Welcome And Mission Of Age Gracefully

SPEAKER_00 0:14

Hi, I'm Veronica, and welcome to Age Gracefully. We're here to share with you tips for living a long, healthy, and fulfilling life.

SPEAKER_01 0:23

Hello, I'm Mark, and I'd like you to remember your genes do not define your destiny.

SPEAKER_00 0:28

And together we will explore the intersection of mindset, nutrition, and lifestyle.

SPEAKER_01 0:34

We'll cover cutting-edge diagnostics and therapeutics aimed at enhancing your longevity and health span.

Event Hosts, Partners, And Luna Study Invite

SPEAKER_00 0:40

We're sponsored by Grandevity.

SPEAKER_01 0:42

Check out the website GrandevityLife.com.

Founders’ Background And Longevity Center

Heart Health Month And Knowing Your Numbers

Mindset, Sleep, Exercise, And Daily Habits

SPEAKER_00 0:46

Let's get started. Hello, everybody. Thank you for coming to Longevity Lounge. This is our first event, and we're so glad that you made it here and took time out of your day to join us. I'm Veronica, and Mark is my business partner. We have a longevity center in Carlsbad, California. We do cardiovascular health along with lifestyle coaching. And here I am again, and well, longevity lounge, and this is our logo for our wellness center, and Grandevity is our longevity supplement. For those of you who don't know me, just a little bit of background about myself. I grew up in Tacoma, Washington, and then I moved to Los Angeles to do some modeling and acting. So I have some modeling, some acting. I'm a screen actor skilled actress 40 years ago. So now I'm working with Mark for lifestyle coaching, and my skills are mostly with people, working with people. I've traveled the world. I've been to Germany, Australia, England, the UK, United Kingdom, Italy, Japan, China, Brunei, Bahrain, Philippines, and also Canada, Mexico. So I have a lot of worldly experience, and so that's kind of my level of expertise. But luckily, you guys are here with some real experts that have a lot of knowledge about medical science and longevity. So you're in for a treat. So these beautiful offices are BioShift, and here with us tonight are Shannon and Ron Penna, and they are involved with legendary foods as well as the Research Foundation. And thank you very much for allowing us to have our presentation in your beautiful space. So give us a nice welcome and thank you to Ron and Shannon. And also tonight we have John, Dr. John Sledge. He's also the person we spoke about for our Luna study. Him and Mark Gordon are involved with Ron Panna as well for the Luna study. In addition to that, we have Bruce Cardenas with the Bioship team and Isabella. They've been a great great help for us to put this event on. So thank you for all of your help. So we talked about the Luna study and the invitation. This month is Heart Health. And you know, we're really excited that you're here to learn about, you know, information that with science and cutting-edge technology that can help you learn about keeping your heart clean. And the the most important thing is to know your numbers. And what I mean by that is to get an advanced lipid panel so that you can find out if you have any issues with your heart. And like I said, I'm just an expert traveler, but John or Ron or Dr. Gordon, they're going to go into deep detail about the Luna study. And if any of you are interested in joining the Luna Study, we still have a few spots available for that. So speak to myself or Dr. John Sledge after the event, and we'd be happy to have you join us. So longevity tips. So for me, basically, um, there's a quote that I love, and it's like um just um life is a gift, it's a present. So for me, just be present in your life, like live in the now and enjoy each day. Try not to hold grudges or think about what you shoulda, could have done. Just be in the now. And like right now, you're here learning about heart health. So kudos for all of you for attending our event tonight. And I'm not an expert in lifestyle skills or anything like that, but this is just a quick reminder of what you can do to keep yourself healthy and happy. So I'm gonna just run through this really quickly because most of you are probably smarter than me about all of this stuff, and hopefully, you're doing all of these things on a daily mindset. That's so important. Just you know, just wake up every day and plan your day and think about you know what you can be grateful for each day. Believe in yourself, stay positive. Consistency is the key. So for myself, I'm gonna be 63 next month, March 31st, and that's when we're launching our grandivity. But I hope all of you will just stay consistent. And if you get off track with exercise, don't beat yourself up about it. Just, you know, give yourself a kick in the ass and get back on it. Here's our little puppies. That's Harley and Jackson. Jackson's pretty old, but he's he's doing really well. So they're a perfect example of sleep. So if you have dogs, listen to them, watch them. They'll they'll show you how to get your sleep. Sleep is so important. Try and aim for seven to eight hours every evening if you can. Exercise 150 minutes a week, strength training two to three times a week. And strength, strength training, combat sarcopenia, which is loss of muscle mass as you get older. So try and incorporate strength training if you can. No excuses. Like I said, get back on track if you get behind or you have a bad day. That's okay. Water is so important. Drink one half of your body weight in ounces daily. And Dr. Gordon recommends a Mediterranean diet, but do whatever works best for yourself, but try to eat natural foods, avoid processed foods, incorporate protein to build muscle, and eat legendary snacks. Those are a great choice. Supplements, we take a lot of supplements, and like for myself, we just get a tray and we dipby them out every Sunday. I think Mark probably takes about 30, I take maybe 25. So pick, you know, pick and choose what you like. We recommend vitamin D3 and a multivitamin and also targeted personalized supplements. Like once you have your advanced lipid panel, it's going to show you if you're missing something, and there's other testing you can do as well. So I believe love heals, and it's good to have a relationship or a companion or a dog or something. So, because you know they have like emotional support dogs and they show that there's really good benefits of having a companion. Happy Valentine's on Saturday. So if you haven't gotten a Valentine, find one for this weekend. And these are the five longevity pathways that we believe in that help you age gracefully and create a longer health span: Nerf2, mTOR, AMPK, telomeres, and sertuans. Okay. And so this next slide is I know some of you don't want to go to the doctor, maybe you have the white coat syndrome. So Mark and I decided to put a slide together so you guys won't be scared to go to the doctor. So, Flash Gordon, your longevity cardiologist. So please give a warm welcome for Dr. Mark Gordon.

