Ep. 12: Dr. Rhonda Patrick on Life Extension, Performance, and More

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

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Tim Ferriss?

  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.

• 0:43Tim Ferriss?

  My guest is none other than Rhonda Patrick, PhD, friend of mine who works with Dr. Bruce Ames, who is 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. Dr. Patrick, 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.

• 1:28Tim Ferriss?

  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 3X 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/tim.

• 2:12Tim Ferriss?

  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 to shake.

• 2:25Speaker 01

  Can I ask you a personal question?

• 2:27Speaker 02

  Now we're seeing an appropriate time.

• 2:40Tim Ferriss?

  There we go.

• 2:41Speaker 03

  Okay, cool.

• 2:42Tim Ferriss?

  We are live. 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?

• 2:57Speaker 03

  We first connected because originally I read your book for our work week in the sauna, no less.

• 3:03Tim Ferriss?

  That's where all the trouble starts.

• 3:04Speaker 03

  I read it in the sauna in graduate school. Of course, the book fell apart because of the heat.

• 3:09Tim Ferriss?

  Right.

• 3:10Speaker 03

  But.

• 3:10Tim Ferriss?

  Glue in saunas.

• 3:11Speaker 03

  So I first came aware of you. 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.

• 3:24Tim Ferriss?

  Ah, that's right. That's right.

• 3:26Speaker 03

  I thought they were really cool. 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.

• 3:46Tim Ferriss?

  Right.

• 3:47Speaker 03

  And so I went to this event that Wellness FX had, Fireside Talk, where you had attended.

• 3:52Tim Ferriss?

  Right, with Justin Major.

• 3:54Speaker 03

  Justin Major, who, that's where I first became aware of him. I don't really know much about him, but I became friends with Jim Kane.

• 4:00Tim Ferriss?

  Yeah.

• 4:01Speaker 03

  And so.

• 4:02Tim Ferriss?

  Jim's a beast.

• 4:02Speaker 03

  Jim's cool. He's really cool.

• 4:04Tim Ferriss?

  Yeah, for those of you who don't know, so Jim was the CEO of Wellness FX. I think he's 50 or 51 and the guy can do like 20 handstand pushups, outplay me in any possible sport. I mean, he's.

• 4:17Speaker 03

  Guinness Book of World Record holder, which, by the way, I share that in common with him.

• 4:21Tim Ferriss?

  Wait a second. All right, so hold on. So we're gonna 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.

• 4:46Speaker 03

  I was a professional jump roper when I was a young child. I know.

• 4:51Tim Ferriss?

  Wow.

• 4:51Speaker 03

  It's not a very common thing that people are a 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 like SeaWorld, LA, traveling around the world, starting jump routines at different schools, got into commercials when I was a kid because I was just that good at it.

• 5:13Tim Ferriss?

  Were you a solo jump rope or was that a team?

• 5:16Speaker 03

  Oh, yeah, it was a team, but we do solo, we did team stuff. And I got into the Guinness Book of World Record 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 as many times, have the most people jumping as many times, and we'd break our world record every year.

• 5:37Tim Ferriss?

  Got it.

• 5:37Speaker 03

  So I was probably in it like four or five times when I was nine, 10, 11. So, yeah.

• 5:43Tim Ferriss?

  That's amazing. Where'd you grow up?

• 5:45Speaker 03

  I grew up in San Diego.

• 5:46Tim Ferriss?

  San Diego, the jump rope capital of the world?

• 5:48Speaker 03

  No.

• 5:49Tim Ferriss?

  No kidding?

• 5:50Speaker 03

  Definitely the surfing capital. I was a surfer as well, but...

• 5:54Tim Ferriss?

  So, let's, 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, 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 hypothermic conditioning for endurance and other type of purposes. But for those people who don't have any baseline, like what are, what are some of the bullets?

• 6:39Speaker 03

  Bullets are, so I was a biochemistry chemistry major at UCSD and decided that I wanted to get a, 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, you know? 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 Cholton's Research Hospital in Memphis, Tennessee.

• 7:14Tim Ferriss?

  Yeah.

• 7:15Speaker 03

  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 this, 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.

• 7:39Tim Ferriss?

  What does that mean?

• 7:40Speaker 03

  Well, sometimes clinical research involves looking at some endpoint like, you know, myocardial infarction or a 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, you know, cell culture where you're like, you're teasing apart pathways and doing all these, you know, looking at mechanistic interactions. I decided I want to apply that to people. And you can do that by getting blood cells.

• 8:14Tim Ferriss?

  Right.

• 8:15Speaker 03

  And, you know, looking at what's going on inside their body through this lens of what's going on in their blood cells.

• 8:20Tim Ferriss?

  Right.

• 8:21Speaker 03

  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 magnesium, vitamin K, you know, 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 was, I have no doubt that I made the right decision.

• 9:01Tim Ferriss?

  And your mentor was, let me get this right, what was he, the most, most or second most cited?

• 9:07Speaker 03

  The most cited.

• 9:09Tim Ferriss?

  The most cited.

• 9:10Speaker 03

  In from, you know, I'm probably going to botch this as well. It was like, Ten year, over a ten year period.

• 9:16Tim Ferriss?

  Over a decade.

• 9:16Speaker 03

  Right, in all, in all the fields.

• 9:19Tim Ferriss?

  That's ridiculous.

• 9:20Speaker 03

  So, it is ridiculous.

• 9:20Tim Ferriss?

  That's, that's crazy, yeah.

• 9:22Speaker 03

  He's, he's pretty awesome. He's eighty-five years old now. He used to be the chairman of the biochemistry department at Berkeley, and he's professor emeritus there, but he moved his lab because he's, he was always on the forefront of translational research. He moved his lab to Children's Hospital because, you know, he can work with M.D.s and we get a lot of patient samples.

• 9:39Tim Ferriss?

  What do you mean by translational research, in this case? Are you talking about DNA? Are we talking about...

• 9:43Speaker 03

  Translational research means applying mechanistic discoveries that we find in science by, you know, doing a lot of mouse model work.

• 9:52Tim Ferriss?

  Into practice.

• 9:52Speaker 03

  Into practice.

• 9:53Tim Ferriss?

  Okay, got it.

• 9:54Speaker 03

  Where we're like, you know, getting, getting...

• 9:55Tim Ferriss?

  Going from the lab to the hospital.

• 9:57Speaker 03

  To the bench.

• 9:57Tim Ferriss?

  Or the bench.

• 9:58Speaker 03

  Exactly.

• 9:58Tim Ferriss?

  Got it.

• 9:59Speaker 03

  Exactly.

• 9:59Tim Ferriss?

  Okay, now this makes sense. So, you know, I've, I've read your work and followed your work for a while now, and have, 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, uh, what would it be? I always mess these up. In vitro, translating sort of in vitro to...

• 10:35Speaker 03

  In vivo.

• 10:35Tim Ferriss?

  In vivo.

• 10:36Speaker 03

  Yeah.

• 10:37Tim Ferriss?

  Uh, prematurely, but, uh, the, but let's talk about the micronutrient inadequacies, because I've noticed, for instance, and this was chronicled in The Four 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, uh, what, what are the causes? Like, why do people not get enough of these? Assuming, let's just say for the sake of argument,

• 11:21Tim Ferriss?

  that they're not consuming purely empty calories.

• 11:23Speaker 03

  Right.

• 11:24Tim Ferriss?

  So, if they're not on the fast, you know, the McDonald's, Wendy's, Burger King, breakfast, lunch, dinner, diet.

• 11:29Speaker 03

  Right, that would be clear. 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.

• 11:49Tim Ferriss?

  Right.

• 11:49Speaker 03

  You know, you're not, when you, when you have scurvy, you're not, that's not the first sign of deficiency, that's pre-mortality. I mean, that's the sign of you're going to die.

• 11:57Tim Ferriss?

  So inadequacy could mean it's in the labs within the quote "normal range," but it's not...

• 12:03Speaker 03

  Not necessarily.

• 12:05Tim Ferriss?

  Okay.

• 12:05Speaker 03

  Inadequacy means you're not so deficient that you're going to have a clinical symptom that's measurable, like

• 12:12Tim Ferriss?

  Okay.

• 12:13Speaker 03

  Your gums are falling out.

• 12:14Tim Ferriss?

  Yeah.

• 12:14Speaker 03

  But you will, for example, not be making collagen properly.

• 12:19Tim Ferriss?

  Right.

• 12:19Speaker 03

  Because that's what vitamin C is a cofactor for.

• 12:21Tim Ferriss?

  Right.

