell yeah.
00:24:44
Who's gonna be in the snake hole, loyal?
00:24:47
So, so I would describe innovations as anything that
00:24:53
looks an awful lot like other preventative medicines that we
00:24:58
can like draw a Direct Line from that work to us.
00:25:02
Right. And there's a series of
00:25:04
preventative medicines that I think are really going to be
00:25:06
useful comparators to the first true drugs that we think of as
00:25:11
coming out of the longevity or aging biology space that like
00:25:13
everyone's going to draw comparisons to like statins,
00:25:16
right. So we already talked about
00:25:17
Ozempic, which I think is going to have a lot of comparators
00:25:20
because a lot of these drugs are going to come in for cardio
00:25:22
metabolic disease. Statins is the other fantastic
00:25:24
example where like you have a risk factor and you.
00:25:28
They start giving people a drug based on their risk factor to
00:25:31
prevent heart attacks and strokes and so.
00:25:33
So I think those parallels which like Selena already touched
00:25:36
upon, they are every single one of them small molecules that
00:25:41
have a really good safety profile that target well
00:25:45
understood molecular mechanisms mostly having to do with
00:25:49
treating metabolic health. There's this big mess of cardio
00:25:53
metabolic, like how our heart works and how our our metabolism
00:25:56
work. That's sort of where the first
00:25:59
wave of innovation, I call it the first dominoes to fall, are
00:26:03
going to be in that innovation bucket.
00:26:05
My second bucket is moonshots, which is like we have some
00:26:09
really powerful, interesting ideas, many of which are getting
00:26:13
funded, that are sort of like a next layer of where this space
00:26:18
could go. And things like, you know,
00:26:20
probably the interface between innovations and moonshots is
00:26:23
like biologics that we have. For example, there's a protein
00:26:26
that's naturally produced in people that when it's present
00:26:31
prevents a woman from going into folliculogenesis, prevents
00:26:36
someone from ovulating so. So with an injection of this
00:26:39
protein, one could potentially completely control ovulation,
00:26:43
which we think if you then maintain the ovarian reserve,
00:26:47
could prevent menopause. Like, that's a cool ass idea,
00:26:51
right? It's more complicated than a
00:26:53
small molecule daily pill that's affecting metabolic disease.
00:26:57
But like, that's the kind of cool moon shot type approach
00:27:02
that one of the ones that we're taking.
00:27:04
There's also stuff like reprogramming.
00:27:07
The epigenetics of a cell is one that's talked about a lot to
00:27:10
like a more immature state. So that then it can become kind
00:27:13
of repair damaged tissues. It's another moon shot that has
00:27:16
like some really promising data coming out.
00:27:19
Especially there's a company called Life Biosciences that has
00:27:22
reversed like eye diseases or optic nerve damage in monkeys
00:27:27
already and like so that will be probably used for more specific
00:27:32
functions, right? Like in the.
00:27:35
Menopause case, it'll probably be used in IVF first.
00:27:38
The epigenetic reprogramming will probably come out in like
00:27:41
nerve degeneration in the eye 1st.
00:27:43
And then if it's safe, if it's really, really safe, then it can
00:27:48
expand, especially if it can walk in the sort of footprints
00:27:53
in the snow made by the innovative drugs, right.
00:27:56
And one of the reasons I'm so excited about the work that
00:27:58
Selena's doing is because of the strategy that she's taken in
00:28:01
Dogs Like She's. Jumped ahead of the rest of us,
00:28:06
you know just human people in terms of talking about this
00:28:09
multi disease prevention, correcting metabolic dysfunction
00:28:13
to prolong health span and like hopefully that will allow us to
00:28:18
walk in loyal's footsteps a little bit as we talk about
00:28:20
doing this in people. Yeah, you guys are welcome.
00:28:24
I think it should take a tax on all the longevity companies.
00:28:27
Like you guys need to give me like 5% of your fund.
00:28:32
Especially the epigenetic companies that raise like a
00:28:34
billion dollars. I mean, and to be honest, I
00:28:37
wanna say like this, this moon shot category, I don't wanna
00:28:41
throw any shade at that because I think that those techniques
00:28:45
and technology and the biology underlying a lot of this is
00:28:48
really damn exciting. It's.
00:28:51
Throw some shade, I can throw your well, yeah, we're all
00:28:54
waiting for the snake oil category.
00:28:56
Come on. Okay.
00:28:57
And then the third. 1 can be thrown here too though.
00:28:59
Right. The third one for me is then the
00:29:01
snake oil category, which is basically everybody who is
00:29:05
taking advantage of the fact that longevity has become one of
00:29:08
the biggest, let's call it mega trends of like fascinations of
00:29:12
people, especially in the developed world over the last
00:29:15
three or four years. And realize that even without
00:29:20
validating any new technologies, we can just like sell stuff to
00:29:24
people who are scared of their own mortality and scared of
00:29:27
their own decline the way that humans are.
