Scientists Disrupt the Aging Game - James Peyer #569

Scientists Disrupt the Aging Game – James Peyer #569

(distorted electronic music) – [Announcer] Bulletproof Radio, a state of high performance. – [Dave] You're listening to Bulletproof Radio with Dave Asprey. Today's cool fact of the
day is that if you're more than 100 years old, you're probably biologically younger than
your chronological age. Some researchers at UCLA look at aging as a biological program
written on your DNA, and they've seen evidence that
there's a biological clock that marks milestones
along your life's path. These guys are monitoring aging in mice by examining molecular
tags called methyl groups, which attach to various locations on DNA in a process called
methylation, and if you've read any of my books, like The Bulletproof Diet or Head Strong, I talk about methylation and how about a third of
us suck at methylating, which will make you old and
inflamed unless you address it by taking the right forms
of nutrients, like 5-MTHFR, but hey, if that was
completely Greek to you, that's all right, it's all
over the Bulletproof blog. Methylation is an epigenetic
modification of your DNA, and it's kind of like flagging a passage in a book with sticky notes. You attach a tag. It doesn't change the
information of the book. It just draws attention to those passages and tells you you can
skip the other pages. These researchers at UCLA
measured DNA methylation at 350 different spots
in the human genetic, we'll call it instruction
book or in the genome, and as we age, 193
locations accumulate tags, kind of like when you see
too many flyers posted on a bulletin board, and
at 160 other locations, methylation is stripped away as you age. So knowing how much
methylation is normally found at each spot given your chronological age allows researchers to calculate
your actual, biological age. What that means is that maybe
we don't just have to look at your telomeres at how wrinkly
your face is or how saggy different parts of you are to
figure out how old you are. We can actually look
at very detailed things that go beyond even just
looking at your genes. And the researchers at UCLA
found that supercentenarians, well, they call them
semi-supercentenarians, if you wanted to be
really technical about it, those people who are 105 to 109, they tend to be biologically
younger than their age. So do their kids compared to other people. So the rate of aging of these people and their kids is slower than normal. Now, that's really exciting,
'cause you know what, that sounds like a superpower in humans. Maybe it's one that you and I can also learn how to do, just by changing maybe the number of methyl
donors in our diets. Why don't we play around with
that and live a long time? All right, let's get onto today's show. Today's show is with James Peyer, who is a founder of Apollo Ventures. And you might not have
heard of Apollo Ventures. In fact, when you hear it, you probably either think
space program or Rocky, but he has nothing to do
with either one of them. He has to do with life sciences
and investing exclusively on breakthrough therapeutics
around anti-aging. This is one of the guys allocating dollars to the technologies that
are gonna get me 50% of the 180 number that
you heard me talk about. I'm gonna live to at least 180. I know we can do 120, 'cause I've seen it. In fact, UCLA scientists are studying people who are doing it today. Well, I want the other 50%. I'm counting on guys like James to go out and make investments in areas where we spend very little historically. We spend more on all sorts
of random political things and things that just
don't make a difference. If we applied a tiny
percentage of that towards some of the things that James is
actually putting money into, I think we can solve many
of the problems of aging. We probably won't be immortal, but we'll be a lot closer
to that than we are today. James has a fascinating background, and he's one of those guys
who's disrupting aging by saying, we're gonna take
what the big pharma companies have done, which is take
investment dollars and put it to work on these drugs, and
say, what if we could tie into that ecosystem and
actually make all of us, all of us live longer,
and instead of going out and replacing that stuff, let's just use the existing systems to
make ourselves age less. James, welcome to the show. – [James] Dave, thank you
so much for having me. It's great to be chatting with you. And I don't wanna
disappoint your listeners. After that buildup,
maybe they all expected that Steve Horvath, who
leads that UCLA group, would be here, who is also
a super, super cool guy talking about methylation
and aging clocks, and we can definitely
discuss some of that work, but hopefully they'll be
satisfied with me here instead. – [Dave] Well, okay, you're
not exactly a sloucher. You have a bachelor's degree
in immunology, you started the first biotech company
to get Kickstarter funding, and, let's see, you
have a doctorate from UT and a National Science Foundation fellow working on the basic
biology of stem cells. So you barely made the
cut for Bulletproof Radio. (both laughing) But basically, what's cool
about you is you're just not a money guy, because frankly,
there's a lot of money guys. I've worked in venture capital, and I love what it does
to accelerate startups. It's real, and I have $68 million of venture funding for Bulletproof. So, that model works. But a lot of the people doing investment, they're investment professionals. They're not domain experts,
and then a lot of them are domain experts, and then
when you get the money people plus the domain experts
working on an investment, that seems like that's when magic happens. You're a domain expert. – [James] Yep, I think that's true. My whole group thinks of
ourselves as scientists first and investors second, and so,
we really get super, super excited about a specific
mechanism of action or a cool new way to develop a drug
or a way to target aging. That's kind of the hook that
brings us into a project much more than some of the
traditional financial metrics. – [Dave] All right, I gotta
ask you this question, and I'm gonna give a little
bit of context for people that don't know how venture capital
works, which is most of us. Well, so the way venture capitalists work is we go out there and say, all right, I'm gonna find some
people with lots of money. They're going to give it to
me, I'm going to invest it, and I may give them more
back, but those people who give the money to the VCs
are called limited partners. And half of a VC's job is
to go out and say, hey, you wanna give me some
money that I can invest? So, you just said, we're scientists first
and investors second. Don't your limited partners run
screaming when you say that? – [James] So, (Dave laughs) I would say, if we went back 20 years in the biotech ecosystem
that existed then, and this is all from an
investment perspective, right, so from the perspective
of these limited partners, then yeah, they would, because
what you had 20 years ago was everybody saying, oh,
well, what are the returns, how are the IRRs, which is
the internal rate of return. What are the IRRs for biotech
funds versus other types of funds, and let's just
play a pure financial game. But a series of venture
funds that most people don't know about, 'cause they all exist in the footnotes of
the innovation economy, a couple of biotech venture
funds started a model that was all led by groups of
scientists who would partner with other scientists from academia to actually start biotech
companies together with them around projects that they loved. And because they loved these projects and then built the teams around them, pharma companies started paying attention, and it turns out that
in the last 20 years, these scientist-led and
science-led venture funds have kicked the ass of all of
these finance-focused funds by almost a factor of two. (Dave laughs) And so now, the trend in
the VC Space that thankfully we're able to participate
in is that biotech funds should be science-led and hypothesis-led. And we don't make deals that
don't make financial sense. We care about all the financials
and stuff, but to get us interested in the deal,
it's all about the science, and we think that if you can hang your hat on that nugget of truth, if
you really, really, really believe in the science,
then there's gonna be a way to make it work or at
least take a good shot on goal and developing a new medicine. – [Dave] It makes sense to
me, and one of the things that frustrated the heck
out of me in Silicon Valley, I was a co-founder of
