[Transcript] – The 7 Different Reasons You Age (& Potent, Proven Molecules To Enhance Longevity & Slow Aging).

Affiliate Disclosure



[00:00:00] Introduction

[00:00:50] Books on Longevity

[00:02:09] Podcast Sponsors

[00:04:19] Guest Introduction

[00:06:43] Living in a Ranch and Interest in Longevity

[00:11:22] 7 Tenets of Aging

[00:25:03] The Kaufmann Rating System

[00:30:37] The Kaufmann Protocol App

[00:32:38] Podcast Sponsors

[00:35:31] Most Overhyped and Most Effective of the 15 Ingredients

[00:43:06] Curcumin Brands

[00:44:56] Pterostilbene: Why is it so great?

[00:47:59] Why Astaxanthin is the bomb?

[00:51:12] The Magical Attributes of Carnosine

[00:55:17] Efficacious Dosages of These Compounds

[00:57:25] Thoughts on The Latest Research Regarding Metformin

[01:03:04] Dr. Kaufmann's Anti-Aging Lifestyle Beyond the Supplements and Compounds

[01:08:22] Telomerase and Maximum Potential Human Lifespan Based on The Protocol

[01:14:45] End of Podcast

Ben:  On this episode of the Ben Greenfield Fitness Podcast.

Sandra:  You need to take that information and make it, so regular people can understand it and make it so that you can come up with a regular understandable system. I've been using this stuff way before the Iron Curtain fell. And one of the reasons their athletes were so good once upon a time is because they were on carnosine. Carnosine does two major things. So, it becomes a point system, it becomes a game, but the idea is just to keep people sort of under the gun of, yes, we're aging every day, let's fix it every day.

Ben:  Hey, today's podcast is really cool. It's with longevity researcher named Dr. Sandra Kaufmann. She kind of flies under the radar in the anti-aging realm, but she's pretty dang cool, and you're going to learn a ton during today's show.

Speaking of longevity, my own book, which is jam-packed with thousands of words that I wrote about longevity and a whole lot more, it's over 600 pages long, this huge hardcover book that's coming out in January. You can now sign up to get notifications for when that book is getting a launch. Be the first to get your dirty little hands on it. It is called “Boundless.” You can head over to “Boundless” book. “Boundless,” with two Ss, boundlessbook.com to be the first to get updates on my new book coming early next year. So, be sure to check that out.

Another thing regarding longevity is that when we look at a lot of these longevity hotspots, like Okinawa or Bama County. Many of the natural plant-based compounds that they're consuming, several of which Dr. Kaufmann discusses in her book are related to these. They can do things like lower circulating insulin levels, enhance glucose metabolism, maintain healthy insulin sensitivity, even lower levels of insulin and insulin-like growth factor 1. Two of those compounds are rock lotus extract, and also bitter melon extract. And the cool thing about bitter melon extract is it also activates AMPK, so it's kind of like exercise in a bottle.

These are the two main components of the product that I have over at Kion called Kion Lean. I pop one to two of these before every meal of the day because I'm a little bit of an overachiever. Most people just pop a couple capsules before any meal they're eating that contains any carbohydrates or alcohol. The stuff works like the bee's knees. I don't know if that's the appropriate use of that term. But anyways, it's called Kion Lean. You get a 10% discount on that, or any of the fine, fine products from Kion if you just go to getkion.com. That's getK-I-O-N.com and use discount code BGF10.

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Hey, you may have seen me a few times over the past few months reference this protocol, this anti-aging protocol called The Kaufmann Protocol. It's all based on a book called “The Kaufmann Protocol: Why We Age and How to Stop It,” and also the app and the very helpful website that accompany that book. Now, this is a new book that, in my opinion, is one of the most comprehensive approaches to anti-aging, particularly from a molecular and a compound standpoint in terms of what kind of things you can put into your body that would halt the aging process or enhance longevity in some fashion. The book goes into everything from the top 15 molecular agents that can curb the aging process to kind of like how to rank, categorize the type of things that you might use when it comes to supplements and medications that might go into an anti-aging protocol.

The author of the book is a physician named Dr. Sandra Kaufmann. She actually began her career in the field of cellular biology and got a master's degree from UConn in ecology and plant physiology. But then she went on to get a medical degree at University of Maryland, and did her residency and fellowship at Johns Hopkins in the field of pediatric anesthesiology. However, she also has of late began to churn out some pretty interesting content, particularly in the field of anti-aging, and she's very knowledgeable when it comes to cell biology and human pharmacology and physiology. So, I'm very, very happy that I've been able to finagle her into recording a podcast with me about all of this stuff, her book, her protocol, and how this all works.

Now, before we jump in, A, everything you're about to hear, I will take copious notes for and put them all for you over at BenGreenfieldFitness.com/stopaging, where I'll also give you a link to Dr. Kaufmann's book. And B, before we began recording, Dr. Kaufmann informed me that she would apologize for any horse noises in the background because she's at a dude ranch. And so I have to ask you, Dr. Kaufmann, as my first question, why the heck are you at a dude ranch? Is this some sort of like underground fringe longevity enhancing tactic?

Sandra:  Well, number one, it's really nice to be on your show. I'm at a dude ranch because it's fun.

Ben:  You know what, I'm going to come right and say, “I don't really quite understand what goes on at a dude ranch or what a dude ranch is.” So, when you say it's fun, what do you mean?

Sandra:  Well, it's sort of like adult camp. You come with your family, you live in a cabin, you ride horses, you hike mountains, you go kayaking, you go whitewater rafting. It's just fun.

Ben:  Okay. I thought it was just like hanging out with cowboys and eating baked beans and getting forced to take care of the horses, but that actually does sound like a good time. So, it's like a vacation?

Sandra:  Oh, it is a vacation, and I can totally plug it. It's called the Majestic Dude Ranch. We don't eat baked beans. The food is awesome. Everyone's excellent. There are, in fact, cowboys. That part is cool. It's just fun.

Ben:  We do know a lot of the Blue Zones eat legumes, so maybe baked beans would fit into your whole longevity protocol.

Sandra:  Perhaps yes. I'm going to guess that the gas that is produced, maybe not be so much fun in a communal sense.

Ben:  Yeah, yeah, that's true, that's true. They might have to change the title from Majestic Dude Ranch to something else more methanogenic than the word–well, you could just call that, The Methanogenic Dude Ranch. Anyways though, we digress. We've gone for two minutes now and not giving anyone any helpful information about how to live longer. So, I guess we should probably dive in. And I'm actually curious because you as I mentioned, we're formally trained as a pediatrician, how you got interested in like babies and kids and children, too. Instead, I guess ensuring that we don't wind up in diapers and dying early in old age.

Sandra:  Well, I can tell you that there is absolutely no correlation at all between being a pediatric anesthesiologist and not wanting to age. I guess the only true association is that we're all made out of cells, so I'm sort of an expert in pharmacology and pharmacodynamics, human biology, that sort of thing. But it's completely not related. I decided not to age because I hit the age of 40, 45 and I'm an adventurer; I rock climb, I mountain climb, I swim, I bike, I run and it dawned on me at some point that unless I figure out how to stop aging, that all of my fun was going to come to some crashing halt at some point.

Ben:  Yeah.

Sandra:  So, I spent a lot of time doing what doctors do, or at least researchers do as I've read. I don't have a research lab, but I certainly have the ability to read and synthesize information. And it dawned on me at some point that there's a lot of really smart people out there, but they live in silos, they don't communicate, and there was no overarching theory of aging, and no way to actually put together a comprehensive system that made sense. So, I decided to be the person to do that.

Ben:  Yeah. Well, I mean, there is–what's his name? Aubrey de Grey. You're no doubt familiar with him and his SENS Research Foundation where he has certainly proposed a host of different mechanisms for aging. To my knowledge, he doesn't actually have a systematized approach as you do to tackle each of those different mechanisms of aging. But are you familiar with him?

Sandra:  Oh, of course. The man is brilliant. I've met him several times. He's absolutely brilliant. But the problem is what do you do with this list? And I don't want to degrade him in any way, shape, or form. The man's a genius. All of these guys are geniuses. But you need to take that information and make it, so regular people can understand it and make it so that you can come up with a regular understandable system. And it was kind of chaos out there and it still is. Not too many people know who I am yet. Hopefully, they will, but the idea is to introduce anti-aging not as a crazy snarky, but as a real system to prevent disease and improve health out there.

