Gladden longevity — Episode #15

Speaker 1:   Welcome to the Gladden Longevity Podcast with Dr. Jeffrey Gladden, MD, FACC, Founder and CEO of Gladden Longevity. On this show, we want to answer three questions for you. How good can we be? How do we make 100 the new 30? And how do we live well beyond 120? We want to help you optimize your longevity, health and human performance with impactful and actionable information. Now, here's today's episode of the Gladden Longevity Podcast. The Gladden Longevity Podcast is provided for informational purposes only. It does not constitute medical advice. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition. The use of any information and materials linked to this podcast is at the listener's own risk.

Dr. Jeffrey Gladden:  Welcome, everybody, to this edition of the Gladden Longevity Podcast. Today, I don't have a guest with me, but I would like to take some time to open you up to a trial that we're getting ready to start at Gladden Longevity that I think has the possibility to be the first trial to actually show that we can reverse aging. What I mean by that is there's a lot of research that's gone on in different technologies and people have shown that if we increase NAD that we can get mice to get younger, if we lengthen telomeres in mice, they will get younger, if we do plasmapheresis in mice and replace half their blood volume with albumin, they will get younger and you can activate stem cell activity. Some of these technologies have also been used in humans, but nobody's actually ever orchestrated them together in a way that I think makes sense and gives the biggest possibility for age reversal. Let's break it down for you.

The name of this trial is Life Energy Resilience and Antifragility Trial. So life energy, the first circle of our four circles is life energy. And really, if you don't have your life energy circle dialed up, in my mind, it doesn't really matter how much biochemistry you throw at the situation, you're never really going to optimize your health, your performance, or your longevity. And the things that we focus on in the life energy circle are things like having a growth mindset. I can't over emphasize this enough, that it's so important for people to be married to their questions and not their answers. And I see this over and over again, whether it's in a researcher, whether it's in a client, people come in and they think they have it figured out. And it's really important I think to be very humble and realize that we don't have it figured out. There's so much more for us to understand and it's the questions that will drive us to that deeper understanding.

The other is optimizing mental health. There's so much mental disorders in the world. When you think about people that are struggling with anxiety, depression, et cetera, it's really rampant. And they say it's 20%. But I feel like in talking with people, it's more like 85% of people are struggling with something. And then also on this circle is the concept of feeling loved. So a lot of people don't feel loved. They don't feel loved for themselves. They're constantly beating themselves up. When you talk to them, it's like, "I'm harder on myself than anybody else. I have a hard time loving myself." And the flip side of that coin is they have a difficult time receiving love from the outside. So what I've come to understand in terms of your own energy and psyche and health is that being able to receive and give love freely back and forth without any barriers, even in situations where a relationship may have gone awry. When relationships go awry, our tendency is to withhold love.

It's like, "Well I used to love that person," or, "I used to feel affection for that person. I'm no longer going to feel that," right? But in actual fact, whenever we try to dam up that energy, it has repercussions for our biology. And I think getting that straight and realizing that even though something hasn't worked out with somebody else, you can still have love in your heart for that person. And you can still feel love flowing back and forth. I think that's really critical. It lowers stress and it takes you off this whole idea of being on the defensive side all the time. And the next one is optimizing relational health. And this is really critical. And I think doing deep dives on yourself, doing deep dives on the relationships that you're in with the most significant people that you're in those relationships with, understanding what really comprises a great relationship and then working hard to make that happen, not just putting up with whatever you have, really creates a sense of joy and peace that I think is also critical for the mission here. And then feeling joy.

Many people feel like they're part of a grind, right? They feel like they're really... "I go to work, I work hard, I'm doing this, I've got to pay these bills, I've got to do this, I've got to take care of that, I've got to, got to, got to, got to," and there's no joy in it for them anymore. And I think that when we feel joy, when we feel gratitude and joy in the things that we're doing, it's a blessing for me to be able to be on this podcast with you, right? I mean what a joy this is for me to be able to express some things that I've been thinking about and interact with you on this. Or the workout I just did this morning. Even though my recovery was in the red, it's like what a gift this is to be able to do this Vasper, to be able to get on the AllCore360. What a gift that is, right? So feeling joy really in everything that we do. And then optimizing spiritual health, where you feel this sense of being centered and connected to something greater than yourself.