00:29:30
If you're super rich post post wealth, what do you wanna spend
00:29:33
your money on Like living longer?
00:29:35
Higher quality of life? And especially if you control a
00:29:38
venture fund, not even your money.
00:29:40
What do you wanna throw it at? Things that could.
00:29:42
Yeah, it's interesting, I think that.
00:29:46
Where the bigger bucket of snake oily things are living is
00:29:50
outside of the venture backed company space.
00:29:52
It's more in the direct to consumer space stuff that's like
00:29:55
we want to sell stuff to people. Now what can we sell?
00:29:57
What can we make profit on today?
00:29:59
That's the biggest snake oil bucket.
00:30:01
We're like the red flag that jumps in my mind is like, OK, is
00:30:05
your R&D and clinical trials, is that coming out of an actual R&D
00:30:09
budget or is it coming out of your marketing budget so that
00:30:11
you can run ads on Facebook and Instagram saying?
00:30:15
Clinical trials suggest this. And if it's the latter category,
00:30:18
it's probably in the snake oil bucket.
00:30:20
I think there's been a bunch of efforts over the past three or
00:30:25
four years to try to establish some kind of standard around
00:30:28
what good looks like and it all kind of funnels down to are you
00:30:33
going to run clinical trials to test whether this thing actually
00:30:39
works before you start selling it?
00:30:41
And if the answer is yes, you're probably in bucket one or two.
00:30:44
If you're serious and the answer is no, or you say you are, but
00:30:48
you've really got no shot at it and there's no real plan there,
00:30:51
you're probably in bucket 3. The snake oil companies are, you
00:30:55
know, you could argue that they're like trying to get
00:30:57
things to consumers immediately. Drugs take years to get approved
00:31:00
da da da da. But I think that they don't
00:31:02
realize, like the biggest hurdle I have to overcome when I'm
00:31:04
educating veterinarians and regulators, what we're doing is
00:31:07
that it's legit, right? Like the number one pushback we
00:31:11
get is It sounds too good to be true or.
00:31:14
Is this, is this really real? Is this just like, you know
00:31:16
fountain of youth stuff And that's dangerous.
00:31:19
It's dangerous for a field because it means legitimate,
00:31:21
skeptical people are not going to engage in it or much more
00:31:24
difficult to engage in it. So all the kind of, you know,
00:31:28
we're here to make thousand year lifespans, even 120 year
00:31:31
lifespans. Like, maybe it's possible, but
00:31:33
leading with that is was so unnecessarily controversial was
00:31:36
often just an attempt to get, you know, earned media so more
00:31:39
people will buy their thing versus leading with, you know?
00:31:44
Good science and that these are preventative medicines to reduce
00:31:46
risk of future disease, which is the most consensus thing on the
00:31:49
planet, right? To reduce the risk of developing
00:31:52
a future disease cheaply and safely.
00:31:54
So yeah, these people piss me off.
00:31:56
What are people shit every day? You know this?
00:31:59
I mean, it's like they're sort of like vitamin type pitches or
00:32:02
what? Vitamins are common, yeah.
00:32:06
So I think there's also a bunch of like.
00:32:09
Interventional stuff that can be done without regulation.
00:32:12
So there's a big push in stuff that.
00:32:15
And like, the big tragedy for me is some of these things may
00:32:17
actually be helpful. We just don't know because no
00:32:19
one's really like the worst. People are so busy selling this
00:32:23
that no one's really asking the scientific questions, right.
00:32:25
So there's like people out there, you know, offering 10s of
00:32:30
$1000 for your daily hyperbaric oxygen containment and like.
00:32:36
You know, you got to do these ice baths and you got to do
00:32:38
these skin treatments and you got to do this, you know,
00:32:42
plastic transfusion. Yeah, OK.
00:32:44
That like. Like those things do exist.
00:32:46
Blood transfusion in the room. Like do you where is that fit in
00:32:51
in this because I mean blood boys, I feel like that's what
00:32:54
sort of the regular persons taken from Silicon Valley or the
00:32:57
show or whatever, you know? So I think it's a perfect like
00:33:00
microcosm of. Both the scientific potential
00:33:04
and the hucksterism and snake oil possibilities of this.
00:33:08
Cuz like if you go down to what got people excited, there are
00:33:11
some mouse experiments where you took young plasma, put it into
00:33:15
an old mouse, and the old mouse just got better in a lot of
00:33:19
ways, right? And you take the old plasma, put
00:33:21
it into the young mouse, the young mouse behaves worse.
00:33:24
Figuring out why exactly has been.
00:33:28
Actually kind of a fraught scientific odyssey where we
00:33:30
still don't have good answers as to why after almost 15 years of
00:33:34
looking at it. And there have been some
00:33:37
companies. The one that I'm most admiring
00:33:40
of is called Alkahest, which spun out of Tony Whiskerrey's
00:33:43
lab at Stanford and actually created what they called drugs
00:33:47
based on chrono kinds. So things that either go up as
00:33:52
you age and therefore you want to remove, or go down as you age
00:33:55
and therefore you want to replace.