a part of the company that held Google's first
server, and I ran a program at the University of California
for five years teaching engineers how to build horizontal
scale internet systems, so like, kind of a deep
geek on that stuff. And I just realized, over and over, the best technologies never won. It was always the best marketing. But when you can get the best technology
with the best marketing, that's when you have the
biggest impact on the world. So it's not enough if you're
a crazy inventor and you make the ability to double rat
lifespan or something. If no one hears about it,
you failed as an inventor. So you have to have both,
and the role of having a science-led fund like
you guys looking at aging is, well, maybe you don't want
someone who's just marketing, because you're gonna
lose your shirt on that. – [James] For sure, and
actually, we were just talking a little bit before the
start of the show about using social media and media reach
and these sorts of things, and this is something
that I freely confess I know very, very little about. It's not at all my domain expertise. But one of the reasons that,
when we started Apollo, we were thinking, all right,
well, are we gonna do stuff like what you were
getting really interested in and what you're doing with Bulletproof? Are we gonna do longevity foods? Are we gonna do nutraceuticals? Are we gonna do supplements, cool devices that can
play a role in longevity, or are we just gonna do drugs? And what we realized is that, you know, my team is more than 50%
PhDs in aging biology, and so, what we realized is
that we didn't really know a whole lot about that whole
marketing aspect of things. – [Dave] You guys must have
the coolest dinner parties. (Dave laughs) – [James] It's a pretty great group. It's really become a family over the last few years
since we've started. But so, we didn't know
enough about how to win in that space to do exactly
what you're talking about, bring together the efficacy
with the right marketing, but one of the cool things
about drug development is that, for better or for
worse, the marketing is done mostly by the pharma companies
after you do clinical trials, and until then, there is a
marketing component to it, and you have to do the right PR and you have to be noticed
by the right people, but everyone who you're talking to has deep domain expertise
and is gonna be looking at your full data package
that you put together, and so we can kind of
nerd out on the science and really let the science drive much more of the value of these
companies than we could. We just couldn't invest in confidence in these other domains. – [Dave] So what you're basically saying, if I put words in your mouth,
is that you are investing in core technologies that you think are going to reverse aging
or extend human lifespan, and you're going to then take those things that you develop and
infiltrate the pharma industry in order to get the
pharma companies to start doing that instead of
the other stuff they do? – [James] That's essentially correct, yeah, and we can talk in
a little bit more detail. I think it would be a fun
conversation to have of like, how we're going to do that,
because it's something that I think is the core
platform or the core conceit of Apollo as a fund, is the
strategy of how we're going to trick the pharma and biotech industry, and I say trick with big air quotes, to really, really investing
heavily into drugs that will dramatically extend
healthy human lifespans. – [Dave] It sounds like
I just got you to admit that you're going to hack big pharma. – [James] I wouldn't say that. I like to use the term
collaborate, collaborate is good. (both laughing) – [Dave] You know, I'm cool
with whatever word you choose, because there are a good number of people listening to the show right now who come from a functional
medicine or a naturopath, and a lot of anti-aging
people who are listening, and some of them have this,
if it's a drug, it's bad. But the Bulletproof perspective, and certainly my experience
is that you know what, some of these pharmaceuticals
are really powerful. You can turn on and off
PPAR delta and gamma. You can take smart drugs that
actually protect your neurons from all sorts of bad things,
and they're pharmaceuticals. I took three different
pharmaceuticals to extend my life this morning, and
I'm grateful for them. But most pharmaceuticals
have more side effects than benefits, especially for regular use. So if you can change that equation, you're actually helping big pharma, but you're helping the rest of us too. – [James] Yeah, so, I mean,
I think that observation is generally true and it's
a reflection of the fact that most pharmaceuticals
were developed to treat really bad, acute conditions, right? Things like even a relatively humble drug like a statin, which lowers cholesterol, statins were first
developed to treat like, highly dangerous familial
hypercholesterolemia, people who genetically
had such high cholesterol that they were in danger
of having a heart attack or a stroke starting from 15 years old, and they were tested for
the safety profile there, and then they made their way to preventing heart attacks and strokes
in the rest of us. – [Dave] If they really do that. (Dave laughs) That might be the marketing guys. – [James] Yeah, they
definitely do some work on heart disease, but the
new data that you alluded to came out that there's not
an overall lifespan extension, because they didn't look
at this more holistically. There's increases in cancer
rate and neurodegeneration rates for people who are longterm statin users. – [Dave] It turns out that the liver makes cholesterol for a reason. – [James] How 'bout that, right? (Dave laughs) And so, that's almost another
topic that we could dive into, which is like, how the fundamental shift that's gonna have to happen
in the medical industry that's occurring in the
functional medicine world already and I think will
infiltrate the pharma world in the next decade or
two, which is this shift from thinking about diseases
in individual silos. Oh, this is heart disease,
we only have to care about the heart, we only have to care about the elasticity of
the arteries and that's it, to thinking about, okay,
well how does the damage that accumulates to increase
the risk of heart disease, what are the similarities
between that risk and the risk of Alzheimer's disease and the basic mechanisms linking the two? That's the shift that pharma's gonna have to get over
in the next 20 years. – [Dave] I hope it's a
lot faster than 20 years. Being interested in the
food side of things, and having run an anti-aging nonprofit group for a long time, I also realized that a
pharmaceutical company can make this treats a disease claim. As a food company, it
is, at least in the US, expressly illegal for me to
tell people that my stuff, the stuff that I make could possibly or even in studies that
are out there do things like reverse Alzheimer's
disease and all that. So I did a calculation in my head. I can't say it was too
quantitative, but I said, all right, if I know,
based on the science, that I'm creating a certain
set of benefits for people, which I am required by
law to be vague about, if I do that marketing job
well, of driving behavior change in a direction that is in
people's best interest, even if I'm not allowed to
say expert that it does, I am morally and ethically
okay with that, like, I'm doing a solid for people,
but it's really frustrating, because if we could
just let food companies say what our stuff does, it
would transform everything. But the second I say, medical
condition and food, the food magically transformed, with a
wave of a wand, into a drug. – [James] Yeah, you can't
make capital C claims, right, claims of an effect of any kind
of tool, whether it's a drug or a food or whatever,
as if it were a drug. – [Dave] Exactly, and
even for supplements, you really can't do the same thing. Even if there's 500 studies
that says a supplement does something to whatever,
heart disease or whatever, you simply are not allowed
to say that your think it supports healthy
cardiovascular whatever, but you can't actually say,
you know, 90% of the people who take this live
longer, stuff like that. So it's very frustrating,
but as an investor, I think you have to pay attention to that. It's harder to invest in companies who can't say that the do. – [James] Absolutely. This is one of the reasons
that we kind of talked a little bit about before
that we only invest in stuff that's gonna through an
FDA clinical trial system and can eventually make
those capital C claims, and one of the reasons that
