The Tim Ferriss Show - Ep. 12: Dr. Rhonda Patrick on Life Extension, Performance, and More

Episode Date: June 10, 2014

My guest this episode is Rhonda Perciavalle Patrick, Ph.D., who works with Dr. Bruce Ames, the 23rd most-cited scientist across ALL fields between 1973 and 1984 (!).Dr. Patrick also conducts clinical trials, performed aging research at Salk Institute for Biological Studies, and did graduate research at St. Jude Children’s Research Hospital, where she focused on cancer, mitochondrial metabolism, and apoptosis. Whether you want to extend life, buy a stem-cell "insurance policy," or guard against cancer and premature death, she will have a surprise insight for you.Find her on Twitter at @foundmyfitness.Enjoy! Tim***If you enjoy the podcast, would you please consider leaving a short review on Apple Podcasts/iTunes? It takes less than 60 seconds, and it really makes a difference in helping to convince hard-to-get guests. I also love reading the reviews!For show notes and past guests, please visit tim.blog/podcast.Sign up for Tim’s email newsletter (“5-Bullet Friday”) at tim.blog/friday.For transcripts of episodes, go to tim.blog/transcripts.Interested in sponsoring the podcast? Visit tim.blog/sponsor and fill out the form.Discover Tim’s books: tim.blog/books.Follow Tim:Twitter: twitter.com/tferriss Instagram: instagram.com/timferrissFacebook: facebook.com/timferriss YouTube: youtube.com/timferrissPast guests on The Tim Ferriss Show include Jerry Seinfeld, Hugh Jackman, Dr. Jane Goodall, LeBron James, Kevin Hart, Doris Kearns Goodwin, Jamie Foxx, Matthew McConaughey, Esther Perel, Elizabeth Gilbert, Terry Crews, Sia, Yuval Noah Harari, Malcolm Gladwell, Madeleine Albright, Cheryl Strayed, Jim Collins, Mary Karr, Maria Popova, Sam Harris, Michael Phelps, Bob Iger, Edward Norton, Arnold Schwarzenegger, Neil Strauss, Ken Burns, Maria Sharapova, Marc Andreessen, Neil Gaiman, Neil de Grasse Tyson, Jocko Willink, Daniel Ek, Kelly Slater, Dr. Peter Attia, Seth Godin, Howard Marks, Dr. Brené Brown, Eric Schmidt, Michael Lewis, Joe Gebbia, Michael Pollan, Dr. Jordan Peterson, Vince Vaughn, Brian Koppelman, Ramit Sethi, Dax Shepard, Tony Robbins, Jim Dethmer, Dan Harris, Ray Dalio, Naval Ravikant, Vitalik Buterin, Elizabeth Lesser, Amanda Palmer, Katie Haun, Sir Richard Branson, Chuck Palahniuk, Arianna Huffington, Reid Hoffman, Bill Burr, Whitney Cummings, Rick Rubin, Dr. Vivek Murthy, Darren Aronofsky, and many more.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

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the number one, drinkag1.com slash Tim. Last time, drinkag1.com slash Tim. Check it out. Hello, ladies and gentlemen. Welcome to another episode of The Tim Ferriss Show. So happy to have you listening. Let's start off with a line of wisdom for this episode. And that is don't sweat the petty things, pet the sweaty things from none other than George Carlin. What a genius. Check out his workflow, his creative process, an amazing comedian, an amazing thinker, and an awesome haircut. Moving on, this particular episode is for all the nerds out there, all the dorks out there, all the biohackers out there, or really anyone who's interested in life extension, the dangers and promises of supplements, performance enhancement, all that kind of stuff.

And quite frankly, you should be interested in that stuff. My guest is none other than Rhonda Patrick, PhD, a friend of mine who works with Dr. Bruce Ames, who's famous for developing a number of tests, and he's also the 23rd most cited scientist in all fields between 1973 and 1984. More than a decade. That's nuts. Rhonda in this case, also conducts clinical trials, has performed aging research at the Salk Institute for Biological Studies, and did graduate research at St. Jude Children's Research Hospital, which I highly recommend you donate some money to. I've done some work with their child genome project. And there she focused on cancer, mitochondrial metabolism, and apoptosis. So she's very, very smart. She is very, very well-armed with data. She knows how to perform research, and she knows how to translate it for a lay audience. We do get deep in the weeds in a few spots, and what I would say is just bear with us, grit your teeth, listen through it, maybe listen to it at 2 or three X speed, and you will find nuggets in this podcast,

in this episode that make it very worth the listen. This episode is brought to you by Bluehost, which is the hosting company I used to host my very first website, very first blog, and they're very strong with WordPress. So check out what they have to offer. And you can find special offers for listeners of this podcast at bluehost.com forward slash Tim. So without further ado, I would like to introduce you to Rhonda Patrick. And thank you so much for listening. At this altitude, I can run flat out for a half mile before my hands start shaking. Can I ask you a personal question? Now would have seen an appropriate time.

What if I did the opposite? I'm a cybernetic organism living this year over a metal endoskeleton. The Tim Ferris Show. There we go. Okay, cool. We are live at another

spectacular, well I shouldn't say that, another fascinating, for me at the very least, episode of The Tim Ferriss Show. Dr. Rhonda Patrick is here with me. How did we first connect? How did that come together? We first connected because originally I read your book before our work week in the sauna, I know that. It's where all the trouble starts. I read it in the sauna in graduate school.

Of course, the book fell apart because of the heat right but um glue and saunas so i first came aware of me i was like this guy's pretty cool and we kind of think alike in terms of some of the scientific thinking and also efficiency and i moved to the bay area and i got in touch with wellness fx that's right i thought they were really cool i I'm like, this is great. I love the idea of quantifying different levels of minerals, vitamins, hormones, lipid profiles, being able to measure what you're doing at baseline and then make dietary changes and then measure again. Cut out the middleman of the physician who most of the time doesn't know a lot about nutrition. And so I went to this event that Wellness FX had,

Fireside Talk, where you had attended. Oh, that's right, with Justin Major. Justin Major, that's where I first became aware of him. I don't really know much about him, but I became friends with Jim Kane. Yeah. And so... Jim's a beast.

Jim's cool. He's really cool. Yeah, for those of you who don't know, so Jim was the CEO of Wellness Effects. I think he's 50 or 51, and the guy can do like 20 handstand push-ups, outplay me in any possible sport. I mean, he's... Guinness Book of World Record holder, which, by the way, I share that in common with him.

Wait a second. All right, so hold on. We're going to come back to that. So Jim is... Bruce Lee wanted to be the fittest 50-year-old in the world. He didn't make it that long. But I would say Jim has to be at the very top. I think he's currently training for the Masters Division at the CrossFit Games. And just an incredible human being.

So I didn't realize that, I'd forgotten that you were at the Fireside Chat. So Guinness Book of World Records, tell me about this. I was a professional jump roper when I was a young child. I know. Wow. It's not a very common thing that people are professional at, but I was. And I started jumping rope when I was seven, and I joined this international rope skipping organization where I was basically doing demonstrations at SeaWorld LA, traveling around the world,

starting jump rope teams at different schools, got into commercials when I was a kid because I was just that good at it. Were you a solo jump roper or was that a team? Oh yeah, it was a team, but we do solo, we did team stuff. And I got into the Guinness Book of World Records multiple times because of a teamwork where we, every year at jump rope camp in Denver Colorado would cram a bunch of people under one long rope and we could jump the many as many times have the most people jumping as many times and we'd break our world record every year so I was probably in it like four or five times when I was nine ten eleven so yeah that's amazing well where'd you grow up I grew

up in San Diego San Diego the jump rope capital of the world? No. No, I'm kidding. Not so much. Definitely the surfing capital. I was a surfer as well. So let's sort of flash forward then from the jump roping empire to your scientific career. For those people who might not know you, what's just a sort of a brief

number of bullets in terms of some of the credibility points that you bring to the table with this type of thing? Some people may be familiar with your work through visiting your site or your Twitter handle. Of course, you also did a guest post on my blog related to heat adaptation and how to use hyperthermic conditioning for endurance and other type of purposes. But for those people who don't have any baseline, what are some of the bullets? Bullets are, so I was a biochemistry chemistry major at UCSD and decided that I wanted to go to graduate school, but I wanted to get experience in biology. So I worked at the Salk Institute for Biological Sciences for two years where I did research on aging using small nematode C. elegans worms where I could genetically manipulate them

