The Underpinnings of Aging and What to Do About It

our ability of our immune system to identify them and rid them and basically kill them through apoptosis becomes less and less effective. And we go from 20 to 30 and say, well, okay, that was 10 years. I aged a little bit. 30 to 40, we seem to increase that aging process. It accelerates. And it is because these senescent cells are building up in our body till we get to an elderly population where we're in our older or our later years. And we have so many senescent cells, we have so much inflammation that our quality of life really starts to deteriorate. And those senescent cells really start to increase about after age 60, where our immune system starts to falter and the senescent cell numbers start to increase.

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Hello, this is Dr. Kenton Holtorf with another episode of the Peptide Summit. Today we are honored to have Dr. Joseph Kleever, who's going to be talking about Senolytics, the cornerstone of longevity. Thank you, Joe, for being on. Appreciate it. You're one of the busiest doctors I know, and you're all over the country. Where do we have you now?

You're in North Carolina, I think. Yes, sir.

And you practice Dallas and your winery in Sonoma where, you know, we went to conference mastermind too. It was great. But a little bit about Joe. It's, it's such an honor to have him. He's a fellow of the American Board of Anti-Aging and Regenerative Medicine. In addition, he's board-certification internal medicine. He's board-certified in anti-aging and regenerative medicine, has achieved certification by the ABAARM. So he has a lot of initials after his name. And advanced metabolic endocrinology specializing in bioidentical hormone therapy. He sees patients Paradigm Wellness Medical Group. He's in Dallas, Sonoma, but also looks like North Carolina. And I had the honor to be invited to one of his masterminds at his winery, Lucanda. Great wines, by the way. I don't know if there's any spots for the wine club, but we're similar. He does successful wine. I started a beer company after medical school. We had a hangover-free beer. Double-blind placebo-controlled studies. But as soon as we brought it out, the Bureau of Tobacco and Firearms said, you can't make a healthy beer. So we got shut down. But then we came with an energy beer before anyone had it. And, but our business plan was not very good. It costs us $7 to make it at that time. You couldn't sell a six-pack for more than $5. So we tried to make it up in volume.

I'm a doctor.

I don't know these finances and it didn't work. We kept losing money. But it was a great, a fun experience. He's the real deal. Patients come from all over the world to see him. He is so generous with his knowledge. He trains doctors from everywhere. He does a lot of aesthetics with threads and a plasma pen, which scares me. It's hotter than the surface of the sun, but in his hands, he can work wonders. And it's really neat. So I've been to a couple of his masterminds conferences at his winery, which is beautiful setting in Sonoma, that it's just some amazing minds on peptides, on longevity, senolytics coming together. And it was just a wonderful experience of like-minded physicians that, you know, they're geeky on one end, you know, Joe's Mr. Suave, good-looking guy. But he's also a geek. You can tell he just researches like crazy. He's on the cutting edge of everything. And again, everything from cosmetics to the sickest person to— but it seems like his passion is really having people live better, longer.

And he has a whole new way of looking at this longevity.

We hear longevity, oh, take this, take that, which really goes after getting rid of your cells that are causing the problem. So thanks, Joe. Thanks for being with us. It's an honor and I just learn so much every time we get together.

Well, thank you for that wonderful introduction. It's an honor to be here and to be able to share just some knowledge and education with my colleagues and peers.

And just thank you for inviting me. I really appreciate it.

Thank you so much.

Yeah.

So Synaletics. Versus longevity. It's kind of like, okay, everyone wants to live longer, but one, how do you achieve that? Or is that kind of the goal? Or how do you, yeah, how do you achieve that? What, what's so important about Sinalytics and what is it, I guess?

Yeah.

The, the, when, as we've developed what used to be called anti-aging, and you think about the largest educational, you know, institution outside of medical medical schools and, and looking for integrative medicine programs, the American Academy of Anti-Aging Medicine, you know, coined that term decades ago. And we've used anti-aging for a lot of years and that anti-aging foundation and the fundamentals of our endeavors to slow the aging process started and still are true today with lifestyle, the purest form of medicine. It really is. And if we can prevent disease and live a longer life. That's where I really kind of cut my professional teeth, if you will, at the Cooper Clinic in Dallas, Texas. But, you know, back in the '90s, we looked at— we have the largest— I worked on the database there for a lot of years, and we look at the impact of lifestyle on longevity. And the mortality data, all-cause mortality data, is compelling. It it's all, all the evidence is, is there if we live a, live a healthy balanced lifestyle.

Hey, but I don't, I want, instead of lifestyle, I want the pill. We got, we got peptides that makes your body think it's exercising, makes your body think it's fasting.

So, uh, we've, we've made a lot of advancements in integrative and regenerative medicine that apply to longevity medicine. So, uh, you know, we've coined the term longevity medicine and on the underpinnings of the mechanisms of improving healthspan and lifespan. When we drill down deep into the literature and the science of where we used to focus on, we have to control inflammation. We still know that we have to control that low-grade inflammation and oxidative stress. And we were taking all these antioxidants and there's still a very important role for it. But the life— first of all, lifestyle creates some of that low-grade inflammation. Some of our genetics creates the low-grade inflammation. What we, you know, yeah, certainly what we eat every day creates low-grade inflammation, stress, et cetera. And so we would try to balance those things out with supplements, et cetera. Well, we've become a lot more sophisticated because we know the, one of the most important end results and important drivers of premature aging is something called a senescent cell. And that senescent cell is produced in greater quantities from healthy stem cells, healthy cells in the body. If we do those things wrong on a daily basis in lifestyle and we don't pay attention to what we— this low-grade inflammation everybody talks about, and we start getting genetic or DNA damage in our cells that accelerate the number and speed at which we create—

you go back and what, what is a senescent cell?