SPEAKER_01 9:20

Thanks, Veronica. Thank you. You're welcome. It's great to be here. This is such a wonderful facility, and we're excited to be a part of the Luna study. So I'm gonna let Dr. Sledge go into much more detail about the Luna study. But for me as a cardiologist, and for Veronica and I in our wellness center in Carlsbad, the predominant thing that we do is educate people on preventive cardiovascular medicine. So people come to us, maybe they have a family history of heart disease, they want to know what they can do to reduce their risk in the future. And so when we learned about the Luna study, we were very excited, and uh it's it's just right up our alley for what we do at our longevity center. So John is going to talk more about this, but this is the advanced um cardiovascular study that we recommend for most patients. It's called Clearly, it's a coronary CT angiogram in which we do an artificial intelligence overlay algorithm that defines the plaque force much more easily. And this particular person, this is the artery stretched out. So the arteries obviously are curved in your body, but we stretch them out straight because it's just easier to look at them that way. And it color codes it very nicely. The yellow here is soft plaque, and the blue is calcified plaque. So this is a cross-sectional area through this line right here. And you can see this person has a fairly long soft plaque. This is in the right coronary artery, and then right in the middle of it is a piece of calcium. This can also differentiate stable versus unstable plaque. Uh, this particular patient doesn't have any unstable plaque, but this is the uh imaging study that is currently being used in the Luna trial. So, with that, let me turn things over to Dr. John Sledge, who will fill us in more about the Luna study and more about BioShift.