and extend their lifespan by like twofold. And so then I loved biology at that point when I was just like, wow, this is so cool. So I decided to go to graduate school. I wanted to do cancer research and specifically I was interested in pediatric cancer. So I went to St. Jude Children's Research Hospital in Memphis, Tennessee. And I trained there for six years, did research on mitochondrial metabolism and apoptosis and its relationship to cancer. Got a really good paper, nature cell biology paper out of that. And then I decided that I wanted to try, I wanted to apply these really good scientific techniques and all this knowledge I'd learned in graduate school. And I wanted to do clinical research, but I wanted to bring real science to clinical research. What does that mean? involves looking at some endpoint like myocardial infarction or heart attack or some sort of

event that occurs. And they don't really look at mechanism. So I decided that I was going to try to use some of these techniques that I learned from doing mouse work, from doing cell culture, where you're teasing apart pathways and looking at mechanistic interactions, I decided I want to apply that to people. And you can do that by getting blood cells and, you know, looking at what's going on inside their body through this lens of what's going on in their blood cells. And so that's kind of what led me to go to the lab that I went to with Bruce Ames, who also is very interested

in nutrition and micronutrients, which is another interest of mine. I think preventative medicine, I think preventing micronutrient deficiencies, things like in magnesium, vitamin K, vitamin D, these essential minerals and vitamins that we need for a variety of different biochemical pathways in our body. I think that these deficiencies over time cause insidious damage that rears its head as age-related diseases later, like cancer and neurodegenerative diseases, type 2 diabetes, things like that. So I thought it would be a great match. And I have no doubt that I made the right decision. And your mentor was, let me get this right, the most or second most cited?

The most cited. The most cited. And from, you know, I'm probably going to botch this as well, it was like over a 10-year period. Over a decade. Right, in all the fields. That's ridiculous. So it is ridiculous. That's crazy, yeah. He's pretty awesome.

He's 85 years old now. He used to be the chairman of the biochemistry department at Berkeley, and he's a professor emeritus there, but he moved his lab because he was always on the forefront of translational research. He moved his lab to Children's Hospital because he can work with MDs, and we get a lot of patient samples. What do you mean by translational research in this case? Are you talking about DNA?

Are we talking about- Translational research means applying mechanistic discoveries that we find in science by doing a lot of mouse model work into practice. Okay, got it. Going from the lab to the hospital. Exactly. Okay, now this makes sense. read your work and followed your work for a while now, and have found exactly that type of translation, what makes a lot of what you do interesting to me and I think applicable to other people.

Now, of course, there are many other people who prematurely jump from sort of theory to practice, sometimes looking at, say, what would it be? i always mess these up in vitro translating sort of in vitro to uh in vivo in vivo yeah uh prematurely but uh the let's talk about the micronutrient inadequacies because i've noticed, for instance, and this was chronicled in the 4-Hour Body a bit, but identifying micronutrient deficiencies, in my case, had a very dramatic selenium deficiency, which adversely affected testosterone production, among other things. So what causes these micronutrient inadequacies or deficiencies?

I mean, vitamin D, magnesium, vitamin K. Obviously, vitamin D gets a lot of play in the media. But what are the causes? Like, why do people not get enough of these? Assuming, let's just say for the sake of argument, that they're not consuming purely empty calories. Right. So if they're not on the fast, you know, the McDonald's, Wendy's, Burger King, breakfast, lunch, dinner diet. So, you know, the, the reality is, is that if we're talking about when I say micronutrient inadequacy versus a deficiency, you know, I'm not talking about

someone that is when you're really deficient and you're at the point where you're having a clinical, you know, manifestation of that deficiency, for example, vitamin C and scurvy. Right. When you have scurvy, that's not the first sign of deficiency. That's premortality. I mean, that's the sign that you're going to die. So inadequacy could mean it's in the labs within the, quote, normal range, but it's not where you would...

Not necessarily. Okay. Inadequacy means you're not so deficient that you're going to have a clinical symptom that's measurable like okay your gums are falling out yeah but you will for example not be making collagen properly right because that's what vitamin c is a cofactor for right so in the case of you know micronutrients like like magnesium vitamin k so magnesium is at the center of a chlorophyll molecule, so it's found in dark green leafy vegetables. Men need around 400 milligrams

a day, women about 320 or so. And people aren't meeting those requirements because they're not actually eating enough of the foods that have magnesium. And there's a bunch of reasons for that. There's also a lot of confounding factors. Athletes often sweat out more, so they actually require more than non-athletes. And then you have things like magnesium being tied up in phytates, which is like the phosphorus source in plants. And that is hard for us to digest, or our absorption isn't that, you know, we still get it, but it's not as bioavailable.

There's a lot of things. I think mostly the number one thing is we aren't eating enough dark green leafy greens. Got it. And for that, for magnesium, magnesium is essential for about 300 different enzymes in your body. Yeah. And we, in our lab, we have a theory which we are now starting to prove, which is called the triage theory. Yeah. a theory which we are now starting to prove, which is called the triage theory. And what this theory is, is that during our evolution, we went through periods of starvation where we couldn't get enough food.

And there are these periodic points where we go through starvation. We think that our body has very strategically set up mechanisms that it can ration micronutrients to the proteins and enzymes in our body that are essential for survival, for reproduction, the sodium potassium pump, your clotting, you don't want to hemorrhage out. So all these proteins that require micronutrients for short-term survival get their pick first, whereas ones like enzymes involved in DNA repair, which repair DNA damage, well, DNA damage accumulates over time and that doesn't end, you know, have a problem until the fifth or sixth decade in your life. So we started to test this. Well past your Darwinian usefulness.

Exactly. And we started to test this. We were looking at, if you look, you know, cofactors, the way they work, you have enzymes in your body and these enzymes are what are doing everything. You have a DNA repair enzyme that needs magnesium. There's a binding constant. That protein will bind to this cofactor, to this mineral at a certain rate. And so you can look at proteins that are involved, for example, vitamin K that's involved in the clotting of your blood versus other proteins that require vitamin K, which are involved in making sure you don't get calcification in your bloodstream. So clotting is a very essential short-term survival protein. As I just mentioned, you don't want to hemorrhage out.

Versus this other protein that needs vitamin K to work is essential to make sure you don't have calcification of the arteries. Well, that's something that doesn't rear its head until later in life. So we look at the binding constants of those two proteins. Sure enough, the one that's involved in clotting has a much tighter binding, so more of it's going to that protein. What we think is going on, let me just mention about 60% of the U.S. population has inadequate levels of vitamin K. 45% of the U.S. population has inadequate levels of magnesium. For my own clarification, so it would seem then in this particular case, if you have an inadequate intake of magnesium or vitamin K, that what you do consume will be shunted to these short-term needs, but you'll suffer the consequences of a then

non-suboptimal level of DNA repair, for instance. Exactly. Which could lead to mutations that lead to cancer. Exactly. Got it. Exactly. And with the vitamin K, you'll have calcification in arteries, which can lead to cardiovascular diseases, can lead to brain vascular diseases. So what we think is going on is there is these micronutrient inadequacies are causing what we call insidious damage, where it's just a little bit of damage every day.

Just a war of attrition. Right. It's just going on, going on, going on. And by the time you're 50, 60 years old, you start to come down with these age-related diseases. They're age-related diseases for a reason. So we think that getting people up to snuff on their micronutrient intake is a very important role in preventative medicine because instead of trying to patch someone up after they're falling apart, we're going to extend the healthier part of their life, so extend their health span. It's very difficult to acutely reverse a chronic condition that has reached a precipitation point where you're exhibiting

massive symptoms like Alzheimer's. What would you suggest consuming for vitamin K, for instance? Vitamin K is also in plants, dark plants. Vitamin K1 is. K2 you'd find in fermented food. Right, like natto, I think. Yeah, natto. But if your liver... Or kimchi.

Right, kimchi I think maybe has some levels of it as well. But most people don't eat kimchi and natto. Is it natto or natto? It's, well, natto. Natto. Okay. Yeah. Because you're a Japanese.

But yeah, most Americans are not going to eat natto. Right. For sure. It is, I mean, Japanese feed natto to foreigners as, as like a parent might feed a child like a lime to see them make funny faces so i'd guess most americans are not going to eat that but uh i mean you could i fermented food sources if you want to really go off the deep end with that you can read weston price's stuff yeah i mean he's very much for the fermented foods but you were saying so so green yeah you convert k1 to k2 in your liver so So I mean... Let your liver do the work.