So senescent cell is a, a, a cell in the— that is at the end of its lifespan in the human body. It's no longer functioning. And every system in the, in our body has, first of all, healthy stem cells, stem cells that reproduce skin cells, epithelial skin cells so we don't get wrinkles in our heart so we don't get heart disease or heart failure, or our lungs, our brains, so you don't get Alzheimer's, et cetera. And as we age, our ability to maintain those stem cells, they also age over time. Senescent cell, or excuse me, a senescent cell, a healthy stem cell turns into that senescent cell. And it gets stuck in a state of suspended animation, if you will. It's one of the ways the human body prevents that cell from becoming a cancer cell. So in one of the phases, G0, of the life cycle, the cell cycle, it gets stuck. Normally, a good healthy immune system can destroy that stem cell through apoptosis and autophagy.

How does it take in general for a stem cell to become a senescent cell?

So the literature supports about a 22-day cycle.

That's it.

That's it. So about every, every 22 days, we see this migration of, you know, stem cells, healthy cells turning into morphing into these senescent cells. And as we get older, as we go out, go throughout the decades of life, our ability of our immune system to identify them and rid them and basically kill them through apoptosis becomes less and less effective. So look at ourselves in the, you know, we go from 20 to 30 and say, well, okay, that was 10 years. I aged a little bit. 30 to 40, we seem to increase that aging process. It accelerates. And it is because these senescent cells are building up in our body till we get to an elderly population where we're in our older or our later years. And we have so many senescent cells and we have so much inflammation that our quality of life really starts to deteriorate. And those senescent cells really start to increase about after age 60, where our immune system starts to falter and the senescent cell numbers start to increase.

So the senescent cells, when they switch to senescent cells, they're not just sitting there, they're actually causing problems.

So true. What happens is every place in our— every system in our body has stem cells. And that has a ratio of healthy stem cells to senescent cells. And those senescent cells become eventually the worst case scenario is they become SASP cells and they're secretory phenotypes. In other words, they turn into a, basically a factory that produce inflammatory substances that also pollute the milieu in the environment around this healthy stem cells and start recruiting those stem cell, stem cells to become more and more unhealthy and convert to senescent cells.

So vicious cycle.

Accelerate the aging process.

So everything's a vicious cycle.

It becomes a vicious cycle if we don't know how to target them, those senescent cells, and to prevent them from becoming senescent. And then if we have them understanding the science as we know today, and we're just still scratching the surface, but we do have tools at our fingertips to be able to prevent senescent cells from occurring. And then if we do have them, we understand ways to actually rid them from the body. And that is for me, my focus of approach to my therapy, my, my therapies, my senolytic therapies, my longevity therapies for my patients today in, in, in 2020, that's, that's the most current literature and science that I know that has a significant impact on our endeavors to improve our longevity and our healthspan also.

See, I love that because, you know, you have Okay, this is good for you. This is good for the cells, good for the cells, but you don't want to be feeding these senescent cells. You want to get rid of them.

So all your protocols, it depends on the order of things, right?

Is you don't just say, oh, this is good for you. Take it. No, you got to do this first, the second, this third. Can you talk about the timing of your protocols?

Well, if we look at and understand that we have, have a group of senescent cells in the body, we have a group of healthy stem cells and if we try to nourish or feed or improve the health of a healthy stem cell, the same mechanisms that are improving the health of a healthy cell actually improve a cell we don't want to improve their function. Now we can take a senescent cell and pull it back from— occasionally we can pull it back from that senescence and make it healthy again. But more often than not, it's this, that last step on the pathway of senescent cells, that SASP cell that we do not want to promote its health because we do not want that cell to become more efficient in producing inflammatory substances that accelerate the aging process.

Yeah. It seems like you're taking a step so-called forward, but you're, you're causing a cell that's causing problems to live longer. And you may be better for a bit, but it's going to quick— it's going to be one of the ones that first to go back.

To senescence. So yeah.

And that's rare. So the most important concept that I explained to my patients that I understand from, from, you know, the literature and research, which quite frankly, been around a long time, senolytics, that is in the literature for decades. It's just coming to the fore now and understanding that this is one of the most powerful imbalances. This is one of the most powerful concepts that have identified in human body. That have been linked to premature aging and that premature aging begets diseases of aging, diabetes. There's no shortage of that. Heart disease, Alzheimer's, dementia, et cetera.

Yeah. It's like, you know, with diabetic patients and if people do like stem cells, bone marrow or fat, we find they don't work. Right. Because you just got these crappy stem cells that are senescent. You're just basically giving them more than that. And you know, what's interesting is that there's a lot of research on this. One is that, again, I don't want to be doctor bashing, but you know, how many doctors even, you know, your standard doctor knows about senescence, you know, and senolytics, or do they care?

I mean, they're in a, they're in a model that if they did care, they'd be miserable because how, you know, they're gonna have to take 20 minutes to explain it. No, they already— that's twice their time they have. And it's interesting. And like everyone looks for new research, but you may find this as well. You look back, especially on peptides, there's people go, oh my God, how do I not know about these hundreds of studies? Well, they've been around for 50 years, you know, and it's just gets overlooked because there's no drug rep tapping on their door 3 times a day trying to get them to buy a drug. And so it's really the old literature And I really think you could go back and look at the old literature in any specialty except for surgery or something like that for 2 months and be better than the specialist. You know, they're just doing the same thing they've been doing in residency. And because that's what they need to do. Where you are on the cutting edge and you're always, it's amazing, you know, you're finding new stuff, but it may be old research that was done, but fascinating stuff.

Fascinating.

And this, this whole synolytics is kind of blown a hole and everything. Oh, take this. This is good for you. Good for you.

Good for you.

Well, at what time, you know, do you wanna feed these sick cells and make them better at making you sick? You know?