Ben:  Yeah. I think what would probably help you quite a bit is if you were to grow a beard like Aubrey. I think that's probably one of the first keys to actually really identifying yourself as a pioneer in the anti-aging industry. Just a massive beard.

Sandra:  We know that's really too bad because I just shaved mine off.

Ben:  Yeah. Recommended for attendance at the Majestic Dude Ranch. Don't come in with a lot of facial hair, especially if you're a woman. Anyways, let's dive into the platform that underlies your approach in the book. I believe there were seven different pathways that you proposed that we would need to target if we were going to have real success when it comes to anti-aging. Can you dive into what those pathways are?

Sandra:  Absolutely. So, let me explain something very quickly. A lot of people don't know the words we're going to use. And I understood that when I wrote the book, I wanted more people to understand this just in science geeks. So, I used two different systems of vocabulary. The one thing I do is I have a system as if it's a factory, as if our cells are factories. And I kind of bounced back and forth between factory vocabulary and scientific vocabulary. So, I hope people don't find that confusing. But if you look at your cells to try to figure out why we do age, I broke it down into seven systems. You're absolutely right. I call it the 7 Tenets of Aging. The first thing I talk about is things that affect your DNA. And the factory analysis model, I call it the company operating manual. And very briefly in DNA, that has to do with epigenetic modulation and effects on the telomeres.

Ben:  Okay.

Sandra:  I'm going to fly through these quickly. Stop me because there's so much information.

Ben:  Yeah. Yeah, that's fine.

Sandra:  The second category, every company or factory needs an energy source. In our world, that's mitochondria, and they fail for two specific reasons. We have pathways in our bodies. There are specific pathways to aging. Very specifically, we have the AMP kinase system, the sirtuins, and the mTOR system.

Ben:  Okay.

Sandra:  The fourth category, I call quality control. Someone has to check the widgets in the factory. And we have DNA and protein repair mechanisms, and I throw autophagy in there, just sort of be inclusive. The next system is your security system–

Ben:  And if I could interrupt you real quick. That mechanism number four, where you're talking about DNA and protein repair mechanisms and somehow repairing the ongoing damage that's inside the cells, how is that different than the first mechanism you described, which is just basically stopping the accumulation of DNA damage? Why do you categorize those separately?

Sandra:  Okay. So, category one, epigenetic modulation is a little bit different. It has to do with methylation of the DNA histone. You get acetyl groups phosphorylation, all sorts of things that get added onto your DNA. It has to do with the Horvath clock, genetic drift, that sort of thing.

Ben:  Okay.

Sandra:  And telomerase issues, it has to do with more the nuts and bolts of how DNA actually works.

Ben:  Okay.

Sandra:  Right? In terms of quality control, it's more like fixing your widgets.

Ben:  Okay. Got it. With the widgets, when you say widgets in a more scientific terminology, what are you referring to?

Sandra:  Right. So, if you look at your DNA, every day in every cell, you have 10 to the 5th DNA errors. It could be a double-stranded error. It could be a single-stranded error. All sorts of errors, but every cell every day has 10 to the 5th errors, and you have four very specific DNA repair mechanisms that fix this. At the same time, proteins go through a very sophisticated system of making them, and they fail over time as well, and you have four very specific protein repair mechanisms. So, I consider this the category of self-check and repair.

Ben:  Okay. So, one's more based on proper expression of DNA and telomere modification, one's more based on actual protein repair mechanisms.

Sandra:  That's correct. And what's interesting about this is there are specific molecular agents that you can take that increase your ability to fix your own DNA.

Ben:  Okay. Got it. And I'm sure we'll delve into those. Okay. So, you said the first was things like methylation, histone modification, telomerase, and basically all the things associated with genetic expression. The next would be your mitochondria and inhibiting some mitochondrial degradation. The third you said were some of these pathways like AMPK and sirtuin and mTOR. Basically, enzymatic pathways that can direct the cells to age or not to age. The fourth you said was just stopping ongoing damage to proteins and upregulating protein repair mechanisms, or I guess we also used the word autophagy quite a bit when it comes to that. And then what would be the next three, I guess?

Sandra:  So, the next one is the security system, and it's basically your immune system, and your immune system fails you for three big reasons. Number one is your immune system is less able to fight infection over time. The cells that make up your immune system or likely become cancerous, which is why older people have lymphomas and leukemias more frequently. And lastly, it upregulates the systemic inflammation. So, as we get older, we are more and more inflamed. So, that's sort of the security division.

Ben:  Okay.

Sandra:  The sixth category, I consider the workforce of the factory. And as much as I like to, in my book and in my speeches, tell people that most cells are the same, they're obviously not. And I divide them into three categories based on how long they live. So, there are the very short-acting cells that last anywhere from hours to a few days. There are the Goldilocks cells that last between eight to twelve years. And then there are the cells that last pretty much forever; the inner ear cells, your neurons, all sorts of those cells. And they've required different things over the course of your lifetime. As well, I put stem cells into that category. And ultimately, there's a little bit of a conversation about senescence in that chapter in the book, but I'm writing a huge dissertation on that right now, so I don't want to give anything away. But that's the workforce category.

Ben:  Okay. And when it comes to senescent cells, by the way, since you're writing a whole book on this, I should ask you this question real quick because I think some people get confused. Is the goal to eliminate senescent cells and stop their formation, or is the goal to enhance senescence or some kind of variation of those two?

Sandra:  So, a senescent cell, I consider–some people call them zombie cells. I like to think of them as old grumpy cells that have sit in the corner and they're just very malignant, not in a cancerous way but in just evil cytokinin way. What happens is when a regular cell gets DNA damage, it puts itself in a state of lockdown, and the DNA tries to repair itself. And while it's in a state of shutdown, it's sort of quiescent. So, people sometimes confuse quiescent with senescent.

Ben:  Okay.

Sandra:  Quiescent is reversible. The cell fixes itself and all goes back to normal. If the damage is horrible, it kills itself. It's cell suicide, otherwise known as apoptosis. Somewhere in between, the cells sort of repairs itself, but doesn't really go back to the way it was supposed to have been, and it becomes senescent. The morphology of the cell changes. The expression of it changes. It puts out a lot of cytokinins. I call them evil cytokinins, which really they're not, they're interleukins and such. And what that does is it creates a sort of a baloo of evilness in your tissues. So, that senescent cell makes more cells senescent, and it just increases the pathology of wherever it is in your body.

And so, there are some cells that slow that process down. They're xenomorphic. And there are some agents that kill these cells, and that's senolytic, and you want to kill them, but you want to do it in a very regulated fashion. And there are probably, I don't know, dozen or so agents right now that are senolytic. A lot of them you can get, a lot of them you cannot get, some of them are sort of out of control agents. So, I'm trying to take all that information and make it understandable for folks.

Ben:  Okay. Got it. Now, it's my understanding the senescent cells could play some kind of a role in cell signaling. We know that in the cases of cellular damage or wound healing, for example, that the inflammatory products produced by senescent cells could be beneficial. But is there any reason to make sure you're not just completely kind of nuking all your senescent cells?

Sandra:  Right. So, obviously, anything in your body had a positive effect at one point. You need them when you're growing, when you're changing, when you're modifying your structure, when you're going from being a toddler to an adolescent. And it's true, they help with wound healing. They do a variety of things. Generally speaking, from what I can ascertain, and this is the best guess, anywhere in healthy tissue, you have between 5% to 8% of senescent cells. When you become more pathologic, it can go up to 20%, 25% of your cells.

Clearly, you don't want to get rid of all of them because you're right, they do have these signaling pathways, and they do actually bring the immune system in to help clear themselves out. And they do, they do have some beneficial qualities. But overall, a huge accumulation of them has negative effects. And there's really no way we're going to get rid of all of them anyway because they're constantly increasing in number. From what I can tell is it starts in a linear–if you were to graph it, it's linear at the beginning, and then as you get older and older and you have more points of pathology, it becomes more exponential. And the idea is just to get rid of some of them to shift the curve to the right.

Ben:  Okay. Got it. And then what would be the seventh mechanism?

Sandra:  So, the last thing I like to think of is waste management because you have to take out the trash, right? Any company, you can't leave it sitting in the corners. So, in this category, I put AGEs and lipofuscin. An AGE is advanced glycosylated end products, right? It's when glucose bonds non-enzymatically to DNA lipids and proteins, it sort of makes them non-functional, and then it wreaks havoc on your collagen, and a variety of other things.