Yeah, I mean, I don't see a problem with that. You know, it's... Sure. But... No, no, I'm fine with letting the liver do what it does best. Right. You want to keep your liver happy. So if your liver's working, it should do it.

So green leafy vegetables. Green leafy vegetables are really good for magnesium and vitamin K. What does your diet currently look like? I know you mentioned, because I did a bit of inadvertent intermittent fasting today. What, what is, what is your daily food look like? I mean, you mentioned the smoothie. I mean, I'd love, I'm sure people would love to hear about that. I highly recommend, I have a Vitamix, but I mean, whatever your favorite blender of choices, I mean, whatever, I don't blend tech, you know, whatever it is you like. A blender that basically has a good, you know, power.

Yeah, powerful motor. Exactly. The Vitamix for you guys, I do have Vitamix. I put off getting one for 15 years, and now I wouldn't trade it for anything. I mean, it'll outlive me. It's going to last forever. Right? I use it every day.

And what I do is right in the morning, I make a smoothie that consists of a lot of kale spinach spinach or chard depending on what i have two large carrots a tomato avocado and then i put an apple banana the avocado and banana are really nice because it gives the consistency of a smoothie right and like frozen berries or you know sometimes i'll switch out with different citrus fruits almond milk almonds are really high in magnesium almond milk i like unsweetened because i don't want a bunch of extra crap yeah so i get unsweetened almond milk and you know sometimes i'll put my protein powder or glutamine you know right my gut likes glutamine so yeah i take glutamine on an empty stomach almost every morning nice. So, and then I blend it up and that, that is my

breakfast brings me into lunch, lunch. I usually have leftovers from, from dinner. I try to eat pretty healthy. What might that look like? It could be some leftover salmon or, you know, I, turkey chili. Yeah. So, you know, it's pretty much along the paleo ish lines. Yeah. You know, I'm not quite certain on all the paleo. Well, I want, I'm going to, I'm going to get to, I want to ask you about some common misconceptions slash exaggerations. Well, I may or may not know because I'm certain, I don't know really exactly what paleo is honestly i think it meat meat and berries and vegetables and not processed foods that's kind of my understanding i haven't really read a lot about it it makes sense to me but but it appears that in general you're avoiding refined

carbohydrates i do consuming a lot of green and getting a spectrum of colors exactly a spectrum of colors just that's my good way to go good way to go exactly uh the as it relates to diet i'm curious to know if you have any thoughts on the somewhat religious fervor with which a lot of paleo folks rally against phytic acid saponins and so on yeah um i at one point tried to do a little bit of reading on that and i just i didn't find the phytic acid convincing enough for me to start cooking my kale and then blending it or right so but you know i haven't done extensive research on that so i can't say for sure yeah it's you know not a great thing to do or it is a great thing. I really personally, I just go with my raw kale. I mean, I haven't convinced myself.

Okay. All right. No worries. So there are a couple of things that related to this we can talk about, so take magnesium, for instance. So there are many people out there, I'm sure, who take magnesium supplementation. Right. Ditto for selenium, ditto for fill-in-the-blank. I mean, this is a country known for the most expensive urine in the world. Right. At the Olympics, at least. That's sort of the running joke. Vitamin minerals, good, bad? I know you've said before that context matters. Where do you stand on supplementation? It's a little complicated when it comes to supplementation.

Now, if we're just talking about minerals, for example, minerals are really tricky because they are required as cofactors for a lot of enzymes. And because they're very small, a lot of these minerals are very similar in their structure like magnesium and calcium they're right next to each other on their periodic table they both have you know this two plus charge and what happens is if you take a bunch of magnesium you're supplementing with a bunch of magnesium and you're not getting enough calcium yeah you're the enzymes in your body that need calcium start to take the magnesium and it kind of trashes those enzymes they don't work as well body that need calcium start to take the magnesium and it kind of trashes those

enzymes they don't work as well because they need calcium not magnesium but they think and this is this is something that happens yeah if you're gonna supplement with you know minerals i think you really need to be careful you want to make sure you're getting the right balance of them you want to make sure you're not getting too much as well of one or the other so like magnesium i've seen studies where they show that like the maximum dose you absorb from a single dose is somewhere like 123 milligrams. And anything over that's not bad. Sometimes you'll get like a relaxing effect in your gut. So it can help your bowels. It'll help with peristalsis. And there's other things as well I think that's been shown to

do. But taking like 700 milligrams of magnesium a day and if you're not getting your calcium, that could be a problem. So I'm always a little hesitant about supplementing with minerals. Okay. All right. And in terms of vitamins, I think that… Now, hypothetically, do you think it's possible to achieve that type of disruption with natural foods? If you're consuming an overabundance of foods containing magnesium, do they typically also provide the calcium? You do typically have the calcium there with them. There seems to be a pretty balanced ratio.

I don't know for certain if you were to like do excessive amounts of dark greens but there are the calcium is also you know in the greens as well like kale and char right right so potassium's in there you know so and that's the other one sodium potassium so um but you know that's actually a really good question i haven't really thought about that well i'm just i'm curious because uh people seem to figure out a way to kill themselves with an excess of just about anything, including water, where you'll find people die of hyponatremia, which would be excessively low levels of sodium after overconsumption of water. So the sodium-potassium pump ceases to work properly and they have heart attacks when they're running marathons, for instance. Especially in the U.S. where there's this more is better mentality, I always wonder what the dose is that will make the poison, even for the naturally occurring stuff.

Anyway, we don't have to go down that rabbit hole continuously. It's obviously harder to achieve that than just popping a handful of pills, which you can do in a handful of seconds. You can. It is always good to be aware of what doses you're taking with vitamins and minerals. In terms of vitamins, I think that there are widespread micronutrient deficiencies, as I mentioned. 70% of the population has inadequate vitamin D, and we talked about vitamin K and magnesium. There's calcium as well. There's a

lot of these micronutrient deficiencies. So supplementation can be good because it can help fill those gaps. However, if you're a person that is unhealthy in terms of you have a disease like cancer, then all bets are off because cancer cells like everything that normal cells like, but it's like fuel for the fire. So for example, this is folic acid. Folic acid is a vitamin. We need folate in our body, right? And folate's important for thymine synthesis. So thymine is one of our DNA nucleotides. So if you don't get enough folate or folic acid supplementing with folic acid, you can actually cause your DNA to misincorporate uracil, which is part of RNA, into where the thymine is supposed to be. And this causes strand breaks in your DNA. It causes double strand breaks.

Actually, our lab did an experiment where we did folate deficiency and compared it to UV irradiation. And it was just getting UV irradiated, not having enough folate. So it can cause strand breaks in your DNA, which lead to cancer. However, if you already have cancer, because cancer cells are, you know, they've overcome a variety of different signaling pathways, they're growing and reproducing rapidly because of that, they're making daughter cells. Well, their daughter cells need DNA to make these cells. So they like stuff that helps make them have DNA. You know, if you're supplementing with folic acid and you have cancer,

you're actually giving these cancer cells the precursors they need to make more cells. And if you think about one of the most famous, like, chemotherapy drugs out there, methotrerexate it inhibits folic acid synthesis oh interesting because it's you know these these cancer cells are rapidly proliferating you know cells in your gut and your skin and also hair your immune cells they're also rapidly proliferating cells and they get affected as well but cancer cells yeah you know it's so tough because i i think about a cancer fair amount. A lot of my, of course, just with,

if you have a couple million readers, I mean, eventually you're going to have a subset that suffers from cancer of various forms. So I've had very sort of personal experience with interacting with people in my family, but also my readership with cancer. And it seems like by the time you're say 40 or 50,

you have microscopic cancer cells, but it's a disease-free state in so much as they're not proliferating out of control. So then the question becomes, if you have the seeds of cancer cells, how do you behave? So for instance, right, and I know that people all the way up to Sloan Kettering, in some cases are using non-methylphenidate. That's Ritalin. They're using glucophage, metformin, prophylactically to control their fasting glucose levels and to obviously manipulate how their liver handles glycogen and things like this so that they

can avoid going pre-diabetic, but keep it at an even lower state to effectively starve cancer cells of glucose, right? That's the idea, to extend lifespan, functional lifespan. So if you have the dietary interventions, right, which would be potentially limiting processed carbohydrate intake or high glycemic or high glycemic index load rather foods at what point do you decide to say try to starve of starve your body of folic acid right so for instance i know that i i appear to be a bad methylator and uh have had a number of people recommend to me that i use l-methylfolate do you have an mthfr yeah polymorphism? Yeah, I do have an MTHFR polymorphism. The MTHFR

gene, also nicknamed the motherfucker gene for precisely that reason. Yeah, very highly related. So I do have an MTHFR polymorphism and have been taking L-methylfolate, but like, all right, so now I'm 36. I tend to follow a slow carb diet, my fasting glucose, my hemoglobin A1C, which is kind of, I mean, vastly oversimplified, but like kind of a running average over three months of your fasting glucose level, all very good. But at what point, like at what point, if I know that cancer cells are likely present in some nascent form, do I make changes? That's something that I struggle with, right? I don't know. Maybe you just keep tracking it until you have something that can be imaged. Dr. I think in the sense where if you have a small amount of precancer cells

in your body, having a good immune system becomes critical. Your immune system needs folate. I think focusing on having good mechanisms in play that can get rid of those pre-cancer cells. So there's a variety of different mechanisms our body has. When those happen, we activate genetic pathways like p53, which induces the cell death of these cancer cells. We've got our immune system. If your immune system is working well, then it's going to kill those cancer cells.