Right.

Yeah. Well said. And that's a, the, what I've termed now is more precision synolytics. When the fact that we have to, if we look at all the, anything from a natural occurring substance in mother nature, whether it be a flavonoid flavonoids such as quercetin or fisetin or long pepper, that all these, all these substances actually are very powerful senolytics and they can prevent healthy stem cells from becoming— they can prevent senescent cells. And they also, in addition, can actually induce apoptosis of a sick, of a senescent cell and get rid of them. So that's where diet comes in. And then there's supplements that actually can enhance that. The, um, what, what the, um, the science shows, and that's all I— I base my therapeutics on the literature and take clues from many, many decades of not forgotten, but there's so much literature out there that we have to go back and actually revisit some of the very powerful science that has been forgotten, such as even in peptides. Peptides are very powerful in senolytics and in many areas of application of regenerative and integrative medicine.

Oh yeah. Now wait a minute, you're an anti-aging doctor.

You're not supposed to look at the literature.

So much. Yeah. And so much of that literature, so much of the science, so much of the basic science that those mechanisms of action and the science supports the, the, a clinical application in many, in many, in many ways. Anecdotally, there's so much science that supports what, how we approach longevity.

And it's, it's interesting. And again, I don't, I kind of get on soapbox with the whole healthcare machine. And, but it's like, you get the less a doctor knows, the more adamant they are, like, okay, that's wrong. You know? Okay. Well, how much have they read?

And I'm like, you know, I read more in a day than they do in a year.

And I'm sure you're the same. And that's what you gotta do. And it takes a long time. And it used to be, I remember like, you know, going to the library and like picking out the journal and then going to the damn fax machine and then Like, you know, the journal's not there, whatever. Now it's information overload, right? It's just so much stuff coming at you with 80% of it is just, you know, whatever, just political stuff.

And so much is hitting that really the consumer, the layperson, the person and your patient who will, you know, contact you and talk to you through, you know, my patient satisfaction is, and my patients, for example, in Dallas are word of mouth. I didn't do no advertising. I just. Do my best and follow my passion taking care of my patients. They will come in with so much literature, so much, so many ideas that they see on, on, you know, online. And I feel that one of the most important jobs that we do as integrative medicine physicians is to be the gatekeeper for them. We have to be able to weed through, wade through all the potentially dangerous things that, that they, that they find that they'd want to try and find them the most effective, safest, and cost-effective therapies for them. That's our responsibility.

And I agree.

I tell patients, go to the internet, get all the stuff. There's great information. There's misinformation.

Bring it in.

We'll talk about it. So many doctors that I hear, they go, are you the doctor now? No, you have to be an active participant in your health now. And if a doctor tells you, stop reading the internet, run because they can't support their therapies. I think it's great. And I get patients bringing in obscure journals. Hey, look at this. I'm like, oh, that's interesting. Oh yeah. Well, and, and there is so much great information that is just bypassed because there's not a patent on it. There's no drug rep and, you know, and that's where all the excitement is. And I'm telling you the excitement in this, and I hate the term anti-aging or alternative. I hate that. Me even more, you know, because they go, there's no evidence. Like, are you kidding me? You know, I'm very evidence-based. I've always been. And, but I was told never go to this alternative. And I went and I'm like, oh my God, they're more evidence-based than, you know, and, and a lot of doctors rely on societal recommendations and you look at levels of evidence. So you got your double-blind placebo-controlled study. You got your meta-analysis, you got your single-blind and you got case studies, anecdotal Total. And then below that are societal recommendations. And why is that? They've shown to be wrong such a high percent of the time because they don't change for 20 years. They're very biased. So they get one side and they're terrible. But what do doctors quote? The, you know, the American Academy or the Endocrine Society says go by the TSH. Okay. Well, that's—

I got one patient that says it's not true. That's better evidence than the societal guidelines, you know?

So, you know, all physicians, I think as a profession collectively, are some of the most dedicated professionals on this earth. And we're, we're all just trying to do a good job. Just that our toolbox and our tools may be a little bit different and our, our thought processes, the way we approach patients may be a little bit different. And what we, our depth of knowledge and our understanding We're just trying to do the best for them. I just know that I'm, I'm held to get up at 4:00 AM in the morning and comb through. I know what you do. I could text you 4:00 AM and find out what are you looking at on PubMed, right?

I'm still up. I can't get up early, but you see, there's no incentive for these doctors because they're in a system that they could find a cure to cancer. They can't do it. You know?

So why should they find these things? You know, and so I get mad at the doctors, but I used to be kind of just so angry, but they're in an untenable situation. They, if they want to, they're going to make themselves more miserable, you know?

No, I mean, and I, um, so true. Well said. And I think the, that balance that, that is even more finely honed in longevity medicine and senolytics is the fact that we, as I mentioned before, there's a A lot of science out there, but we are just getting an early understanding, just scratching the surface on longevity and how we can improve our, you know, just our quality of life. And, but the, it's more fine-tuned because we don't have the luxury of waiting, you know, a whole lifetime to see how well our approaches work. We know that, you know, short-term, the same parameters that we use in longevity to certainly improve lifestyle. Hormone balancing. If we take a closer look at balancing hormones in men and women, there's literature out there that does support that, you know, the humans do live longer when you do balance sex hormones. But, and then when you dig a little bit deeper into basic science, you see that that hormone balancing has a direct effect, for example, on mitochondrial health and function and efficiency. It's like, wow, okay. Yeah, you can define hormone balancing as a longevity approach.

Yeah. And, and you look at, you know, the doctors will say, don't take hormones, they cause cancer. Well, yeah, synthetic hormones do. If you want to give a woman breast cancer, give her synthetic progestin. If you want to prevent breast cancer, give her progesterone. And, you know, and would you say most of things work epigenetically or change, change that gene expression?