• 12:22Speaker 03

  So, in the case of, you know, micronutrients like magnesium, vitamin K, so magnesium is at the center of a chlorophyll molecule, so it's found in dark green leafy vegetables, you know, you need, 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, you know, 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.

• 13:06Tim Ferriss?

  Right.

• 13:06Speaker 03

  There's a lot of things, I think mostly the number one thing is we aren't eating enough dark green leafy greens.

• 13:12Tim Ferriss?

  Got it.

• 13:13Speaker 03

  And for that, for magnesium, magnesium is essential for about 300 different enzymes in your body.

• 13:19Tim Ferriss?

  Yeah.

• 13:20Speaker 03

  And we, in our lab, we have a theory which we are now starting to prove, which is called the triage theory.

• 13:27Tim Ferriss?

  Yeah.

• 13:27Speaker 03

  And what this theory is, is that, you know, during our evolution, we went through periods of starvation where, you know, we couldn't get enough food. And you know, 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 and potassium pump. You're clotting, you don't want to, you know, hemorrhage out. So all these proteins that require micronutrients for short-term survival get the pick, 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

• 14:12Speaker 03

  the fifth or sixth decade in your life.

• 14:14Tim Ferriss?

  Right.

• 14:14Speaker 03

  So we started to test.

• 14:15Tim Ferriss?

  Well past your Darwinian usefulness.

• 14:17Speaker 03

  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, there's a binding constant, that 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're, 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. Whereas this other protein that's involved, 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 till later in life.

• 15:01Tim Ferriss?

  Right.

• 15:02Speaker 03

  You know, 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, going to that protein.

• 15:12Tim Ferriss?

  Yeah, got it.

• 15:12Speaker 03

  And so what we think is going on, so let me just mention about 60% of the US population doesn't have inadequate, has inadequate levels of vitamin K. Forty-five percent of the US population has inadequate levels of magnesium.

• 15:24Tim Ferriss?

  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 the, what you do consume will be shunted to these short-term needs, but you'll suffer the consequences of a then...

• 15:42Tim Ferriss?

  Non-suboptimal level DNA repair, for instance.

• 15:46Speaker 03

  Exactly.

• 15:47Tim Ferriss?

  Which could lead to mutations that lead to cancer.

• 15:49Speaker 03

  Exactly, 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 a little bit of damage every day.

• 16:07Tim Ferriss?

  War of attrition.

• 16:09Speaker 03

  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, or 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 we're going to, 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.

• 16:37Tim Ferriss?

  It's also very, I mean, it's very difficult to acutely reverse a chronic condition.

• 16:42Speaker 03

  It is.

• 16:43Tim Ferriss?

  That has reached a precipitation point where you're exhibiting massive symptoms like Alzheimer's. What do you, what would you suggest consuming for vitamin K, for instance?

• 16:53Speaker 03

  Vitamin K is also in plants, dark plants. Vitamin K1 is.

• 16:58Tim Ferriss?

  K2 you'd find in fermented.

• 17:00Speaker 03

  Right, like natto.

• 17:02Tim Ferriss?

  Yeah, natto.

• 17:03Speaker 03

  But if your liver, if you're...

• 17:04Tim Ferriss?

  Kimchi.

• 17:05Speaker 03

  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 nato?

• 17:13Tim Ferriss?

  It's, well, natto.

• 17:14Speaker 03

  Natto, okay. Yeah, because you're a Japanese.

• 17:16Tim Ferriss?

  But yeah, most Americans are not going to eat natto.

• 17:19Speaker 03

  Right.

• 17:19Tim Ferriss?

  For sure. It is, I mean, Japanese feed natto to foreigners 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, I mean, you could, fermented food sources.

• 17:36Tim Ferriss?

  If you want to really go off the deep end with that, you can read Weston Price's stuff.

• 17:39Speaker 03

  Yeah.

• 17:40Tim Ferriss?

  I mean, he's very much for the fermented foods. But you were saying, so green.

• 17:44Speaker 03

  Yeah, you convert K1 to K2 in your liver. So I mean.

• 17:47Tim Ferriss?

  Let your liver do the work.

• 17:48Speaker 03

  Yeah, I mean, I don't see a problem with that, you know, it's.

• 17:51Tim Ferriss?

  Sure.

• 17:52Speaker 03

  But.

• 17:53Tim Ferriss?

  No, no, I'm fine with letting your liver do what it does best.

• 17:55Speaker 03

  Right. You want to keep your liver happy. So if your liver's working, it should do it.

• 17:58Tim Ferriss?

  So green leafy vegetables.

• 17:59Speaker 03

  Green leafy vegetables are really good for magnesium and vitamin K.

• 18:02Tim Ferriss?

  What does your diet currently look like? I know you mentioned, because I did a bit of inadvertent intermittent fasting today. 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.

• 18:16Speaker 03

  I do. 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.

• 18:29Tim Ferriss?

  Yeah, powerful motor.

• 18:30Speaker 03

  Exactly.

• 18:31Tim Ferriss?

  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 gonna last forever.

• 18:40Speaker 03

  Right. I use it every day. And what I do is right before, 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. Then I put an apple, banana. The avocado and banana are really nice because it gives the consistency of a smoothie.

• 19:02Tim Ferriss?

  Right.

• 19:02Speaker 03

  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.

• 19:12Tim Ferriss?

  Yeah.

• 19:13Speaker 03

  So I get unsweetened almond milk and, you know, sometimes I'll put my protein powder or glutamine, you know.

• 19:19Tim Ferriss?

  Right.

• 19:19Speaker 03

  My gut likes glutamine, so.

• 19:21Tim Ferriss?

  Yeah, I take glutamine on an empty stomach almost every morning.

• 19:24Speaker 03

  Nice.

• 19:24Tim Ferriss?

  Yeah.

• 19:24Speaker 03

  Yeah. So, and then I blend it up and that, that is my breakfast. Brings me into lunch. Lunch, I usually have leftovers from dinner. I try to eat pretty healthy.

• 19:36Tim Ferriss?

  What might that look like?

• 19:37Speaker 03

  It could be some leftover salmon and spinach or, you know, turkey chili.

• 19:43Tim Ferriss?

  Yeah.

• 19:44Speaker 03

  So, you know, it's.

• 19:45Tim Ferriss?

  Yeah. Pretty much along the paleo-ish lines.

• 19:49Speaker 03

  Yeah, you know, I'm not. Quite certain on all the paleo.

• 19:54Tim Ferriss?

  Well, I want, I'm gonna, I'm gonna get to, I want to ask you about some common misconceptions slash exaggerations.

• 20:00Speaker 03

  Well, I may or may not know, because I'm cer, I, I don't know really exactly what paleo is, honestly. I think it, 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.

• 20:15Tim Ferriss?

  But it, it appears that in general, you're avoiding refined carbohydrates.

• 20:18Speaker 03

  I do.

• 20:19Tim Ferriss?

  Consuming a lot of green and getting a, a spectrum of colors.

• 20:23Speaker 03

  Exactly. A spectrum of colors. Just, that's my.

• 20:26Tim Ferriss?

  Good way to go.

• 20:27Speaker 03

  Good way to go. Exactly.

• 20:29Tim Ferriss?

  The, as it relates to diet, I'm, 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.

• 20:46Speaker 03

  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.

• 21:00Tim Ferriss?

  Right.

• 21:00Speaker 03

  So, but you know, I haven't done extensive research on that, so I can't say for sure.

• 21:06Tim Ferriss?

  Yeah.

• 21:07Speaker 03

  It's, you know, not a great thing to do, or it is a great thing. I, I really, personally, I just go with my raw kale. I mean, I haven't convinced myself.

• 21:16Tim Ferriss?

  Okay, all right, no worries. So there, there are a couple of things that, uh, related to this that we can talk about, right? So, take magnesium, for instance. So, there are many people out there, I'm sure, who take magnesium supplementation.

• 21:28Speaker 03

  Right.

• 21:29Tim Ferriss?

  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, the running joke. Uh, vitamin minerals, good, bad? I know you've said before that context matters. What is, what's, where do you stand on supplementation?

• 21:52Speaker 03

  It's a little complicated when it comes to some 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.

• 22:21Tim Ferriss?

  Yeah.

• 22:22Speaker 03

  Your, 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 because they need calcium, not magnesium. They think, and this is, this is something that happens.

• 22:33Tim Ferriss?

  Yeah.

• 22:34Speaker 03

  If you're gonna supplement with, you know, minerals, I think you really need to be careful. You wanna make sure you're getting the right balance of them. You wanna 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, you know, a single dose is somewhere like 123 milligrams.

• 22:54Tim Ferriss?

  Okay.