But something that... You bring up a really important point, which also gets me back to this whole context thing, is what you're talking about is you've already initiated cancer. So you've already gone through that cancer initiation where you've acquired enough damage to make a cell abnormal. Right. Meaning what usually happens when you can't... Cancer initiators are different than cancer promoters

which allow cancer cells to grow and proliferate initiators are usually that damage to your dna from oxidative damage nitration you know uv there's a variety of micronutrient deficiencies too much flying right you know so basically you get a mutation in a gene that can end up having an abnormal cell once you have that abnormal cell, this is where promote cancer promotion comes into play where you're, you know, things that can give growth factor signals. And this is where something like IGF-1. So this is what I want to talk to you about because so IGF, well, I bring, you know, let's, let's jump into IGF-1, right? So just maybe you can explain what IGF-1 is. It stands for insulin-like growth factor one,

but it's also something that has been promoted as, for instance, a sports ergogenic, right? So you can use IGF-1 for performance enhancement, but continue. So IGF-1 does great things. I mean, IGF-1 is downstream of growth hormone. So when your pituitary makes growth hormone, it induces your liver to make IGF-1. But also other things induce IGF-1. Exercise for one. So exercise is a potent inducer of IGF-1.

What type of exercise? I don't know if there's a certain type. I know that exercise itself can induce the muscle cells to make it. So independent of the liver. So your muscle cells will make its own IGF-1. So it's sort of a different mechanism than it going through the whole growth hormone pathway. But a very potent nutrient inducer of IGF-1 is actually protein.

There's a very good reason for that. Protein induces IGF-1 because IGF-1 activates the mTOR pathway, which is required for protein synthesis. So it makes sense that when you're eating protein and taking in amino acids... You need more IGF-1. Right. You're basically going to induce that whole pathway that's like, okay, I'm going to incorporate this to make new proteins in my body. So it's well known that protein is actually one of the most potent inducers of IGF-1,

which is probably another reason why eating protein helps pack on muscle. So IGF-1 is a very potent growth factor. It can promote the growth and the repair of skeletal muscle. It also is very important for, it can cause neurogenesis in the brain, so it can cross the blood-brain barrier. You can also make it. And it's a growth factor, so it's helping your neurons grow. Yeah. So IGF-1-

Side note, exercise. If you want better cognitive performance, get off your ass and do some exercise. Quite aside from IGF-1, I mean, you have BDNF. Exactly. Brain-derived neurotrophic factor. There's a book called Spark that gets into a lot of this. But the cliff notes is you want, you know, better dendrite growth and cognitive performance, physically move. Get out and physically move.

Completely agree. So IGF-1 is good, right? Yeah. But there's a flip side. And that flip side is, first of all, if we're talking about IGF-1 activates AKT pathway. And AKT is, well, there's a lot of things. One of it's involved in the glucose metabolism like you were talking about. But another thing that it does is that it inhibits something called FOXO, which is a very important transcription factor.

And FOXO, when FOXO is not inhibited, it gets into the nucleus and it activates a variety of genes that are involved in stress resistance. Like it activates a variety of antioxidant genes, genes that are involved in DNA repair, genes that are involved in degrading bad proteins. How does IGF-1 affect FOXA? It negatively regulates it. When I was doing this research back at the Salk with worms, these worms have genes that we have. It's really amazing.

But when we would inactivate IGF-1, cut it off- Longevity went up. The worm would go from living 15 days to 30. And it was amazing because I would look at just a wild-type normal worm versus the one that we would inactivate their IGF-1 pathway. And they would be, let's say it's 13 days. That 13-day-old worm that was normal was barely moving around. And he was like, this other dude was just moving, it was like a young worm

James Dean of worms it's just, yeah they've done a variety of mechanistic investigations to figure out why and a lot of it has to do with the FOXO pathway where it's like these worms are just resistant to stress so anyways, that's the one

that's a bad thing about having too much IGF-1. The other bad thing is the context. If you're healthy and you don't have a bunch of precancerous cells, well, IGF-1 is great because it's muscle repair, muscle growth, neurogenesis. But if you do have a bunch of precancerous cells around, it's not a good idea to have a lot of IGF-1 because it's a growth factor. It's a proliferative signal that's letting these cancer cells grow, grow, grow, grow, grow, grow. So how do you thread the needle and hit that Goldilocks point, right? Because the more I read, and this sounds so depressing, but the more I read about longevity,

the more it seems that life is sort of a quality versus quantity proposition where you can, for instance, if you want to extend your lifespan as a male, there's a pretty compelling evidence that stopping ejaculating is a pretty good idea. Like the less you ejaculate, the longer you live. There's this, I could send you some weird stuff, like looking at, at studies that have not been performed in humans of course but there are caloric restriction now there's there's the debate of whether you need across the board caloric restriction to achieve the life extension benefits that seem to correlate to caloric restriction so maybe it's protein cycling maybe it's any number of things but if you let's say you take a monkey don't't allow ejaculation, give them a subcaloric

diet, like their hair thins out, their testosterone falls to the floor. Yes, they live longer, but they're miserable monkeys. Like they're just not very happy little monkeys. So what I have to wonder is, well, if I want like greater thermic effect of food, I want better cognitive function, one could argue for a higher protein diet. That would give you a day-to-day superior experience, right? Feel free, I want you to like pick anything apart that you can. But on the flip side, you're increasing IGF-1

and basically pouring fuel on a potentially fatal fire if you have pre-cancer cells, right? Yes. And also the FOXO is getting inhibited. And the FOXO is getting inhibited, right? So you're having like a day-to-day superior experience with what would seem to be a Faustian bargain in cleaving off life extension benefit. So do you think that is a sort of either-or proposition?

Or how do you get the best of both worlds? Is that possible? I think there is a possible way to get the best of both worlds. I think that, you know, I don't know. It depends on what eating a high protein diet means. For me, eating a high protein diet is like eating some sort of meat every day. If you're looking at getting some of those benefits of having genes expressed that are involved in stress resistance, there's ways to do that through hormetic response where they activate NRF2, which activates a whole host of genes involved in like glutathione peroxidase, all these antioxidant genes.

Really? I didn't know that. Yeah. So heat stress, exercise, these are all forms of stress that stress your body. Right. And what happens is your body's response to that stress is to activate genes involved in stress resistance. So I think that doing things that like a little hormetic responses where, you know, little types of good stress, like heat stress, exercise, green tea,

curcumin is another one that's also a hormetic, red wine, the polyphenols in red wine do it. Of course there's the whole alcohol part, but anyways anyways so i think hormesis is a way to kind of get those stressed response genes activated right and uh you know like the princess brad like wesley he what is he i love that movie but i'm just not following he inoculates himself against the poison that's, that's right. That's right. Yeah. To kill the Sicilian when death is on the line. Exactly. So I think that's a, hormesis is kind of a cool way to do that. And then getting all your micronutrients, making sure your DNA repair genes are working, you know, because there's an environmental component as well. Environmental meaning the way we age, stochastic damage happening in our body from just damage, metabolism, our immune system,

all that stuff. It's breaking down stuff. It's causing damage to our DNA. It's causing damage to our lipid cell membranes, causing damage to our protein, and these things get dysfunctional over time. So making sure we can keep all those systems working well by getting those micronutrients is another great way. You know what would be really fascinating, man? My dream list of studies, right? And we can talk about the state of science and funding and all that as well but just we'll we'll stave that off for a little bit longer the i would be really fascinating to look at the uh sort of biochemical and genetic profiles of two cohorts first cohort is high protein, moderate to low fat, moderate to low carbohydrate. So very, very common. A lot of paleo folks, a lot of quote, you know, healthy folks are just avoiding processed carbohydrates. And then in the second cohort, ketogenic people who are following very