Yeah. And I think there's a lot of unknown epigenetic phenomenon occurring in all our therapies that have just haven't been discovered. One of, when I give one of my talks on presentations on longevity and peptides, and I love referring to GHK-Cu or copper peptide because the Broad Institute at Harvard has over 4,000 studies looking at the impact that copper peptide has on genomic genetic expression and resetting your human genome to a reset or healthier set and downregulating cancer genes, upregulating anti-cancer genes. It have the impact it has on misfolded proteins and making a cell healthier. There's, there's so much not in literature on a peptide that is, I think, overlooked in sinalatops. And I use a lot of it in my, in my, in my in my programs just as a, just to improve skin health.

And so, yeah, GHK.

And for everyone out there, it's a copper peptide, a tripeptide.

You'll see it a lot for skin. It's a little blue, or it should be. Now, are you giving it as an injection?

I do. I use it systemically and topically.

Yeah, it makes sense. It's doing the same thing. And really anti-aging the whole body, or do you want, you know, just the skin? And can, can you talk about like the so-called theories of aging and how Senolytics fits into that?

Well, the end result of the theories of aging where we're looking at mito— or excuse me, DNA damage, the end result is, is a senescent cell. Can just as we mentioned, copper peptide can actually reverse some of that damage. Polymerase activator actually can go into the mitochondria and help reverse some of the mitochondrial DNA damage. Fundamentally, every day our DNA is being scarred hundreds of thousands of times. I mean, depending on what, what literature you refer to, our collective DNA damage results in essentially our demise and how, how we protect our DNA and how we maintain and manage our senescent cells. Because remember those senescent cells I mentioned, that all the inflammatory substances that are produced go back and in the, in the environment, in that stem cell environment, cause DNA damage and accelerate other cells to become senescent. So it's that vicious cycle you were referring to before. So protecting DNA in, in, in an environment such as we have with pesticides and radiation, irradiation, and radiation in this world. Is, is one of the fundamental reasons why, why we age.

Yeah. I mean, I think we're in a more toxic environment than we've ever been, you know? I mean, it's, you know, yeah, pesticides, plastics, you know, pollutants, the EMFs, you know, all this stuff, pandemics, stress, and stress, stress is the killer. And it's interesting, all the theories of aging, you know, you got your free radical, da da da. But they do all kind of come down to, they argue over all these things, but wait a minute, it's all about the senescent cell.

Like they're arguing over here, but the common denominator is over here.

Yeah. And, and that, that took, that term coined Inflamma-Aging is the really the result of all those insults we were talking about. And that's, that's a term in the literature that, that has been used for many, many years and is adopted by many physicians in integrative medicine. That talk about inflammaging. And because we want to prevent disease, we need to address inflammaging because that inflammaging is linked to those diseases of aging, which are— they're everywhere. They are pandemics, diabetes, heart disease, et cetera, and cancer.

And it's all, it's all about inflammation. And you look at like diabetes, inflammation, hypothalamus causes diabetes. You get insulin or leptin resistance, you know, the receptors are inflamed. They don't they don't see the leptin and, and the insulin, you know, and, and you lower that, then lo and behold, they're, they're better. Interesting. What types of things do you, or how do peptides play a role in this and the order of things? How, how does that work?

Well, certainly if I start with, because I'm really not gonna get into, there's some very exotic peptides. That are cell-penetrating peptides that get into the DNA and the nucleus and can reprogram cells to become healthier, can target senescent cells through various mechanisms in the body, such as p53, and induce apoptosis. But if we want to swing back the other end of the spectrum in terms of prevention, we always falls on a healthy immune system. One of the major reasons why we develop cancers and our demise later in life is the fact that our immune system starts to falter. And the thymic peptides are, are integral in maintaining immune vigilance and preventing immune senescence. And you can certainly, there's supporting evidence in, in science that shows that synergistically, if we restore thymic peptides to a, a more youthful level, that our immune system becomes more vigilant and can see a cancer cell starting in the, in the body, for example. And to then be able to identify it and eliminate it. So those are some of the most important peptides in, you know, I think in the cetylitic space, in the longevity space, are the thymic peptides.

Yeah.

And it's interesting and looking at studies and you look at, and this is what I hear all the time, but say someone gets metastatic colon cancer and then they go, oh, you're cured. And I'm like, you know, I didn't, don't tell 'em this, but in 6 years it's gonna come back. You know, a cure is 5 years, right? So, and what they have found is after chemo, your chance of relapse is totally dependent and directly dependent on the level of your immune system. Of, for instance, natural killer cells monitoring your body for cancer. So the chemo wiped that out and now you don't have anything monitoring.

So of course it's gonna come back.

Right.

And, uh, you know, you have a bunch of senescent cells that they could be there, which are showing even like with chronic fatigue syndrome, uh, they found that 25% have low natural killer cell number. Okay. They're there. Most of them are there, but 75% have low natural killer cell function. So it doesn't work. The cells are just dysfunctional. And, um, And it's amazing that that's not, not addressed, but it's, it, it's key again, that immune system.