00:33:56
And they were able to use this to say like, oh, well, these
00:33:58
could be good drug targets. And they were actually bought by
00:34:02
the biggest plasma company in the world called Grifols, which
00:34:06
is a Spanish pharma company. And they were as like a positive
00:34:09
story both from a pharma perspective and from a venture
00:34:13
kind of like investment perspective.
00:34:15
So like, that's a nice little story that I can get behind and
00:34:18
I have a lot of respect for the people of Alca Hest doing
00:34:20
something hard and pioneering and then on the other side you
00:34:23
have like. Whether it's people trying to
00:34:25
open individual clinics or or physicians or non physicians who
00:34:30
are like OOH, I'll bet we can sell plasma for whatever $4000 a
00:34:36
pint to people who heard about these mouse experiments and for
00:34:40
whom we have really no evidence that this will help them.
00:34:42
But you know, there was a piece in the Guardian or whatever
00:34:46
saying that it worked parentheses in mice.
00:34:50
And like that's that snake oil bucket.
00:34:52
And like I would say 98% of the conversation that we hear in the
00:34:56
media or out in the lay press is about that second bucket and 10%
00:35:01
is about the actual science that has been making some positive
00:35:05
steps. And there's a couple of other
00:35:06
companies that are trying quietly to do some hard but
00:35:09
interesting work in that space. We're not one of them.
00:35:12
But I have a ton of respect for those people and I think that
00:35:15
the core scientific insight, like there's probably something
00:35:17
there that could be important. We just don't know exactly what
00:35:20
it is. Yeah.
00:35:21
All right. I feel like this is the time to
00:35:23
bring up Brian Johnson, which I have generously not led this
00:35:26
conversation with. But, you know, he's the rich guy
00:35:30
who's, you know, doing a bazillion different things to
00:35:33
extend his life, recaptures youth.
00:35:35
The media is, like, fascinated by it, you know.
00:35:39
Yeah. As serious people in the space,
00:35:41
what do you make of what he's trying to do?
00:35:46
My short answer is I think the best thing Brian Johnson could
00:35:49
do to extend his lifespan would be investing in loyal or
00:35:53
Cambrian or another legitimate aging company.
00:35:57
Does it have to be us? I understand the grift, but I
00:36:02
think he doesn't understand pharma and drugs and the reality
00:36:07
of actually getting something approved.
00:36:09
I don't think he's ever going to work getting something approved
00:36:12
or statistics, you know, science.
00:36:14
Physics, you know, all these things, which is fine.
00:36:18
You don't have to. I mean, I I can't code right,
00:36:21
but it actually slows down the progress of the field.
00:36:26
Like the biggest issue I have to worry about when I'm fundraising
00:36:31
is making sure people don't feel like we're the next serrano's or
00:36:34
like other illegitimate thing that's going to embarrass them.
00:36:36
Embarrassment insurance. Trump Insurance is a huge thing
00:36:39
that I have to build into everything I do when I'm
00:36:42
fundraising for this company. And I'm a really fucking good
00:36:45
fundraiser, right? So think about like, how many
00:36:47
people who have, like, interesting scientific concepts,
00:36:50
new drugs that should get piloted.
00:36:51
I just aren't happening because there's such a negative bias
00:36:54
when you're coming in with this field.
00:36:56
It's not just because of him. But he sure as hell isn't
00:36:58
helping, and I wish you'd use his platform to educate in a way
00:37:04
that would promote the entire field and not become a problem
00:37:06
that I I literally have to explain away probably once or
00:37:10
twice a week. Are there things that he's doing
00:37:14
that make sense or don't, or I don't actually know all the
00:37:16
different? Do you have a sense of what he's
00:37:18
actually doing? People are constantly
00:37:21
experimenting with their own sort of personal fitness to try
00:37:26
to make themselves healthier. This is something that at
00:37:29
different scales, we're all doing right.
00:37:31
Many of us are taking some supplements, whether it's just a
00:37:33
multivitamin or fish oil or more exploratory things.
00:37:37
Beyond that, we change our diets, right people go keto
00:37:40
people, do paleo people. Get breakfast right?
00:37:44
So, like that kind of playing around with diet and exercise
00:37:50
and supplements is something that so many people are doing
00:37:54
day-to-day by themselves. And this is just sort of like a,
00:37:57
you know, twenty 20s. Internet like look at the far
00:38:01
extreme and trying to spotlight on that version of what people
00:38:04
have been doing forever. But as far as scientific value
00:38:07
like what this could give to the community of like understanding
00:38:10
something, there is 0 value in any of the stuff that he is
00:38:14
doing. Like anyone who has thought
00:38:16
about like how we move from theory to truth in medicine
00:38:22
knows that you have to change one variable at a time.