I think it's really important to do this is, you know, also,
you alluded to this before, is that that 50% of the 180
years that you're gonna get from the 120 to 180 part,
that's gonna have to come not just from the new
medicines that we know are possible right now, like the things that are working in mice
to extend mouse lives now, but it's gonna have to
be the current generation of things and then the
next iteration of those and then the next iteration of those. And the thing that makes me
most, shall we say concerned or the thing that
animates me about thinking about the future here
is trying to make sure that this moment that
we're having in longevity and anti-aging and so on
is persistent, and the way that I think it will be
persistent and spread beyond the experimenters in
the world who are willing to try new things and live
longer and live healthier, is showing even the most doubtful people, even the most skeptical
in the most robust way, that this is really,
really, really working and you cannot deny this, because we went and played by your rules,
we went into your system and showed you that this is
all real, and so now that this is real, let's let
this change the whole world. And I think that that's
the way we're gonna unlock the second and third generation,
things that aren't invented yet in order to get to that
180 that you're wanting, yeah. – [Dave] How do you overcome
the skeptical mindset, one that says, that can't happen; therefore, it didn't happen. So you present evidence
in a study that says this just happened, but then, based on what we used to
believe to be reality, then sort of the current crop
of researchers or doctors or scientists will say, no,
no, no, we simply are going to reject that science
and say it's not real because it can't be real. On its face, that's
anti-science, but I've seen that so much in anti-aging and
nutrition and everything else. What do you do as investors when you deal with people like that? – [James] So the approach that
we have to building companies in this space is even more
subtle than having to have those conversations, and we
can talk about it maybe first on a theoretical level, and
then do a little case study. So the way that we approach
developing a new medicine for longevity, let's call
them longevity therapeutics, right, that's this whole
class of new medicines, is by starting out saying,
okay, here's something that can extend healthy lifespan of
a mouse, or at least target one of the hallmarks of aging that we know builds up in our bodies to
cause the diseases of aging. Start with that in a mouse,
and then find some existing indication every single medical
professional in the world agrees we should be using a drug to treat, and whether that's cardiovascular disease or Alzheimer's disease or, in some cases, things that are not just
aging-related diseases, like rare genetic disorders
and these sorts of things, and apply that drug to
that condition and build a little biotech company just
focused on that condition, not necessarily talking
about and waving the flag of anti-aging, at least not
right away, and then saying, oh, by the way, after we
treat this first condition, we'll go to a second and
a third and a fourth, and it turns out that
there's all of this evidence in mouse models that this same
drug that we're developing will be applicable to 15 different things. And then, when you start
getting your second and your third and your
fourth thing approved, there's a mechanism within the
FDA to flip a switch to say, oh, we should just give this
to everybody who has this risk. – [Dave] Got it. – [James] And that mechanism,
thankfully, already exists. We don't need to do as dramatic as redefining aging as a
disease or any of these other things that people
sometimes talk about. We just have to be very,
very strategic in the way that we plan our clinical
trials with these drugs. So that's, on a theoretical level, not just Apollo Company's, but
most of the drug development biotech companies in this space are following a model
somewhat similar to that in their development of new medicines. – [Dave] James, how old are you? – [James] I'm 32. – [Dave] So, I gotta say this. I really got into anti-aging
at around age 29, for me. I'm in this nonprofit. Most of the members that
sit on their boards, they're 60, 70, 80, 90, pretty much at least three
times my age on average. (James laughs) So, why are there so few
people under 35 or 40 into anti-aging, and
why are you one of them? – [James] Interesting. Well, it's funny that you say
that, because I always feel like the demographic
distribution is the opposite. If you go to interest group
conferences, and I guess my world is maybe a little
bit different in exposure, but like, when I go to the
big pharmaceutical conferences and talk with a bunch of
guys who have been getting cancer drugs approved
for the last 30 years, and then I go and spend the
next day at a conference talking about aging biology,
the guys talking about cancer and Alzheimer's disease tend
to be 20 years older than me, and the guys talking about aging biology tend to be around the same age. – [Dave] Because you're
talking to academics. – [James] Yeah, academics, but
also industry professionals. – [Dave] Oh, industry professionals, okay. – [James] Yeah, just
because drug development is a really tough career to go in, most people have MDs and PhDs. Then they spend time at
big pharma companies. Then they go into the biotech world. Success takes a long time, so by the time you
reach the upper echelons of the biotech ecosystem, most of the CEOs in our companies, for example,
are usually 50 and over. – [Dave] Just because
it takes 20 years to get the experience you need
in order to do that job. – [James] Exactly, yeah, yeah,
'cause those are the guys who, by and large, have
the right experience to take something forward
and who can take the energy of a younger guy like
me and then combine it with the fact that they
have 30 years experience developing drugs or 25 years
experience developing drugs in order to kind of form the team there. In any case, but getting
back to your direct question, I think there is some truth
to it, which is that people respond to their incentives, and people are inherently short termists. So if you're young, there's
this age-old thing of, you know, you're young
and you feel immortal, and if you feel immortal,
why do you care about aging? If, once you're getting on a little bit, and for many of us, including me, it was kind of triggered
by a traumatic experience, where age-related diseases
hit you in the face. So I got interested in aging when I was 15 and my grandfather got cancer, and then as he was
dealing with his cancer, I was kind of dealing with
what that did to my world and the way that I thought about life and what life meant and what
we were all moving towards, and emerged from that, for
a little while, in a really dark space where I started
thinking, oh my God, the best that we can
ever hope for is to spend a little bit of time
faffing about and then wait for one of these diseases
to hit us and then die. And then after a little
bit more reflection and a lot of reading
and so on, I was like, ah, wait, there's something I can do here. If I spend my life trying to
push that barrier back as far as I can, to beat it back
with all the force that I can, then that can be something
that provides a very nice sense of meaning and
sense of purpose for me. I describe it to some
people from time to time saying like, if you have
a bomb, an explosive vest strapped to your chest,
and it was counting down, no matter what the timer was
on the countdown to detonation, if it was five minutes
or if it was 70 years, you would probably not
be able to focus on a ton of other things until
you took the vest off. And so that's kind of
the way I'm engaging. – [Dave] Okay, that makes good sense. So you see it affect someone you love, and you realize this is unjust. I mean, I got into it because I had pretty much the diseases
of aging before I was 30. Like, I had arthritis
since I was 14 in my knees, lots of stretch marks from
being obese, high blood sugar, pre-diabetes, all this
stuff that is now gone, because a lot of it was
optional, and it was lifestyle-related, and now
I'm exceptionally healthy and younger than I was, and
maybe a little bit wiser. – [James] Yeah, the diseases of aging hit you in the face in
a really personal way. – [Dave] Yeah, and like,
I'm not going back. (Dave laughs)
It kinda sucks to be old, and granted, I'm sure I
wasn't actually old, but I can tell you, you wake up in the