Well, and, and that's on the— I agree. And that, that is one of the key components on the prevention side is to prevent senescent cells from developing and identifying them, destroying them. So it's one of the fundamental cornerstones of longevity of medicine and longevity therapeutics. The overview of senolytics. Draws on so many areas of therapy that are really quite different. I mean, there, as I mentioned before, there's some very natural therapies and very powerful senolytics. There are mitochondrial peptides. We get into peptides. We talked about thymic peptides, but there are mitochondrial peptides, which I don't use a lot of. And I, if I do, I use them after I've wiped out those senescent cell population in the body and think about how do I want to optimize mitochondria? Mitochondria. We talked about theories of aging before we talk about DNA and DNA and mitochondrial function are the fundamental underpinnings of a healthy stem cell and longevity. So they, they, you connect the dots every single time from lifestyle, exercise, optimizing mitochondria, certain things we eat in our diet, are, are, are helpful to mitochondria. Then we move into nutraceuticals that help improve mitochondrial efficiency, whether it be, you know, ALA, resveratrol, and activating SIRT1, et cetera, optimize mitochondrial function. Then we get into mitochondrial peptides. Like, I, I don't use, you know, I, I, the literature says supports some the function of certain peptides that improve mitochondrial function. So you can even look at telomerase activator. Telomerase activator, it lengthens telomeres. But when you look at the non-canonical functions of telomerase activator, it has the ability also, as we were talking about GHK-Cu before, but it has the ability to, to impact mitochondrial DNA and repair mitochondrial DNA. And that's one of the reasons why my telomerase activator is extremely important. I think telomere length is a surrogate marker of stem cell health and longevity. But if you have very long telomeres, doesn't mean you are going to live the equivalent of, you know, the— my telomeres are twice what they should be and I'm a 15-year-old, I'm not gonna live another 100 years. But it is a great marker of, I think, mitochondrial health and mitochondrial DNA health. And where, how far that gets you in terms of longevity, no one knows. But the fact that, that is when we improve mitochondrial DNA, mitochondrial efficiency, it actually has a positive feedback back to telomere health and, and healthy telomere ends on the, on our DNA that help also to promote longevity or contribute to our ability to live longer or potential to live longer, I should say.

I got you.

And the mitochondria, you know, we're taught in medical school, you know, that, oh, the mitochondria are just for energy. But a sick mitochondria, they do so much more. You know, they sense danger and they go into danger response and they start pumping out, you know, basically, you know, all this oxidation and sickness. So yeah, you're better off getting rid of that cell than, you know, trying to say. Can, can you just mention real quick, like, what is a telomere?

Well, telomeres are the end caps on our DNA and they are identified or measured in units. And let's say we assign when we are first born, our telomeres are 10 units long. And each time a cell reproduces, we have to, you know, read our DNA and our, when that happens, our, our telomeres on our end caps become slightly damaged. And the amount of telomerase we have in our body, which we have more early on in life, has the ability to go in or into that telomere and help heal that injury so it doesn't shorten. Each time the cell reproduces itself, the telomere shortens a little bit. And it's kind of like, it's a clock of aging. And when that cell—

every time they replicate, shortens.

That's right. Each replication, the telomere shortens. And when we reach 3 units, that cell can no longer replicate. And in, in essentially we've, we've reached the end, end of our lifespan.

Now, does that cell just sit there until there's a signal to die, or is it still functioning? Or the fact that it can't replicate, does it automatically go to apoptosis? Does it die? Or—

I, and I, I think there's a, um, uh, there's a parallel between the two. There's, there are cells that will reach senescence earlier on because of, of DNA damage. But your telomeres may potential, may not be as, as short as cell death. In other words, that cell is still viable, still alive, but it, when it, when it converts to a senescent cell and the body can't, it, it becomes very resistant to death actually. So it's, it's still in a, it's still a, a, a cell that's living, but it's not contributing to the health of tissue any longer. It's a detriment and we have to get rid of it. And it doesn't necessarily mean that telomeres have reset that, that those, those 3 unit lengths and actually done.

So it's not the defining thing, as you were saying, but it's a marker. It correlates with, with everything. I mean, that's there. I'm just thinking there's so many things that I think of theories of age or so many things that, but they're all taking little parts of it. What, what do you like to do to, I guess, get rid of these senescent cells first before you use your quote unquote longevity therapy?

To rid the body of senescent cells, one of the most powerful things we can do is intermittent fasting. We basically starve out a senescent cell. We, if we create protocols that integrates intermittent fasting periodically throughout a calendar year, for example, we can maintain a lower level of senescent cells because we basically starve them out. And I add the various senolytics to, for example, an intermittent fasting program and an exercise program and all the things we can repeat over and over again. That is one of the most potent ways and most powerful ways to clean up senescent cells in the body.

It's only done 2 hours once. Does that work?

So interesting comment. So, you know, in my— this is a topic of conversation in so many blogs and webinars, et cetera, et cetera. My experience with senescence and, and literature is there is a, there's a cut point at about 15 hours that will improve metabolic health, may impact senescent cells to some degree. I personally use a 3-day fast on my patients, or I'll use fasting mimicking diets at 5 days where they still get some caloric or calories and they still have some food. But they do enter certain, certain states that will create that cycle or start that cycle of cell senescence, cell senescent death.

So that fasting is the lack of nutrients that kills them, or is it something else, or do we know?

I don't think we know. I, you know, I think senescent cells do not like a ketotic state, but in, in, in simple terms, when I speak to my patients that we're, we're basically starving out those senescent cells. They're, they, they succumb to that state of, it's not starvation, but that state of fasting where they can no longer survive.

Gotcha. And you said you do a 3-day fast.

So you actually not eating anything for 3 days, just water, or what, what do you do?