Ben:  Right. Why you don't want to over-barbecue your meat.

Sandra:  Yes, that's exactly right. And then, of course, lipofuscin is remnants from autophagy that gets stuck in your vesicles in and your cells and sort of makes them non-functional just out of being overstuffed.

Ben:  Okay. So, lipofuscin, that's just basically like a cellular waste product, right?

Sandra:  Yup. It's garbage.

Ben:  Okay. So, lipofuscin and advanced glycation end products would be like the two primary factors you're going after when it comes to cleaning up waste within the body?

Sandra:  That's the way I like to think of it, yup.

Ben:  Okay. Alright, got it. So, you identify, and I really like the systematic approach here, these seven different mechanisms of aging. And I would imagine that a lot of the things that folks talk about these days would fit into one of these mechanisms. One example, for example, a lot of people are talking about NAD, like how the NAD pool will decline with age. Therefore, supplementation with NR or NMN, or using NAD IVs or patches could potentially be a successful anti-aging protocol. When we take something like that, which category would something like NAD fall into?

Sandra:  So, I have the NAD in the mitochondrial department.

Ben:  Okay.

Sandra:  NAD, let me back up a little bit, does four essential things in your body. The biggest thing that it does is it's obviously in the electron transport system. It shuffles protons, right? NAD, NADH. When you have a deficiency in NAD, your mitochondria are just not as efficacious, so you get less energy production. So, the first thing people notice when they supplement with NAD is their energy comes back. It takes about 10 days with an oral supplementation plan, and that's the most important.

But it also falls into other categories because it is a necessary cofactor for the sirtuin family. For example, if you augment your sirtuins but you're NAD deficient, you're going to see absolutely no effect. So, that's number two thing that it does. Number three thing it does is the actual molecule gets taken apart, and they use it to patch holes in your DNA. So, that's very important. So, without NAD, your protein repair mechanisms aren't going to work. And then lastly, it serves as a communication device between the nucleus and the mitochondria via the OXPHOS system. So, many things fall apart with an NAD deficiency, but I put it under mitochondria because that's sort of the prime issue.

Ben:  Okay. Got it. Now, based on these seven different mechanisms of aging, you called them the tenets of aging?

Sandra:  Mm-hmm.

Ben:  Okay. Am I pronouncing that right, by the way, tenets?

Sandra:  I believe so.

Ben:  Okay. Good, because I'm well-known for mispronouncing and getting in a big trouble on this podcast. It's something I've done since I was a child. Because I read so much, I often read words, and inside my head pronounce them one way, and then later, be embarrassed in public when I say them the way I've been saying them to myself for years. Probably the biggest example would be I used to commonly read this word called misled. Often, I'd see it in fiction, sometimes in non-fiction, like, “The King misled the soldier,” or, “The dragon was misled by the Hobbit,” or whatever. And it wasn't until I was about in my mid-20s when I used this word and someone commented about how they'd never heard the term misled, that I realized that it was actually misled. I literally went for decades of my life thinking there was this word–I mean, this language called misled.

Okay. So, the tenets of aging. Now, based on this, you have developed something I think is very unique that I hadn't seen before, but that I appreciate quite a bit as I was reading your book, this whole rating system that's based on this mechanism of aging. So, go into the rating system that you developed based on these seven different pathways.

Sandra:  Right. So, I wouldn't want to misle you here.

Ben:  Yeah, don't misle me.

Sandra:  I will not misle you. Okay. So, what drove me nuts getting into this was that someone would say agent X was anti-aging. And I would say, “Well, that's great, but what exactly does it do?” So, I would look it up and spend tons and tons of time on agent X. And it started as a positive and negative check system, and I had this monstrous grid. And then I realized that some things were far more efficacious than others in any particular category. So, it turned into a number system.

What it turned into is if agent X did nothing in a category, it got a zero, absolutely nothing. If it did an incredible job in a category–and the way I looked at that was, number one, does something work in theory? Does it work in a test tube? Does it work in a small animal model? And lastly, does it work in humans? Is there a human evidence of something being efficacious? So, if the evidence was spectacular, I would give it a three. And obviously, in between, it got ones and twos. People say that's kind of ridiculous. Why is it zero to three? It just worked out that way. I mean, obviously–

Ben:  It would get a three in relation to that specific pathway. So, if you're looking at a pathway like DNA repair and something's very good at DNA repair, then in ten at number one, you would rank that compound as a three.

Sandra:  That is absolutely correct.

Ben:  Okay.

Sandra:  So, as a consequence, this was an extremely time-consuming process, but it was worth it. Every molecular agent has a seven-digit number associated with it. So, just for fun, it was number.number.number, which allowed it to go into a huge grid. And then I decided that all of the numbers were cumulative, so that if you lined up, say, five agents and you had this grid of five times seven, and you added them up, you could tell which categories you are trying to tackle well and which ones you had completely ignored.

Ben:  Yeah. Interesting. Okay, cool. So, basically, there are some compounds I would imagine, and we'll get into the good stuff here in a second because I know you're going to talk about some of these that would have a number for multiple categories, or have a three for multiple categories that would therefore give them a very high numerical ranking and allow them to be something you might identify as giving you more bang for your buck in terms of targeting multiple anti-aging pathways or targeting a few of them particularly well. And then there are others that we might potentially be wasting some of our money on, or that might potentially be lower on the totem pole for someone who's budgeting their anti-aging protocol.

Sandra:  You hit it exactly. The idea would be this gives people an educated guide to make decisions for themselves because everybody is different. I like to use the example, if you're a diabetic or you like to eat sugar, and I'm guilty, I'm a junk food junkie on occasion, you're going to weight your system to have more numbers in the waste management column, right? If you have a family history of cancer, meaning, your DNA is not so great or yours–a lot of cancer is associated with the inability to repair damage, you're going to put more points in that category. So, this is just the way of translating information so people can make educated decisions.

Ben:  Now, I'd be jumping the gun on this question a little bit, but I know that, for example, you've developed an app that has some different algorithms in it that help people to choose which protocols are going to be best for them, whether it'd be blood sugar management or cancer or something like that, have you yet been able to weave something like genetic analysis if someone has like their 23andMe results or something like that to be able to feed those in to look at specific genetic risks and identify whether, for example, putting more of their budget into the cancer protocol would be a prudent approach?

Sandra:  The answer is yes and no, and that's a terrible answer. The app itself, the reason I wrote the app–and it seems probably silly to some people. I'm a pediatric anesthesiologist. I don't have an anti-aging office. This whole thing is a hobby. The problem is just sitting in my anesthesia office, I got bombarded with people wanting me to build them protocols because one person would have their particular protocol. They would tell everyone in their department, be it radiology or general surgery or whatever. And I just got bombarded and people would say, “This is great, but I also have rheumatoid arthritis. I also have a history of this or a history of melanoma.”

So, I built this algorithm by default to help me build people's protocols. But I don't have an anti-aging office. So, I wanted to give people a tool, whereby, they could pretend like they were sort of talking to me and they would get the same algorithm. It's not as sophisticated as analyzing your DNA. I think that's definitely the direction that this is going in. I think my best guess would be in five to ten years, I will have an office and all that will be incorporated. But at the moment, I don't have the time to do it.

Ben:  Okay. So, I should have, if I would have been a good little podcaster and completely done my homework part of this call, downloaded and used the app, but I focused more on the book and haven't yet had a chance to use the app. When someone downloads it, because I know it's available on Android and Apple, the–what's it called? The Kaufmann Protocol app?

Sandra:  Yup, correct.

Ben:  Okay. So, if someone downloads that, are there like a series of questionnaires that they would then answer, or Apple health data that they would input, or how are they being directed to choose a specific regimen?

Sandra:  It starts out with a quiz, basically about your health. And the reason it starts out with a quiz is because people come to me, they tell me they've got a variety of issues, back pain [00:31:26] ______ pain. They're on my protocol for two months. They come back and I say, “How is your back pain?” And they're like, “I never had a back pain.” So, people have their short-term memories when it comes to things that we're looking to fix.

So, it starts with a quiz just to sort of keep track of where you are and then where you're going. It then asks you, “Do you want a standard protocol? And there are three standard protocols on the app. Or do you want to build your own?” And if you want to build your own, there's a series of questions, like, “What is the most important to you?” And it's a list of, I believe, 13 different health issues, and you could pick five of them, and then you have to basically pick a level of commitment. Meaning, how many things would you really want to swallow on any one given day? And then it goes into the algorithm and it spits out what you should be taking.