• 22:54Speaker 03

  And anything over that's not bad. You'll, sometimes you'll get like a relaxing effect in your, in your gut. So it can, you know, help your bowels. It'll help with peristalsis, you know, so. And there's other things as well, I think that's been shown to do. But, you know, 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, you know, a little hesitant about supplementing with minerals.

• 23:16Tim Ferriss?

  Okay, alright.

• 23:17Speaker 03

  And in terms of vitamins, I think that.

• 23:21Tim Ferriss?

  Hypothetically, you could achieve, is it, 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, do they typically also provide the calcium?

• 23:37Speaker 03

  You do, you do typically have the calcium there with them.

• 23:41Tim Ferriss?

  Okay.

• 23:41Speaker 03

  There, there seems to be a pretty balanced ratio.

• 23:44Tim Ferriss?

  Okay.

• 23:45Speaker 03

  I don't know for certain if you were to like do excessive amounts of dark greens. But there are, the calcium's also, you know, in the greens as well, like kale and charcoal.

• 23:54Tim Ferriss?

  Right, right.

• 23:54Speaker 03

  So potassium's in there, you know, so. And that's the other one, sodium potassium. So, but, you know, that's actually a really good question. I haven't really thought about that.

• 24:02Tim Ferriss?

  Well, I'm just, I'm curious because. 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, what is it, 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 US where there's this more-is-better mentality. I always wonder what the doses 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 less, it's obviously harder to achieve that than just popping a handful of pills,

• 24:46Tim Ferriss?

  which you can do in a handful of seconds.

• 24:48Speaker 03

  You can. And 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. Seventy percent of the population has inadequate vitamin D, and we talked about vitamin K, 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.

• 25:13Tim Ferriss?

  Yeah.

• 25:14Speaker 03

  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 make fol-, we need folate in our body, right? And folate's important for thymine synthesis, so thymine's 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 your cell, which is part of RNA, into where the thymine's supposed to be. And this causes strand breaks in your DNA, it causes double strand breaks.

• 25:59Speaker 03

  Actually, our lab did an experiment where we... Did folate deficiency and compared it to like UV irradiation. And it was just like getting UV irradiated, not having enough folate.

• 26:09Tim Ferriss?

  Wow.

• 26:10Speaker 03

  So it can cause strand breaks in your DNA, which lead to cancer.

• 26:13Tim Ferriss?

  Hmm.

• 26:14Speaker 03

  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 their, 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.

• 26:42Tim Ferriss?

  Huh.

• 26:42Speaker 03

  And if you think about one of the most famous, like chemotherapy drugs out there, methotrexate. It inhibits folic acid synthesis.

• 26:49Tim Ferriss?

  Oh, interesting.

• 26:50Speaker 03

  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.

• 27:02Tim Ferriss?

  Yeah, you know, it's so tough because I, I, I think about cancer a 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 in my readership with cancer. And it seems like by the time you're, say, 40 or 50, you have microscopic cancer cells, but they're, it's, they are, 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,

• 27:47Tim Ferriss?

  in some cases are using, not methylphenidate, that's Ritalin. They're using glucophage, metformin.

• 27:52Speaker 03

  Metformin.

• 27:53Tim Ferriss?

  Prophylactically to control their.

• 27:57Speaker 03

  Pre-cancer.

• 27:58Tim Ferriss?

  Fasting glucose levels and to obviously manipulate how their liver handles glycogen and things like this so that they can avoid going prediabetic 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 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? For instance, I know that I appear to be a bad methylator and have had a number of people recommend to me that I use L-methylfolate.

• 28:43Speaker 03

  Do you have an MTHFR polymorphism?

• 28:46Tim Ferriss?

  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, alright, 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, 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.

• 29:25Speaker 03

  Yeah.

• 29:26Tim Ferriss?

  Maybe you just keep tracking it until you have something that can be imaged.

• 29:29Speaker 03

  I think in the sense where you're, if you have, you know, a small amount of precancer cells in your body, having a good immune system becomes critical and you do, your immune system needs folate, you know?

• 29:41Tim Ferriss?

  Right.

• 29:42Speaker 03

  So I think focusing on having, having good mechanisms in play that can, you know, get rid of those precancer cells. So there's a variety of different mechanisms our body has, you know? 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, you know, your immune system's working well, then it's gonna, you know, kill those cancer cells. But something that, you bring up a really important point, which also gets me back to this, this whole context thing is that... You know, 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.

• 30:22Tim Ferriss?

  Right.

• 30:22Speaker 03

  Meaning, what usually happens when you can't... Cancer initiators are different than cancer promoters, which allow cancer cells to grow and proliferate.

• 30:30Tim Ferriss?

  Right.

• 30:30Speaker 03

  Initiators are usually that damage to your DNA from oxidative damage, nitration, you know, UV, there's a variety of micronutrient deficiencies.

• 30:38Tim Ferriss?

  Too much flying.

• 30:40Speaker 03

  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 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.

• 30:57Tim Ferriss?

  So this is what I want to talk to you about, because, so IGF... Well, I bring, you know, let's jump into IGF-1, right? So just, maybe you can explain what IGF-1 is. It stands for insulin-like growth factor 1, but it's also something that has been promoted as, for instance, a sports ergogenic, right?

• 31:14Speaker 03

  Right.

• 31:15Tim Ferriss?

  So you can use IGF-1 for a performance enhancement, but continue.

• 31:19Speaker 03

  So IGF-1 does great things. I mean, IGF-1 is, it's downstream of growth hormone.

• 31:25Tim Ferriss?

  Yeah.

• 31:25Speaker 03

  So growth, when your pituitary makes growth hormone, it, you know, induces the... Your liver to make IGF-1, but also other things induce IGF-1. Exercise for one, so you can really, you know, exercise is a potent inducer of IGF-1.

• 31:38Tim Ferriss?

  What type of exercise?

• 31:39Speaker 03

  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.

• 31:47Tim Ferriss?

  Okay.

• 31:47Speaker 03

  So it's, you know, 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. And there's a very good reason for that. Protein induces IGF-1 because...

• 32:02Speaker 03

  IGF-1 activates the mTOR pathway, which is required for protein synthesis. So it makes sense that you, when you're eating protein and taking in amino acids.

• 32:12Tim Ferriss?

  You need more IGF-1.

• 32:13Speaker 03

  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.

• 32:27Tim Ferriss?

  Right.

• 32:28Speaker 03

  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 blood-brain barrier, you can also make it, and it's a growth factor, so it's helping your neurons grow.

• 32:45Tim Ferriss?

  Yeah, side note, if you want better cognitive performance, get off your ass and do some exercise, quite aside from IGF-1, I mean, you have BDNF.

• 32:55Speaker 03

  Exactly.

• 32:56Tim Ferriss?

  Brain-derived neurotrophic factor. There's a book called Spark that gets into a lot of this, but the Cliff Notes is, you want better dendrite growth and cognitive performance, physically move, get out and physically move, anyway.

• 33:11Speaker 03

  Completely agree. So IGF-1 is good, right?

• 33:14Tim Ferriss?

  Yeah.

• 33:15Speaker 03

  But there's a flip side, and that flip side is, first of all, if we're talking about IGF-1 activates AKT pathway, okay? And AKT is, well, there's a lot of things, one of it's involved in the glucose metabolism like you're 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's 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.

• 33:52Tim Ferriss?

  So how does IGF-1 affect FOXO?

• 33:54Speaker 03

  So it negatively regulates it.

• 33:56Tim Ferriss?

  Oh, negatively.

• 33:57Speaker 03

  So 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.

• 34:07Tim Ferriss?

  Longevity went up.

• 34:08Speaker 03

  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.

• 34:19Tim Ferriss?

  Yeah.

• 34:20Speaker 03

  And they would be, let's say it's 13 days, that 13-year-old, 13-day-year-old worm that was normal was like barely moving around, and it was like, and this other dude was just moving, I mean, it was like a young worm.

• 34:32Tim Ferriss?

  James Dean of worms.

• 34:33Speaker 03

  It's just, yeah. And, you know, they've, they've done a variety of, you know, mechanistic, you know, investigations to figure out why. And a lot of it has to do with the foxo pathway where it's like these, these worms are just resistant to stress. So, yeah, so anyways, that's the one, that's, you know, that's the, a bad thing about having too much IGF-1. The other bad thing is the context. If you, 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, you know. But if you do have a bunch of cancer, 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.

• 35:16Tim Ferriss?

  So how do you, 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.

• 36:01Tim Ferriss?

  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 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, what I have to wonder is, well, if I want, like, greater thermic effect of food, I want better cognitive function, da, da, da, da, da, da, da, 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 are increasing IGF-1

• 36:41Tim Ferriss?

  and basically pouring fuel on a potentially fatal fire if you have precancerous cells.