00:38:25
You have to do it in a large number of people and.
00:38:29
Then you can Start learning little things and it would takes
00:38:33
years to learn little things. So saying like, hey, I'm gonna
00:38:37
change this and that and I'm gonna combine 20 different
00:38:40
things into my protocol and like what's gonna come out of it is
00:38:43
like I feel a little better. I feel a little worse for one
00:38:46
person. There's no scientific value in
00:38:48
that. There's only media value in it.
00:38:50
Yeah, this is such a meme with Silicon Valley tech people, I
00:38:54
cannot tell you the amount of tech what for to talk out is.
00:38:57
Massive combo studies. So like, Wow Pharma is so dumb.
00:39:01
They only use one drug at a time, but aging is complex and
00:39:05
they should use multiple drugs at a time.
00:39:07
And we're going to do these combo studies and I'm like 1.
00:39:10
Like the path of getting that approved is like, good fucking
00:39:12
luck. But two, you can't actually
00:39:15
attribute and tell like aging is such a complex thing.
00:39:17
We haven't even gotten one thing through.
00:39:20
You're not going to be able to then like, start.
00:39:23
Like all the all the other way and have like multiple things
00:39:25
that you're permitting over a long period of time.
00:39:28
Like these studies take even for us and dogs, we're running a
00:39:30
pivotal lifespan extension study.
00:39:32
It's going to be at least four to five years and that's in
00:39:35
dogs. Like in people it's going to be
00:39:37
way longer. So like usually with somebody
00:39:39
saying, oh, pharma is so dumb, why didn't they just realize
00:39:42
XYZ? The answer is they have realized
00:39:45
and there's probably a reason they're not doing it.
00:39:46
And there's a lot of other things wrong with pharma to be
00:39:48
clear that like, you know, me and James are like, you know,
00:39:51
working on countering. But they're not done.
00:39:54
That was exactly my question. I mean, yeah, it seems like a
00:39:57
premise of some of the longevity spaces, that there's something
00:40:00
wrong with Pharmaceutical industry, sort of traditional
00:40:05
medical investing, drug development.
00:40:07
Like. Another way of asking that is
00:40:09
why should venture capitalists who aren't experts in this be
00:40:12
the ones asked to fund something?
00:40:14
It sort of suggests that there's something broken about the
00:40:17
traditional model, or that this is fundamentally different in
00:40:20
approach. I see that on you know some of
00:40:23
the moon shot ones you guys are talking about, but if you're
00:40:25
positioning yourself as more as we believe in standard clinical
00:40:28
trials, we want to be you know incrementalist to the extent
00:40:31
that's that's possible. Yeah.
00:40:33
So I I would say this is probably the stake around which
00:40:37
I've built my whole career and something that I've brought to
00:40:42
what attribution I can claim for it myself versus all of the
00:40:45
other people who have been. Kind of touting a similar idea.
00:40:49
But the fund that I built before Cambrian and now Cambrian as one
00:40:54
of the larger sort of drug developers in this space was
00:40:57
premised around the idea that it's not that the FDA is broken,
00:41:01
it's not that pharma is dumb and ignoring this, It is in fact
00:41:04
that we are at the precipice of a brand new revolution in
00:41:09
science that is just now ready and mature enough for drug
00:41:12
development. And it is this.
00:41:14
Fertile ground of new science that is going to make the great
00:41:18
drugs of the next 10 or 20 years.
00:41:21
In the same way that, like, you know, 20 years ago you'd want to
00:41:24
be studying basic mechanisms in cancer, which made the best
00:41:28
drugs of the 20 Tens and the and the 2000s.
00:41:33
And like 15 years ago, you might have been wanting to study basic
00:41:36
mechanisms of metabolism and obesity, which led to like the
00:41:39
GLIP ones and these sorts of things now.
00:41:42
This is not different than the rest of pharma innovation, and
00:41:45
it's going to create drugs that are going to be the most
00:41:48
important drugs of the next 10 or 20 years.
00:41:50
That's the investor pitch and the pitch to pharma and to the
00:41:55
FDA that is both most rooted in what the actual scientific
00:41:59
reality is and gives the most upside for people spending their
00:42:04
time and money making this space happen.
00:42:07
So I think that's like the stake.
00:42:09
I, I always called it the stepping stone approach to kind
00:42:13
of bringing these aging drugs to their best and highest use,
00:42:16
which is try to find whichever way makes sense to make those
00:42:19
discoveries coming from the basic biology of aging, show
00:42:23
that they're safe, effective and ultimately profitable right as
00:42:27
quickly as possible. And then you can start doing
00:42:31
what me and Celine are most excited about, which is what
00:42:34
happens when you start giving this sort of tool.