Ben:  Okay. Got it.

Sandra:  That's basically the gist of it. To keep people enthused and encouraged, it follows you every day, trying to get you to do various things. And of note, also, I rated exercise because I'm a huge exerciser. So, I rated resistance and aerobic exercise. And then I rated a variety of foods. So, it becomes a point system. It becomes a game, but the idea is just to keep people under the gun of, yes, we're aging every day, let's fix it every day.

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Okay. That's interesting because foods and exercise aren't necessarily discussed in detail in your book, although each of the different–I believe there are 15 different molecules you do mention for some of them, some of the different food sources for them. So, that's good that you've worked some of that stuff into the app as well. And speaking of these 15 different ingredients, I mean, to save you the trouble, I could list them real quick, but then I want to ask you some questions specifically about some of the most overhyped yet least effective, and some of the more effective. But you've got resveratrol, and its lesser-known cousin of pterostilbene. You've got astaxanthin, NAD which you already mentioned, curcumin, carnosine, metformin, alpha-lipoic acid, apigenin, sulforaphane, quercetin, EGCG, astragalus, melatonin, and pyridoxine. Those are kind of like the main ones that you cover in the book.

Now, based on that, my first question for you is, using your numerical system, because a lot of things are talked about in news headlines these days as being popular anti-aging agents, which that you think are talked about quite a bit do you think are the most overhyped, but based on your numerical ranking system, probably the least effective when it comes to anti-aging?

Sandra:  So, I went through a lot of the ones. I started out with a lot of agents that, you're right, people hype about. I'm thinking, “Why are they so exciting?” And I threw them out because they were terrible. They just didn't rank. I think my biggest gripe is vitamin E. Everyone loves E, and it is an endogenous sort of free radical scavenger. But compared to the other ones, it's useless.

Ben:  Okay.

Sandra:  But people seem to love vitamin E. I don't know why. It sounds good, I guess. But people take it. I don't tell them not to because it's not doing them any harm. But for example, astaxanthin is far more powerful; delphinidin, far more powerful, but people like it.

Ben:  What did you say, delphinidin is more power–what's delphinidin?

Sandra:  You're right, there are 15 agents on the book. There are 30 agents on the website because I just kept going. And there's probably five more in my unprocessed file on my computer. So, if you want more options, there are 30 of them on the website, as I mentioned. So, delphinidin comes from the maqui berry in Argentina. It is extremely powerful free radical scavenger. It also helps with osteogenesis. So, it has a variety of other benefits as well, but they're all more powerful than E.

Ben:  Okay. Got it. In your research, by the way, because I recently did an interview with Dr. Barrie Tan about vitamin E and the relative absence of a complete spectrum of mixed tocopherols and tocotrienols in most forms of vitamin E, but he was very bullish on something called annatto, this red plant extract that I believe designs for health. The supplement company is harvesting from somewhere in South America, and it has a much higher amount of a blend of these tocopherols and tocotrienols. Did you come across that at all in any of your research?

Sandra:  I've looked at it. It's actually on my list of things to research. I haven't gotten to it yet, so I don't want to give anyone any false information, either beneficial or the other way. If you bring me on six months, I'll have all the information you want.

Ben:  Okay. Got it. Yeah. Look up Dr. Barrie Tan as you're doing that research or check out my podcast with him because we took a deep dive into that one, and I'd be curious if it's a little bit more effective than vitamin E, particularly, when it comes to anti-aging. Any others that you think folks talk about a lot but that you're kind of–when it comes to their effectiveness?

Sandra:  Well, I think coenzyme Q–I think if you're 80 years old and you have cardiac issues, it's probably beneficial, but for most people, I don't think it's all that great. The fish oils, I don't think are all that great. I mean, they're the beneficial; they just don't rank up there. And I think when you make decisions, people come in various varieties and some people want to take everything under the sun, and some people want to be more picky. And I think if you're going to be more picky, you wanted things that, as you had mentioned before, more bang for your buck.

Ben:  Now, imagine that CoQ10 would fall into that tenet of mitochondrial support. But would there be something more effective than CoQ10 that you think works much better, specifically for that mitochondrial contribution?

Sandra:  So, CoQ10 falls in the mitochondrial transport chain, right, the electron transport chain. And to be honest, most people are not deficient in CoQ10. As you get older, you probably will be. Aging starts at roughly–

Ben:  Or if you're [00:40:21] ______.

Sandra:  Right. No, exactly. There are reasons to take it; there are reasons not to take it. Aging starts between 30 and 35. Most men don't realize they're aging until 38 because they think they're immortal. But when you're 38, you're not CoQ10 deficient. You're probably nicotinamide deficient and your free radical scavenging capability is falling, but you're probably not CoQ10 deficient. So, a lot of these things have to be placed into the spectrum of where you are in your life and what concomitant illnesses you have.

Ben:  Okay. Got it. What would be something that would support the electron transport chain that you have in your book or on your website that would rank high?

Sandra:  Well, so the rate-limiting thing in the transport chain is nicotinamide. So, that's crucial, right?

Ben:  Mm-hmm.

Sandra:  And then basically, it's free radical scavengers. The best one that unfortunately at the moment is only an eye drop is something called SkQ1. It's a mitochondrial-driven–

Ben:  Visomitin, I think that goes by.

Sandra:  Yes, it does. And I get the Russian eye drops, and I'd tell you they're fantastic. My vision is superb and I'm old. So, it's amazing stuff. You can't get it systemically. I've tried. It does it work. That's amazing.

Ben:  No. It's pretty expensive. I'd talked about it in a book that I'm working on that includes a chapter on anti-aging and longevity. And some of the research on Visomitin or SkQ, particularly I think at rodent models, complete or near reversal of some retinal damage and restoration of eyesight with aging. It's pretty interesting stuff, this Visomitin eye drop.

Sandra:  Oh, it's incredible. If you combine Visomitin eye drops with carnosine eye drops, your vision is unbelievably good.

Ben:  My wife has more vision problems than I do, but that's something I should mention to her. So, you combine it with carnosine eye drops, huh?

Sandra:  So, Visomitin has to be refrigerated because it's enzymatic. So, that goes in the fridge. I use it in the morning, and I use carnosine eye drops at night because it's a transglycosylating agent. One takes care of your retina, the other one takes care of your lens. Can't beat it.

Ben:  Okay. Got it. What ranks the highest out of these different agents, not one single agent, but which collection of agents would you say are the most effective as far as your rating scale goes with a host of threes or acting across multiple pathways?

Sandra:  The most efficacious combination is something that I call the panacea. And conveniently, I took the letters, obviously, move them around and kind of made it spell that. It's not exact, but it sounded good at the time. And it covers pretty much everything that you need when you hit 40. And most people, I have to say, are on the panacea and they love it. And that is the pterostilbene, astaxanthin, nicotinamide, curcumin, and carnosine. The curcumin is a little tricky because you have to make sure you take the appropriate formulation. People say, “Oh my goodness, I eat turmeric. I should be fine.” And the answer is it's not good enough. You need to take a specially formulated type to increase the bioavailability. But if you take the right stuff, then you're golden.

Ben:  What would be the right stuff when it comes to curcumin? Is there a brand that you like?

Sandra:  Yeah. I don't get paid by anybody, so I don't want to be too specific, but I'm going to be because I love it so much. Basically, 10 years ago, they started coming up with formulations to make it better. And if you take it with pepper, it helps, but that's sort of long in the past. The top two at the moment, tip top, is something called MetaCurcumin made by RevGenetics. Stuff walks on water. It's a nanomicelle. If I take three pills, I turn yellow. So, I know the bioavailability is good. I take it twice a day. Right below that, there's a formulation called BCM-95. That is sold in two other brands. So, if you pick a bottle and you read it in the ingredient list, you know you're good.

Ben:  But what about Meriva? I've heard Meriva, form of curcumin, talked about quite a bit.

Sandra:  The bioavailability of Meriva is not as good. It was probably great five years ago, not as good today. I'm sure the company is going to call it [00:44:17] ______ now, but that's what the numbers in the literature show.

Ben:  Okay. So, BCM-95 and MetaCurcumin would be the two top forms of curcumin?

Sandra:  I believe that to be true.