Nutrition, Hydration, And Supplement Strategy

SPEAKER_03 11:20

All right, good evening. Thank you guys for coming. Um, in the next five to 10 minutes, which I have, I'm gonna do three things. First is I'm gonna make a bold statement. Second is I'm gonna change your mind about a topic. And the third one is I want you to see a problem in a slightly different light. So, first, the bold statement. I think the medical community has no excuse if anyone dies of a heart attack or cardiovascular disease five years from now. There's not much we can do about the people who are reaching the end game now, but in five years, there's no reason anyone should die of a heart attack in particular. The oh, they dropped dead from a heart attack and they didn't know they have heart disease, that story should be over. But as you think about that story, what comes to your mind of the person who did drop dead from the sudden heart attack? That's one of the things I want to change. So, who is BioShift? We're a philanthropic research organization uh funded by the PENAS through Legendary. And our goal, our mandate is to find modalities to treat people who have disease that's often overlooked by the pharmaceutical or standard research groups because those treatments don't have a path towards patentability and therefore don't have a path towards profitability. So, so to avoid white coat syndrome, I'm wearing my uh Ray Orbison all black here. Um, but but the PEN has have had a history in health over the last 10 years from their founding of Quest 15 years ago all the way through BioShift and the Bioshift Research Foundation, which is the latest incarnation of their interest in health and particularly metabolic health. So we exist to try to fill this missing piece of research that can be done to actually try to decrease the burden of disease upon society. And there's lots of things that we know make people better. You know, we just heard about some supplements. Those don't go through an FDA pathway. So it's kind of hard to figure out do they work or do they not work because most people aren't willing to spend the millions of dollars it takes to run a really well-done study to find out if something works, if what you're testing is already on the market and you can buy it for a dollar, you'll never make that money back. So Bioshift sort of fills that gap in studying investigational therapies that really have potential benefit, but don't have a financial reward, but they can really make a large impact in terms of public health. So we try to optimize discovery of what these potential treatments are and then further this sort of bench to bedside philosophy. How fast can we take something that we think works, determine whether it does work or not, and then move that out into the community to help those patients who have those diseases. So, in terms of the Bioshift Research Projects, we cover a large portfolio, but our two major programs are cancer and cardiovascular disease, since those are the two biggest killers. We also have programs in glaucoma, diabetic retinopathy, peripheral neuropathy. But what I'm gonna focus on tonight is I'm going to focus on the Luna program, which is our cardiovascular study that uh the Gordons are helping us out with. So, what we're trying to do is shift people from cardiology 101 to cardiology 201. And I'm gonna explain that literally in three minutes and you'll understand it. Cardiologists are still struggling with this, um, but it I think you'll understand as we touch on this. So, cardiology 101, you went in to see the doctor, they did a whole bunch of blood panels, and based upon your stress tests and some imaging modalities, they place you in a risk category. Oh, you're high risk, your medium risk, and your low risk. And those risk categories are really good at predicting how people in that group will do, but they're really bad at predicting how the individual do. Because remember, we're looking at group statistics. In cardiology 201, we're using that image modality that Dr. Gordon just discussed with AI overlays, so we can actually do disease assessments. So this is a CT scan that they do after an injection. It takes at least two minutes. Sometimes it takes up to seven minutes, so it's very fast. They do it gated with your heart, so we get these wonderful images. We then send those off to a diagnostic system, and it takes those tortuous arteries you just saw, straightens them out, and gives us nice clear pictures of what it looks like. What's unique about this is that this data set we can then use to examine each artery in that individual, and we get assessment of that individual's disease burden. So we're no longer measuring what your risk is of having disease. We're now actually measuring what your actual risk, your actual disease is. So if what we're trying to avoid is the cardiovascular disease event, that's the event. Nobody dies of high lipids. Nobody dies of plaque. You die of the heart attack, you die of the stroke. So if you're talking about disease risk groups, you're way back here somewhere. It's not a good predictor. If we can measure disease burden, we're getting much better at predicting who has disease, who doesn't, and therefore who's going to have an event and who is not. So I'll go through this super quick because I know Dr. Gordon just touched on it. But what we're able to do is we're able to take those images, the twisty vessels you just saw, generate these nice images, and then determine where the plaque is, what type of plaque it is, and how much that person is at risk from that plaque. And some of the newer systems not only look at the plaque, but they look at the periovascular inflammation, which may or may not be a better predictor of who's going to have an event or not. So this is one artery, and you can see it in 180 degrees, showing where all the plaque is and what that type of plaque is. They then give us this composite image, which shows us exactly what type of plaque, where that plaque is, and what type of plaque it is. So instead of trying to guess what your disease is, we now can actually measure your disease to the cubic millimeter of what kind of disease you have and where it is. So it's a much more accurate depiction of that individual's disease. So we can make much better guesses and suggestions as to what the appropriate treatment ought to be. So here's what one of those summary forms look like. When the doctor's reviewing this report with you, this is what they're going to be looking at.