high fat, low carbohydrate, moderate protein diets, right? And so. So the Atkins are even more so sort of epileptic diet, where they're consuming cream and cheese and all of this stuff to see sort of what their FOXO status is. I'd be really curious to check that out. That would be very interesting. I think that if you're looking at someone who's following, from what my understanding is, of a paleo diet, I think even though they're eating a lot of protein and getting a lot of IGF-1 because they're not getting all this other excess damage, and I think they

try to get enough micronutrients from my understanding. They try to get a lot of these micronutrients as well from their greens. In fact, if you look at their look at their, you know, inflammation levels, there's been some people, they don't call it a paleo diet in some of these studies, but if you look at what they eat, it's kind of paleo-like. They've got low C-reactive protein, low inflammation, you know, so it's like, I think in that sense, it's kind of like, you know, you're eating protein, you're activating IGF-1, but you're exercising, you're cutting out all the other crap, you're getting all your micronutrients to repair the damage. You know, I think there might be a healthy balance there where you're not, you're cutting out all the other crap. You're getting all your micronutrients to repair the damage.

I think there might be a healthy balance there where you're not- Yeah. Well, it could also just be that everything you consume will have, as we currently understand them with our current state of the art science, positive and negative effects. Right? I do. Definitely. It's not a matter of choosing good things and avoiding bad things it's about

choosing the right combination of things all of which have pros and cons so that your like personal balance sheet if you're running a company would be in the black and not in the red right and sort of choosing those combination factors speaking of which can you i let's talk about epigenetics a little bit so like i up methylation and the mother f***ing gene and so on earlier, but we didn't really explain what that means. Could you explain to people what methylation is? Maybe delve into that a little bit? Yeah. I can explain a little bit about epigenetics and the role that methylation plays in that.

Epigenetics is basically referring to changes in gene expression. And when you have a gene, it has to be expressed, it has to be expressed to be active, to do what it's supposed to do, to make the protein it needs to make do that function. And what you have here is your DNA is wound up in protein called histones, and this makes up your chromosomes, and they're wound up real tightly. And you'll have methyl groups, which can attach to certain regions of your DNA, CPG islands in your DNA. And usually when those methyl groups attach to your DNA, what happens is transcription

factors have to come, Fox was one of those, come and bind to a promoter region of a gene to activate it, to turn it on. But when methylation groups are there, it's physically impossible for that transcription factor to come by. There's something covering that lens. Yeah, it's literally a physical block. And so what happens is a gene will be turned. It's there, but it will be off. It won't be active. And so methylation usually refers to turning a gene off, but not always.

You can also have methylation of the histones. So acetylation is another epigenetic mark. Acetyl groups, acetyl groups. Is it acetyl or acetyl? I've always wondered because I only read the damn thing. You know, sometimes I call it acetylation. You know what? It's one of those potato, potato.

You say tomato. I say tomato. I don't think there's really a convention. I hear both. All right. It's kind of like with autophagy and autophagy. I hear that in scientific seminars. Autophagy.

Autophagy is actually what I hear more frequent now. That sounds very Queens English. I like it. Yeah, autophagy. That sounds better than autophagy. Yeah, you'll get a little. I used to say like democracy when I was a a little kid and it always bugged me like i knew it was wrong but i couldn't say it the other way so every time i say autophagy i feel like i'm saying democracy right so autophagy

autophagy that's i think that's pretty standard yeah but sorry side note autophagy is a cell eating itself yeah destroying itself yeah it's destroying all the dysfunctional organs, like the dysfunctional mitochondria ER, and it's a very healthy thing to be able to do because you don't want nasty stuff building up in your cell. Yeah, that makes sense. Right. Ooh, I'm so happy that I have autophagy. Autophagy.

I'm glad I could help. Yeah, yeah, no problem. So I interrupted this. So methylation is usually referring to these methyl groups effectively blocking the turning on of genes. Exactly. Got it. So what's really cool is that...

So when someone says they're a poor methylator, does that mean that they're bad at putting those methyl groups in place or that they're bad at then removing those methyl groups so that those genes can be turned back on? You know, I think when someone says they're a poor methylator, they probably don't know what they're talking about. I'm sure that's the case, which is why I avoid saying it in the future. Yes. There are enzymes that add methyl groups on, and there are enzymes that demethylate, and there's whole classes of them.

And, you know, the MTHFR is a specific enzyme that's very involved in the methylation pattern of homocysteine, methylating it back to methionine, you don't want a bunch of homocysteine. But it also does generate some of the methyl group. So it's not that you're not adding it to all your other genes, but I think specifically the MTHFR. Got it. Enzyme. So I was told, yeah, basically the sort of the diagnosis that I was given was you have this polymorphism of the MTHFR, which is an enzyme or a gene or neither? Is it a SNP?

A gene. Oh, what the polymorphism is? Yeah. So a polymorphism is just a variation in the gene that changes its... So you could have like nonsense allele or whatever. Right. And so you make a protein, the protein is this enzyme. Got it. Okay. Got it. Got it. Got it. So the MTHFR is the enzyme. It's both. There's a gene and the gene makes an enzyme. Makes the enzyme. Okay. Got it. So your gene is the DNA blueprint, which then makes RNA. The RNA gets translated into protein.

So I was told, all right, you have this particular variant or polymorphism. Your blueprint's screwed up. The empty HFR, it's screwed up. You are a bad methylator. Therefore, you have more trouble recovering from exercise. That was roughly the train of thought that I was delivered. So is that accurate then? I mean, it would kind of make sense if I have this variant that screws up my ability to, you're saying take homocysteine and turn it into. Yeah, well, actually that's,

it also does generate methyl groups that are used in this other cycle called the SAM cycle, which actually does make a lot of methyl groups for a variety of different other epigenetic marks, you know? So, so I think ultimately someone with that polymorphism that's not aware of it can not have enough methyl precursors around, if that makes sense, for other enzymes to go and add them to different gene regions. I see. It's fascinating because diet and lifestyle can actually change that. There was a study, a classic study that was done at Duke University a few years ago,

where they took mice that are lab mice that have yellow fur. And they have yellow fur because a gene they have called the agouti gene makes them have blonde hair, basically. Sounds like a lot of handbags. It's really a bad thing, though, because that same gene predisposes them to type 2 diabetes and obesity and cancer so these mice not a good trade off yeah it's like blonde hair looks nice but they get it fat and they come down with cancer just get cancer yeah so what does these

researchers at duke did was they took female mice and they fed them a really high folate diet nb12 three weeks before they got pregnant. And what they found was that the offspring of those agouti mice no longer had yellow fur. They had brown. And when they looked in their DNA, what they found was that the agouti gene had been silenced, methylated, turned off the gene. So these mice no longer had blonde fur, and they also weren't predisposed to get cancer earlier and they weren't obese. You know, this high folate diet in the female mouse before, you know, she was impregnated, turned off that agouti gene in her eggs actually. So it's really kind of cool. There's other things, stress, for example, inflammation affect methyl groups. So

the whole epigenetic field, I'm like on this epigenetic kick right now. I just think it's so amazing. Now epigenetic, just so I can understand this, but also it's a term I've heard a lot. And epi, as I understand it, is sort of on top of, right? I mean, just like epidural or epidermis. So epi is, epigenetics represents the class of or the spectrum of factors, exterior factors, behavioral factors that can affect your hardware, so to speak, right? Your genetics. Your blueprint. Exactly. You know, it's- Turn them on, turn them off. It's exactly like you said. You'll have a methyl group sitting on top of your DNA in this really important region where things need to bind to turn it on.

Yeah. And it'll stop it. Or you'll have acetylation in part of your, mostly it's histones, which open up the histone DNA complex and allow stuff to come in. So it kind of does the opposite. Acetylation usually turns on genes. So epi, exactly. These things sit on top of your DNA and they turn them on or off just based on the sense

that other things can't come in. I see. It's a physical... So the methyl groups and the acetyl groups would be examples of epigenetics. Exactly. The two best known examples.