And optimizing wisdom. I think wisdom is so important in life, right? What have you learned, right? Problems that come up, it's not always about the other person, right? It's more about us than it is about the other person. What are we bringing to the table? How do we approach this more wisely? And how do we learn to discern when a situation's going to be good for us, when it's not going to be good for us? How do we avoid making the same mistakes that we've made previously? And how do we help other people increase their wisdom as well, right? And when you're doing these things, when you're involved in that activity, you'll find that your psyche just settles down into this really, again, peaceful, joyous place. The other one, there's two more on this circle, and the next one is feeling safe. I find that a lot of people fundamentally don't feel safe. And I actually struggled with this issue for a while. And we all really come out of a background, right? We all come out of a family, we've all run a gauntlet in my terminology.

We've all had to navigate things, "Bad things," that have happened to us, things that were done to us, things that weren't done for us, our childhoods, our adolescents mistakes we made, et cetera, et cetera. And ultimately, it can lead to us living our lives on tilt. In other words, we're living in reaction to those things. We're not really living from our true sense of self. And ultimately, when you get down to the bottom of it, on one hand, we don't feel loved, but on the other hand, we don't feel safe. And being able to get to a point where you actually do feel safe and you can actually give that gift to yourself of being safe. It doesn't matter how much money you have. It doesn't matter what position you have, what status you have, how many people are applauding in the audience, how many books you just sold, none of that matters. Nothing about that is ever going to make you feel safe. This is work that has to be done on the inside.

And again, when you feel safe, all of a sudden stress inside your body goes way down. It enables you to basically really connect with people, not to live on tilt. And that's massively important, again, for health and longevity and performance for that matter. And the last one is basically feeling what I call energetic resonance with the universe. So I've done some energy work where I've had some experiences where I have gotten really aligned with feeling a part of something much bigger. And it's a spiritual element, but there's also an energetic to it which is why it stands on its own. And when you actually feel that, it's actually dramatic. All of a sudden, it's very peaceful. You see and read these stories about people that have had these near death experiences, right? And they cross over in their own minds and then they come back and their lives are forever changed. I mean they understand that really love is running behind all of this, that we are connected, that there is an energy here that's supporting us.

And when you have that, it's just so common again. And when you put all these things together, it enables us to ultimately find what our purpose is. So when we think about purpose, right, we're talking to young kids all the time. "You need to do what you're passionate about. You need to do what you love," right? And that's great advice. I told that to my kids. But it doesn't necessarily equate to a sense of purpose just because you're doing something that you're passionate about. It's when you feel this energetic alignment, "This is what I'm truly supposed to be doing. These are the gifts that I'm supposed to be bringing forward to the world. I would do this if I wasn't paid at all. It's not that I'm just passionate about it, this is actually defining who I am as a person." When you get to that point, that's when you really find a sense of purpose. And I think that becomes integrating all the different elements that I just talked about here on the life energy circle if you will.

So in this trial, life energy is the first thing. Then resilience. Now, why did I pick resilience? Resilience is critical because our resilience is biological organisms gets cut in half every eight years. So think about that, right? Just think about that for a second. You're 44. You're 52. You're 60. You're 68. You're 76. You're 84. You're 92. You're 100. Half, half, half, half, half, half, half, half, half, that is an exponential equation. That is an exponential decline in your resilience, in your longevity, your health and your ability to perform. And that is the game that we're playing. We're playing an exponential game, not a linear game. When we look at ourselves chronologically, it's a linear game, right? It's, "Well I'm 42. I'm 44. I'm 52. I'm 60," whatever it is, that's linear. But biology is working on an exponential scale. And so the concept that just getting healthy is going to be enough, if I work out and exercise and get that dialed in and figure out what to eat, and I start to meditate and sleep better, that that's going to be the answer.