Introducing Advanced Imaging: Clearly CCTA

SPEAKER_02 17:00

And it's going to show you what that person's total disease is, break it up into different types of plaque they have, the different arteries where that plaque is, what their level of stenosis are, where in the vascular tree that stenosis is, and what degree the stenosis is.

SPEAKER_03 17:18

So this is so much more information than what we're used to looking at, and this is much more predictive for that individual. So the overlay read allows us to do one other thing that we really haven't been able to do previously, which means we're now actually to look at treatment effect. So what we used to do is give you a medicine and it would lower your cholesterol a little bit, say. And we would say, we feel so much better because your cholesterol is lower. We still have no idea what's happening in your disease. Your disease may be progressing at the same rate, it may be going backwards. We don't know because all we're measuring is a risk factor. Now we can actually measure disease. And if you look at these two images on the top, these are two and a half years apart, and you can see where they're measuring plaque in this first one.

SPEAKER_02 18:02

Two and a half years of treatment, and you can see resolution of a plaque release a portion of it. And you see the same thing here: much larger black volume, much smaller black volume.

SPEAKER_03 18:12

So now we can actually give a patient a treatment and determine for that patient is that treatment effective or not. We're no longer guessing. So we're now looking at a sense of reality. So instead of guessing what's happening to somebody's disease state, we can measure it. And we can measure what impact our different treatment interventions have. So before, if we treated somebody and their cholesterol went down, we'd say we're doing great, but we didn't know what was happening to their disease. Now we can measure the disease. If their disease is going down, we're moving in the right direction. If it's not going down, then we're not moving in the right direction. So there's no longer this sort of black box mystery of cardiovascular disease, because we can actually measure what that is. Now, what's kind of unique about cardiovascular disease is it's years between the initiation of plaque and clinically relevant disease. And then it's also years from clinically relevant disease to the plaque. So this gives us a long timeline in which to intervene in this disease, which is why I'm saying that five years from now, no one should die of undiagnosed cardiovascular disease. It just shouldn't happen. So we're now actually measuring the disease burden and the disease response to treatment. So we can personalize the treatment modalities significantly better. This also opened a different avenue for us. And it also scared us. And why it scared us is if you look at this number here, this is a calcified plaque.

Bioshift’s Goal And Why Luna Exists

SPEAKER_02 19:32

So in this patient's 233 number, what the CAC score measures is that calcified plaque. Now I showed you one earlier that has 290, 296. So these patients would have had the same CAC score.