morning and I sure felt old, that's for sure, and it was frightening. – [James] It would be interesting to know if the methylation biomarkers
that you had changed. – [Dave] They probably did. – [James] Is there evidence? – [Dave] I mean, I did
the very early methylation genetic testing with a woman
named Amy Yasko who was the first to really call this
out in the autism community, and I'm a poor methylator
and things like that. So I've been on methylating
nutrients for 15, 18 years, because they make a difference,
right, and you can tell. Oh, I wake up and I don't feel old. I think I'll do that some more, and since then, so much lab
testing has become available. It's to the point where now we know, a third of people don't folic
acid that's added to our food. For them, it's pretty much toxic. It builds up in your cells,
and you can't get rid of it. For everyone else, it's probably good. Like, what if we use the
right form for everyone? In fact, things that people
wouldn't think about. Right now, if you wanted to use the biocompatible form of
folic acid in food everywhere, you couldn't do it, and the reason is that there is no accepted way of measuring low levels of that form of folic acid. So if you put on the back
of your label that there's 50 milligrams of folic acid
in something, well, if it's the old school folic acid
that's based for a third of us, you can do it, but for the new stuff, there's no way to prove it's in there and that it's still in there a year later, so from a labeling law
perspective, you can't do it. So there's stuff like that
that completely limits. – [James] Wow, I didn't know about that. – [Dave] I mean, it's one
of millions of things, where we're saying, well,
we wanna do the right thing as food companies, and we're
working really hard on it, but we're dealing with
rules that were written in an era where we didn't
have the science we have now, and so you see stuff happening
in China or Singapore or Med City in India, where
people are just going ahead and doing what they wanna
do, and it's a little bit frustrating, but also, we
have a lot of food safety here that is enviable in other
countries, and that's why if you go to China, they pay
extra for American foods, because they know that it
doesn't have weird stuff in it. So, I don't know the answer to that, but it's just an example of
that one little nutrient, how deep you could go with it, right? – [James] Mmhmm, interesting. Yeah, I think that the question
of the regulatory aspect and like, how this will interface
with this dramatic shift in how we prevent disease,
'cause it's not really gonna be about treating
disease anymore, right? You and this broader group
of thinkers and physicians who are thinking about functional medicine and thinking about health
span have already made the shift, but the healthcare
system will have to catch up to thinking about prevention,
and figuring out how we're going to regulate
prevention in this aging space is really one of the key driving questions that I think many kind of
observers on the fence, so people who aren't hilariously against slowing down the aging process, but who also aren't, like
you and I, so gung-ho for it, they're like, oh, well, how
are you gonna test this? How are you gonna get this regulated? How is a drug gonna enter
common, widespread use within the existing system, whether it's through good
marketing and a tool there or changes to the FDA and food labeling or changes to the FDA and drug approvals? And I think that it's awesome actually that you started your show
with this methylation clock, because I think that this
technology is actually at the core of one of the things that's
gonna help drive this bridge, like we talked before about
how Hall is developing all of these new medicines that we think can get you your 40 or
your 60 extra years, from 120 to 180, and they'll
be approved for other things. They'll be approved for genetic diseases, they'll be approved for
heart attacks and whatever, and then the challenge is,
you get those drugs approved. You still need to do a clinical trial to get your capital C claims from the FDA, and you can't do a trial
that's just a lifespan trial, give it to a bunch of people
in their 30s, 40s, and 50s, and see when they drop off
or see when they get cancer or see when they start developing
mild cognitive decline. And what we'll have to
do instead is use things like the aging clock,
things that are predictors of what we call multi-morbidity risk. And the FDA's made some
signals that they would be willing to accept one
of these good biomarkers and use that, and interestingly, we were talking about cholesterol earlier. Cholesterol did the same thing. It was established as a biomarker, and then Lipitor and the
statins were approved based on the ability
just to move cholesterol in the blood, which has
problems, as we discussed. But it also allowed the
pharma companies to justify the cost of the clinical
trials, 'cause they could then have some time on the patent
lifespan of those drugs so that they could make some money there. The same thing is gonna
happen with the aging drugs. There's gonna be a compressed
clinical trial time so that we can prove, quote-unquote
prove whether they work on these aging biomarkers
in shorter trials, two, three, four years, get them approved, and then that's when they'll
enter wide distribution. Anyway, that's the idea that
we have for the space overall. – [Dave] I love it,
because it's really hard to prove that something
will double human lifespan, because if you wanted to
take it to double yours, you'll be dead before
you know that it worked. – [James] Exactly, right? That's the key problem there. – [Dave] What's your stance
on, I'm gonna call it bio-freedom, and this is the
idea that it's your biology and you have a fundamental
human right to do whatever you want to
manipulate it without anyone telling you you're not allowed to do that. Where do you stand on that spectrum? – [James] So, I put myself
completely in favor of it, but I don't want to be,
and I don't think anybody should be in the business
of telling people what they truly can and can't do. I've talked at conferences
and so on about the fact that I'm on Metformin
because I think that it's an interesting longevity
drug, even though I, you know, there's no FDA approved
condition that I have that should allow me to take Metformin. – [Dave] Let me define
Metformin for people who haven't heard me talk about it before. Metformin is a very
common and well understood anti-diabetes drug that
in multiple studies is tied to life extension,
and I've written about it in Head Strong, actually,
about the pros and cons of it. So anyway, keep going. – [James] Okay, so I believe in this idea that we should be able to experiment in n=1 experiments and
self-organize into bigger self-experimentation groups
and these sorts of things. I think that there is,
we should first of all be allowed to do it, and
second of all, there is a way to get useful data to make
real progress from that, but kind of where I come into
the field is that right now, there isn't a widely established mechanism to move an entire field
of scientific inquiry forward dramatically without
the mechanisms that exist of like, the clinical trials
an the capital C claims that we were talking about
and this sort of proof, that you'll have little
threads of progress where knowledge will be
sequestered in groups of people who have tried it on
themselves or who have really, really dove quite
deeply into the data and figured out something that works, and it's gonna be hard to
spread it to a wider audience until you play within the existing system. And so, I think that there's
one huge piece of work to do to try to figure out
how to establish that system, where we can unite these n
of one trials into things that can be convincing enough datasets to convince skeptical
people, but then secondly, figure out how to play
within the existing systems so we can ensure there's
funding and there's development for the second and third
and fourth generation of these compounds, which
are the ones that are really gonna deliver the massive
gains in lifespan extension. – [Dave] One of the reasons
that I am a huge fan of bio-freedom, that idea
that you have the ability to do whatever you want to your body, you don't have to convince the skeptics. They can remain perfectly skeptical while you basically outlive them. I mean, or I love talking,
this is gonna sound rude, but I love talking with fat skeptics. It's like, hey, man, I
used to weigh 300 pounds, and I also had a 46-inch waist. I have a 33-inch waist. I don't experience hunger. I can tell you eight different ways that my recommendations