It's never not going to be part of the answer, but it's never going to be the answer either. And so this is a Life Energy Resilience and Antifragility Trial. Now, let's talk about fragility and antifragility. So Nassim [inaudible 00:11:48] wrote a book called Antifragile, and I love this book. I love the concept of this book. And his hypothesis is that in all of human languages, he could never find a word that was actually the opposite of fragile. So he coined the term, "Antifragile." And if we ask ourselves, "Well what's the opposite of fragile?" The first thing that we would say is that, "Well it's strong. It's durable. It's resilient. It's resistant. It's tough," things like that. His argument, however, is that if something is fragile, when it meets an unexpected stress, it's damaged. If something is strong and it meets an unexpected stress, it's minimally impacted. But if something is antifragile, when it meets an unexpected stress, it actually grows stronger, right? That's the definition of antifragile.

And so as we're going through this life of ours, and we're actually playing a game of exponential decline in biological systems, for us to actually run into COVID, run into a sprained ankle, run into a broken bone, run into whatever we're going to run into and actually come out of that stronger than when we went into it as opposed to being depleted by it, that's really the goal here. So the name of the trial is Life Energy Resilience and Antifragility Trial. And when you put that together, the acronym becomes LIFE-RAFT. So that's the trial, life, L-I-F, then a capital E for energy, R for resilience, A for anti, F for fragility and T for trial. So it's LIFE-RAFT. And I like the acronym because one of the analogies that I use in aging is that it's like a river, like the Niagara river. And the current is not too strong at certain points. And you go out and play in it and have fun and everything's great.

And then the current picks up and you can't go out and swim anymore because you're now launching from further down the bank as the chronological years go on. And all of a sudden, it's like you've got a choice. You're going to say, "Well okay, I can't swim anymore so I'm going to start knitting," or, "I'm going to start doing something else." Or you say, "No, I'm going to get stronger. I'm going to learn how to swim in this current." And so you go back and you get healthy, right? You get stronger, you start to work out, you eat better, you exercise, you sleep, all the different things that are important. And sure enough, you can swim out there in the current again. And that feels great. But every year, you're basically launching from further down the bank. And the reason that you are is that every get healthy strategy does not really address the underlying drivers of aging. And so eventually, the current becomes strong enough that your get healthy strategy no longer works and you end up going over the falls.

Yes, you had a healthier life. Yes, you had greater longevity and you had higher levels of performance, but you still got swept over the falls. So with LIFE-RAFT, what we're really addressing here is the whole concept of what are the key drivers of aging? And how are we going to address them? And I'm building that out into a year long protocol that people will be able to come into. It'll be an IRB approved trial. And essentially, we'll be working on all the known nine hallmarks of aging that you're familiar with. Things like genomic instability, telomere attrition, the epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intracellular communication. And I'll run through those for you in just a minute, but I just wanted to rattle off all nine for you. And then we've added to that cross-linking or glycosylation of proteins.

Immunosenescence, the oncogenic potential that shows up. And then hypothalamic stem cell status, because it turns out that when the stem cells and the hypothalamus start to deteriorate, exosomes are released from the brain saying it's time to get old. And so if we're not rejuvenating the hypothalamus and the stem cells there, we're going to be in trouble. So this trial is basically designed to address all 13 of these elements of what I think are the key drivers of aging. And we have now technologies where we can approach all of these. I won't go into great detail about all the technologies. I want to get the trial to the IRB. But we now have ways and we're developing ways to actually test the status of each of these using transcriptomics and proteomics and metabolomics. We can measure genomic instability. We can measure DNA repair, telomere attrition. We have a good handle on that. Epigenetic alterations, we have great methylation clocks that we can use for this from Steve Horvath, et cetera.