• 36:47Speaker 03

  Yes, and also the foxo is getting inhibited.

• 36:50Tim Ferriss?

  And the foxo is getting inhibited, right? So you're having like a, 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, how do you get the best of both worlds? Is that possible?

• 37:10Speaker 03

  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, 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 responses, hormesis, which is basically having, giving yourself a little bit of stress. Things like polyphenols, like the EGCGs and green tea. That's what they do. That's how they exert a lot of their, their positive effects is through a hormetic response where they activate N R F two, which activates a whole host of genes involved in like glutathione

• 37:53Speaker 03

  peroxidase, all these antioxidant genes.

• 37:56Tim Ferriss?

  Really? I didn't know that.

• 37:56Speaker 03

  Yeah, yeah. So heat, stress, exercise, these are all forms of stress that stress your body.

• 38:04Tim Ferriss?

  Right.

• 38:04Speaker 03

  And what happens is your body's response to that stress is to activate genes involved in stress resistance.

• 38:09Tim Ferriss?

  Right.

• 38:10Speaker 03

  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's another one. That's also a hormetic.

• 38:22Tim Ferriss?

  Yeah, yeah.

• 38:23Speaker 03

  Red wine, the polyphenols and red wine do it.

• 38:25Tim Ferriss?

  Yeah.

• 38:26Speaker 03

  Of course, there's the whole alcohol part, but anyways. So I think hormesis is a way to kind of get those stress response genes activated.

• 38:33Tim Ferriss?

  Right.

• 38:33Speaker 03

  And, you know.

• 38:35Tim Ferriss?

  Like the Princess Bride, like Wesley.

• 38:37Speaker 03

  What is he? I love that movie, but I'm just not following.

• 38:41Tim Ferriss?

  He inoculates himself against the poison.

• 38:44Speaker 03

  That's right, that's right.

• 38:45Tim Ferriss?

  To kill the Sicilian when death is on the line.

• 38:47Speaker 03

  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. And environmental meaning. The way we age, toxic damage happening in our body from just damage metabolism, our immune system, all that stuff is, 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.

• 39:22Tim Ferriss?

  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 stave that off for a little bit longer. The, I would be really fascinated to look at the 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 who are just avoiding processed carbohydrates. And then, in the second cohort, ketogenic people, who are following very high fat,

• 40:03Tim Ferriss?

  low carbohydrate, moderate protein diets, right? So the, the Atkins are even more so sort of epileptic diet, right, where they're consuming like cream and cheese and all of this stuff.

• 40:15Speaker 03

  Right.

• 40:16Tim Ferriss?

  To see sort of what their foxo status is. I'd be really curious to check that out.

• 40:23Speaker 03

  That would be, that would be very interesting, you know, I think that if you're looking at someone who's following, from what my understanding is of a paleo diet, I think, you know, even though they're eating a lot of protein and getting a lot of IGF-1 because they're, they're not getting all this other excess damage, and I think they try to get enough micronutrients, from my understanding.

• 40:40Tim Ferriss?

  Oh yeah, sure.

• 40:41Speaker 03

  They try to get a lot of these micronutrients as well, from their greens. They're, and in fact, if you 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.

• 40:53Tim Ferriss?

  Yeah.

• 40:53Speaker 03

  They've got low C-reactive protein, low inflammation, you know, so it's like, I think in that sense, it's It's kind of like, you know, you're eating protein, you're activating IGF-1, but you're exercising, you're not, you're cutting out all the other crap, you're getting all your micronutrients to repair the damage. You know, I think there, there might be a healthy balance there where you're not...

• 41:11Tim Ferriss?

  Yeah, well, it could also just be that, that everything you consume will have, as we currently understand them, with our current state-of-the-art science, positive and negative effects, right?

• 41:23Speaker 03

  I do, I understand.

• 41:24Tim Ferriss?

  And so 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.

• 41:40Speaker 03

  Yeah.

• 41:41Tim Ferriss?

  Right? And sort of choosing those combination factors. Speaking of which, can you, let's talk about epigenetics a little bit. So, I brought up methylation and the motherf- gene and...

• 41:50Speaker 03

  Right.

• 41:50Tim Ferriss?

  And so on earlier, but we didn't really explain what that means. Could you explain to people what, what methylation is? Maybe delve into that a little bit?

• 41:59Speaker 03

  Yeah, let me, I can explain a little bit about epigenetics and, and the role that methylation plays in that. So, you know, 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 to do that function.

• 42:19Tim Ferriss?

  Yep.

• 42:19Speaker 03

  And what you have here is, um, 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.

• 42:35Tim Ferriss?

  Yeah.

• 42:35Speaker 03

  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.

• 42:47Tim Ferriss?

  Okay.

• 42:48Speaker 03

  But when methylation groups are there, it's like physically impossible for that transcription factor to come by.

• 42:53Tim Ferriss?

  There's something covering that light switch you can't flip.

• 42:55Speaker 03

  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, acetal groups, acetal groups.

• 43:16Tim Ferriss?

  Is it acetal or acetal? I've always wondered, because I only read the damn thing.

• 43:20Speaker 03

  It, you know, sometimes I call it-

• 43:23Tim Ferriss?

  Like, is it acetalcholine or acetalcholine?

• 43:25Speaker 03

  Acetylation, you know what, it's one of those potato-

• 43:28Tim Ferriss?

  You say tomato, acetomato?

• 43:29Speaker 03

  I don't think there's really a convention, I hear both.

• 43:32Tim Ferriss?

  Alright, alright.

• 43:32Speaker 03

  It's kind of like with autophagy and autophagy, I hear that in scientific seminars.

• 43:37Tim Ferriss?

  Autophagy?

• 43:37Speaker 03

  Autophagy is actually what I hear more-

• 43:39Tim Ferriss?

  That sounds very Queen's English, I like that.

• 43:42Speaker 03

  Autophagy, and so-

• 43:43Tim Ferriss?

  That sounds better than autophagy.

• 43:45Speaker 03

  Yeah, you'll get a little-

• 43:46Tim Ferriss?

  I used to say like, "democracy" when I was 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."

• 43:57Speaker 03

  Right, right.

• 43:57Tim Ferriss?

  So autophagy.

• 43:58Speaker 03

  Autophagy. That's, I think that's pretty standard now.

• 44:01Tim Ferriss?

  Now, sorry, side note, autophagy is a cell eating itself?

• 44:06Speaker 03

  Yeah.

• 44:06Tim Ferriss?

  Or destroying itself?

• 44:07Speaker 03

  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.

• 44:16Tim Ferriss?

  That makes sense. Ooh, I'm so happy that I have autophagy.

• 44:18Speaker 03

  Autophagy, glad I could help.

• 44:20Tim Ferriss?

  Yeah, yeah, no problem. So I interrupted this. So methylation is usually referring to these methyl groups effectively blocking the turning on of genes.

• 44:29Speaker 03

  Exactly.

• 44:30Tim Ferriss?

  Got it.

• 44:31Speaker 03

  So, what's really cool is that-

• 44:33Tim Ferriss?

  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?

• 44:44Speaker 03

  You know, I think when someone says they're a poor methylator, they probably don't know what they're talking about.

• 44:49Tim Ferriss?

  I'm sure that's the case, which is why, so I avoid saying it in the future.

• 44:53Speaker 03

  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-

• 45:07Speaker 03

  Enzyme that's very involved in the methylation pattern of homocysteine, methylating it back to methionine, you know, want a bunch of homocysteine. But, you know, it also does generate some of the methyl group. Like, so it's not that it's adding it, you're not adding it to your, all your other genes, but I think specifically the MTHFR.

• 45:26Tim Ferriss?

  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?

• 45:40Speaker 03

  A gene, oh, what the polymorphism is?

• 45:43Tim Ferriss?

  Yeah.

• 45:43Speaker 03

  So a polymorphism is just a variation in, in the gene.

• 45:49Tim Ferriss?

  Right.

• 45:49Speaker 03

  That changes its...

• 45:51Tim Ferriss?

  So you could have like nonsense allele or whatever.

• 45:53Speaker 03

  Right. And so you make, you make a protein, the protein is this enzyme.

• 45:56Tim Ferriss?

  Got it. Okay, got it, got it, got it. So the MTHFR is the enzyme?

• 45:59Speaker 03

  It's both. It's, there's a gene and the gene makes an enzyme.

• 46:02Tim Ferriss?

  Makes the enzyme. Okay, got it.

• 46:03Speaker 03

  So your gene, it's the DNA, you know, blueprint, which then makes RNA, the RNA gets translated into protein.