From Risk Groups To Individual Disease

SPEAKER_03 19:48

So some cardiologists might have given this patient the same sort of risk factor. You've got the same sort of amount of disease, same risk factors. But if you look at this person's stenosis profile, who has a high CAC score, which is higher than the next one I'm about to show you, it's clearly much better than this person's. And they're going to end up, this person has a lower CAC score. So until we have this type of modality, we're really guessing at what somebody's disease burden is and truly guessing at what their risk factors are for a cardiovascular event. Knowing this information, however, creates a conundrum. We now have to reevaluate our treatment. All of our treatment previously, or at least most of it, has focused on risk factors. How do we mitigate risk factors? Now people are starting to look at how do we mitigate disease? So as soon as we came up with this technology, people rushed to study the present medicines we have. And a lot of them decrease the rate at which plaque is created. But so far, nobody's come up with a consistent medication that decreases plaque. So we and others are now looking at different modalities that don't necessarily address the risk factors, but may potentially address the disease. Because where we were before measuring the groups of risk, we're now measuring an individual's risk factor, assessing treatment modalities based upon that individual's response. So now we're directly able to measure an individual's response to a specific treatment and decide whether to continue or not. We're also able to look at different treatment modalities and find out what's your most successful in decreasing plaque in that individual patient. So it's changed sort of our treatment objectives and how we look at this. Yes, we need to mitigate the risk factors, but there's a great search on now to how we can find things that will decrease the actual plaque because it's the plaque that creates your risk. So this major shift from decreasing risk factors towards decreasing disease burden since we can now measure it. There's a whole list of things that people are starting to look at. And one of those I think Dr. Gordon is going to touch on in much greater detail in a moment. So in the Luna study, we are now cycling through some of these factors that we think will actually decrease disease burden, therefore decrease individuals' risk. The present study we're running is looking at some orally active. Enzymes. So these are enzymes that you can eat. They make it so they survive through your stomach, your body absorbs a portion of them, and they're functional within your bloodstream. So these are what are called fibrinolytic enzymes, which means they digest fibrin, which is one of the things that holds that plaque in place. If we remove some of that fibrin, other groups have shown that that plaque is now exposed to your body's normal reparative processes and that plaque decreases. And we have some early preliminary results in our study that show that same thing. Now, this study is still in enrollment, so I don't know what's going to happen in the end. We're going to have to wait and see. But it's a 12-month study with enrollment with CCTAs, clearly, blood work, the diagnostic modalities Dr. Gordon spoke about, and then one year follow-up. The other thing we're doing within the Luna study is we're doing a subgroup analysis. And the reason we're doing this is because we have no really good metrics to determine in women who's going to get cardiovascular disease and who isn't. More women die of cardiovascular disease than men. Change number one for you. More women die of sudden death from cardiovascular disease than men. Number two, you weren't thinking about. Women over the age of 65 have a one in three chance of dying of cardiovascular disease significantly greater than the risks of dying of breast cancer. And they shouldn't, because as we've just shown, we have modalities to measure it and we have good medicines in order to treat it. So this is the initial roadmap for Luna. We've screened 200, over 200 people with ultrasounds as they run through this diagnostic inclusion-exclusion criteria. This is a little bit of an older slide. We now have slightly over 40 people that are enrolled in the Luna study, and we're starting to get some of those early markers, so we know how those patients are doing. So the Luna project has two things. One, can we decrease plaque? Two is can we determine what the risk factors are for cardiovascular disease in women, particularly those that are post-menopausal, particularly those that miss the decade of hormone replacement due to the women's study? Any questions about Bioshift or the Luna study? Thank you. So we're using the same criteria that we've been using historically, all the blood work and all the measurements. So we still put people in those risk factor groups. But what we also do is we get the CCTA and the clearly. So we can say, okay, based upon your previous blood work, I would have put you in the moderate risk group, but based upon your CCTA and your AI overlay, you've got significant platforms. We need to be way more aggressive. So two things have really changed. And I would say, and and Dr. Board is really the expert here, not me, but the big change I've seen in the last couple of years is one is we now can actually measure the individual's risk factor. So I know what your risk factor is, not what member of group you're in's risk factor is, but yours individually. The second is we used to use CAC scores as a measure of the progression of the disease. The CAC score is not particularly good at that, and the calcified plaque is not clinically relevant. It's biologically inactive. Much more interesting and predictive are the non-calcified plaques, which we can't see well on other modalities, but we see extremely well with the new imaging modality. So it's now gone from thinking of you as a member of a group to thinking of you as an individual and treating you as an individual. And then measuring your response to the treatment we induce with you by once again measuring your specific risk factors through the CCTA, clearly.

unknown 25:30

Okay.

SPEAKER_03 25:33

Yeah. I will now pass it off to Dr. Gordon for the main event.