work that are borne out by what we understand
about biochemistry today, and you can try it for two weeks, and if I'm wrong, then stop, but the odds of your harming
yourself are very low. To be able to do that,
it's like, hey, skeptics, you can stay skeptical. Just, you'll stay skeptical, fat, tired, and you'll probably die before me. And it's okay, right? And by the way, if you try
it and it doesn't work, please tell me, so that we can figure out what's weird about you and we can hack it. – [James] Completely agree with you there, and we take kind of a similar approach, this, if you'll forgive
the corny reference, it's like, there was this line
in the second Matrix movie where, you know, they're saying not everyone believes as
you believe, and he's like, my beliefs do not require them to. (both laughing) And I think that taking
that approach in any kind of innovation development
is really, really important. You wanna be able to pull
the world along behind you as opposed to having to convince everyone before there's technology there. The systemic risk that I see
in the aging space specifically is that I think that the tools
that we have available to us with the existing amount of aging research and the rate that progress
is going is promising, but not as fast as it could be going. And so, the systemic risk to
me is that unless we figure out how to pull those skeptics
in as early as possible, as we possibly can, if they're
a wall between our industry and billions and billions
of dollars of R&D, insurance money, big insurance
companies, pension funds, these are the people who are standing behind the huge walls of
money that can be deployed into keeping us healthier
longer and figuring out how to activate those groups of
people as early as possible is key not just for figuring
out the longevity effects of natural compounds and
tools that we can use and this first generation of
new drugs that are gonna come up, but the second and third
generation of those things. We won't have to go through
a 20-year development period if we can unlock those people to find the next
generation of those things. I wanna unlock those things
in a four-year period after they realize that
they're so important. – [Dave] I think it's going
to happen, and, I mean, I may be one of those people
who gets research compounds that are very well studied that
aren't necessarily approved for use and may decide to use
them with or without needles. (Dave laughs) And I know lots of biohackers and people who speak off the record,
like yeah, I did this, and my telomeres are way
longer than they were before, and you can already do things that are in the realm of science fiction, but you're not supposed
to do these things. And it's sort of like,
I'm gonna really piss a lot of people off right
now, but someone in my mind who's a great hero is Lance Armstrong. The guy had testicle cancer,
and he came back from that, and he used every tool available
to him as a human being to do the impossible,
like, the truly superhuman. The only thing he did that
was wrong is he lied about it and he didn't disclose everything he did so we could all learn from it. But what he did was so impressive, regardless of the controversy
about all that stuff. That should not have been
possible, and the fact that he did all that,
what about those of us who didn't have testicular
cancer who just took advantage of some of those things
to be better parents, to be able to handle whatever life. Don't we have a moral
obligation to do that? That's my question for you. – [James] Yeah, so let's
talk about that a little bit, 'cause actually, I share
your view, not necessarily of the ethics behind what
Armstrong did, but like, of the ridiculousness
of the rules in which we view competition and
naturalness in the space, because, and this kind of ties back to an earlier part of our
conversation, which is like, if we wanna be showcasing
and pushing the limits of the best that humankind has to offer, how come an herb that activates
the wind signaling pathway, that can count as natural,
but a small molecule that activates the wind signaling
pathway, that doesn't count? (Dave laughs) – [Dave] It's absurd. – [James] How come exercise
to increase the rate of red blood stem cells
genesis counts as natural, but supplementation
with EPO, which creates increased red blood cell
genesis, doesn't count? And so, whether we're
thinking about competition or living a good life
or optimizing our cells to our best performance, I
think that the distinction between natural and unnatural
will really have to be broken down, and most
importantly, there's this idea of, if we wanna be our best
selves, if we wanna maximize our own performance, maximize
our own health spans, we'll have to use all of this
power that modern medicine has unlocked, genetics,
genomics, drug development, all of these different things
are going to have to be tools in our toolkit, just as great foods and lipid modulation and
devices to track our calories and meditation and mindfulness and all of these things
are tools in that toolbox. I think we're gonna
have to use all of them if we wanna really, really
make a dent on aging. – [Dave] Aren't you a little bit concerned about this idea, well, if
one competitor uses this, then everyone else has
to use it to keep up? – [James] Competitor in
what sense do you mean? 'Cause usually I think about competitors in terms of companies. – [Dave] It could be in Tour
de France, or it could be just competing for resources
in the hard scrabble of human life, however
you wanna look at it. – [James] So, I'm not a
professional competitor in that way, and I totally get, right,
there is this sense that everybody should be
able to do the Tour de France if they tried hard enough, and it sucks if you have to do the EPO injections, and it especially gets
epically sketchy when you talk about other types of
steroids that have positive short-term effects but
deleterious long-term effects. There are trouble ethical
questions there, I get it. But frankly, I'm also not someone who's super interested in sport
and competition in that way. And so when I look at it, I'm just like, yeah, but people can be so much better. (Dave laughs) – [Dave] Yeah, so, I'm with you there. The problem is it
generalizes to everything, and the response that I
have there, and I wanna hear what you think about this
as an investor, like, look, I'm using a laptop right
now, and a mobile device. So, if you look at it, those are massive unfair advantages over someone
who doesn't have those. – [James] Mmhmm. – [Dave] Right? So, if they don't have them,
they won't be able to keep up. What's the difference
between using technology, or we can go back. Hey, I'm a caveman. I have fire, you don't. – [James] Yeah. (Dave laughs) – [Dave] It seems like these
are just basic technologies, and why are we treating 'em all weirdly? – [James] Yeah, so, I mean,
my favorite book of all time is probably Richard Dawkins' Selfish Gene, in which he described and
first established the term meme and this idea of memetics, right, technologies that behave
like genetic traits, but exist in our minds and
in our culture and so on, and I think that, you
know, when we think about our interactions with any
sort of competitive system, like our society, a
game that we're playing, whatever it is, then all
memes are functionally equal. It's just about, how does
this improve your fitness towards achieving the end
goal, and if your end goal is communication with the
other side of the world, then having a laptop is
probably gonna get you much further than having a
piece of paper and a pen, and those are just the
mimetic differences. Similarly, if you have, I don't know, a brand-new drug that's going
to reduce your mTOR signaling and increase autophagy levels and reduce the free radical burnout
rates of your mitochondria, then that's probably gonna
be a better tool for you than a salad with some nice oils on it. That's my take on it. – [Dave] I think it's
a really nuanced take, but it opens the next
question, then, and this is one that I know both of us have
probably answered before, but I wanna get your take. What's going to happen
to the global population if people live 50% longer? – [James] Yeah. So, I actually just finished
doing a research paper with the University of Oxford
that's not published yet on exactly this question,
where we wanted to model both the population effects
and the potential impact economically of extending
healthy human life, and the short version
is that if everything that we think is gonna
happen kind of comes to be, it doesn't change population
that dramatically. The UN projects that