• 46:07Tim Ferriss?

  Got it. So I was told like, all right, you have this, this particular variant or polymorphism.

• 46:12Speaker 03

  Yeah, your blueprint's screwed up.

• 46:13Tim Ferriss?

  The MTHFR, it's screwed up. You are a bad methylator, therefore you have more trouble recovering from exercise. That was roughly the, the train of thought that I was delivered. So is, 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...

• 46:33Speaker 03

  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, methyl groups for a variety of different other epigenetic marks, you know, so, so I think ultimately someone with that polymorphism that doesn't, that's not aware of it

• 46:52Tim Ferriss?

  Yeah.

• 46:52Speaker 03

  can have, not have enough methyl precursors around.

• 46:57Tim Ferriss?

  Yeah, okay.

• 46:58Speaker 03

  If that makes sense. For other enzymes to go and add them to different gene regions.

• 47:02Tim Ferriss?

  I see.

• 47:03Speaker 03

  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 are, that have yellow fur. And they have yellow fur because a gene they have called the agouti gene makes them have blonde, have blonde hair, basically.

• 47:22Tim Ferriss?

  Sounds like a lot of handbags.

• 47:23Speaker 03

  It's really a bad thing though, because

• 47:25Tim Ferriss?

  It's bad.

• 47:26Speaker 03

  that same gene.

• 47:27Tim Ferriss?

  Yeah.

• 47:27Speaker 03

  predisposes them to type 2 diabetes and obesity and cancer.

• 47:31Tim Ferriss?

  Not a good trade off.

• 47:32Speaker 03

  Yeah, it's like blonde hair looks nice, but they get fat and they come down with cancer faster.

• 47:37Tim Ferriss?

  Get cancer.

• 47:38Speaker 03

  Yeah, so what these researchers at Duke did was they took female mice and they fed them a really high folate diet and B12, 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.

• 48:00Tim Ferriss?

  Oh, wow.

• 48:02Speaker 03

  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.

• 48:14Tim Ferriss?

  Right.

• 48:15Speaker 03

  Turned off that agouti gene in her, in her eggs, actually. So it's really kind of cool. There's other things, stress, for example, inflammation effect, methyl groups. So the whole epigenetic field, I'm like on this epigenetic kick right now. I just think it's so amazing.

• 48:29Tim Ferriss?

  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 is, so epi is, epigenetics represents the class of, or the spectrum of factors, exterior factors, behavioral factors that can, that can affect your hardware, so to speak, right? Your genetics?

• 49:01Speaker 03

  Your blueprint, exactly.

• 49:02Tim Ferriss?

  Yeah, turn them on, turn them off.

• 49:04Speaker 03

  Exactly, like you said, you'll have a methyl group sitting on top of your DNA in this really important region where, you know, things need to bind to turn it on.

• 49:11Tim Ferriss?

  Yeah.

• 49:12Speaker 03

  And it'll stop it. Or you'll have acetylation in a part of your, mostly it's histones, which open up the histone DNA complex and allows 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 this, that other things can't come in.

• 49:32Tim Ferriss?

  I see.

• 49:32Speaker 03

  It's a physical.

• 49:33Tim Ferriss?

  So the methyl groups and the acetyl groups would be examples of epigenetics?

• 49:37Speaker 03

  Exactly.

• 49:38Tim Ferriss?

  I see.

• 49:39Speaker 03

  The two best known examples.

• 49:40Tim Ferriss?

  Which can be affected by diet, exercise, et cetera.

• 49:44Speaker 03

  Exactly.

• 49:44Tim Ferriss?

  I see.

• 49:45Speaker 03

  Affected by stress, diet, exercise.

• 49:46Tim Ferriss?

  Okay, so the epigenetics is not the exercise and diet that can affect A, B, and C itself. It's actually those intermediary groups.

• 49:53Speaker 03

  Exactly.

• 49:54Tim Ferriss?

  Like the methyl and the several groups.

• 49:55Speaker 03

  Yeah, exactly. And the cool thing about epigenetics is that you're, you're, they're, they're working on this right now. So they've figured out the human genome. Now they're trying to figure out the human epigenome.

• 50:05Tim Ferriss?

  Yeah.

• 50:05Speaker 03

  So that, you know, there's tons of genes, there are patterns of methylation, acetylation, all these things. And what they're finding is that, you know, this, this stuff can actually be passed on to your offspring through the sperm DNA, through, you know, egg, you know, your eggs. So, well, not your eggs, but, you know.

• 50:23Tim Ferriss?

  Don't judge.

• 50:24Speaker 03

  You get it.

• 50:24Tim Ferriss?

  You're right.

• 50:25Speaker 03

  You know, so it, like, I'll give you an example. There is another study that was published a couple of years ago. Actually, there's been a series of these studies where they take these male mice.

• 50:33Tim Ferriss?

  Yeah.

• 50:33Speaker 03

  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 six and just crap.

• 50:46Tim Ferriss?

  Yeah.

• 50:46Speaker 03

  And these mice get obese and they get type two diabetes. But what they found is that they have offspring, female offspring, that are skinny. They, 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, they get type one diabetes. And what they found was that in the, 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.

• 51:16Tim Ferriss?

  Wow.

• 51:16Speaker 03

  Isn't that scary? Well, I mean, epigenetics is kind of terrifying in the sense where you're like beholden to what your parents did, but they're also, you can, you can change your diet and lifestyle.

• 51:26Tim Ferriss?

  Better stop drinking those phytoestrogens shakes or whatever.

• 51:30Speaker 03

  Yeah, right? So, so that, you know, the epigenetic factors, it's basically you're altering the expression of your genes without actually doing an, you know, any sort of nucleotide change. There's no nucleotide change in the sequence of the DNA. It's just.

• 51:44Tim Ferriss?

  It's like, pit my, pit my DNA.

• 51:45Speaker 03

  Yeah, on and on.

• 51:46Tim Ferriss?

  Pit my ride, right? It's like, the chassis is the same, you're just slapping on, God knows what.

• 51:50Speaker 03

  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 aging cells.

• 52:02Tim Ferriss?

  Yeah.

• 52:02Speaker 03

  And they've done it from, and they started out with, with, with blood cells from, 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

• 52:45Speaker 03

  and tell them, it's, it's almost like measuring telomere length. Now, telomere length is also.

• 52:49Tim Ferriss?

  Now, is that, does it, is it corresponding to their chron, their calendar age? Or is it a biological age?

• 52:56Speaker 03

  Great, great, great question. So there are outliers. So it does correspond to their chronological age for the most part, within four years, plus heroinist.

• 53:05Tim Ferriss?

  Right, okay.

• 53:05Speaker 03

  But there are outliers. And so now they're trying to figure out, some people look biologically much younger than their chronological age. Their methylation pattern looks.

• 53:14Tim Ferriss?

  Right.

• 53:15Speaker 03

  Younger. Right. And some people look much, biologically look much older than their chronological age. And so then they started comparing males and females.

• 53:24Tim Ferriss?

  Yeah.

• 53:24Speaker 03

  And they found that males had their methylation patterns aged like 4% faster. Looked, looked 4% older than, you know, the female counterpart. And then they started looking at cancer cells and cancer cells. And they'd, they'd get a cancer tissue from a person and then they'd get a tissue that was non-cancerous from the person, person. And they found that the cancer cells looked like they were methyl, their methylation patterns were aged like 40% faster, like those cancer cells had accelerated their aging.

• 53:51Tim Ferriss?

  Weird.

• 53:52Speaker 03

  It's really kind of.

• 53:53Tim Ferriss?

  Cancer cells are so weird.

• 53:54Speaker 03

  Well, here's, they are weird.

• 53:56Tim Ferriss?

  Yeah.

• 53:57Speaker 03

  They're, they're extremely smart.

• 53:59Tim Ferriss?

  Yeah.

• 54:00Speaker 03

  I mean, they, they figured it out.

• 54:01Tim Ferriss?

  Yeah.

• 54:01Speaker 03

  You know, well, to a certain point, because then they take over the host and then they can't survive anymore. But the thing that really gets me is, it seems like there may be a genetic program for aging.

• 54:11Tim Ferriss?

  Yeah.

• 54:12Speaker 03

  And of course, people will say, well, no, aging's, you know, it's a stochastic damage, it's happening, you know?

• 54:17Tim Ferriss?

  Yeah.

• 54:18Speaker 03

  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. 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 it's 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 our tissues. And so what they found is that this, 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.

• 55:00Tim Ferriss?

  The ARF gene.

• 55:01Speaker 03

  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, it's activated with inflammation. Inflammation activates NF kappa B.