Measuring Plaque Types And Inflammation

Tracking Treatment Effect Over Time

Rethinking CAC And Personalized Care

Women’s Cardiovascular Risk Spotlight

Precision Medicine Versus Population Rules

Nrf2 101: Oxidative Stress And Aging

SPEAKER_01 25:40

Thanks, John. That was a great uh overview of the Luna study. So as John mentioned, and Joseph, you were asking about the difference between treating a group versus treating an individual. Um, in cardiology, change moves very slowly. It's like turning around a cruise ship as opposed to turning around a Mini Cooper, you know? And so it's hard for a lot of big cardiology institutions to get their arms around something that is effective for an individual, but not necessarily for an entire group. But you'll see the trend in medicine now is to move more towards personalized precision medicine, where we're focusing on the individual rather than a group population. And the analogy that I use for that is if you give statin drugs to a million people in the United States, you're going to reduce the risk of cardiac events. But you're going to be giving those statin drugs to a lot of people who really don't need them. If they have an elevated LDL cholesterol, but the LDL is predominantly the large fluffy type, which doesn't lead to plaque formation, that particular individual isn't going to benefit from the risk of lowering their cardiovascular risk, but they're going to be exposed to all the side effects. So unfortunately, historically, a lot of cardiovascular medicine has focused on how do we treat a population rather than how to treat an individual. But that's starting to change. So what I'm going to talk about here for the next 10 minutes or so is heart health, longevity, and nerf two, and how that plays a role in it. So let's talk a little bit about what NERF2 is. Nerf 2 is a protein, a transcriptional protein or a messenger protein that's in every cell of your body. And its goal or its job when it gets activated is to turn on genes that code for antioxidant enzymes, things like superoxide dismutase, catalase and glutathione, and so forth. In addition to that, it leads to the upregulation of over 2,000 genes that are associated with longevity. And in particular, with regard to reducing oxidative stress, it increases the production of SOD or superoxide dismutase, glutathione and catalase. As I mentioned, it upregulates longevity genes. But as we get older, the NERF 2 activity in our bodies begins to decline. So, what NERF2's main goal is, or main objective, is to reduce oxidative stress. So, what is oxidative stress? Every day of our lives, our bodies make energy in the form of ATP. That process takes place in the mitochondria. But there are waste products that occur as a result of that process of forming the ATP. And those waste products are called reactive oxygen species. And the reactive oxygen species can damage any part of the cell that they bump into, and that is the oxidative stress. And as we get older and we lose the ability to fight the oxidative stress because our nerve too goes down, we start to accumulate more junk in our cells. Our cells don't work as efficiently and they become damaged. ROS can cause damage to the cell wall, which can lead to problems. It can cause damage to the mitochondria. And most importantly, it can cause damage to the DNA. And if it causes damage to the DNA, that can lead to mutations, which can lead to cancer. There's a quiz at the end, guys. Okay, so for you biochemists, here's how it works. Nerf, if you take a nerf 2 activating compound, we'll say sulforophane in broccoli for this example, the nerf 2 activator binds to a holding protein that's in the inside of the cell wall held to an actin strand. And once the nerf 2 activator connects to the nerf to the keep 1 protein, the nerf 2 itself gets released from keep 1 and then it migrates from the cytoplasm into the nucleus of the cell. It attaches to a very specific segment of the DNA called the antioxidant response element, and then downstream, all the genes that are downstream from that area get affected by the nerve 2. Essentially, the good things get upregulated, the bad things get downregulated. So what are some things that can increase nerve 2 activity? Phenolic antioxidants, gamma and delta tacopherals, the vitamin E's, omega-3s, carotenoids, things like carrots and so forth, isocyanates from cruciferous vegetables like broccoli, sulfur-containing compounds and vegetables like onions and terpenoids. But the problem with these is they don't do it at physiologic concentrations, meaning that they will increase the nerve 2 a little bit, but not enough that it's really going to do much good. So these are some other factors that can enhance nerve 2 production. Moderate exercise, over-exercise actually reduces nerve 2 and increases oxidative stress. Calorie restriction, which nobody is a fond person is fond of. Mediterranean diet can help. The Okinawan diet can help, and the Paleo diet. All of those can increase Nerf 2. But again, not to a significant degree. So Nerf 2 plays a role in all of the 12 hallmarks of aging. If you go around this circle, some of you know what these are. I'm not going to go into them for the sake of time. But NERF2 has a positive impact on each of those. Our knowledge about Nerf2 has expanded dramatically in the last 20 years. This is what we knew about Nerf2 in 2007. It's pretty much the slide that I showed you before. Something causes Keep 1 to release NERF 2, it goes into the