Ben:  Okay. Got it. So, this panacea, in addition to curcumin, and as you mentioned, nicotinamide, would also be–you said pterostilbene, astaxanthin, and carnosine?

Sandra:  Correct. The reason is it gives you a–like no agent, in particular, does everything, and the idea is you need to cover everything. So, it is the easiest to get most easily processed system that people have sort of just loved. That's how it evolved.

Ben:  I noticed that pterostilbene actually has a number associated with every single mechanism that you list in the book. So, let's unpack that a little bit. What exactly is pterostilbene? How would one take that?

Sandra:  Alright, here we go. Pterostilbene, why is it so great? You ready?

Ben:  I'm ready.

Sandra:  So, pterostilbene is an epigenetic modifier. So, it does beneficial things for your DNA. It is a really strong free radical scavenger. It increases the activity of your endogenous antioxidants including catalase, your SODs, your glutathione peroxidases. It activates your sirtuins. It activates your AMP kinase. It actually serves as what we call a caloric restriction mimetic, telling your body that you're starving when you're not, which is nice. It actually increases DNA repair mechanisms, so that's category four, increases autophagy, still category four. In your immune system, it's an anti-inflammatory. It hits tumor necrosis factor-alpha and some of the interleukins. It doesn't do too much for individual cells that we know of. And it's a mild hypoglycemic agent. So, then when you count all the numbers up, it does pretty well in most categories.

Ben:  Yeah. Now, to my understanding, it's chemically somewhat similar to resveratrol, but seems to be far more potent than resveratrol.

Sandra:  Right. So, the bioavailability is much higher. So, historically, we do about resveratrol because of the whole French paradox business where they eat like crap and they are pretty damn healthy. And we know why that happens. But interestingly enough, so resveratrol is more common in grapes and wine. Pterostilbene is more common in blueberries, which clearly makes it less sexy. But they do a lot of the same things.

So, a lot of the research you can extrapolate from one to the other, but because the bioavailability is so much higher, pterostilbene in my opinion wins. And I think other people think that as well because it's part of the basis. The product made by the company that–it combines it with NAD and it's called basis, and they charge as far as I'm concerned far too much. But it's very efficacious.

Ben:  Oh, is that the Elysium basis product? Actually, it's not just NAD, it's also pterostilbene?

Sandra:  It's the combination of the two, yes.

Ben:  Okay. I wasn't aware of that. Interesting. What are some other supplementation forms of pterostilbene that you like or that you found in the book to be some of the better versions?

Sandra:  So, pterostilbene is interesting because it's a really easy thing to make, so it doesn't really matter what brand you buy. ChromaDex makes pTeroPure, which is essentially just the chemical version made in a laboratory. And it sounds–it is pure. It's not organic, but it's pure. It's very clean. But I really actually don't think it matters too much. Some of these agents, it really matters, and others, it really doesn't. And I think this falls into the category of it really doesn't.

Ben:  Okay. Got it. Another one that appears in the panacea kind of stack based on the most effective things you found in the book is astaxanthin. Which category would astaxanthin fall into?

Sandra:  I love astaxanthin. And astaxanthin falls into the “you got to buy a good one” category. BioAstin is probably my favorite brand.

Ben:  That's from the Big Island, right?

Sandra:  Yes. Yes, it is. I think they just do a phenomenal job. It comes from algae. They got these huge algae farms. They make it physiologically stressful. It makes this delightful orange goo, and that's the astaxanthin. And I think it really does matter which company makes that one. Of note, it comes in four sixes and twelves. I tell athletes to take 12, non-athletes to take 4s, only because you produce more free radicals as an athlete.

Ben:  Yeah. It's kind of funny because I first began using astaxanthin when I was racing Ironman triathlon down in Hawaii. And at the swim start, every single day leading up to the race, folks from that astaxanthin company were actually there at the swim start giving out free samples. And I found it to be incredibly effective at protecting my skin from the bright sun during long periods of time racing. It's almost like edible sunscreen in a way.

Sandra:  Oh, it is edible sunscreen. It absolutely is. In fact, I give it to my 13-year-old. She plays competitive tennis. And she's a redhead, so she's pale as can be. If she doesn't take the astaxanthin, she just turns into a tomato. If she takes it, she's blocked. And the reason is because a lot of sun damage causes free radical accumulation near your DNA and it blocks it. It's just really miraculous.

Ben:  Yeah, it is. It's actually in the–I use a form of fish oil called SuperEssentials and it's packaged with astaxanthin. But the other thing is that it has a very interesting effect on fitness. In rodent models, they've done–I believe it's swimming to exhaustion studies and found that astaxanthin supplementation seem to improve exercise capacity very significantly.

Sandra:  Oh, it absolutely does. That's been shown over and over and over again. What's interesting is different cultures like different agents. Actually, a small caveat here, you keep calling everything a supplement. And in real-world, a supplement is something that you are adding to something that you already have, right? So, if you already have a substance in your body, you're supplementing it. If you don't have that substance in your body, it's an adjuvant. So, technically, astaxanthin is an adjuvant because you have no endogenous astaxanthin, which is why I call them molecular agents because it's kind of a catch-all phrase.

Ben:  Yeah, yeah. That's interesting. Some of these things, of course, you could get from whole food form, like I suppose if you were cooking with turmeric, for example, or–there are some things that have some nicotinamide precursors in them like the beta-lapachone containing Pau d'arco bark tea. And I know many teas and coffees and dark berries and fruits, et cetera, they've got a lot of these sirtuin precursors in them as well. But yeah, most people I know in the anti-aging sector, they are popping a handful of pills to get this stuff in a far more concentrated form, or in combination, like the pterostilbene with NAD, for example. One other one that you have in the panacea in addition to pterostilbene, astaxanthin, nicotinamide, curcumin is carnosine. Why did you put carnosine in there?

Sandra:  Because carnosine is magical. Very simple. So, what I was going to say before, and I just run amok all the time because I have too much to say about everything, astaxanthin is loved by the Japanese. So, every study on astaxanthin is done by Japanese. Carnosine is just loved by Russians. They've been using this stuff for way before the Iron Curtain fell. And one of the reasons their athletes were so good once upon a time is because they were on carnosine. And carnosine does two major things. Number one, it gets into your muscle and it's a buffer. So, when you exercise a lot and you get lactic acid development, you don't get the burn because you are buffering it. So, that's kind of fun from an athletic point of view. What it also does from an anti-aging point of view is it's a transglycosylating agent. So, it can actually lift the AGEs. Actually, that's not completely true. It blocks the formation of AGE products. And some evidence suggests that it can lift it off of your collagen.

Ben:  Interesting. So, would this be something that would be efficacious if taken hand-in-hand with something like a bone broth or a different collagen source?

Sandra:  Not really. It works in different ways. So, if you picture a glucose molecule floating around your body, it sticks, not because glucose is sticking on the inside, it's sticking on the outside. It's going to stick to something, a protein, a piece of DNA, a lipid. It takes six non-enzymatic steps for it to become a locked-in AGE product, right? That globular mass is sticky as well and that sticks to your collagen. And the way I sort of described that process is if you picture a table cloth with sliding fibers and you put a glob of this stuff like superglue on a collagen fiber and you try to slide it, break, right?

Ben:  Mm-hmm.

Sandra:  The same thing happens. You put an AGE on your collagen. You try to move your collagen and they break. This is why your skin sags. It's why you have heart failure with time. It's one of the reasons that you have high blood pressure over time. But if you block the glucose from, number one, becoming an AGE agent, that helps, and number two, some of it can get lifted off making your collagen more back to where it was, right?

Ben:  Okay. Got it. And interestingly, because I've looked into carnosine for exercise support before, it does work on some of those acid buffering pathways that you mentioned. But it's interesting because it appears there are some sex differences as well, like men seem to have a higher available pool of carnosine compared to women.

Sandra:  Oh, yeah. This is one of those things that are just not fair in life. Men have way more than women, and young people have way more than older people. So, as a young man, you're fine, you probably don't need it. As an older lady, you are extremely deficient. Interestingly, you can only get it from meats and fish, anything that uses muscle. So, vegetarians tend to be deficient in carnosine. So, I tell people that if you're going to be a vegetarian, it's one of those things that you probably should sort of take as well.