• 55:18Tim Ferriss?

  So you hit like, you, you hit a critical mass of inflammation at a certain age and that demethylates ARF?

• 55:23Speaker 03

  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 NF kappa B activates this group of demethylases called the Jumanji demethylases. I know, isn't this great? And Jumanji-

• 55:38Tim Ferriss?

  Isn't that a movie with Robin Williams? No, no.

• 55:40Speaker 03

  No, yeah. So these Jumanji, um, uh, demethylases get activated and pull off these methyl groups. But what I think's going on is there's a chronic signal with age, and I think it's inflammation that's activating these enzymes, these demethylases, and it's changing the genetic patterns. So I think there's a connection.

• 55:58Tim Ferriss?

  Do you think that could be reversible?

• 55:59Speaker 03

  I do.

• 55:59Tim Ferriss?

  Okay.

• 56:00Speaker 03

  I mean, I really think we are figuring out, first of all, we're figuring out how to reprogram our, our stem cells. Now we can do that.

• 56:08Tim Ferriss?

  So, uh, stem cells, let's talk about it. So stem cells, uh, 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, 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.

• 56:30Speaker 03

  So that's one thing, yeah. Actually, I just recently banked some stem cells of my own.

• 56:34Tim Ferriss?

  You did?

• 56:34Speaker 03

  Yeah.

• 56:34Tim Ferriss?

  How old are you? Tell me about it.

• 56:35Speaker 03

  I'm, thanks for doing it publicly. I'm 35.

• 56:38Tim Ferriss?

  Okay, all right. So, so, you know, around 36, I think I've done a lot more damage to myself. You look a lot younger.

• 56:44Speaker 03

  Oh, thank you.

• 56:45Tim Ferriss?

  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?

• 57:00Speaker 03

  Well, so, there's a variety of different ways you can bank your stem cells. Chord 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.

• 57:10Tim Ferriss?

  I would have been really impressed if they pulled that off.

• 57:12Speaker 03

  I would have been really impressed. I would have been really impressed.

• 57:14Tim Ferriss?

  Ahead of their time.

• 57:16Speaker 03

  Yeah, so, the wisdom teeth have, so I had two, I had impacted wisdom teeth.

• 57:23Tim Ferriss?

  What does impacted mean?

• 57:24Speaker 03

  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 first removed, there's gotta be some positive thing to it. So I started reading, and I was, and I found out that there's stem, dental pulp stem cells in the teeth.

• 57:41Tim Ferriss?

  I have all my stem, I have all my stem cells, I have all my wisdom teeth.

• 57:44Speaker 03

  Do you? Okay, so let me continue. So, there's dental pulp stem cells.

• 57:48Tim Ferriss?

  This is crazy, alright.

• 57:49Speaker 03

  No, it's, I, 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, you know, teeth, eventually. So, they can also be sort of coerced, if you have the right stromal cells and like, stuff around, to neuro type of populations, neuronal type of populations. And what I found, studies where they've took human wisdom, so they extracted wisdom teeth from humans, took out the dental pulp stem cells, and then they trans, they did 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,

• 58:34Speaker 03

  along with a variety of growth factors and things that.

• 58:36Tim Ferriss?

  Cocktail of things.

• 58:37Speaker 03

  Yeah, the cocktail of things, and it replaced their damaged motor neurons.

• 58:40Tim Ferriss?

  That's crazy, from humans?

• 58:42Speaker 03

  From humans.

• 58:43Tim Ferriss?

  So is there no risk of host rejection, that type of thing?

• 58:46Speaker 03

  What they do, yeah, there is, but they do a lot of things where they'll irradiate the bone marrow and like make the immune system so it doesn't like 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.

• 59:07Tim Ferriss?

  Oh.

• 59:07Speaker 03

  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.

• 59:18Tim Ferriss?

  Yeah.

• 59:19Speaker 03

  And I found a couple of companies that, that I had thought were pretty trustworthy, you know, most of them-

• 59:25Tim Ferriss?

  That had a sign at an intersection, like, all now banking?

• 59:28Speaker 03

  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, the teeth. And so what they do is they'll send your oral surgeon a kit, which is essentially like a balanced saline solution.

• 59:43Tim Ferriss?

  Yeah.

• 59:43Speaker 03

  And they'll, 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 cryopreserve the tooth in 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'm 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. Cause I, you know, looked, looked through the way it's supposed to be done. Anyways, you know, it, 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 banged his. Primary teeth are really great source of kids. They have even more dental pulp stem cells in their teeth that they just throw away.

• 1:00:28Tim Ferriss?

  Oh, wow. So if your kids are losing teeth, parents.

• 1:00:32Speaker 03

  Yeah.

• 1:00:33Tim Ferriss?

  Get, get yourselves a balanced saline solution. So what, what'd you say?

• 1:00:37Speaker 03

  Stem Save is one of the, the companies and then there's National Dental Pulp Laboratory. Yeah.

• 1:00:43Tim Ferriss?

  Stem Save's more memorable. What was the other one?

• 1:00:45Speaker 03

  National Pulp Dental Laboratory. Yeah. I actually went with them just because I spoke to their cell biologist and went through the whole.

• 1:00:53Tim Ferriss?

  All right.

• 1:00:53Speaker 03

  I went through the whole, I'm sure they were irritated with me, but-

• 1:00:55Tim Ferriss?

  Where they, where they based?

• 1:00:56Speaker 03

  Uh, they're in New England.

• 1:00:57Tim Ferriss?

  Okay.

• 1:00:58Speaker 03

  Area, so.

• 1:00:59Tim Ferriss?

  Makes sense, doesn't it?

• 1:01:00Speaker 03

  It does.

• 1:01:00Tim Ferriss?

  Yeah.

• 1:01:01Speaker 03

  So.

• 1:01:01Tim Ferriss?

  In Boston somewhere with all the biotech.

• 1:01:03Speaker 03

  Yep. So, cool stuff, right? But-

• 1:01:07Speaker 03

  The other cool thing is the reprogramming part, what I was talking about, where they can take your skin cells.

• 1:01:12Tim Ferriss?

  Yeah.

• 1:01:12Speaker 03

  They can even take...

• 1:01:14Tim Ferriss?

  What is the difference, just to sort of interject?

• 1:01:16Speaker 03

  Yeah, yeah.

• 1:01:16Tim Ferriss?

  Between the modifier mesenckymal and the modifier pluripotent? Because they seem to indicate the same thing. Are they different?

• 1:01:24Speaker 03

  Yeah, so pluripotent, those, okay. Mesenckymal 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.

• 1:01:35Tim Ferriss?

  Yeah.

• 1:01:35Speaker 03

  Bone marrow can form like blood cells, they can form your red blood cells, white blood cells, you know, they have a distinct limit to the type of cells they 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.

• 1:01:57Tim Ferriss?

  Right, right.

• 1:01:58Speaker 03

  Yeah, anyways, the cool thing is...

• 1:02:00Tim Ferriss?

  And then mesenckymal.

• 1:02:01Speaker 03

  Oh, the mesenckymal just means the type of tissue where it came from, like, you know, the origin.

• 1:02:08Tim Ferriss?

  People use mesenckymal and pluripotent interchangeably, which is why I'm trying to figure.

• 1:02:12Speaker 03

  No.

• 1:02:13Tim Ferriss?

  They do not.

• 1:02:13Speaker 03

  No, I don't think they do.

• 1:02:15Tim Ferriss?

  Okay.

• 1:02:15Speaker 03

  Yeah, mesenckymal...

• 1:02:17Tim Ferriss?

  I'm not saying that people don't know what they're talking about, dude.

• 1:02:19Speaker 03

  Yeah, oh, oh, you're saying you've heard people.

• 1:02:21Tim Ferriss?

  I've heard people use them interchangeably.

• 1:02:22Speaker 03

  No, no, that's not interchangeable.

• 1:02:23Tim Ferriss?

  All right, all right.

• 1:02:24Speaker 03

  No, no.

• 1:02:24Tim Ferriss?

  Got it.

• 1:02:25Speaker 03

  Yeah.

• 1:02:25Tim Ferriss?

  Okay.

• 1:02:25Speaker 03

  So...

• 1:02:26Tim Ferriss?

  Good to know.

• 1:02:26Speaker 03

  Yeah, they're wrong.

• 1:02:27Tim Ferriss?

  All right, got it.

• 1:02:28Speaker 03

  I 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.

• 1:02:40Tim Ferriss?

  Yeah.

• 1:02:41Speaker 03

  And people have figured out, actually, I think his name is Shinya Yamanaka.

• 1:02:46Tim Ferriss?