00:42:37
Into the hands of someone where they can use it for prevention
00:42:40
before they get sick. And that's not an easy thing to
00:42:42
do first, because you need to know in humans that something is
00:42:45
really safe and really effective before you can start doing that,
00:42:49
generally speaking. Yeah, one thing I will say here
00:42:52
that was that I think loyal is a really good example.
00:42:55
So I agree with everything in jail said.
00:42:57
Like one of the things we've done is like, we try to be like
00:43:00
the hill we die on, the hill that we're radical on as a drug
00:43:02
approved for lifespan and healthspan, extension and
00:43:04
everything else, we are extremely.
00:43:07
Traditionally competent on right.
00:43:10
It's like I'm you know the the young techie founder, da, da,
00:43:15
da, whatever of the company. But like my executive team are
00:43:17
experienced pharma executives right?
00:43:20
Like they're the best possible people for a job.
00:43:22
One thing I will give tech a lot of credit for is loyal never
00:43:24
would have been funded by traditional biotech investors of
00:43:27
biotech funders, right. I was 24 years old when I
00:43:30
started the company. It was basically my first job,
00:43:32
like I worked for Laura, but it was a two person fund.
00:43:36
We were working on dogs, we were working on lifespan extension
00:43:39
and we didn't have anything right.
00:43:41
It was an idea and an insight, and this side ended up being
00:43:44
correct but nothing else. Who took the first bet?
00:43:47
Laura and Greg Rosen, Greg's A Box Group and Laura's at
00:43:51
Longevity Fund and then First Round and Collaborative Fund.
00:43:54
We're also big investors in the seed round and I mean we'll see,
00:43:57
but so far so good but. This is definitely something
00:44:01
that, like, I don't think I could have walked into the
00:44:03
traditional East Coast biotechs. They would have laughed me out
00:44:05
of the room. They would have said, like,
00:44:06
apply for our associate program. Like, we'll consider you maybe
00:44:10
actually, just kidding, you didn't even like finish your
00:44:12
PhD, go home. And so I think there's a line
00:44:15
where I take that very seriously that I've brought.
00:44:19
Like most of my investors, I'm one of the first times they've
00:44:22
invested in a biotech or company like this.
00:44:25
I have got responsibility. Super.
00:44:26
Seriously. Because I want them to invest in
00:44:28
more companies after us and more weird companies.
00:44:31
But again, it's like I don't take advantage of that situation
00:44:34
by being radical and like doing shit that like reduces
00:44:37
probability of success. Like we still are very
00:44:39
conservative and everything else except for the radical core
00:44:42
ideas of you know a young solo founder woman can build a dog
00:44:46
longevity company and a consumer brand around these
00:44:48
pharmaceutical products and like hopefully get it approved for
00:44:50
lifespan extension. So it's a balance, right?
00:44:53
But I think like a lot of these snake oil people really take
00:44:56
advantage of the fact that the average Silicon Valley person
00:44:59
doesn't understand science or how a drug is approved at all.
00:45:02
Yeah, you know, there's this sort of meme that Silicon
00:45:05
Valley, you know, hasn't been friendly enough to women.
00:45:08
I mean, certainly there aren't sort of as many women founders
00:45:11
as you would like. But it's interesting that you're
00:45:13
saying in some ways that you found VC sort of more open to
00:45:18
the idea of sort of young founder type at least then and
00:45:22
you think would. Have been totally.
00:45:24
I mean, there's a ton of sexism in Nessa.
00:45:27
Like, don't get me wrong. Like the way I would explain it
00:45:30
is like when I walk into a room, the assumption of my competency
00:45:33
is not zero or positive. Like it might be of a much
00:45:36
traditional like bro founder. It's usually negative and then I
00:45:39
have to work within that conversation to get them to zero
00:45:42
and positive. We're just frustrating because
00:45:43
I'm like, I have a lot to learn, etc.
00:45:47
But I am a really good operator. Like, we've gotten this company
00:45:49
really far in four years with a lot less money than a lot of the
00:45:52
other groups have had. And again, starting from zero.
00:45:55
But I've kind of gotten like, I used to just get so pissed.
00:45:58
Like, I remember I pitched one fund and afterwards I called the
00:46:00
partner. I was like, do you not realize
00:46:02
your stupid GP was mansplaining longevity to me the entire time?
00:46:05
Like, I got so, so irritated, and now I'm just like, whatever,
00:46:10
it's fine. I'm gonna be richer anyhow than
00:46:12
these guys. And like, I'll create my own
00:46:14
fund and support. People building interesting
00:46:18
stuff, but you just gotta play the game to win the game.
00:46:20
And the game has the rules it has.
00:46:21
So I've just been wondering, this whole time, is loyal only
00:46:25
about dogs, or is this like a road map to humans?
00:46:28
I'm sure there's a world where it's like you get the perfect
00:46:30
drug, you're ready to go. But like, how do you think about
00:46:33
it in terms of your focus? So it's both loyal has I believe
00:46:39
a relatively like. Hard but straightforward path to
00:46:43
a multi billion dollar company just off the dog aging drugs.