But it's true. As a woman, I'm 50, when I take it, I feel spectacular. And when I don't, I can feel less energy in my muscles. So, I think it's very efficacious. But one of the most interesting experiments I've ever read about, a bunch of Australians took a bath of fibroblastic human cells, and they were old and grumpy, and they put them in a bath of carnosine, and the cells rejuvenated. They became youthful. And if they took them out of the carnosine, they became old and grumpy cells again. So, they actually do have a rejuvenating power. And I always kid that I take baths in carnosine. Essentially, I do because I eat it every day and I put it in my eyeballs. But it's just a very potent dipeptide that we all have.

Ben:  Interesting. And I know as we went through the ingredients in the panacea, we didn't necessarily discuss dosages. But you on your website, just for free, on a page there, you have listed the efficacious dosages for many of these compounds we've discussed and others that are both in your book and also on the website. And when you're researching dosages, are you just looking at, for example, a PubMed research and human clinical studies? Are you extrapolating from rodent models? Or do you have a specific kind of strategy for determining the efficacious doses for these, particularly when it comes to anti-aging? Because I know they can widely vary.

Sandra:  Right. So, there are so many variables that go into this, which is why it's really hard to be absolutely right on with everybody because everyone's a little bit different. To start with, you're absolutely right. I do look at human models if they have them. Astaxanthin has many, many human models. So, that one was easy. Other ones don't. You do look at rat models. There are formulas that you can go from one to the other. For things that people already have i.e. supplements, it depends on where you are in your life cycle. If you're young, you need less. If you're old, you need more. So, that's kind of tough. For people with medical issues, you're going to need more or less. People with kidney failure or liver failure, you're going to need a little bit more or less. So, it's kind of hard to give a dose. So, the dosages on the website are sort of middle-of-the-road doses, as well as things that people can easily get.

Ben:  Okay. Got it.

Sandra:  Because I don't want people going, “Oh, you told me to take 17.4 milligrams of this. It doesn't come in at 17.4.” I try to make it as easy as possible. And I've gotten some serious hate mail, like, “Oh, you're one milligram off.” And I'm like, “You know, I'm really sorry.” I can't be specific to everyone because everyone's a little different.

Ben:  Yeah. Relax, people. It doesn't have to be 301 versus 300. Now, when it comes to the sweet tooth or the anti-glycation stack that you have listed, for example, on your website where you have a few different protocols based on some of the researches that you've done, I noticed one, kind of similar to pterostilbene, seems to act on every single one of these anti-aging pathways, and even has a three in multiple pathways, and that's metformin. And you discussed metformin in the book. You discussed it on the website.

I know many people are fans of metformin, but relevant to our discussion right now, I mean just three days ago, research study came out on exercising individuals indicating that it may hamper mitochondrial proliferation, or the ability to be able to build endurance or fitness in response to exercise. I know in the past, there have been other issues with metformin such as vitamin B12 depletion, or for example, some microbiome issues, which of course could all be skirted with something like vitamin B12 and probiotic supplementation. But this newer exercise one kind of turned a lot of heads when it comes to metformin. So, I'm curious if you're still a big fan of metformin, or if some of the latest exercise research has given you pause, or where you stand as far as metformin is concerned.

Sandra:  So, metformin and a lot of these agents are very interesting because nothing is absolutely perfect. You have to know why they work and what you're doing, right? So, metformin works on several levels, which is why it gets such a high rating, but one of the things that it does is it uncouples to a small degree your mitochondria. It uncouples the electron transport chain, which is one of the reasons that it helps you lose weight, right? If you put X number of glucose molecules in your mitochondria, you're going to get ATP out. But if you uncouple it, it's going to be less efficient, right?

So, that's not an unusual thing. If you are an athlete, you want to be as efficient as possible. Clearly, you can see that those two things are not congruent. So, if you're a die-hard athlete, metformin may not be the truck for you. The other thing to note is that the half-life is it lasts–another half-life, but it lasts for about eight hours. So, if you want to take metformin and you are an athlete, take it at night. It'll work while you're sleeping. And then during the day, your mitochondria will go back to functioning normally.

Ben:  Interesting. That's something I was unaware of. So, you could dose metformin in the night, and then let's say your exercise session is taking place the next afternoon, you wouldn't necessarily run into the same mitochondrial issues.

Sandra:  You shouldn't. No. It goes away. That's why when you take it for diabetes, it's either twice a day or three times a day dosing. And there is no anti-aging dosing. We don't know. All of this is best guess. Therefore, why not take it at night? That's what I do. But again, everything has drawbacks. So, for example, you mentioned–it's a partial mTOR inhibitor. And as a consequence of that, as you get older, you become more sarcopenic. So, the other thing I tell people, number one, timing is important. And two, you've got to take your branched-chain amino acids or you're going to become sarcopenic. And then lastly, it does decrease the absorption of B vitamin. So, you need to make sure you're on a B.

Ben:  Yeah, yeah.

Sandra:  Everything has its cost.

Ben:  Yeah. I'm a bigger fan of essential amino acids versus branched-chain amino acids just because some of the data I've seen shows that some of the high leucine and a branched-chain may actually hamper insulin sensitivity a little bit, which is why although they're more expensive, I'm a bigger fan of using eight to nine different amino acids and essential aminos blend, and then branched-chain amino acids.

But when it comes to metformin, I'm still skeptical just because–there's one other study that showed a decrease in VO2 max with long-term use, which whether or not it's in or out of your system, it was like a 3% to 4% decrease. And again, moot point for most folks, but especially for athletes–I'm still competing professionally in a couple of different sports. For me, I'm not yet on the metformin bandwagon, but I thought it was very interesting how many different pathways it targets when it comes to anti-aging. So, it is one that I think is definitely one to keep an eye on. And I'm not opposed to everyone using it, but I don't recommend it to the athletes I work with, or for myself yet.

Sandra:  Well, I think it depends on–let me back up for just a sec. Again, all of these things are not for everybody. This is why you get personalized pads. This is why it depends on how old you are and where you are. If you are an athlete, a lot of these things are not going to be for you. In fact, I'm writing a thing right now on the aging athlete because there's a population of us where you do need to cater to your athletic self while also understanding that life is pros and cons, right?

Ben:  Yeah.

Sandra:  And you're absolutely right. As a young athlete like yourself, metformin is obviously not the drug for you. When you hit 50, 55, you're going to say, “You know what, it's time.”

Ben:  Yeah, yeah. And of course, I would never argue that doing something like an Ironman triathlon or competing professionally in sports or doing CrossFit five times a week is a life-extending strategy. It may, in fact, cause arterial stiffness and advanced glycation end-product formation and some inflammatory downstream issues that hamper longevity. Of course, part of this comes down to joy in life. If it makes you happy to go out and do a Spartan Race, for example, on a few weekends a year, then yeah, I mean except the fact that you might not be extending your life with that. But at the same time, I think you do have to live a little. And that's something I wanted to ask you about as well was, when we shove aside all of these molecules and compounds and supplements, things that go beyond that, you mentioned that you are an exerciser, do you have other lifestyle strategies, whether biohacks or exercise routines or anything else that you think really moves the dial for you from a longevity enhancing standpoint?

Sandra:  Well, in general, I think that most exercises is good for you. It activates your sirtuins, it activates your AMP kinase pathways. It just gets you moving, and I think that's really important. I'm a rock climber. I'm a 5'10”, 5'11” climber, which isn't great, mind you. Real rock climbers are going to laugh at me. But I'm a mountaineer. I swim. I bike. I do all of that sort of things. What I like to do is I think that I outsmart my body, which I may or may not actually be doing. I do really dumb things. I go on what I call Haritaki holidays where I take just a lot of chebulic acid couple weekends, trying to strip my glucose.

Ben:  A lot of what?

Sandra:  So, chebulic acid comes from something called Haritaki. It's from Ayurvedic literature, and it's known to increase life. And I thought, “Well, that's kind of crazy. I wonder why.” So, it turns out chebulic acid is the strongest anti-glycation agent there is. You have to figure out, and I don't know what the answer is because there haven't been any studies, is a little bit every day, better or worse than a lot on any one given day. And so I've decided that with Haritaki, a huge flood of it intermittently is the best way to go. So, I go on what I call Haritaki holiday. So, for three days, I take as much as I could possibly consume, and nothing happens.

Ben:  Interesting. How much do you take?

Sandra:  I take probably about 2,000 milligrams a day for three days.

Ben:  And is this a powder?

Sandra:  No. You can get it in a powder. I hate powders. I think they're repulsive. I take pills. I buy them from India.