We have rates of aging that we can look at that are very predictive of people's outcomes in the future, as good as GrimAge. And then loss of proteostasis, which is where proteins aren't made properly, folded properly, or disposed of properly. We have ways to measure that also with proteomics. And then deregulated nutrient sensing. This is a big one. This is the insulin blood sugar growth hormone axis. It's also the mTOR AMPK axis. mTOR builds us up, makes us strong, gives us bone density and muscle mass. We need mTOR. But if you're standing on the mTOR gas pedal all the time, you die sooner and you have more cancer. So you need to be activating AMPK also with exercise, intermittent fasting, saunas, things like that, and some AMPK activators. We feel like we have a good handle on this and this will be built into the trial also. And then mitochondrial dysfunction. Well I'm going to link mitochondrial dysfunction to deregulated nutrient sensing because NAD plays a role here.

And we have a way to actually measure NAD now that we think is at least helpful. And we also have ways to boost NAD and get the body to boost NAD. So we're super excited about that. Cellular senescence. We now have and are developing ways to actually measure senescent cell burden in the body. And also the secretory status of those senescent cells. As you know, senescent cells, the analogy I've used is that you have 100 people that work for you in your company, or you work in a company that has 100 people. And if 20 of them are senescent, they show up to work, but they don't do anything, they just put their heads on their desk. And it gets worse than that. They become secretory. Now, they're sabotaging the wifi, closing the door, locking the people out, and they're recruiting your other employees to become senescent. So you go from 20 senescent employees to 30, to 40, you can see there's going to be an exponential decline in the outcome and the output, if you will, of your company. And this is one of the key drivers of aging right here.

So we now have technologies basically to be able to remove those senescent cell cytokines. And we have technologies to be able to prune senescent cells from the body. But doing just that on its own is not enough. All these other things have to be addressed simultaneously. And then there's altered intracellular communication, which is, again, inflammation. And we can measure upregulation and down regulation of genes that are controlling senescent cells, altered intracellular communication, DNA repair, et cetera, et cetera, with the transcriptomics that we're currently developing for this trial. And then there's the cross-linking we can measure, glycosylation. So we have a handle on that. We can measure the age of the immune system. We can also measure the status of the thymus gland and then oncogenic potential. We've always been interested in actually preemptively diagnosing the presence of malignant cells. And we know that we all have malignant cells in our body that pop up from time to time.

And our healthy immune systems, particularly our natural killer cells, actually take out those malignant cells. But when the immune system gets old, when the natural killer cells don't work, when the oncogenic potential rises, that's where the problem starts. And so being able to preemptively understand the status of the immune system and whether or not there are malignant cells in the body and what is your risk for developing cancer in the next year, these are tests that we're also working with. And within the next couple of weeks, I'm told that we'll have access to a new test out of India that will actually help us define this even better than we've ever been able to with more precision, more sensitivity, more specificity if you will. So we're very excited about that. And then the whole concept of these hypothalamic stem cells. Dr. Shelley Jordan at UCLA has developed a technique to reinvigorate these stem cells utilizing transcranial ultrasound to open up the blood brain barrier and then deliver exosomes into the hypothalamus to rejuvenate them.

And this is a piece of the puzzle that we're working on with him. We're now part of that trial with him and we'll be doing that here at Gladden Longevity. And then we also have some other ideas about how to do that as well that we're teaching him that I think would be very, very helpful in rejuvenating these stem cells. So really, this LIFE-RAFT trial is going to be focused on these 13 I think key drivers of aging. It will also include by default because you can never get away from this, it'll also include addressing the healthy circles as well, right? How do you optimize cardiovascular health, your vision, your hearing, your balance, your performance, your flow states, all of this is really aimed at answering this bigger question. How good can we be? How do we actually make a hundred to new 30? It's not just about being biochemically someplace where you have one metric that says, "Well I'm 20 years younger than my chronological age." It's like, "Congratulations, but what about all the other metrics of aging?"