So, you know, my patients can do, they, they do, we do water fasts, 3-day water fasts. And you, you should do it under physician supervision in my opinion, because we can have some concern about electrolyte imbalances and if there's any sugar excuse me, blood sugar issues or glucose issues and diabetes, we have to certainly, we certainly need that medical management and intervention. But even healthy patients, they can become dehydrated. They don't drink enough water. They become hyponatremic. The longer you fast, obviously the longer we can run into those, those issues. We can develop those issues. But a 3-day fast is pretty safe. And in the science and the physiology in the human body shows that we start to really start that inflammation really starts to drop off after about 3 days. And the same thing in one of the most studied diets is the fasting mimic, 5-day fasting mimicking diet that has been shown to decrease inflammation dramatically on day 5, improve your cholesterol profile, metabolic health, and all the things that we see that improve when we wipe out a population of senescent cells. Then we can come back and we want to start up regulating mitochondria with NAD. If you want to do NAD, protocols. You wanna use the nicotinamide riboside. But whenever, you know, I, I, there is some benefit, I believe, to, to some of the oral supplementation that improves NAD in the body. As we age, we, our levels of NAD, which is a fundamental substance, we'll call it that, in mitochondria, that mitochondria need to create or produce ATP and produce and, and maintain cell health. Mitochondrial health. At age 60, we have about half the NAD in our bodies that we did when we were, we were 20. And one of the things that is overlooked in my opinion is there's an enzyme in the body as we age. Naturally, we increase this enzyme called the CD38 enzyme that just wipes out NAD. So I don't, and NAD is, you know, to start a protocol, whether it be sub-q or you're in, you hang IVs and you get in your practice. You want to control that CD38 enzyme because as fast as you give NAD, you're going to be destroying it because of the CD38 enzyme. So to control that CD38 enzyme, one of the natural flavonoids is quercetin. And fisetin works also. These are natural flavones that are found in, you know, our, our cruciferous vegetables, but in supplemental form, in supplement form, they have been very integral in decreasing that CD38 enzyme. That's when I'll start after I wipe out senescent cells, give them quercetin, give them the fisetin. They have it on board already. And that's when I'll give NAD. That's when you get your most benefit, your bang for your buck.

Yeah.

If you're just chewing it up and you're like doing these long IVs, it's like, okay, you're just fighting it.

Yeah.

And it's, it's interesting with the flavonoids. I don't know if you do a lot of genetics, but on my genetics, it's like every answer was flavonoids. It's like, okay, you've got a weakness in this, you know, this gene, flavonoid, flavonoid, flavonoid. I'm like, oh my gosh. Yeah.

But they're potent. And they have a lot of, you know, they, they have a lot of mechanisms of action in longevity. Certainly if we, we took all the science that we've been talking about for the last hour or so on, on senolytics, and we just look at the blue zones and how, you know, the most, the best longevity on this earth are driven by genetics, are driven by social networks, are driven by exercise, daily exercise, and nutrition, what we put in our, in our bodies every day.

So, uh, because I think there's a misnomer. Everyone thinks that genetics determine the person, right? And that's my knock on these genetic tests. And they, oh my gosh, I'm gonna get this. But you get identical twins and this person has this environment and, you know, has this type of lifestyle. This person, totally opposite, totally different. So what is it? About 80% is, you know, basically malleable to lifestyle, nutrition, you know, environmental factors where genes are okay, what the hand you're given, but it's what you do with it. And you can turn 'em on, you can turn 'em off, you get Yeah. And that's, I think, the key, right?

Those, those studies are wonderful. There's, I always refer to a Finnish study that looked at identical twins and, and different lifestyles and compared telomere length actually over, over a lifetime and saw and compared their lifestyle with stress and what they have endured, if you will, in terms of that allostatic load and what, how they've focused or not focused on healthy lifestyle. And you see shorter telomeres in the, the identical twin that did not take care of himself versus the, the identical twin that lived a very healthy lifestyle with exercise, et cetera, et cetera.

Yeah.

So your genes aren't your destiny. You know, people freak out, have an APOE4 gene. Oh my God, I'm gonna get Alzheimer's. But there's so many things that you can do now, you know, to, to, uh, basically, uh, prevent those things But with the mitochondria, have you done 5-Amino-1MQ?

Just curious.

It's hard to get and I don't know if you can get it nowadays, but I do not.

No, I, I, I, I, I don't use a lot of mitochondrial peptides.

Gotcha.

And do you like any of the brain peptides? Cerebral lysine, C-Max, C-Lanc, do you like those?

Well, the, one of the areas of interest I have in my practice is, is chronic inflammatory response syndrome, which is an innate immune system imbalance, we'll call it, where our innate immune system, which our first first responder, kind of like that ancient part of the immune system that's, you know, responds real quick to try and knock out a virus or a bacteria but never gets handed off to the rest of the immune system and shuts the holes.

I just love taking the easy patient. Those are tough patients. Yeah.

So getting to that, those senolytics or neurotropes, there's, there's a, uh, we've done a, we've created a small database and follow some patients with some neuro testing, cognitive testing, short-term memory, executive function, et cetera. And we use a, we get a baseline because of what I just described is a systemic inflammation, but we know that that same inflammation is also ongoing in the brain. They have neuroglial inflammation. So they start losing memory, they start losing their ability to function in their livelihood. So we're using a a neuropeptide called, which that is through the mechanism of hepatic growth factor. We have the ability to increase BDNF, a brain-derived neurotrophic factor. And everyone knows that that is basically miracle grow for neurons. And we know we can grow neurons. Now we can heal, heal the brain and decrease that inflammation. And anecdotally in this short and this small database, we've had some very significant success. And I believe it's anti-inflammatory, not just the BDNF that shuts down inflammation. And within 30 days, we see their short-term memory improve. It's part of a protocol that we use for our SIRS patients in addition to—

yeah, there's the hexa.

Yeah.

Yeah.

You know, great studies on Alzheimer's and it's analog of angiotensin IIa. Angiotensin is amazing. And ACTH, I mean, they make so many things. There's a number of trials with it coming out. And it's amazing. Like all these trials, I'm like, okay, when are they going to finish?

I mean, there's a lot of FDA trials and it's always a moving target. I believe that, you know, the FDA is not fond of cerebral lysin currently, but there's probably more studies on that as a—

Oh. Right.