00:46:46
Just if you look at comparable market size dog drugs like
00:46:49
heartworm, preventative heart guard makes half a billion a
00:46:52
year flea and tick next guard made $1.2 billion last year of
00:46:56
revenue, high margin revenue. So there's a clear path there
00:46:59
and if we only do that that's really awesome.
00:47:02
But dogs are also the best or one of the best biological
00:47:06
models of human aging because it Co evolved with us a shared
00:47:08
environment for 10s of thousands of years.
00:47:11
And most importantly to develop age-related diseases over time.
00:47:15
So a dog gets cancer not due to you know it should ton of
00:47:18
inbreeding like a mouse has but just environmental factors.
00:47:21
A dog gets never thought to get nerve disorders.
00:47:24
Dog gets dementia that we've looked at cognitive decline in
00:47:27
dogs. My favorite study we ever ran
00:47:30
was a cognitive decline study in dogs.
00:47:32
They get osteoarthritis. And so if something works in
00:47:35
reducing the onset of cognitive decline or cancer or whatever in
00:47:39
a dog, which will learn in this thousand dog companion dog study
00:47:43
we're running later this year, starting later this year, it's
00:47:46
not 1 to 1 to work at a human, but it's as sure as hell really
00:47:49
awesome biological insight that might translate over.
00:47:53
So yeah, I mean my goal is to build an aging pharmaceutical
00:47:56
company. I think agings need larger than
00:47:58
oncology. There's no one oncology company.
00:48:00
There's no one Parkinson's company.
00:48:02
There's gonna be many, but I wanna build one of the defining
00:48:05
ones. And hopefully James does too,
00:48:08
and we'll be able to talk about the good old days.
00:48:10
James, you can go after a bunch of drugs at once, I guess, so
00:48:13
you sort of get to hedge your bets.
00:48:14
Yeah, I think I know where you're going, which is something
00:48:17
along the lines of like we get asked a fair amount, What does
00:48:22
like are all of these people who are trying to do real drug
00:48:25
development within this? Broad aging biology.
00:48:28
Space. Aren't they all competing with
00:48:30
each other? Isn't everyone like trying to
00:48:32
get the first drug to increase health span and that will be
00:48:36
like the pot of gold at the end of the rainbow that one person
00:48:39
wins? And it's really fascinating
00:48:41
because this ecosystem, this kind of community is uniquely
00:48:49
collaborative within any tech or biotech or pharma.
00:48:54
Kind of competitive landscape that I've ever seen because so
00:48:59
many of the drugs are targeting completely different things,
00:49:03
right. So like you have Ozempic and and
00:49:05
like Novo Nordisk has their GL P1, right.
00:49:08
And then Lily has their GL P1 and it's you're going to take
00:49:11
one or the other, right. And and like they both wanted to
00:49:14
go and they're like Headtohead competing with each other.
00:49:17
Celine's drug and all of our drugs, they don't even target
00:49:19
the same molecular pathways. They're just kind of coming from
00:49:23
the same broad field of how we studied cellular biology.
00:49:27
So Cameron has 15 different drugs and development and none
00:49:30
of them are targeting the same two things.
00:49:33
This is something so much broader than just like, oh, we
00:49:37
found a new way to treat obesity like and it's this pathway which
00:49:41
is how you get real head to head competition.
00:49:43
This is instead like we've just opened the doors to hundreds of
00:49:48
new ways of approaching cellular dysfunction, at its core, of
00:49:52
which some will be right and some will be wrong.
00:49:55
And they're even going to be approved for different things
00:49:58
first and then once they're approved, when you get the first
00:50:01
one. That is approved for a healthy
00:50:03
lifespan extension, then that will be a tide that raises all
00:50:06
ships. Cuz now there are footprints to
00:50:09
follow towards a prevention study in the way that the most
00:50:12
successful Staten was like the third Staten that was approved,
00:50:16
not the first one I. Was just gonna add quickly on
00:50:19
here. So loyal is kind of like mini
00:50:22
came written in that way. So we have three programs that
00:50:24
we're developing concurrently. And the way I thought about it
00:50:28
and this is actually like a pretty big fight we had in the
00:50:30
early days on the board because like the traditional tech
00:50:33
company only develops one product, right, And you focus
00:50:36
all your energy on that one product.
00:50:37
But the big difference between tech and biotech is that your
00:50:40
product is locked in, right? And once you start doing your
00:50:44
studies, that is your final product.
00:50:45
And you might do like different formulations that are the right,
00:50:47
but the active ingredient that's driving the lifespan extension
00:50:50
is locked in. And so there is nothing you can
00:50:53
do. There's no iteration.
00:50:54
There's a product market fit finding you can do to make a
00:50:57
drug work if it doesn't work. I always say there's a God in
00:51:00
biology, even if you're not religious, because it is
00:51:02
predetermined whether our drug will work or not.