the 12 billionth human will never be born because
of the demographic shifts that are happening all
over society right now. Every single country is
lowering their fertility rates. (Dave laughs) And so, and so, right now,
we're living in a world where the ever-shrinking
class of working population, right, the people, we're getting to work later and later because we're
doing more and more school, the ever-shrinking group
of the working population is shouldering more and more
elderly, and unfortunately, often sick, people, and
so you can convincingly make the argument that not only do we need to continue, you know,
there's this old adage, if you're not growing, you're shrinking. If an empire isn't
expanding, it's collapsing. And so, I think that
there's a strong habit, that there's some truth in that, that we need to continue
enhancing the amount of healthy people we
have in our ecosystem. Otherwise, the society that
we've built is in serious jeopardy, because we've
set up all of these systems where we're relying on an
ever-shrinking class of people, and this is the first time this has ever happened in human history, right? The first year that there
were more people over 65 than under five in human
history was last year. And I think that because of
these demographic shifts, we actually need more
people, more healthy people, contributing to society,
and every time we've had any shred of a Malthusian catastrophe, the idea of this population
explosion, it's been overblown. Thomas Malthus famously, and right before the
Industrial Revolution, the first big population
scare was when he was like, oh my God, there's gonna
be a billion people, and he advocated genocide
as a way to stop the fact that there were gonna be a billion people, 'cause he thought it would lead
to the collapse of society. And I think technology can increase the carrying capacity
of the world by a lot. – [Dave] It certainly can. – [James] That was a bit
of a rambling answer, but I hope I made some points there. – [Dave] It's a really
important point that, I'm gonna rephrase it,
older people who function like younger people are
necessary for basically the continuing evolution of our species. The fertility rates are declining
precipitously everywhere, so I am not worried about
a population problem, because basically, was
it one in eight couples of child-rearing age just can't conceive no matter what they do,
which is unprecedented. It'll be one in four in another 20 years. If we keep doing some
polluting, it'll be one in two, and of course, the children they're having are less healthy than before as well. So, unless you're doing
some conscious things before and during pregnancy,
I'm not that worried when I put on my I'm
gonna live 180 years hat. I'm more worried about
air quality, soil quality, ocean quality, food quality,
and things like that. And the other thing that I
think we're short on now, and this is why I'm really
passionate about anti-aging, is that when I was 28 and I'm sitting down with a guy who was 88 years old who's on an aggressive anti-aging regimen and frankly has more energy
that I did at the time, I learned so much, and I still do. I've interviewed a good
number of people over 90, Nobel Prize winners like
Eric Kandel who are still going strong, and they have
something that's called wisdom. – [James] Mmhmm. – [Dave] And I want a world
with a lot more wisdom. (Dave laughs) So, we need old people
with functioning brains who've taken enough hits in
their lives to gain wisdom, and who have enough energy
and desire to share it and use that to help the
next two or three generations who are still making the
same mistakes they did. Like, I greatly value my elders, and I think that's missing
from society today. We take our older people, we
put 'em in retirement homes, and we don't value what they've learned. And you talk to a lot of
people, they hit 60, 65, and my parents told me,
they said, you know what, one day, I just realized I'm invisible. I could walk in the store, and it's like people don't
see me as a person anymore. I'm like, are you kidding? These are the people who
know the most, right? – [James] Yeah, and I
think that that's actually the real treasure that's
gonna hopefully be unlocked by this revolution, is
that we'll have people for the first time, imagine
someone dedicating a century to solving a really, really,
really sticky problem that takes a century to unravel. And yeah, being able to spar
with multiple generations of the creators of a theory,
and then its next generation, and then all of the sudden,
the first generation upsets things 30 years later with
new thoughts coming back in. I think that that's absolutely right, that the accumulated
wisdom that we will have, and actually, here's a point. That was a bit rambly
before, but here's a point that might actually be
useful, which is that (Dave laughs) most scientific breakthroughs happen from a confluence of
more than one discipline. There's this famous trope
that Nobel Prize winners are five times more likely
to play an instrument at the symphony level
than any other scientist. I'm not in that category, people who can play an instrument well. But by having very long
lived, healthy people who can explore multiple
disciplines, you'll get so many more opportunities to have
two different disciplines meet in a single mind and come
up with something magical that I think, if you wanted to go to Ray Kurzweil's thoughts
about the singularity, certainly that'll be happening
in AI to some extent, but really, there's
something magical to me about unlocking this capacity
for human creativity. – [Dave] It reminds me
of what Naveen Jain said. Naveen runs Viome. He's been on the show a couple times, spoke at the Bulletproof Conference. But Naveen, same thing, he
said that no great disruption happens except from outside an industry, and one of my favorite posts ever, I'm literally a computer
hacker, like systems architect, deep, like, how are we gonna
make the internet scale and perform well guy, and it was the most important thing I
could think of in my 20s. And when I went and said,
I'm gonna change the process of making green coffee to
focus on human performance, one of my favorite posts ever
was from some coffee snob website, I don't remember which one, and they're like, it's
impossible that Bulletproof has done this, because
Dave is not a coffee guy. And what you just said,
it's like, actually, those crazy innovations come from people who don't think like the people there, and that's why I wanted to interview you, because you're looking at
aging, but you're taking this aging thing, which
is different than the way big pharma does, and
you're going in and saying, hey, I'm gonna take my
outside your domain expertise, I'm gonna bring it into your domain, and that's where real disruption happens. And frankly, drug companies, they kind of deserve disrupting right now. They've got a lot of money. They waste it on hundreds
of millions of dollars to make a drug that lasted for
10 years before they realized there was a bunch of side
effects that any biochemists could have predicted
with their eyes closed, if I could just say that. Maybe there's a better
way, and maybe you're bringing it to them, and I
think that's cool, James. You gotta keep doing that. – [James] Thanks, Dave. Yeah, as you know, I'm a relatively big fan of the pharma companies. To me, they're a really important part of the value chain that ultimately gets these new medicines into
the hands of patients. There's good stories and bad
stories that come out of it. I tend to focus on some
of the good ones as well. – [Dave] Oh, I'm with
you on the good ones. I'm just saying, they waste a
lot of money, a lot of money. I'm not anti-pharmaceutical. I like pharmaceuticals;
they're really useful. It's just, could get
'em a little bit faster, a little bit cheaper, and a
little bit better labeled? (Dave laughs) – [James] I think that
those are all fair requests. (Dave laughs) – [Dave] Yeah, I'm not asking
you to rip on big pharma. I'm just saying that disruption
from outside the industry, when you think of aging as a system, and when you do, they look at diseases, individual, isolated diseases,
but that will change. – [James] And this is the big disruption that's gonna happen in the
pharmeceutical industry, right? Like, it happened once before,
which was when we changed from thinking about infectious
diseases, from like, oh my God, you have swollen
lymph nodes, to, oh my God, you have a bacteria that's
swimming around in your blood that's causing your lymph
nodes to be inflamed. This is the same level of disruption. Right now, we're thinking