Which can be affected by diet, exercise, etc. Exactly. Affected by stress, diet, exercise. Okay, so the epigenetics is not the exercise and diet that can affect A, B, and C itself. It's actually those intermediary groups, like the methyl and acetyl groups. Yeah, exactly. And the cool thing about epigenetics is that they're working on this

right now. So they figured out the human genome. Now they're trying to figure out the human epigenome. So there's tons of genes, there are patterns of methylation, acetylation, all these things. And what they're finding is that this stuff can actually be passed on to your offspring through the sperm DNA, through your eggs. So, well, not your eggs, but you know. Don't judge. You get it. So I'll give you an example. There is another study that was published a couple You get it. So, like, I'll give you an example. There's another study that was published a couple years ago. Actually, there's been a series of these studies where they take these male mice. It's kind of nice to work with males because, you know, then it's not like in utero.

It's not something that's happening during pregnancy. They take these male mice and they feed them a really high inflammatory diet, like corn oil, where they're just getting tons of omega-6 and just like crap. And these mice get obese and they get type 2 diabetes. But what they found is that they have offspring, female offspring, that are skinny. They feed their offspring a normal diet so they don't give them much of inflammation type of foods. And these female mice are lean, but they get type 1 diabetes. And what they found was that in the father, this corn oil diet, this inflammatory diet actually turned off a gene in the sperm DNA that's involved in the pancreatic islet cell insulin production. I know. Isn't that scary? I mean, epigenetics is kind of terrifying in the

sense where you're beholden to what your parents did, but they're also, you can change your diet. Better stop drinking those phytoestrogens shakes or whatever. Yeah, right? So that, you know, the epigenetic factors, it's basically you're altering the expression of your genes without actually doing any sort of nucleotide change. There's no nucleotide change in the sequence of the DNA. It's just, it's an on-off.

It's like, pit my DNA, pit my ride, right? It's like the chassis is the same you're just slapping on god knows what so here's the thing that's really cool that i recently there's a paper a series of papers that have been coming out over the last i'd say five years where they've been able to look at cell aging cells yeah and they've done it from and they started out with with blood cells from from people and they've been it from...and they started out with blood cells from people. And they've been identifying these methylation patterns as we age. So it seems as though, which makes sense to me because all these little, you know, inflammation,

oxidative stress, all these factors are changing methylation patterns, and this is happening as we age. And they're finding now that there's absolutely...there seems to be a systematic change in methylation groups. And they've been able to now look at these methylation patterns from blood cells in people and identify their age with 96% accuracy within four years. I mean, that's amazing to me. It's like, wow. So you're telling me you can look at someone's methylation pattern and tell them. It's almost like measuring telomere length. telomere length is also is that does it is it corresponding to

their chrono their calendar age or is it a biological age great great great question so um there are outliers so it does correspond to their chronological age for the most part within four years plus or minus okay but there areliers, and so now they're trying to figure out some people look biologically much younger than their chronological age. Their methylation pattern looks younger. Younger. Young. Right.

And some people biologically look much older than their chronological age. And so then they started comparing males and females, and they found that males had their methylation patterns aged like 4% faster. They looked 4% older than the female counterpart. And then they started looking at cancer cells and cancer cells, and they'd get a cancer tissue from a person, and then they'd get a tissue that was non-cancerous from the person, and they found that the cancer cells looked like their methylation patterns werelation patterns were aged like 40 faster like that those cancer cells had accelerated their aging weird it's really kind of cancer cells are so weird i mean they're they are weird they yeah they're they're

extremely smart yeah i mean they figured it out yeah you know well to a certain point because then they take over the host and then they can't survive anymore but yeah um the thing that really gets me is it seems like there may be a genetic program for aging yeah and of course people will say well no aging's you know it's a stochastic damage it's happening you know and and i think that's absolutely right and as i the more i think about it i'm like i'm thinking about for example our stem cells uh we have genes that are not expressed in our stem cells for a reason. They're methylated. One certain gene called ARF is methylated and the reason is called ARF. Yeah, like a dog. The reason why it's not expressed because when it gets expressed it causes senescence. It causes a cell to stop dividing. You don't want your stem cells to stop doing that

because you need your stem cells to replenish all the other cellular populations in the tissue. And so what they found is that this specific gene, we, when we're younger, don't express it in our stem cells. And as we get older, we start to express this gene. The ARF gene. The ARF gene in our stem cells. And then our stem cells start to die off. And what they found was that there's a demethylase, the enzyme that takes that methyl group off that gets activated by something called NF-kappa B, which is an

inflammatory. It's activated with inflammation. Inflammation activates NF-kappa B. So you hit a critical mass of inflammation at a certain age and that demethylates ARF? I think what's happening is, I think it's a chronic signal i have this i mean this has to be tested they've shown nfkpb activates this group of demethylases called the jumanji demethylases i know it's great and jumanji isn't that a movie with robin williams yeah no no no so these jumanji um uh demethylases get activated and pull off these methyl groups. But what I think is going on is there's a chronic signal with age, and I think it's inflammation that's activating these demethylases and it's changing the genetic patterns.

So I think there's a connection. Do you think that could be reversible? I do. Okay. I mean, I really think we are figuring out, first of all, we're figuring out how to reprogram our stem cells. Now we can do that. So stem cells, let's talk about it.

So stem cells, I've been interested and I just feel like the clock is ticking and now I'm getting to a point where my stem cells are no longer as good as they used to be. But the idea of banking stem cells and harvesting stem cells from whether it's bone marrow or elsewhere so that you can use them later. So that's one thing. Yeah. Actually, I just recently banked some stem cells of my own. You did? Yeah. How old are you? Thanks for doing it publicly. I'm 35. Okay. All right. So, so, you know, 36, I think I've done a lot more damage to myself. You look a lot younger. You're welcome. I look exactly my age or older. I felt like,

I guess there has to be a benefit to doing it compared to like what better time than now, I guess it would have been better. I assume if I had done it some time ago, how did you, how did you, how did you bank your stem cells? Well, so there's a variety of different ways you can bank your stem cells. Um, cord blood is one, which I didn't, that would have, that was up to my parents. They didn't do that when that happened so i'm kind of screwed there um i would have been really impressed if they pulled that off i would have been really impressed i would have been really impressed ahead of their time um yeah so the wisdom teeth have so i had two i had impacted wisdom teeth what does impacted mean well they're coming in crooked and they're hurting so i had to

have them removed and there's dental i started doing all this reading mean? Well, they're coming in crooked and they're hurting. So I had to have them removed and there's dental. I started doing all this reading. I was like, if they're, if I have to get these mother removed, there's gotta be some positive thing to it. So I started reading and I was, and I found out that there's, um, stem dental pulp stem cells in the teeth. I have all my stems. Um, I have all my stem cells. I have all my wisdom teeth. Okay. So let me continue. So there's dental pulp stem cells. This is crazy. No, I'm on top of it. Yeah, so there's dental pulp stem cells in your wisdom teeth that can,

because they're from a mesenchymal origin, which means they can form bone, they can form cartilage, they can form teeth eventually. So they can also be sort of coercedced if you have the right stromal cells and like stuff around to neuro type of populations neuronal types of populations and what i found studies where they've took human wisdom so they extracted wisdom from humans took out the dental pulp stem cells and then they trans they did a mice where they had spinal cord damage. And they transplanted the dental pulp stem cells from the humans into the spinal cord of these mice, along with a variety of growth factors and things that are needed. Cocktail of things.

Yeah, the cocktail of things. And it replaced their damaged motor neurons. That's crazy. From humans. From humans. So is there no risk of host rejection of that type of thing? What they do, yeah, there is. But they do a lot of things where they'll irradiate the bone marrow and make the immune system so it doesn't respond to the foreign stuff. There's all these crazy things they do for that. But the other cool thing is that in Italy, they did the first clinical trial where they took the dental pulp stem cells from the extracted tooth and they regenerated bone in the person. So these studies have been coming out. They're relatively new. pulp stem cells from the extracted tooth and they regenerated bone in the person. So, you know,

these studies have been coming out, they're relatively new. So anyways, I was like, I'm, I'm, I'm all about it. So then I looked up, you know, companies that potentially could bank my, my teeth. Um, and I found a couple of companies that, that I've thought were pretty trustworthy. You know, most of them had a sign at an intersection, like, call now, banking. Most of them were like, they had already been doing the cord blood. So it's like they're doing the cord blood and they've been doing it for like 40 years. And they're also doing now the teeth. And so what they do is they'll send your oral surgeon a kit, which is essentially like a balanced saline solution.