Ben:  What brand?

Sandra:  I don't want to tell anyone–oh gosh, I don't remember.

Ben:  Okay. If you hunt them down, let me know.

Sandra:  It's on my website. I can find it for you.

Ben:  Okay. It is. Okay. Awesome. I'll hunt them down and link to it. So, chebulic acid. I'd never heard of that as a way to control advanced glycation end-product formation. But that's very interesting. What else? Are there any other strategies that you use? Like, are you a sauna person? Do you have like any other type of technologies that you use or anything like that?

Sandra:  What else do I do? I live in Miami, and people equate the way you look on the outside with the way you are on the inside. If you go to anti-aging places, it's all about Botox and filler and that sort of thing. So, I do have to keep up the impression that I look younger on the outside. Obviously, I self-Botox because that's easy. I recently acquired a centrifuge, so I give myself vampire facials every month. That's kind of fun. I do not have high blood pressure, but I take hydralazine every day because again, it's a transglycosylating agent. And again, I can't tell people to take that because they'll crump out their blood pressure, and their primary care physicians will kill me. But there's a tachyphylaxis to the lowering of your blood pressure. So, I can take as much as I want these days and nothing happens. But I basically am an avid AGE stripper. That's what I do.

Ben:  Tachyphylaxis, meaning, eventual resistance to long-term use of that compound?

Sandra:  Correct. So, normally speaking, the only reason you would ever have hydralazine is if you have very high blood pressure and you need something to emergently get it back down to normal. If you walked into our emergency room, they would give you a hydralazine.

Ben:  Interesting.

Sandra:  It's not a good long-term blood pressure strategy because the half-life is very short. So, it's not going to help you in–for anyone given–if you have high blood pressure as a systemic disease, it's not going to be beneficial to you unless you're in emergency situation. I had to start taking it in little doses because it did destroy my blood pressure. But over the course of time, it becomes less and less effective as a blood pressure medicine. And now, I can take as much as I want and use it as an AGE stripper. And it's extremely good at that according to laboratory studies.

Ben:  Do you use stem cells at all?

Sandra:  I have not used stem cells. I'm sort of in the investigational process of that. I know a lot of people that do. I have not done it yet.

Ben:  And then another–oh, go ahead.

Sandra:  No. The other thing I've tried now that I'm on my senescent cell kick, there's a drug called [01:07:50] ______, which is a chemotherapy agent. Life Extensions actually has a link to a pharmacy where you can get it, because clearly, you can't go to Rite Aid and buy chemotherapy agents. So, I've started taking chemotherapy agents to strip my senescent cells, and I'm developing a protocol for that, which I will release shortly.

Ben:  On your website?

Sandra:  Yes.

Ben:  Okay. Cool. I'll link to your website in the shownotes, which again, for folks listening, it's at BenGreenfieldFitness.com/stopaging. When it comes to–I was going to ask you one other thing about, not stem cells per se, but I guess it would fall into the telomerase category or tenant number one. And that would be some of the research from Bill Andrews, who was also in my podcast. He's very big into some of these compounds developed by Sierra Sciences like TAM-818 and TA-65, almost like a form of astragalus for upregulation of telomerase. Have you looked into those at all?

Sandra:  Well, I have. Small caveat, I'm friends with Bill.

Ben:  Okay.

Sandra:  We got to know each other last year. I gave my book to him and I said, “You're never really going to read this.” And then he did, and we've sort of become good friends, and we're working on a variety of projects together. The guy is a genius. But you already know that. And I have looked at his agents and he has given me some of the secret insider trader information. They are definitely efficacious. The problem is they're extremely expensive, and I don't want to be recommending them to people that can't necessarily afford these things.

There are other ways to increase your telomere length. And part of the strategy that I have for helping people is to make things reachable. I don't want to tell people to go get stem cell infusions because it's really expensive. And young blood infusions are extremely expensive, as are these telomere agents. I think over time the cost will come down. But for now, will I take them? Absolutely. Will I recommend them to people? I'm not so sure.

Ben:  Yeah. And you do have astragalus that you talk about in your book. I took TAM-818 and TA-65 for three months after talking to him. But yeah, I mean, $800 for TAM-818, and I think 500 to 600 for a bottle of TA-65. They are pretty expensive. And I should point out the fact, lest people think that I'm just a spendthrift that–actually, I coach a lot of wealthy clients who are into like biohacking and anti-aging, et cetera, and one of my acquaintances in that sector actually, after listening to the podcast, just purchased a couple of bottles of those and sent them up to my house.

So, I took them for a while, but I can't say that they would fall into my personal budget as something compared to like buying my children new books and taking my wife out to dinner that I would make a part of my routine at least, not until this podcast makes me independently wealthy, which of course it would happen, you never know. If people go to the website and buy enough astaxanthin, it could happen.

Anyways though, I am curious, and this is my last question for you, do you have a hunch, whether based on like the Hayflick limit or other data that you've seen about? If one were to weave in a lot of these compounds or use the panacea or something like that, by how many years we might be able to extend life or what the maximum potential human lifespan could be?

Sandra:  That's an interesting question, and I'm going to divide it up into sections, which you may or may not want to hear. I think you have to differentiate between health span and lifespan, first off. I can tell you without a doubt, without any doubt, that I have increased the health span of hundreds of people. I get emails every day. “My diabetes is better. My arthritis is better. My cancer symptoms have gotten better.” It's just incredible. It's truly amazing what we have done in terms of health span.

Now, the question is does that extrapolate the lifespan? And I think that it does because the longer that you are healthy, the less likely you are to die, right? People die of complications from ages, from issues dealing with age. And if we can put off Parkinson's, Alzheimer's, all of these issues, you are going to live longer. I think that right now, people, if you were on the protocol, if you started it 30s, 40s, and you let a reasonable life and you weren't absolutely stupid, and you didn't jump in front of a bus, or perhaps go rock climbing because that's how I'm going to die, you'd probably, I'm guessing 125, 130. I think longer than that is going to take more DNA manipulation.

Ben:  Yeah, yeah. And there was a recent gal who I think was cited in–I don't know if it's in New York Times or some other media source earlier this week. She is I believe 114, 15 or 16, and it was kind of interesting because of course, as many of these centenarians, these modern centenarians, she doesn't take any supplements but attributed her lifespan to, A, a strong faith and belief or power, and B, very good relationships and lots of time spent with family and friends. So, of course, the end of our long discussion about all the different supplements and compounds you can put into your body, I think, of course, we should remember that it appears one of the most important things that you can do is to care for your soul and have good relationships. So, I think that's one of the best things people can do even if they have zero budget to be able to afford any of these things.

Sandra:  Oh, agreed. Happiness will get you everywhere. And yoga will increase your telomeres. So, anything good in your life absolutely will increase your health span and your lifespan.

Ben:  Yeah. Yoga, breathwork, and meditation. But heck, if you want to just stack a whole bunch of other stuff on top of that and get that life span as long as you can, definitely read Dr. Kaufmann's book. Check out her websites. I'll link to that, and also all the different things that we discussed in the shownotes, which you can get over at BenGreenfieldFitness.com/stopaging. I would imagine, Dr. Kaufmann, you have some like manure to go shovel or a horsie to go take care of or ride across the plains with the cowboys out there at the dude ranch, so I should probably let you go.

Sandra:  Yeah. I think there's a cowboy looking at me right now. I'm on my way.

Ben:  Nice, nice. Sounds like fun. Alright, we'll have fun out there at the Majestic Horse Ranch. And again, I'm Ben Greenfield along with Dr. Sandra Kaufmann, the author of “The Kaufmann Protocol: Why We Age and How to Stop It.” All the shownotes are at BenGreenfieldFitness.com/stopaging, and until next time. Have an amazing week.

Well, thanks for listening to today's show. You can grab all the shownotes, the resources, pretty much everything that I mentioned over at BenGreenfieldFitness.com, along with plenty of other goodies from me, including the highly helpful “Ben Recommends” page, which is a list of pretty much everything that I've ever recommended for hormone, sleep, digestion, fat loss, performance, and plenty more. Please, also, know that all the links, all the promo codes, that I mentioned during this and every episode, helped to make this podcast happen and to generate income that enables me to keep bringing you this content every single week. When you listen in, be sure to use the links in the shownotes, use the promo codes that I generate, because that helps to float this thing and keep it coming to you each and every week.