00:51:05
It's about us finding the truth as effectively as possible.
00:51:08
And there's other execution bits we can do to increase
00:51:10
probability of success post that binary truth, but that's core
00:51:14
importance. So what we did is we have three
00:51:17
programs, two around large dog lifespan extension, 1 around old
00:51:20
dog lifespan extension that share a really concrete core.
00:51:24
That is how do we prove the FDA of the drug works?
00:51:27
What does the pivotal lifespan extension study look like?
00:51:30
There's a regulatory strategy, but like all these different
00:51:32
things and it's an idea that a drug could be developed to
00:51:35
extend lifespan extension. And then it's slightly different
00:51:38
mechanisms or active ingredients on that.
00:51:41
So almost everything is shared that is able to be held true and
00:51:45
then we're able to externalize out the risk that we can't
00:51:48
control, which is the binary, yes, no, whether the drug works,
00:51:51
we're now beyond that like we we have positive data for our drug
00:51:55
programs, which is great. But that's how I designed the
00:51:57
company early on because I was also very cognizant of the fact
00:52:01
that if our first drug failed. It would just blow out in
00:52:04
general the opportunity of me or anybody else to build a dog
00:52:07
longevity company, even though our first drug failing would
00:52:10
have not been at all reflective of the validity of the thesis,
00:52:13
right? There's an expected amount.
00:52:15
Not every drug works, even if you're operating perfectly.
00:52:20
This is the hardest part of pharma that only statistically
00:52:23
only about 12% of drugs that start clinical trials get
00:52:28
approved and. Within biotech companies, it's
00:52:31
slightly better. They do better than pharma or we
00:52:33
do better than pharma. It's but still like nearly 20%
00:52:37
and that's the highest that you get from the statistical
00:52:40
operators. The Brian Johnson idea, I think,
00:52:42
you know, people are so excited about it, partially you know,
00:52:45
because people want to know what to do with their own health.
00:52:48
I mean it's like you know like you sort of said we've had
00:52:51
Atkins, we've had so you know intermittent fasting.
00:52:53
You know there's so many, so many things.
00:52:56
And certainly I obviously like what what you should do in a
00:52:59
societal level to prove a drug versus what an individual who is
00:53:03
actually aging right now and not cannot wait for for things you
00:53:07
know for drugs to get approved. Those are sort of very different
00:53:11
considerations and you know you you both are sort of measured in
00:53:16
science based. So probably the the last people
00:53:18
to sort of like push on everybody what what you think
00:53:22
they should do. But I am curious what you would
00:53:24
recommend for people now that's sort of available to them or
00:53:28
like are yeah, are you taking anything sort of strange
00:53:32
yourself? Like, I'm curious in terms of
00:53:34
just like an individual like who've looked at this space, how
00:53:37
you approach and what you recommend to your family and
00:53:40
friends? So I think one of the best
00:53:43
predictors slash like rough categorizers of whether somebody
00:53:46
you have charlatan or not. Is like how much they work on
00:53:49
their own personal longevity. Like all of the people who are
00:53:52
like super legit in the field, like Laura Deming, the Longevity
00:53:56
Fund founder is like a very famous example of this.
00:53:59
They often do things that are like negatively selected for a
00:54:03
lifespan extension, right? So, like when I was working at
00:54:05
Longevity Fund, all we ate at the fund was like chocolate,
00:54:08
Cheerios and dandelion chocolate, and I was like the
00:54:11
meals we had at the fund. You know, having pumping up your
00:54:16
blood glucose levels that high, not good for longevity.
00:54:19
I don't do anything like I work out I guess, but hey, I'm like
00:54:24
not doing longevity drugs for myself and I think that's
00:54:26
actually a really important thing to like keep cognitively.
00:54:29
Like. I think people who intertwine
00:54:31
their fear of mortality into their pursuit of aging drugs
00:54:35
become dumb, right? Because it's a fear based way of
00:54:38
approaching the field. Versus a logical way, they're
00:54:41
like, God, I have to find something because it's my
00:54:42
mortality on the line. Versus I see this as like my
00:54:48
thing to help other people. And like, I try to think about
00:54:50
it as other people and try not to focus on myself.
00:54:53
Maybe that'll get harder as I get older, I don't know.
00:54:55
But I think it's a pretty good predictor.
00:54:57
You don't take vitamins or anything.
00:55:00
I think literally nothing. Like I'm trying to eat more
00:55:02
vegetables. I'm vegetarian, but like, I love
00:55:05
on frozen and canned vegetables, OK, like I am.
00:55:09
Don't do anything. I do.
00:55:11
Just maybe if the drug is approved and your vet says so
00:55:14
prescribed her drug, I don't steal it.
00:55:18
But no, otherwise not. I don't do anything, James.
00:55:20
What's your approach? So I'm like a decade older than
00:55:22
Selena's and and I still get called like the young kid on the
00:55:28
on the biotech block most of the time.