  Sounds Japanese.

• 1:02:47Speaker 03

  Japanese. Now, he was in Kyoto, Japan, when he first made this discovery in 2006. It was a frickin' game changer, in my opinion, it was like, super cool.

• 1:02:55Tim Ferriss?

  Well, I'm guessing most countries outside the US are far beyond us in research, just due to sort of legislative and regulatory issues that lead then to funding issues.

• 1:03:04Speaker 03

  Right.

• 1:03:05Tim Ferriss?

  Yeah.

• 1:03:05Speaker 03

  And also, you know, work ethic, I think a lot of Japanese...

• 1:03:08Tim Ferriss?

  Yeah, they're hard workers.

• 1:03:10Speaker 03

  They're hard workers. I had a new one that would, had a cut. And would sleep in the lab.

• 1:03:16Tim Ferriss?

  Yeah, well, they have, that's why they, I mean, they have a term for death by overwork there.

• 1:03:19Speaker 03

  Do they?

• 1:03:20Tim Ferriss?

  Karoshi, yeah.

• 1:03:21Speaker 03

  I'm not surprised.

• 1:03:22Tim Ferriss?

  Ka is too much, ro is like working, and then shi is death. Shi also means, uh, well, yong or shi 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 thirteen for

• 1:03:40Speaker 03

  Oh, interesting.

• 1:03:41Tim Ferriss?

  A lot of Western cultures. That's why they don't like the number four.

• 1:03:44Speaker 03

  I didn't know that.

• 1:03:45Tim Ferriss?

  So, uh, shinnyaman, what was it?

• 1:03:48Speaker 03

  Yamanaka. Not Yamanaka, I think. Oh, I hope I didn't butcher it.

• 1:03:52Tim Ferriss?

  It's okay. It's all right.

• 1:03:53Speaker 03

  Anyways.

• 1:03:54Tim Ferriss?

  Yamanaka is like Jones. It's one of those

• 1:03:55Speaker 03

  Is it? Okay, so then probably right.

• 1:03:57Tim Ferriss?

  Yeah, or Yamaguchi, yama, who the hell knows?

• 1:03:59Speaker 03

  Right.

• 1:03:59Tim Ferriss?

  Really, really, really common, yeah.

• 1:04:01Speaker 03

  So, um, he figured out, he had looked at these patterns of gene expression in stem cells, and he'd 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. And, uh, what he found was that there's four different transcription factors. Those genes that like activate a variety of different genes, who I was talking about, Fox was one of them.

• 1:04:24Tim Ferriss?

  Yeah.

• 1:04:25Speaker 03

  He found four of them that were required for a stem cell to be multipotent.

• 1:04:29Tim Ferriss?

  Okay.

• 1:04:30Speaker 03

  And what he did was he took like fibroblast cells. First, they started out with mice, and then they've done it in humans. The first study was in mice, where they took fibroblast cells, and they

• 1:04:39Tim Ferriss?

  What is a fibroblast cell?

• 1:04:40Speaker 03

  Um, skin.

• 1:04:41Tim Ferriss?

  Okay, got it.

• 1:04:41Speaker 03

  Yeah.

• 1:04:42Tim Ferriss?

  Blasted it with all those?

• 1:04:43Speaker 03

  Blasted it with those four. Well, the way we can do it is we can put it in a virus, a viral background, and the virus will then

• 1:04:49Tim Ferriss?

  That's the viral vector.

• 1:04:50Speaker 03

  Retrovirus, or, yeah, exactly. It's a vector, right?

• 1:04:53Tim Ferriss?

  Yeah.

• 1:04:54Speaker 03

  And you can put

• 1:04:54Tim Ferriss?

  That's how they do it, yeah, gene therapy.

• 1:04:56Speaker 03

  Exactly. That's exactly how they're doing it. So, and then

• 1:04:58Tim Ferriss?

  You gotta be careful with that stuff.

• 1:04:59Speaker 03

  You do. Well, in this case, they're using a retroviral background, which means that this virus

• 1:05:04Tim Ferriss?

  Not viral, the retroviral.

• 1:05:05Speaker 03

  Right. It'll incorporate, it'll use its RNA transcriptases to make DNA, and it'll incorporate to random places in the chromosome. So you don't know it could be going anywhere.

• 1:05:13Tim Ferriss?

  Yeah.

• 1:05:13Speaker 03

  You know? And that, 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, so.

• 1:05:22Tim Ferriss?

  But you avoid that.

• 1:05:23Speaker 03

  Avoid that, and instead you make this freaking skin cell a multipotent 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.

• 1:05:33Tim Ferriss?

  In which case you don't have to worry about banking your stem cells.

• 1:05:35Speaker 03

  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 even been able to, they've done it from the urine, what are the renal, the renal fibroblast cells that you excrete in urine, those cells.

• 1:05:50Tim Ferriss?

  Wow.

• 1:05:50Speaker 03

  In urine, which is non-invasive.

• 1:05:52Tim Ferriss?

  Yeah.

• 1:05:52Speaker 03

  Pee and they can isolate these cells.

• 1:05:54Tim Ferriss?

  Wow.

• 1:05:55Speaker 03

  Add these four transcription factors.

• 1:05:56Tim Ferriss?

  So you could be like, yeah, too bad I drank like an alcoholic for 20 years, but that liver cirrhosis, ah, whatever, like, let me just grab my Mormon neighbor's pee and like.

• 1:06:06Speaker 03

  I, I.

• 1:06:06Tim Ferriss?

  Make some stem cells.

• 1:06:07Speaker 03

  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 cemix, which is one of the ones that is required, is also cancer promoting.

• 1:06:21Tim Ferriss?

  Right.

• 1:06:21Speaker 03

  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 like use CasPase or something, where they can actually target a gene and put in the exact locus where it's supposed to be.

• 1:06:51Tim Ferriss?

  Oh, wow.

• 1:06:52Speaker 03

  Instead of it randomly incorporating.

• 1:06:54Tim Ferriss?

  Shotgun it.

• 1:06:55Speaker 03

  Exactly. And so what I, if I were working on that, I would take advantage of that system and try to see if that, if you now use that system to deliver it to this, you know, fibroblast cell, getting it in the right spot.

• 1:07:08Tim Ferriss?

  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.

• 1:07:18Speaker 03

  Right.

• 1:07:19Tim Ferriss?

  But it's, I think it's gonna happen a lot faster than people expect, but it's still gonna be a few years. So in the meantime, like, you should learn how to drive.

• 1:07:25Speaker 03

  Right.

• 1:07:25Tim Ferriss?

  Right? So the, would you recommend that people hold off for that? Or do you think that banking cells is a good insurance, uh, insurance policy?

• 1:07:34Speaker 03

  I think banking your cells now, like if you, you know, for example, if your kids are losing their teeth, or you're, you've got a couple of wisdom teeth, or.

• 1:07:40Tim Ferriss?

  What if you don't have any wisdom teeth? What would your second choice be for banking?

• 1:07:44Speaker 03

  Obviously, if you're a female.

• 1:07:46Tim Ferriss?

  Yeah.

• 1:07:46Speaker 03

  Um, and you're going to have a child.

• 1:07:48Tim Ferriss?

  Yeah.

• 1:07:49Speaker 03

  Something that's really cool that came out, I don't know, four or five years ago, I think, where they found the placenta.

• 1:07:55Tim Ferriss?

  Yeah.

• 1:07:55Speaker 03

  The placenta is like a really rich source of multipotent stem cells.

• 1:08:00Tim Ferriss?

  Huh.

• 1:08:00Speaker 03

  And. 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.

• 1:08:07Tim Ferriss?

  Yeah.

• 1:08:08Speaker 03

  But that's another really good source. Cord blood, stem cells, teeth. Males teeth, I mean.

• 1:08:14Tim Ferriss?

  Males are just.

• 1:08:15Speaker 03

  I think, you know.

• 1:08:17Tim Ferriss?

  A dearth of opportunities.

• 1:08:20Speaker 03

  Invasive and, you know.

• 1:08:23Tim Ferriss?

  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?

• 1:08:31Speaker 03

  No.

• 1:08:31Tim Ferriss?

  He's an M.D., very fascinating guy.

• 1:08:33Speaker 03

  Is he in the Bay Area?

• 1:08:34Tim Ferriss?

  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.

• 1:08:54Speaker 03

  Right, right, yeah.

• 1:08:55Tim Ferriss?

  But yeah, invasive is kind of an understatement. I mean, it's.

• 1:08:58Speaker 03

  I don't think it's very, I think it's painful, basically.

• 1:09:02Tim Ferriss?