And the oral surgeon will take out your wisdom teeth and put it in this saline solution, send it back to them and then they will cryo preserve the tooth of liquid nitrogen well they do a little bit of manipulation but not much they don't want to take out the stem cells until you actually need them so that it's good i did all this reading on the procedure and i like let me talk to your cell biologist i want to see what your procedure is and i figured out you know okay these guys are doing it right because i you know, looked through the way it's supposed to be done. Anyways, you know, it was about $625 for the whole thing. Yeah.

And then it's $125 a year. And my husband got, he had to have one of his wisdom teeth removed. So he banked his. Primary teeth are a really great source of kids. They have even more dental pulp stem cells in their teeth that they just throw away. Oh, wow. You know? So if your kids are losing teeth, parents, get yourselves a balanced saline solution.

So wait, what did you say? Stem Save is one of the companies. It's probably just like stem save.com. And then there's National Dental Pulp Laboratory. Yeah. Stem Save is more memorable. What was the other one? National Pulp Dental Laboratory.

Yeah. I actually went with them just because What was the other one? National Pulp Dental Laboratory. Yeah. I actually went with them just because I spoke to their cell biologist and went through the whole. I went through the whole. I'm sure they were irritated with me. Where are they based? They're in New England. Okay. Area, so.

Makes sense, doesn't it? It does. Yeah. In Boston somewhere with all the biotech. Yep. So cool stuff, right? Yeah. But the other cool thing is the reprogramming part,

what I was talking about, where they can take your skin cells. They can even take... What is the difference, just to start to interject, between the modifier mesenchymal and the modifier pluripotent? Because they seem to indicate the same thing. Are they different?

Yeah, so pluripotent, those, okay. Mesenchymal is like the part of this origin of the cell where it came from pluripotent means like for example if you have a bone marrow cell yeah bone marrow can form like blood cells it can form your red blood cells white blood cells you know they have a distinct limit to the type of cells that can form a multipotent means you can actually form multiple different types of cells. So you can take a multipotent stem cell and you can form heart cells, you can form liver cells, you can form blood cells.

Totipotent means, I mean Wikipedia people. Dr. Right, right. Dr. Anyways, the cool thing is… Dr. And then mesenchymal. Dr. Oh, the mesenchymal just means the type of tissue that it came from, like the origin… Dr. People use mesenchymal and pluripotent interchangeably, which is why I'm trying means the type of tissue that it came from, like the origin. People use mesenchymal and pluripotent interchangeably, which is why I'm trying to figure. No.

They do not. No, I don't think they do. Okay. Yeah. Mesenchymal- I'm not saying that people don't know what they're talking about. Yeah. Oh, you're saying you've heard people-

I've heard people use the interchangeable. No, no, that's not interchangeable. All right. No, no. Got it. Yeah. Okay. Good to know.

Yeah, they're wrong. All right, No, no. Got it. Yeah. Okay. So good to know. Yeah, they're wrong. All right. Got it. Brought a good question up with the pluripotent multipotent because actually what's really cool now is that we can take a cell, a skin cell that's terminally differentiated. I mean, fibroblasts, they're not stem cells. Yeah. And people have figured out actually, I think his name is Shinya Yamanaka.

Sounds Japanese. Japanese. Now, he was in Kyoto, Japan when he first made the discovery in 2006. It was a freaking game changer, in my opinion. It was super cool. Well, I'm guessing most countries outside the U.S. are far beyond us in research just due to sort of legislative and regulatory issues that lead then to funding issues. Right. And also, you know, work ethic.

I think a lot of Japanese researchers are hard workers. I knew one that had a kat and would sleep in the lab. Yeah, well, they have a term for death by overwork there. Did they? Katoshi, yeah. I'm not surprised. Kat is too much, ro is like working, and then 死 is death. 死 also means, well, 永 or 死 is four, which is why a lot of Japanese and Chinese are superstitious about the number four.

So if people ever wonder, they think that's weird. It's kind of like 13 for a lot of Western cultures. That's why they don't like the number four. I didn't know that. So 新野山, what was it?. So Shinya Yamanaka, I think. I hope I didn't butcher it. It's okay. It's all right.

Anyways. Yamanaka is like Jones. It's one of those common things. Is it? Okay. So then probably right. Yeah, or Yamaguchi. Yama, who the hell knows.

Right. Yama. Really, really common. Yeah. So he figured out, he had looked at these patterns of gene expression and stem cells, and he had figured out by looking at a variety of different ones which ones are really important for these stem cells that could be multipotent, could form multiple tissues.

What he found was that there's four different transcription factors, those genes that activate a variety of different genes. When I was talking about those, Fox was one of them. He found four of them that were required for a stem cell to be multipotent. And what he did was he took fibroblast cells. First they started out with mice, and then they've done it in humans. But the first study was in mice where they took fibroblast cells. What is a fibroblast cell?

Skin. Okay, got it. Yeah. Blasted it with all those? Blasted it with those four. Well, the way we can do it is we can put it in a virus viral background and the virus will then incorporate retrovirus or yeah exactly it's a vector right yeah and you can put that's how they do it yeah gene therapy exactly that's exactly how they're doing it so and then be careful with that stuff you do well in this case they're using

a retroviral background which means that this virus not fire the retrovirus right it'll and it'll incorporate it'll'll use its RNA transcriptase to make DNA and it'll incorporate to random places in the chromosome. So you don't know it could be going anywhere. Yeah.

You know, and the potential, you know, harm in that is that you can actually get it in a place where it's like an oncogene where it can cause cancer because you're screwing up stuff.

But you avoid that. Avoid that. And instead, you make this freaking skin cell a multi-plotin stem cell where now they were able to make it turn into a neuron. They can make it turn into a kidney cell. They can make it turn into a liver cell. In which case, you don't have to worry about banking your stem cells.

Exactly. In which case, you don't have to worry about banking your stem cells because now you can just take your skin cells. They've done it from the renal fibroblast cells that you excrete in urine, those cells in urine, which is non-invasive, pee, and they can isolate these cells, add these four transcription factors. So you could be like, yeah, too bad I drank like an alcoholic for 20 years, but that liver cirrhosis, whatever,

let me just grab my Mormon neighbor's pee and make some stem cells. We are heading there i mean right now you know we can do this low efficiency they're now working on finding the problem is is that some of these transcription factors like c-mic which is one of the ones that is required is also cancer promoting so you know they found that you know like if you're doing this in mice 20 of the mice will get cancer they're trying to figure out the subtleties. I think my, I don't know, I could be totally just making, I like to make connections and come up with new possibilities.

But I'm thinking that this new way they can do gene therapy with this targeted, I didn't read the paper. It came out recently, this new technique that they can do. I think they use caspase or something where they can actually target a gene and put it in the exact locus where it's supposed to be instead of it randomly incorporating. Instead of shotgunning it. Exactly.

And so if I were working on that, I would take advantage of that system and try to see if you now use that system to deliver it to this fibroblast cell, getting it in the right spot. How far away do you think that is from sort of consumer use? Because of course, like people could hold out, we were talking about auto driving, you know, self-driving cars earlier, but it's, I think it's going to happen a lot faster than people expect, but it's still going

to be a few years. So in the meantime, like you should learn how to drive. Right. Right. So the, would you recommend that people hold off for that? Or do you think that banking styles is a good insurance and insurance policy? I think banking yourselves now, like if you, you know, for example, if your kids are losing their teeth or you're, you've, you've got a couple of wisdom teeth or what, if you don't have any wisdom teeth, what would your second choice be for banking? Obviously, if you're a female, um female and you're going to have a child. Something that's really cool that came out, I don't know, four or five years ago, I think, where they found the placenta.

The placenta is like a really rich source of multipotent stem cells. I haven't actually done any investigating yet on whether or not there's companies banking that. I would be shocked if they weren't. Yeah. But that's another really good source. Cord blood, stem cells, teeth, males' teeth. Males are just a dearth of opportunities.

It's kind of invasive. So there's a buddy of mine, also a fascinating guy. You might enjoy meeting him at some point. Maybe you've met him, Daniel Kraft. Have you ever met him? No. He's an MD, very fascinating guy.

Is he in the Bay Area? Yeah, he's in the Bay Area. I got to know him through Singularity University. I was an advising faculty member at NASA Ames where they were running Singularity University. I think they still are. And I got to know each other because he develops process and technology for bone marrow harvesting. And so I've been meaning to reach out to him. Right.

Right. Yeah. But yeah, it's invasive. It's kind of an understatement. I mean, it's. I don't think it's very. I think it's painful, basically. Yeah.