00:55:30
And I take a little bit more of an experimental approach like we
00:55:33
were talking about before. I think almost everybody that I
00:55:37
know is thinking about. Especially like, so for example,
00:55:40
in my my family, we've had two people die of Alzheimer's in the
00:55:46
last, you know, in the last five years.
00:55:49
My boyfriend's mom is starting to show signs of this.
00:55:53
And so we're thinking, okay, well, what can we do to maximize
00:55:56
the time that we have healthy to be around and to be with each
00:56:02
other. And so there are things that I'm
00:56:04
doing, I think. The best, like validated things
00:56:07
that we really know will work is don't get diabetes regularly
00:56:13
exercise, eat fruits and vegetables.
00:56:16
Get enough sleep, don't change time zones every week or two.
00:56:21
This is 1. This is one that, like I was I
00:56:24
was in Europe last week, I'm in Europe next week.
00:56:26
Like it fucks with you for, like, a while.
00:56:31
I get sick every time I come back from a big time zone
00:56:33
change. Every single time without fail.
00:56:36
So, you know, I do play with some supplements, but like,
00:56:40
there's some that have real evidence behind them, the best
00:56:42
of which is fish oil for the prevention of heart disease.
00:56:45
I have two grandparents who died of heart attacks in their 50s.
00:56:49
And so, like, I care a lot about my heart health, you know,
00:56:52
beyond that, we just don't have a lot of evidence.
00:56:55
And so whatever, you know, people are doing, like they can
00:56:58
play with this or that, but it's just like it's.
00:57:03
Not backed by facts until it is and and the big part of I think
00:57:08
this whole field and if if there's one message that I would
00:57:11
love someone listening to this to walk away from is like
00:57:14
ultimately we need to create new truth in order to know new
00:57:17
things. And the only tool in medicine
00:57:20
that we have for creating new truth is running randomized
00:57:23
placebo-controlled clinical trials which will create one
00:57:27
little new piece of knowledge at a time and like that just takes
00:57:30
a long ass time. And this is all brand new
00:57:33
science where we have a pretty good idea that, like it might
00:57:36
work in mice, but before we know that it will work in humans and
00:57:40
especially with the diversity of humans that exist, which is way
00:57:43
more than the diversity of mice. Like it's just going to be a
00:57:46
while before we can think about how this longevity science is
00:57:50
going to impact everybody's day-to-day life.
00:57:52
There's just not that much outside of the the stuff that we
00:57:56
knew before. You know 10 years ago that we've
00:57:59
just gotten more and more evidence the placebo effect is
00:58:02
so fucking strong that it would outperform almost any drug on
00:58:06
the market today. So until you can disentangle
00:58:10
what scientifically is going on at their mechanistic level
00:58:14
versus what's kind of happening at the psychosomatic or the the
00:58:17
placebo level, like we just don't know.
00:58:20
So what I advise people is like get excited, do things like try
00:58:25
stuff. Right.
00:58:27
Be healthy, be active, enjoy life, think that you're going to
00:58:30
live a really long time, and then also try to do these basic
00:58:33
things that we know are supported by, like the
00:58:36
Physiology underlying your body. If you have high cholesterol,
00:58:38
take a statin. If you're overweight, like
00:58:42
exercise, have a good diet, maybe end up on one of these
00:58:46
obesity or metabolic drugs that are pretty good if your doctor
00:58:50
recommends but like apart from that.
00:58:53
Wait until the science comes out and see if we have like novel M
00:58:57
Tor inhibitors or caloric restriction mimetics or AMPK
00:59:00
activators that will be coming not that far in the future.
00:59:04
If they show to be safe and effective, that could be used
00:59:07
for people. But that's really like the next
00:59:10
frontier. This is why this whole longevity
00:59:11
space it's going to create a world that is so different than
00:59:14
the one that we have now, because it will be grounded in
00:59:16
truth instead of in speculation. Great.
00:59:22
I think that's a great end point for the show.
00:59:23
Thank you both for coming out this.
00:59:26
Is fun, Celine. I always love doing podcasts
00:59:28
with you. Yeah.
00:59:29
This was sincerely one of my favorite episodes.
00:59:32
I mean, it's such a great topic. So thanks so much.
00:59:37
My pleasure. Yeah.
00:59:38
Thanks for inviting me. That's our episode.
00:59:40
Thanks to James and Celine. Shout out to Tommy Herron, our
00:59:43
audio editor, Riley Kinsella, my chief of staff, Young Chomsky
00:59:48
for the theme music. Annie Wen for booking the
00:59:50
guests, please like comments, subscribe on YouTube and
00:59:54
subscribe to the subsetnewcomer.co Thanks so
00:59:57
much. Goodbye.
00:59:58
Goodbye. Goodbye.
01:00:00
Goodbye. Goodbye.
01:00:01
Goodbye. Goodbye, Goodbye, Goodbye.