In 35 countries, no side effects. And they made it a biologic, you know, so you can't do it as an injection anymore, but you can get it orally now, which actually EEG study shows it absorbs and one capsule is equal to about 2 cc.

Well, I think that's one of the promising new developments in peptides. Where we're moving off the sterile injectables and moving on to oral peptides, intranasal, transdermal peptides that become more and more effective and be, we can use them to a, you know, just to a greater degree in, in, in an integrative medicine practice.

Yeah. And, but they are, let me tell you, we're doing a lot of studies on bioavailability and you think, you know, just a tiny pep tripeptide is absorbable and it's not like they're just throwing everything sublingually and say, oh, How it's going to absorb, you don't know, you know, you have to look at the chemistry. We've hired a CRM that basically works with all the big pharma to develop these ways to make these things absorb. And when you look at, I mean, big pharma has been trying to do it for 20 years, right? I mean, everything's exponentially getting better and better at it, but it's a lot tougher than, you know, putting something in a wafer and putting it sublingual.

We have, you know, we have so many disease processes that have just a paucity of therapeutic success. So we look at TBI, for example, or post-concussion syndrome in the chronic state. And there's, I think there's probably some significant effective therapies in peptides. And one of the products that I work with right now that we're, we're looking at in treating TBI where we have hypoxia in the brain, et cetera. And the current therapies are just fall so short. And, and—

Oh, it, it— Go home and die.

There's, there's a lot of TBI researchers out there that are, you know, are, are all ears looking for just a therapy that has the, the promise to affect a, an improvement on chronic TBI or post-concussion. You know, the players coming out of, professional ball, military, et cetera, that you really need to improve those therapies.

Yeah.

And it's, I mean, not just the, you know, the football player, you know, I was at a stem cell conference and it was actually NIH did a study with SPECT scans. They could tell what position the football player played by where his brain damage was. And that's reversible.

Yeah.

And exosome stem cells, peptides, and I know you've been working with powdered oxygen.

There is a product that is under study right now. We're doing research at, in, in various settings that have been showing more and more efficacy to increase oxygen levels in tissue with a product that actually has benefit by oral ingestion. If you think about the possibilities of being able to drink oxygen and oxygenate tissue. It is effectively, and in various settings, acute and chronic settings, the potential is enormous. And the potential benefit after we get these studies underway in human studies, et cetera, any, everything from just, just sports performance to traumatic brain injury, to wound healing, et cetera.

And even diabetic foot ulcers. I mean, you know, you save limbs.

Yes. Yeah. You know, the product's been around 9 years, been studied for quite a while. It's ready for really getting to more and more human studies that are gonna have a huge impact on a lot of global humanity. The fact is, if you can oxygenate tissue in a world that has a shortage of options such as blood to be able to resuscitate an injured human, an injured body with powdered oxygen. It's a— it's a— when those studies are complete and, and they, they, they come to fruition where I think we're going to see a huge impact on those, on those issues where we're, we have those, those lack of blood supply in the world, for example. So That's what the profound ones that I, that I think of.

No, it's incredible. 'Cause if, you know, a couple things, one, you need blood supply there and then two, you need the lungs working. So you need, like, what about COPD patients? They can get off their oxygen and just drink it.

That's pretty amazing. Or altitude, being at altitude.

Hypoxia, sarcopenia. There's, I mean, it's like the impact long-term of hypoxia on the body is in COPD. COPD is a long-term—

Oh my God. My head's just spinning. I'm just thinking of all these different things. That's, that's very cool. Cause I was like, how the heck? Okay. Cause when you under tremendous pressure, you can make it a liquid, but how the heck do you make it a powder? Yeah. Well, leave that to the patent, but, uh, uh, that's, that's awesome. It's exciting. It's exciting.

It's very exciting. And if we think about applications in regenerative medicine and even longevity, if we have the ability to improve mitochondrial efficiency, I, that, you know, in the future, at some point in time, I see it even playing a role in, in a, as a senolytic or longevity to improve stem cell health. If we put an injured athlete in hyperbaric, as you know, we, we accelerate healing in an acute injury because of increased oxygen, oxygen Yeah.

And, and I think there's gonna be secondary pathway, like, okay, then it makes, you know, uh, nitric oxide, all the things it does. And I think it's gonna be like, yeah, theotrophic effect where you have more oxygen, you have healthier tissues, which stimulate the genes, you know. Um, where I think, cuz you get hypoxia, that's when all inflammation and bad stuff gets secreted, right? Right.

Interesting.

Yes.

Love to hear more, more about that. So, um, kind of in summary, what, what peptides do you, do you like?

You know, I certainly, a large part of my practice is, uh, aesthetics, regenerative aesthetics.

Uh, just, uh, mentioned I'm on the cutting edge of all these aesthetics and like new FDA approved, but they're from like Italy, these threads. I got some, I got But so I'm such a wimp and they're so painless. Just doing everyone is, I remember they were clamoring to get at you, like, treat me, treat me. I mean, you know, so, uh, he's an artist as well, really with, with face. And, uh, and I was amazed you can pick out like exactly what someone needs. Uh, it was very interesting. Like, I don't, I don't have that sense. But, and just always looking for new therapies as well.

Yeah, the, the applications of peptides in aesthetics actually have been around quite a long time. And we kind of repurpose them a little bit into hair restoration. You've been doing hair restoration for quite a few years, and we just dig into the science of the thymosins, for example, GHK, BPC, all of them collectively can repair the scalp as an anti-inflammatory, increasing subcutaneous fat with TB4, activating stem cells, improving their migration down to the hair follicle bulb, and moving a hair follicle into an antigen phase and starting hair growth again. So peptides are key to aesthetics, just starting in the scalp. The GHK has been around since 1970 and studied endlessly for as a topical cosmetic. And if you look at it as a potent, it can potentially be as a systemic peptide, not just for the things we mentioned before, but all those, all those mechanisms of GHK. Yeah. They, they also work on the stem cell, the, you know, the epithelial stem cell, the fibroblasts. So it makes sense to apply it topically for sure it works, but why not systemically if we have a you know, a decrease, you know, increasing, excuse me, a successive decrease in our GHK as we age.