I recently read the book “The Kaufmann Protocol: Why We Age and How to Stop It.

It is the first comprehensive approach to aging that tackles why we age and then recommends a strategic, scientific formulation to decelerate the process. The book brings practical information to everyday people and takes the science of aging out of the laboratory and into the real world.

The first half of The Kaufmann Protocol discusses aging on a cellular level, which separates it from all other anti-aging fads. We age because our cells age, and it is this understanding that allows the protocol to combat aging for people from all walks of life. This is presented in terms of the seven tenets, or categories, of aging which comprises topics such as DNA alterations, mitochondrial energy, and aging pathways. These are explained in both scientific and laymen terms, such that anyone can understand the process. A series of analogies paralleling the cell to a factory assist the reader in following the logic.

The second half of the book reviews the top fifteen molecular agents that curb the aging process. Each agent is examined, discussed, and then rated in terms of the seven categories, thus granting it a Kaufmann Rating number. This number is essentially a snapshot of its anti-aging properties and allows the reader to create a regimen to fit their personal needs.

Alternatively, the book suggests the most common protocol, the PANACEA, which is a combination of five molecular agents. This regimen is fantastic for most people over the age of 40, but it certainly is not comprehensive. With the tools and knowledge presented in this book, the reader can determine what is best for them as individuals. This book is also meant to be a complementary addition to the Kaufmann Protocol App which will allow the user to track their progress and stay up to date with all of the new scientific findings that will continue to make aging truly optional.

Dr. Sandra Kaufmann began her academic career in the field of cellular biology, earning a Master’s Degree from the University of Connecticut in tropical ecology and plant physiology. Turning to medicine, she received her medical degree at the University of Maryland and completed a residency and fellowship at Johns Hopkins in the field of pediatric anesthesiology. For the last seven years, she has been the chief of pediatric anesthesia at the Joe DiMaggio Children’s Hospital, a nationally recognized center of excellence.

Her avid interest in the science of anti-aging begun many years ago as an intense hobby. Utilizing her knowledge in cell biology, human pharmacology, and physiology, this hobby has now become her main focus. The Kaufmann Protocol represents years of non-clinical research leading the first-ever, comprehensive theory of aging, complete with an explanation of why we age and the tools to decelerate the process.

During our discussion, you'll discover:

– How Dr. Kaufmann, a pediatrician, became interested in learning how to increase longevity…

  • She became interested in it simply because she wanted to enjoy her life as long as possible
  • After reading and researching, she realized there was no overarching theory, nor a comprehensive system on anti-aging and longevity
  • Aubrey de Grey's SENS Research Foundation

– Dr. Kaufmann's 7 Tenets of aging…

  • The 7 Tenets of Aging
  • Information Systems (DNA)
  • Cellular Energy (Mitochondria, NAD)
  • Cellular Pathways (AMP Kinase and mTOR system)
  • Quality Control (autophagy)
  • Security System (Immune system) fails for 3 reasons:
    • Unable to fight infection over time
    • Cells become cancerous over time
    • Upregulates systemic inflammation
  • Work Force (Individual Cells)
    • Short-acting cells (few hours to a few days)
    • Goldilocks cells (1-12 years)
    • Cells that live forever
    • Senescent vs. quiescent cells
      • Quiescent is reversible, a state of repair
      • Senescent is partially repaired; damaged but still of some use
  • Waste Management (AGEs, lipofuscin)

– The numerical rating system Dr. Kaufmann created based on the 7 Tenets of aging…

  • The Kaufmann Rating System
  • Ratings are from 0-3 (0 being of no value, 3 being highly efficacious)
  • Criteria to determine efficacy:
    • Does it work in theory
    • Does it work in a test tube
    • Does it work in a small rodent lab
    • Does it work in humans
  • It gives people an educated guide to make decisions for themselves

– How the app Dr. Kaufmann created helps people understand their genetics and longevity…

  • The “My Protocol” app
  • Her work began as a hobby, yet more and more people came to her seeking a protocol; the app was created to help as many people as possible
  • The app experience
    • Starts out with a quiz
    • Asks if you want a standard protocol or if you want to build your own
    • It follows you every day
    • Rates exercise and foods

– The most overhyped yet least effective ingredients, as well as the most effective…

– Pterostilbene: Why is it so great?…

  • Epigenetic modifier
  • Very strong free radical scavenger
  • Increases activity of endogenous antioxidants
  • Activates your sirtuins
  • Activates AMP kinase
  • Caloric restriction mimetic (tells your body you're starving when you're not)
  • Increases DNA repair mechanisms
  • Increases autophagy
  • Similar chemically but more potent than Resveratrol

– Why Astaxanthin is the bomb…

  • Bioastin is Dr. Kaufmann's favorite brand (edible sunscreen)
  • Increases exercise capacity
  • It's not a supplement because there is no endogenous astaxanthin in our system

– The magical attributes of Carnosine…

  • Gets into your muscle and is a buffer (don't get the burn)
  • Transglycosylating agent; blocks formation of AGE products
  • Men have more than women, and young people have more than old people
  • Can only get it from muscle

– Dr. Kaufmann's thoughts on the latest research regarding Metformin and its hampering of mitochondrial response to exercise…

  • It uncouples mitochondria and electron transport chain; becomes less efficient
  • May not be the best for an athlete (unless you take it at night)
  • Everything is “best guess” when it comes to dosing for anti-aging
  • Take branch chain aminos
  • Decreases absorption of B Vitamins

– Dr. Kaufmann's anti-aging lifestyle beyond the supplements and compounds discussed thus far…

  • Rock climber
  • Haritaki holiday
    • Chebulic acid is the strongest antiglycation agent there is
    • A huge flood intermittently is the best way to go
  • Doesn't use stem cells

– The maximum potential human lifespan based on protocols like the Kaufmann Protocol…

– And much more…

Click here to get a PDF version of the show notes for this episode

Resources from this episode:

The Kaufmann Protocol: Why we Age and How to Stop It

My podcast with Dr. Barrie Tan

Visomitin eye drops

Carnosine eye drops

BCM95 Curcumin


Superessentials Fish Oil with Astaxanthin

Organic haritaki powder (for chebulic acid)

My podcast with Bill Andrews about TA65 and TAM818

Compounds recommended by Dr. Kaufmann:

Aloe Vera – 5,000~10,000 mg/day

Alpha Lipoic Acid – 300~600 mg/day (diabetic treatment- 600~1,800 mg/day)

Andrographolide (Andrographis Paniculata) – 400 mg/day

Apigenin – 50 mg/day

Astaxanthin – 2~12 mg/day (Athletes 12 mg/day) – take with food

Astragalus TA-65 – 100~250 mg/day (Cycloastragenol 5~25 mg/day, Astragaloside IV 50 mg/day)

Carnosine – 500 mg – 2 times daily

Chebulic Acid – 200~500 mg/day (Can take up to 1,000 mg/day)

Cistanche Deserticola – 675 mg/day


Delphinidin  (usually available as Maqui Berry) – 500~2,000 mg/day

EGCg – 400~500 mg/day (1 cup Green Tea = 50 mg) – Take without food

Ecklonia Cava – 50 mg/day

Ellagic Acid – 250~500 mg/day

Melatonin – 3~10 mg/day – Take before bedtime

– Metformin – 500~2,000 mg/day

Naringenin – 250~500 mg/day

Nicotinamide Riboside – 250~500 mg/day

Polypodium – 500 mg/day

Pterostilbene – 50~150 mg/day – Take with food

Pyridoxamine – 50~250 mg/day

Quercitin – 500 mg/day (up to 1,200 mg/day)

Resveratrol – 100~250 mg/day (up to 500~1,000 mg/day)

Rosmarinic Acid  (available as Lemon Balm or Rosemary) – 100~400 mg/day

Sulphoraphane – 400 mg/day

Yerba Mate – 600~900 mg/day

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Ask Ben a Podcast Question

4 thoughts on “[Transcript] – The 7 Different Reasons You Age (& Potent, Proven Molecules To Enhance Longevity & Slow Aging).

  1. Margaret says:

    Ben, have you heard about Sanaga drops. I’ve read they can restore eyesight?

  2. Abby Burston Kranitz says:

    Where can we find Visomitin eye drops?

  3. katharine booth says:

    Do you think carnosine raises lipofuscin? I just read only the benefits of carnosine, not any potential downfalls. Thank you.

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