In our practice, we're now actually measuring probably close to 70 different ages. So we're all a mosaic of ages if you will, many, many ages. It's really important to just not latch onto, "Well I had my telomeres test and it said I was 10 years younger than my chronological age so I'm good to go." Well congratulations again, but it's a very incomplete picture of what's actually happening. Same with DNA methylation age, Steve Horvath's clock. It's great, but it's a very incomplete picture. It's only when you actually start to link all of these different pieces together that you start to actually have a chance to do what it is we're here to do, which is to turn back the clock. So I just wanted to bring you up to speed on the progress that we're making. The trial is being written right now and will be submitted to the IRB for approval here shortly. In my parlance for all this, the way I think about it is that this is really like playing in a symphony. And so as I'm writing this trial, I really feel like I'm writing a symphony.

It's because there's a sequence in which these things are done. There's a timing, there's a frequency, intensity, duration with what;s done. And it's different for each person. Baseline testing of the individual will actually determine what the sequence, timing, frequency, intensity and duration is of these different technologies that we have to address these 13 drivers of aging if you will. So we're very excited about this trial. We think it's really the first time that anybody in human beings has linked these things together in a logical way to see how much we can accomplish. And what I've noticed is that these technologies stack very nicely. In other words, you can get an effect from lengthening your telomeres, but you can get a bigger effect when you couple that with pruning senescent cells and clearing out senescent cell cytokines. And you can get an even bigger effect if you start bringing the mitochondria back online and doing other things to improve your function and health and other things. And you're also pruning any things related to malignant cells, and you're rebooting the immune system.

When you start to get all these things working together, and now you're augmenting DNA repair and things are coming back online, it's really like starting up a machine that has many moving parts. And you can start to see the wheels in this machine spinning and starting to go backwards into a much more youthful pattern. So that's really what we're going for. And then using the transcriptomic data, we will actually be able to document that we're doing what we say we're doing. We'll be able to measure all the different mosaic of ages metrics that we have. But we'll also be able to see at a DNA level when a cell gets younger, it will express its DNA in a different pattern. And we should be able to identify that with the work that we're doing. So again, this is super exciting stuff for us. We talk about a lot of things here on the Gladden Longevity Podcast. But quite honestly for me, it comes down to those three big questions and I think this is our first attempt at really addressing them.

So I just wanted to share that with you. I haven't shared with you exactly how we're going to do all of that, but I want to make you aware and we'll be enrolling probably about 20 people. This will not be an inexpensive trial to be a part of because there's a lot of technology that's being brought to bear. There's a lot of very sophisticated testing that's being brought to bear. But it's not cheap to send somebody to Mars either. And if we can prove that we can go to Mars, we can prove that we can actually turn back the clock for people. We will find ways to make it more financially accessible to more people. But first, somebody's got to go to Mars and figure out how to make that work and then you can start to think about how to bring down the costs and everything else. So I just wanted to give you an update as to where we were in this whole thought process. And this has been really a work in progress for the last decade of researching all this information.

So I hope you find that interesting and helpful. If you have questions, please feel free to send them. If somebody's going to ask, "Well what is the cost of it?" It's going to be a custom build for each individual. I can tell you that. And so we won't know the cost, but I can tell you this that once we do build it out, it'll be a flat fee. People will write one check and it'll include the different medicines, the different treatments and any supplements, all those things will be included in a flat fee. And that's how we'll set it up just so people know exactly what they're getting into if you will. So I hope that's exciting to you. And we are super pumped about this. Getting into our new office has really been one of the things that we've been waiting for to have the space and the machinery instruments, et cetera, that we needed to actually be able to do this. So this will be going live here probably sometime in the next couple of months. And again, if you have questions, please feel free to reach out.

Speaker 1:   Thank you for listening to this week's episode of the Gladden Longevity Podcast. If you would like more information on what we've discussed or other topics, please reference the show notes or go to gladdenlongevitypodcast.com. You can also find us on Instagram, Facebook and Twitter by searching, "Gladden Longevity Podcast." If you've enjoyed this podcast, please subscribe to get future episodes delivered to you and share our podcast or this episode with someone in your life that may find benefit. Thank you for listening. We'll be back next week with another exciting episode.