Well, I, I, I'm in LA, so you could just have beautiful outside, but if you're inside, it's just deteriorated. They don't care. It's like, but I'm telling you, every time I see your hair, you have more and more hair.

I've never done a, not one step. This is my hair. Thank God I'm blessed. But yeah, the hair restoration's a lot of fun. The, the thymosins are integral in, in aesthetics in, in Regenerative Aesthetics practice. And the, not only as from a topical application, but we know that the ability to accelerate healing is a systemic phenomenon. And so we can use peptides. There is evidence that using systemic peptides, such as TB4 or even BPC or an oral BPC-157 are very effective in restoring or accelerating that healthy injury, that that we use in aesthetics to restore, restore skin and restore tissue to a more youthful state.

Nice.

Nice. So you, you, you take, you know, I, I, I love that you take the application. I think that's what's lacking so much in medicine is doctors learn this, but they don't take this and apply it over here.

Medications all the time.

And just everyone's in their, in their own little thing.

You got the gastroenterologist, you got the cardiologist, you got the neurologist.

And so patients go to all these different things and it's like, you know, come in with, you know, 22 diagnoses.

And I'm like, what do you think?

It's likely, more likely you have 22 separate diagnoses that aren't related, or there's something, one thing underlying, you know? But, uh, I, I love that. Any new therapies on the horizon? I love this powdered oxygen.

I think we're going to be looking at, you know, One of the areas in, in, in regenerative medicine, obviously, are biologics. And whether we use decellularized growth factors that used to be called exosomes, stem cells, there's always a moving target as to their application and how you can use them and when you can use them. But more and more of those products are becoming— being reinvented, if you will, or redesigned as topicals. So looking at Combining, for example, in wound care, as you mentioned before, in diabetics, but just in aesthetics, the post-procedure healing time is of extremely key to your success. And if we can combine a topical biologic with a, something like a powdered oxygen that supplies that wound, that healing with oxygen and those growth factors of all the things we need to accelerate the healing. Without dampening down that inflammation too much. Because we wanna call on those stem cells naturally to come in and heal. And I think we can find that balance and accelerate that healing and affect a great outcome. Taming those stem cells with the peptides in addition that tell that stem cell to go down that path of healthy healing, laying down the right collagen, collagen 3 and collagen 1, and not going off and creating scar tissue. So for me, that's a very exciting area of development going forward over the next 6 to 12 months.

Yeah. And I think with peptides are so synergistic with someone, but especially, you know, stem cells. And I've given a lot of talks on the synergy, even with the latest virus that's out. I don't want to say it because the, you know, with the COVID-K, whatever, pig Latin, but is that stem cells are reversing that, especially added with peptides and, you know, the stem cells will secrete peptides. Whether it needs to be antimicrobial peptides or actually thymosins. And then all the, like, the thymosins and BPC stimulate the stem cells, you know, so it's, they're really a nice combo. And I think you get, you know, 1 1 5 type thing when you use them together.

Wonderful synergies there that need to be explored and created into products then and utilized in in all these areas we just mentioned.

Yeah. I just worry the FDA is so, you know, they're really the enforcement arm of big pharma, but you know, if you have something that's exceedingly, totally safe and works, yeah, they're probably gonna try to take it away.

But anyways, this has been fascinating. I just love all the stuff you're doing and just your, your passion. And I've seen you work in person and lecture, and I appreciate your, just your your basically generosity and sharing everything that you do. And yeah, just, just seeing everyone huddled around you and, and there's no shortage of free models for you, but, uh, um, yeah, so I mean, you're just doing great work.

Keep it up.

And, uh, again, all the mastermind conferences you have, please keep 'em up. I just learn so much and just meet so many interesting people that are very cool, but a little nerdy side, you know, and so far we, well, we've been very successful.

Our next one's gonna be the end of February and then we're gonna have a, just the all things regenerative medicine coming up in May. So we all, we already have people signed up and we're excited for the, just put on the next conference.

Nice. And afterward you get some beautiful wines at Laconda. Do you have any more spots in your wine club?

We, yeah, there are some spots left. Just have to call the main number. My winemaker will set you up because the, we know, I mean, the wines speak for themselves. You've, you've been to the winemakers dinner at, at Loconda Conference. And I, I think that's certainly the big draws. Everybody says when they leave the conference, it's like, I learned a lot and I felt like it was on a mini vacation. Just got to relax.

A little touch of paradise. And you obviously use your, your power of geekiness to the wines too, and the scientific. And you know, I could just see you in there. Analyzing to get that, that ultimate wine and it comes through. But again, you're just doing some great things for people and, you know, and, and I think so many people that see you, like they probably don't realize, hey, I'm going to live 10 years longer and not in a nursing home. What's that worth? Right.

It's, and when, well, what is it now? 80% of the money is spent in the last year of someone's life, you know? They're just sitting there in a nursing home or ICU at the time, coming in and out, a liver transplant. And you know, you could prevent that.

We endeavor to, and yes, endeavor to make sure that our patients don't end up in those nursing homes prematurely.

Yeah. So you are a godsend to so many people. And I thank you. I'm proud to say your colleague and friend, and thank you for all, all that you do.

Thank you, Ken. Thank you for having me today. I, I thoroughly enjoyed it. Thank you.

Thank you. I know you're just so busy running around, so I do really appreciate it.

Thank you.

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