I think there are less painful ways to do it. I mean, given all the crap I've done to myself, I'm sure it would be just another kind of. Although getting your teeth yanked out. mean i was not exactly well it wasn't painful it was like psychologically screwed me up because i was like twilight so you know i was calm but like twilight like the werewolf twilight the twilight like you know i was like i thought they were gonna put me under i was like yeah just put me on oh they didn thought they were going to put me under. I was like, yeah, just put me under. Oh, they didn't. They were just like, no, no, just hold still. They put me in. It was like I was relaxed and calm. But I was like, wait a minute, I'm still awake.

Have a martini. You ready? Yeah, I'm still awake. This is really, you know, it was like pulling your teeth. I mean, it's, yeah. It wasn't pleasant, but I got my teeth cryopreserved. They are in New England now and liquid nitrogen. Besides the dental pulp stem cell storage,

what other types of things are you doing to potentially extend healthful lifespan? What are the other kind of low-hanging fruit? What other things are you thinking of? Well, low-hanging fruit is what we started this conversation with, micronutrients. Yeah, fix your diet. I really, and not just yet, really focus on these micronutrients. You've got hundreds and hundreds of enzymes in your body that require these minerals and vitamins as cofactors to function. And you know what? You're not going to notice these things not functioning right.

It's just not, you're not going to notice it when you look in the mirror. It's not, you know what, you're not going to notice these things not functioning right. It's just not, you're not going to notice it when you look in the mirror. It's not, you know. So taking care of those micronutrient inadequacies really is the low-hanging fruit. It's just, I mean, it's work, I guess, but it's a lot easier than. It's also routine, though. I mean, it's a habit that you get into. Right. Just like anything else.

That's why the Vitamix, for me, it makes it so much easier because, you know, while I do also eat salads and I and I also you know cook my vegetables too and I getting that broad spectrum like I think there's micronutrients in there we probably haven't even discovered oh I'm sure yeah I said there are yeah absolutely I am too I'm convinced we you know so and and not only that you know biology is so complex there is nothing more complex than biology. No technology will ever, ever, ever compare. So we don't even understand how everything's working, you know.

And so making sure. Yeah, I would imagine, you know, 20 years from now, we're going to look back at the state of the art today, and it's going to look like leeches and bloodletting and phrenology. Right. It's going to be like, holy shit, I can't believe we used to do that. I think the stem cell reprogramming is is huge well and it's huge like i'm shocked i don't hear more people

talking about it you know in the next 10 years i mean we're talking about i think i think there's such a unwarranted stigma associated with stem cells because of the religious furor over embryonic stem cell use. And it just completely threw the scientific research sort of to the side of the road in the last administration. So it's really unfortunate that sort of mass misinterpretation of the options led to this lack of funding. And like, you know, I mean, your day job is researcher, right? And you're working within institutions. And it's like, if something politically falls out of favor, and there are other people who are interested in getting tenure or whatever the f**k it might be, or remaining on the

board of blah, blah, blah of the journal A, B, and C, funding's just not going to, it's not going to, it's not going to happen. It doesn't materialize out of nowhere. To your point, though, I think that we were chatting about this before we started how when it comes to diet, there's such a focus on what not to eat, right? Don't do this. Don't do this. Don't do this.

And that's the extent of the guidelines for a lot of folks. Now, I do think there's a benefit there. Like don't eat refined carbohydrates. Fantastic. But the absence does, the absence of bad things does not guarantee the presence of necessary things. It doesn't. Right?

And so what I try to do very often with people who are, say, 200 pounds overweight, 100 pounds overweight, whatever it might be, and I've met many, many, many readers who have now lost over 150, 200 pounds. I mean, amazing amounts of weight. I've personally met at least a dozen. And there are many, 200 pounds. I mean, amazing amounts of weight. I've personally met at least a dozen and there are many, many others. And the way that I have people like that start,

because it's too overwhelming to give them a hundred rules. It's too restrictive and unrealistic given their current set of behaviors to say, change these, you can no longer do these 12 things. And I'll say, all right, we're going to start with what to add first. So like you need 30 grams of protein within 30 minutes of waking up. You need, uh, you know, a fist size serving of green on any plate that you eat off of. That's it. Those are the two things you're going to do. And, or like start drinking water. How about that? You know, like no more drinking calories or just like one, like one tiny thing, but the additive stuff would be, it's so beneficial. Like, so the way that I, I generally interact with those folks is I'll say, look, you can eat, you have to eat the following things after that. If you're still hungry, eat whatever the you want. You could

have like 15 liters of ice cream. I don't care, But you have to get these, cover these bare necessities, these bases first. And I think that that's such a, for whatever reason, an uncommon approach in the US where it's usually a sort of a no smoking sign that gets placed on a handful of things. And that's the extent of the guidance. But yeah, you know, it's like, it makes sense. Your body is designed, it's very resilient it makes sense. You know, your body is designed, it's very resilient. We are, we can deal with stress. We have whole host of enzymes in our body and proteins that deal with crap, but those things need cofactors to do that. So it's like, you said, I wouldn't say 15 gallons of ice cream, but you know, the point is,

leaders, leaders, let's not go crazy. Give your body what it needs. Well, here's the thing. I can say that understanding full well that they will not eat the 15 liters of ice cream because if they, if they're getting enough, uh, if they're getting the enzymes, if they're consuming fibrous greens, people are constantly amazed. They're just, I'm just like, look, you don't have to eat. This is part of the reason why, for instance, I'm a proponent oftentimes of legumes and beans and whatnot.

Right. Somewhat kind of hilariously controversially among the paleo community because they help to control glycemic response. And the fiber content and the duration of digestion prevents overeating. I personally like consuming legumes and I love lentils. Lentils are the bomb. Because the fiber in them gets broken down into short-chain fatty acids in the gut. I mean, this is great for your gut. Keeping your gut happy is so for your gut. Yeah. I'm keeping your gut happy.

Yeah. It's so, it's so important in so many ways. And that, that would be a whole other topic for like, you know, gut health pretty much. Yeah.

But you know, I, I, it's kind of weird how the, the paleo community was against that. I don't know who started that meme, but well, it comes down to a lot of the stuff that we're talking about,

the anti-nutrients. Oh, oh, right. It's related to that. And there are, but let's get heat inactivated. Well,

that's, yeah, this is a whole separate story. Yes. I mean the, the lectins saponins and all of this, right. In my experience,

typically get either inactivated or removed with conventional preparation or cooking. The thing is, is I think it comes back to this focusing on not focusing on what not to eat not focusing on you know i mean plants have a whole host of you know genes in them and proteins in them that are you know insecticides and pesticides that are being produced to keep bugs away themselves like without us putting you know so it's like you can focus on every little bad thing that's in

something i mean there is there is you know you'll find it in everything yeah and everything so it's like i think a better approach rather than focusing on these little minute possible bad things that are may or may not you know do something is focusing on what our body needs to function properly like indefinitely like you know, you just need to make sure that you are getting the things that you need for your body to deal with stress. You need to make sure that you're getting the things that you need to make sure your body can deal with DNA damage, that it can deal with like all the crap of just normal living, metabolism, immune function.

These things produce inflammatory molecules, like also reactive nitrogen species, reactive species these things are just from normal living yeah you know so agreed i am getting you're making me jones for a uh a jake shields green drink uh that is a local mma fighter and there's a place called sidewalk cafe down in the mission that uh serves uh freshly blended greens awesome so. So I think that is, is probably my next stop. Well, we can talk about tons of things for hours and hours and hours. I'm sure we'll do a round two, but, uh, in the meantime, obviously during the days you're, you're still working in the labs. Um, but where can people find more about you and follow you online? They can find me at foundmyfitness.com.

That is my Twitter name as well, foundmyfitness, and my Facebook name, and it's the name of my platform where I break this all down for people. Awesome. Well, this is super fun stuff, very important stuff, and to be continued. So thanks very much for making the time. Awesome. It was a blast.

Yeah. Until next time. Thank you. Cool. If you want more of The Tim Ferriss Show, you can subscribe to the podcast on iTunes or go to 4hourblog.com, where you'll find an award-winning blog, tons of audio and video interview stories with people like Warren Buffett and Mike Shinoda from Linkin Park, the books, plus much, much more. Follow Tim on Twitter at Twitter.com slash T-Ferris. That's T-F-E-R-R-I-S-S. Or on Facebook at Facebook.com slash Tim Ferriss. Until next time, thanks for listening.