nucleus, turns on the genes. Back here in 2007, we knew that if there was a way to get NERF2 to be released, you could increase the production of these antioxidant enzymes and the survival genes. But now we know if you look at all of these numbered areas, one, two, three, four, et cetera, all the way around, there's over 28 places in the NRF2 pathway that can be impacted by things that can cause upregulation of that pathway. So if you just act on one, if you take one compound that activates NERF2, say at this point, you've got all these other pathways that if you're not affecting them, you're going to get a tiny little increase in NERF2. So what we've learned is that activating multiple areas simultaneously can greatly enhance the NERF2 activity. So these are two Nerf 2 activating compounds that I don't have any association with. This particular compound was from uh 20, 2004, I believe it came out. And this one came out, I believe, in 2020. But there are five individual ingredients in this combination. And if you look at each one of the individual ingredients, they don't do very much to activate nerve 2. But when you put the five together, there was a huge synergistic effect that greatly enhanced the nerve 2 activation. Likewise, this newer product had rosemary, ginger, and luteolin in it. The rosemary did a fair amount, but when you put the three together, it was more than the additive effect. So there really is enhancement of the nerve 2 activation when you activate at multiple points in this pathway. So what are some of the things from a cardiovascular standpoint that NERF 2 can do? Well, one of the things it can do is it can decrease cholesterol production. And this was a very elegant study that was done, I believe this was in 2018 or 2019. And they showed that this combination nerf 2 activator that included rosemary, ginger, and luteolin significantly reduced cholesterol synthesis in liver cells. So, as I mentioned, activating nerf 2 at one point in the pathway doesn't do very much. You have to activate it in multiple at multiple spots. But the individual ingredients that you use are important as well. So not all nerf 2 activators are the same. Some NERF2 activators have this activity called electrophilic toxicity. Let me explain to you what that means. When you're activating NERF 2, one of the ways to activate NERF 2, the analogy that I like to use is Nerf 2 gets activated due to some kind of stimulus that might be negative to your body, some insult to your body. So you can like breathe on a thermostat to make the air conditioning come on, or you can start a fire in your fireplace. Okay. Some of these nerf two activating compounds actually are more like starting a fire in your fireplace and causing the whole house to heat up rather than just giving a puff of air on the thermostat. And so the more gentle way doesn't deplete the antioxidant enzymes like the more aggressive approach starting a fire. So carnosic acid, it's been found, which is one of the extracts from rosemary, is a very potent nerve 2 activator, and it doesn't have this electrophilic toxicity problem. And the other nice thing about carnosic acid is it crosses the blood-brain barrier, so you can get the beneficial effects of nerve 2 activation in the brain. These are three different nerf 2 activating compounds. Dimethylfumarate is now a drug that's used to treat multiple sclerosis. Its mechanism of action is nerf 2. This is an over-the-counter supplement that came out in 2004. It's a nerf 2 activator. And this is a carnosic acid-based nerve to activator, one that comes from rosemary. One of the interesting things about most nerve 2 activators is there's a very sharp peak and then a drop-off in activity when you reach the level of toxicity. So your therapeutic dosing window is very small. But with the carnosic acid-based nerve to activator, there is more of a plateau, and you don't get that toxicity because it doesn't have the electrophilic toxicity that I talked about. The other thing that's important to realize about nerve to activators is not all nerf to activators activate SIR2 in genes. Most nerve to activators are advertised as activating SIRTUINES, but this is a product that won from 2004. And if you look at this baseline here, if you're above the baseline, it's activating these SIR2 engines. If you're below the baseline, it's not. So overall, this product really doesn't activate SIR2 engines at all. But this carnosic acid-based NERF 2 activator has a much more significant impact on the SIR2 engines. So you can take your Nerf 2 activator from 2004 and have the best phone that was available back then, the Motorola flip phone. I had one of those. Or you can take a carnosic acid-based Nerf 2 activator and have an iPhone 17 Pro Max, which is what I currently have. So state of the art in 2004, state of the art in 2026, state of the art in 2004, state of the art in 2026. So technology changes not just with phones, but with supplements, and as you heard from John, the way we approach cardiovascular disease. So NERF 2 has been shown to have beneficial effects on glucose homeostasis, cardiomyopathy. Interesting, I was involved with a study. One of the drugs that's given for breast cancer can have a toxic effect on the heart muscle. It can weaken it. And I was approached by an oncologist saying, hey, we want to do some studies on agents that might reduce this cardiomyopathy from this drug in these breast cancer patients. So they did a study on NERF 2, and they found