  Yeah, I think there are less painful ways to do it. I mean, given all this crap I've done to myself, I'm sure it would be just another kind of.

• 1:09:07Speaker 03

  Although getting your teeth yanked out, I mean, I was.

• 1:09:10Tim Ferriss?

  It's not exactly walking the park.

• 1:09:11Speaker 03

  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.

• 1:09:19Tim Ferriss?

  Twilight, like the werewolf Twilight?

• 1:09:21Speaker 03

  The Twilight, like, you know, I was like, I thought they were gonna put me under. I was like, yeah, just put me under.

• 1:09:25Tim Ferriss?

  Oh, they didn't. They were just like, no, no, it's all stuff.

• 1:09:27Speaker 03

  They put me in, it was like, I was, I was like relaxed and calm, but.

• 1:09:32Tim Ferriss?

  They're like, here, have a martini, you ready?

• 1:09:34Speaker 03

  Yeah, I'm still awake. This is really, you know, it was like pulling your teeth. I mean, it's, yeah. It was, it wasn't pleasant, but I got my, I got my teeth craft preserved. They're in New England now and, you know, liquid nitrogen.

• 1:09:47Tim Ferriss?

  So, besides, besides the dental pulp, stem cell storage, what other types of things are you doing to potentially, you know, extend healthful lifespan? What are the other kind of low hanging fruit? What other things are you thinking of?

• 1:10:04Speaker 03

  Well, low hanging fruit is what we started this conversation with, micronutrients.

• 1:10:08Tim Ferriss?

  Yeah, fix your diet.

• 1:10:09Speaker 03

  I really, and not just yet, really focus on these micronutrients. They're, you know, you've got, you know, 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 gonna notice these things not functioning right. It's just not, you're not gonna 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.

• 1:10:38Tim Ferriss?

  It's also routine, though. I mean, it's a habit that you get into.

• 1:10:41Speaker 03

  Right.

• 1:10:41Tim Ferriss?

  Just like anything else.

• 1:10:42Speaker 03

  That's why the Vitamix, for me, it makes it so much easier because, you know, while I do also eat salads and I also, you know, cook my vegetables too. Getting that broad spectrum, like, I think there's micronutrients in there we probably haven't even discovered.

• 1:10:57Tim Ferriss?

  Oh, I'm sure 100% there are.

• 1:10:58Speaker 03

  Absolutely. I am too. I'm convinced.

• 1:11:00Tim Ferriss?

  Definitely.

• 1:11:02Speaker 03

  So, 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.

• 1:11:16Tim Ferriss?

  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.

• 1:11:23Speaker 03

  Right.

• 1:11:24Tim Ferriss?

  It's just going to be like, holy shit, I can't believe we used to do that.

• 1:11:27Speaker 03

  I think the stem cell reprogramming is, is well in the food. 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 regenerating.

• 1:11:39Tim Ferriss?

  I think there's such an unwarranted stigma associated with stem cells because of the religious fear over embryonic stem cell use. And it just, it 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

• 1:12:04Speaker 03

  Right.

• 1:12:04Tim Ferriss?

  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 people are, and there are other people who are interested in getting tenure or whatever the [__] it might be, or be remaining on the board of blah, blah, blah, the journal, A, B, and C.

• 1:12:22Speaker 03

  Exactly.

• 1:12:22Tim Ferriss?

  Funding's just not gonna, it's not gonna, it's not gonna 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.

• 1:12:52Speaker 03

  It doesn't.

• 1:12:52Tim Ferriss?

  Right?

• 1:12:53Speaker 03

  It doesn't.

• 1:12:53Tim Ferriss?

  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, you know, over 150, 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 100 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, alright, we're gonna start with what to add first. So, like, you need 30 grams of protein within 30 minutes of waking up.

• 1:13:33Tim Ferriss?

  You need, uh, you know, a fist-sized serving of green on any plate that you eat off of. That's it. Those are the two things you're gonna do. And, or like, start drinking water. How about that? You know, like, no more drinking calories. Just like one, like, one tiny thing, but the additive stuff would be, is so beneficial. Like, so the way that I, I generally interact with those folks is I'll say, like, you can eat, you have to eat the following things. After that, if you're still hungry, eat whatever the [bleep] 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,

• 1:14:17Tim Ferriss?

  where it's usually a, sort of a, a no-smoking sign that gets placed on a handful of things, and that's the extent of the guidance.

• 1:14:23Speaker 03

  Right.

• 1:14:24Tim Ferriss?

  But, yeah.

• 1:14:24Speaker 03

  Yeah, you know, it's like, it, it makes sense, you know, your body is designed, it's very resilient. We are, we can deal with stress. We have a whole host of enzymes in our body and proteins that deal with crap.

• 1:14:37Tim Ferriss?

  Yeah.

• 1:14:38Speaker 03

  But those things need cofactors to do that.

• 1:14:42Tim Ferriss?

  Yeah.

• 1:14:42Speaker 03

  So, it's like you said, I wouldn't say 15 gallons of ice cream, but, you know, the point is.

• 1:14:46Tim Ferriss?

  Liters, liters, let's not go crazy.

• 1:14:48Speaker 03

  Right. Give your body what it needs.

• 1:14:50Tim Ferriss?

  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. 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.

• 1:15:16Speaker 03

  Right.

• 1:15:17Tim Ferriss?

  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.

• 1:15:32Speaker 03

  I personally like consuming legumes and I like, I love lentils.

• 1:15:37Tim Ferriss?

  Lentils are the bomb.

• 1:15:38Speaker 03

  Because, you know, these fibers, you know, the fiber in them gets, you know, broken down into short chain fatty acids in the gut. I mean, this is great for your gut.

• 1:15:46Tim Ferriss?

  Yeah.

• 1:15:47Speaker 03

  Keeping your gut happy is so, it's so important in so many ways and that, that would be a whole other topic for like,

• 1:15:54Tim Ferriss?

  Gut health?

• 1:15:55Speaker 03

  Pretty much, yeah. But, you know, I, it's kind of weird how the paleo community was against, I don't know who started that meme, but...

• 1:16:02Tim Ferriss?

  Well, it comes down to a lot of the stuff that we're talking about, the anti-nutrients.

• 1:16:06Speaker 03

  Oh, oh, right.

• 1:16:08Tim Ferriss?

  It's related to that.

• 1:16:08Speaker 03

  The lectins, but lectins get heat inactivated.

• 1:16:11Tim Ferriss?

  Well, that's, yeah.

• 1:16:12Speaker 03

  And that's awesome, anyway.

• 1:16:13Tim Ferriss?

  This is a whole separate story, yes. I mean, the lectins, saponins and all of this,

• 1:16:17Speaker 03

  Right.

• 1:16:17Tim Ferriss?

  in my experience typically get either inactivated or removed with conventional preparation or cooking.

• 1:16:25Speaker 03

  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, in everything. So it's like, I think a better approach, rather than focusing on these little minute possible bad things that may or may not do something, is focusing on what our body needs to function properly indefinitely.

• 1:17:07Speaker 03

  You 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 all the crap of just normal living, metabolism, immune function. These things produce inflammatory molecules, also reactive nitrogen species, reactive oxygen species, these things are just from normal living.

• 1:17:30Tim Ferriss?

  Yeah. Agreed. I am getting, you're making me Jones for a Jake Shields green drink. That is a local MMA fighter, and there's a place called Sidewalk Cafe down in the Mission that serves freshly blended greens.

• 1:17:47Speaker 03

  Awesome.

• 1:17:48Tim Ferriss?

  So I think that is probably my next stop. We could talk about tons of things for hours and hours and hours. I'm sure we'll do a round two. But in the meantime, obviously during the days, you're still working in the labs, but where can people find more about you and follow you online?

• 1:18:08Speaker 03

  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.

• 1:18:20Tim Ferriss?

  Awesome. Well, this is super fun stuff, very important stuff, and to be continued. So thanks very much for making the time.

• 1:18:28Speaker 03

  Awesome. It was a blast.

• 1:18:30Tim Ferriss?

  Yeah. Until next time. Thank you.

• 1:18:33Speaker 03

  Cool.

• 1:18:34Speaker 04

  If you want more of the Tim Ferriss Show, you can subscribe to the podcast on iTunes or go to fourhourblog.com.

• 1:18:43Speaker 05

  F-O-U-R-H-O-U-R-B-L-O-G dot com.

• 1:18:46Speaker 04

  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, it's twitter.com/TFerriss.

• 1:18:59Speaker 05

  That's T-F-E-R-R-I-S-S.

• 1:19:02Speaker 04

  Or on Facebook, at facebook.com/TimFerriss. Until next time, thanks for listening.