like, oh my God, you have the cancer, and we're
gonna change that to, oh my God, your DNA is
mutating and you're living in an inflammatory cellular environment, and that's increasing
your risk of developing an evolutionary anomaly called cancer. That shift is going to
hopefully bring about the same sort of reduction
in mortality rates that we saw from 1900 to
1950 in infectious diseases, that we'll see hopefully from 2000 to 2050 in the age-related diseases. – [Dave] Beautiful, I fully agree with what you're saying there. Now, you've talked about sort of the areas that have the most
potential for anti-aging. We have about 10 minutes to do this. So I'm going to list each of these things, and I want you to tell me in
one sentence that everyone listening can understand what
it is, and then in another sentence, what's really
interesting to you about it, and you have something, what
we can do right now about it. So here's number one, genomic instability. – [James] Genomic instability is the idea that our DNA is constantly mutating. From the moment that we're fertilized, from the single cell
stage until we're dead, there is a mutation rate that
can both contribute to overall tissue dysfunction and also
mainly contribute to cancer. There are a number of things
interesting about this. It's one of the trickiest problems to get at from a drug
development standpoint, but the way of disrupting
this is finding compounds that can enhance DNA repair mechanisms and using those prophylactically. So in the cancer case, you
have to do it long before you ever get a cancer, which is
gonna make them tricky to do clinical trials on, although
I think we have some ideas. We don't have an investment
in this space yet, and the compound that I know
that has been most associated with DNA damage repair is
NAD and the nicotinamide, the NAD precursors, which
seem to enhance DNA repair. – [Dave] I love that you said NAD. I had a couple podcasts on that. I've had 20 intravenous infusions of NAD. We do it at Upgrade Labs in Santa Monica and in Beverly Hills. Yes, there's some good science for that, and I would double down on NAD or taking NAD precursors
that you can learn about. Just Google Bulletproof Radio NAD. You'll find all that, or it's
in the show notes for this. Okay, love that one. Telomere attrition. – [James] So, telomere attrition, related to genome instability,
but different cause. Ends of our chromosomes
are constantly shrinking. When they shrink too much, they start causing big problems for cells. Cause cancer, but also
cause cells to just shutdown and not being able to replicate anymore. I think telomere attrition
is less of a problem in most aging than we
thought it was 20 years ago. We're still really interested in it. One of the things that I'm
most interested in it for is figuring out how to
use telomere elongation as a way of boosting the
effect of cell therapies, because one of the big
problems in cell therapies is you take cells out of your body, you have to rejuvenate those
cells and expand them out so that you can give a lot
more stem cells back in, and I think that actually
telomere therapies are gonna be most important
first in that space, but there's not a lot I
know about that really could work right now there,
although we are thinking about making some
investments in the space. – [Dave] Okay, cool. I think that there are some
things around sleeping better that might give you longer telomeres? – [James] For sure, yeah. Any sort of systemic stress
we know lowers telomeres bit by bit over time as you're
constantly exposed to stress. So like, for example. – [Dave] Like being in a bad
relationship makes you old. There you go. – [James] For example. – [Dave] All right,
epigenetic alterations. – [James] Like we talked
about at the beginning, there are a bunch of different
changes, chemical changes to our DNA within our cells
that happen as we get older. This is through the
addition or subtraction of these methyl groups,
which affect these, you know, we have A, T, G, C letters in our DNA. They affect the G's and
C's, these pairings, and change them so that
it silences the DNA. Having those marks around prevents the genes from being properly expressed. And I love that you pointed out at the top of the show
that as we age, some things get turned on, and other
things get turned off. And so, this is one that I
think is, of all the hallmarks, the trickiest one to deal with, because you can't use a blunt
instrument to address it. You can't just say, oh, we want more methylation or we want less. You have to figure out ways where you can be really
targeted with these things. You mentioned a couple of
supplements that you take. I don't know that much about those. On our end, we haven't seen
too much that takes this nuanced approach where you
figure out where you need to add things, and it doesn't
add things so broadly. – [Dave] Yeah, it's mostly
methylated forms of B vitamins are kinda where it's at for
that versus like, when you take P5P versus Vitamin B6, for
instance, or methylfolate or 5-MTHFR versus folic
acid, stuff like that. Okay, loss of proteostasis. – [James] So, proteostasis
is the process by which our proteins are recycled
and the amino acids that make up those proteins
are used in new things, and we kind of keep a churn of, you know, we're constantly making new proteins, so we have to constantly
be degrading old proteins. Otherwise, they're gonna build up, and when you build up too much of anything that you're not
using, it can cause problems. – [Dave] Like a high-protein diet is probably not an anti-aging diet? – [James] Exactly, yeah. – [Dave] There you go. (Dave laughs) – [James] There's some
interesting nutrition studies that you can change around
the carb and fat loads a lot without having dramatic
impacts on mouse healthspan, but you get protein diets above
20% or something like that. – [Dave] Yeah, it's right at 20%. Like 400% more cancer when you cross 20%, especially for animal protein. – [James] So with
proteostasis, the coolest thing about it to me is this
process of autophagy, which means self-eating,
which is part of this protein breaking down process that
happens naturally when we fast. And this, the activity of
this process of autophagy declines as we age, and figuring out ways to boost it however we
can seems to be correlated with lifespan in almost
all organisms tested. So, we are really, really
interested in this space. I think that there are going
to be ways of doing chemical activators of autophagy to
activate it really strongly, but in the meantime, I
practice fasting regularly. – [Dave] Yeah. – [James] Which I think is the
best way of turning this on. – [Dave] And if you're
listening to this show, by now, I'm hoping you've
read one of my books. First one 2014, the Bulletproof Diet, I talked about intermittent fasting. If you haven't at least tried
skipping breakfast and having a late lunch every now and
then, seriously, it actually saves you money and time
and makes you live longer. It's a pretty high ROI activity. You owe it to yourself to try it. All right, I love that
one, and by the way, yes, give me some autophagy
drugs, because, you know, fasting for three or four
days, which is something I do on a regular basis,
without suffering, for people who are
like, oh my God, really, it's not that big of a deal
when your metabolism works. You're like, oh, I guess I could eat, and it's just not a big deal. Okay, altered intercellular communication. We gotta go faster on these too. – [James] Okay, yeah, sorry, I'm to wordy. – [Dave] No, I love it. (Dave laughs) – [James] So, this is
a kind of complex one, 'cause it means everything
about how our cells change and the way that they're
signaling to each other can be both in inflammation,
but I think that the one people usually talk about
is insulin signaling. And as we age, we become less
insulin sensitive, and this is one of the things that causes
type II diabetes really badly. One of the things we're
most excited about here is related to autophagy,
which is mTOR inhibition, which is partially related to
proteostasis, but partially also related to the signaling
of insulin into the cell. Rapamycin is the famous drug
that plays in the space. – [Dave] Do you take it? – [James] I don't recommend taking rapa. I think that the side effects, like, at clinically relevant
doses, I think the side effect risks are far too high when
it's been used clinically. We have an investment, in
fact, our first investment was in a company that made a version of rapamycin that does
not have side effects. – [Dave] Oh, sweet, I want some. Hook me up.
(Dave laughs) – [James] Yeah, it's a really cool one. – [Dave] Next up, well,
mitochondrial dysfunction. This is my favorite aging thing, because it affects how you feel right now, and let's go fast on that
one, 'cause I think people who listen to more than
probably five or 10 episodes have heard me ranting about this. – [James] Right. So, I guess, yeah, really fast. Our mitochondria stop
working as we get older. There are a lot of different ways we could potentially target them. I like the idea of enhancing mitophagy, which is like autophagy,
but for the mitochondria, where you're actually recycling the pieces of the mitochondria themselves. – [Dave] Kill the ones that are weak and make your body grow young ones. – [James] Exactly. And we haven't made investment there yet. I don't know much about drugs, but I think that's the
way to play in that space. – [Dave] And cryotherapy would
be an easy way to do that. If they can't get warm fast enough, the body will get rid of 'em. So that's I think a good way
to focus on it that's cheap. All right, next up, cellular senescence. – [James] This is the big
one where a lot of people have been making a ton of progress here in the last couple of years. So as we get older, in all
of our tissues, we develop these old zombie cells called
senescence cells that secrete inflammatory proteins and seem
to cause a ton of problems. You get rid of these
cells, you, at least mice, live much longer, 35%
healthy extended life. The thing that we're excited about here is finding the mechanisms
specific to senescent cells that differentiate them from normal cells, exploiting those with drugs to
eliminate them from the body. We have an investment
called Cleara Biotech that found the first mechanism unique to senescent cells, built
a drug based on this, and we're moving that
towards the clinic now. – [Dave] There are a bunch of supplements that show promise here. One of them is in Smart Mode, which is the cognitive enhancing
nootropic that I formulated. It's different than the
other stuff on the market. It's called apigenin, and
apigenin in some studies seems to have a pretty
good effect on that, as a senolytic, and even quercetin, another basically antioxidant
seems to have effects, and I'm talking with a bunch
of researchers about those, because I think it's the
point where, given that these compounds have other
benefits anyway, taking them knowing they have those
benefits and probably help with senescent cells, it's
probably not a bad things. – [James] Yeah, we remain
a little bit skeptical about the data that we've seen
from the supplements space, but I would agree, with
something like quercetin, it's not gonna hurt you. – [Dave] That's what all you big pharmeceutical companies say. (James laughs) I'm just kidding.
(Dave laughs) And it sucks too because supplements, and you know, a small part
of what Bulletproof does is supplements, but it's
a very meaningful part, and for me, as a formulator, I care a lot. A lot of times, like, wow, I'd love to run a $50 million clinical trial
on this, but as soon as I do, there's no patent protection for it, so the competitors just come
out there and steal your stuff and don't even feel shame about it. It's kind of amazing, the
number of knockoff artists out there who actually think,
oh, I'm an entrepreneur. It's like, no you're not. You're a thief.
(Dave laughs) So that's a big problem itself
in general, but I hear you. There isn't enough data yet. All right, well, it's
been so cool to ask you all these questions, and
I have one more question that I've started asking people, just very recently as
I'm turning my attention more towards just talking
about longevity and anti-aging, and it's this: how long
are you gonna live? – [James] So, I know that you're on record saying that you wanna live to 180. – [Dave] At least 180. – [James] At least 180, okay. As someone who spends a lot
of my time talking about this, I tend to think that that's
kind of the wrong question, because asking a 30-year-old
how long he or she wants to live, you'll
start getting answers like, not from me, but for an
average person, like 80, 90, and then when you ask
an 80- or 90-year-old how long they wanna live, they say like, you know, 100, 110 if
they're in good health. And so, my constant answer
for that, and I hope it's not dodging the question,
is, at least until tomorrow, and I'll let you know
when I change my mind. (Dave laughs) – [Dave] You know, that is so honest. Here's my real answer. 180 is just based on math
and very basic assumptions that are defensible and
I believe conservative, given the exponential growth
in our technologies here. But the real thing is, I
would like to die at a time and biomethod of my choosing. – [James] Sure. (Dave laughs) – [Dave] There you go, right? I got to pick, when I'm done, I'm done, and if I decide to go, it was my choice. And that's the ultimate place of freedom, where like, you know, you
don't have to be immortal, which would also kind of suck. There's all sorts of myths
about people like that. – [James] So, we're fully agreed there, at least until tomorrow.
(James laughs) – [Dave] All right. Well, it has been a real pleasure
to speak with you, James. Your work is mostly at I think where people can find out about what you're working on. Really, really appreciate
that you're putting so much of your life's energy into
getting our financial investments and our drug institutions
aligned around this mission, to have more people who are older with more wisdom and more health. Thank you. – [James] Dave, thanks
so much for having me on. This has been a ton of fun. – [Dave] If you liked today's episode, you know what to do. If you wanna be a limited
partner in a large VC and you're an accredited
investor who absolutely James did not pitch, you should probably
call James up and pitch him. (James laughs nervously) See, he's not allowed to say
that, and he didn't ask me to say that, and we have no
agreement, and right now, he's going, I can't
believe you did this, Dave. (both laughing) Anyway, if you're one of the
many very successful people who listen to the show, and
you wanna put your money where your mouth is, you
should talk to guys like James, because, come on, if you have
more money than you need, you could invest in
something that matters. I kind of like that. If you loved this episode,
it was worth the hour of your time, please give
me 20 seconds of your time by going to Amazon and
leaving a review, thank you. (distorted electronic music)

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