that nerve 2 activators can actually prevent the cardiomyopathy that develops from taking that chemotherapy drug for breast cancer. Nerf 2 activation can have a positive effect on atherosclerosis, not only by reducing cholesterol production, but it seems that there are some studies that suggest that it may have an effect on actually reducing atherosclerosis in arteries. So it may be something else to consider in the lunatrial down the road. It improves vascular integrity, particularly the endothelium. It helps with cellular metabolism as far as improving ATP production. It's been beneficial in helping obesity, wound healing, and nephropathy. So this is from a landmark article about NERF 2 activation. But for today's event, I want to concentrate on the things that NERF2 has been reported to be helpful in the prevention and treatment of in either animal or human models. In cardiovascular disease, atherosclerosis, ischemic heart disease, vascular endothelial dysfunction, and heart failure, those things that I mentioned before. But as you can see from this list, there's a lot of other things that NERF 2 can help with: Alzheimer's, Parkinson's, cancer prevention, certain types of kidney disease, type 2 diabetes, sepsis. There were some big studies on COVID that showed that NERF 2 activation can calm the cytokine storm that was causing people to get terribly sick from COVID. It's been beneficial in HIV and AIDS and multiple sclerosis. There is a foundation, Michael J. Fox Foundation, that is actually studying nerve 2 activators now for the treatment of MS. And I mentioned dimethylfumarate became the largest prescribed drug for multiple sclerosis, and it too is a nerve 2 activator. So for cardiovascular disease, nerve 2 upregulation protects the arterial endothelial cells from inflammation. It can protect against ischemia by regulation of detoxification enzymes, glutathione in particular. It can help improve mitochondrial biogenesis or production of mitochondria in heart tissue, which is difficult because cardiac muscle is the only type of muscle that does not automatically regenerate mitochondria when they get lost. It's critical for protecting the cardiovascular system against oxidative stress. It can prevent right heart failure due to pulmonary hypertension. There was a very elegant study that showed that it could dramatically reduce pulmonary artery pressures in people with pulmonary hypertension, which led to a drug company now producing a drug, the name of it escapes me, to treat pulmonary hypertension that is a nerve 2 activator. And there was another very elegant study that showed that you could prevent when somebody has coronary artery bypass graft surgery, when they get the vein taken out of their leg and they use it as a bypass graft, those get plugged up over time. Typically, I tell patients eight to 10 years is the life expectancy of a vein graft, but they don't get plugged up by the same process that led to the atherosclerosis in the first place. It's more due to inflammation in the wall of the artery, wall of the vein, because veins were never designed to carry the oxygenated blood of an artery or the pressure of an artery. So that constant increased oxygen and high blood pressure that the vein's not used to leads to inflammation in the wall of the vein and it causes this crud to accumulate in a vein graft. And if you've ever been in surgery and they take a vein graft out that's full of that crud, it squeezes out of the vein like a tube of toothpaste. It's just gross. But nerf two activation has been shown to prevent that. It's called entimal hyperplasia. So could it potentially make vein grafts last longer? Yeah, it could. We haven't done those studies yet. Another landmark article about NERF 2, the guardian of health span and gatekeeper of species longevity. This is a statement from there. There is mounting evidence across evolutionarily distinct species that nerf two-dependent components are associated with both longevity and extension of health span. And another landmark article, Nerf 2 may well become the most extraordinary therapeutic and most extraordinary preventive breakthrough in the history of medicine. So, what can we conclude? So NERF2 significantly reduces oxidative stress, which is the root cause of hundreds of different health conditions associated with aging. It upregulates over 2,000 genes, most of which are beneficial anti-aging longevity genes. It positively affects the 12 hallmarks of aging. It's been shown to be beneficial in cardiovascular health, neurodegenerative conditions, metabolism, obesity, kidney cancer prevention, MS, you name it, it seems to help. There's no other single pathway that has a more profound effect on aging than Nerf 2. Certain dyes can activate NERF 2, certain phytochemicals can activate NERF 2, but the combination of finding the right ones and putting them together really seems to be what enhances the NERF 2 the most. So the synergistic combinations are really the way to go. Helps much more than just eating a bowl full of broccoli every day. So not all nerve 2 activators activate the same longevity genes. I showed you the study about the sertuans. And the electrophilic toxicity from some nerve 2 activators may actually deplete the exact antioxidant enzymes you're trying to increase, like glutathione, because they chew them up, because they're starting the fire in the living room instead of gently blowing on the thermostat, so to speak. So the carnosic acid-based nerve 2 activators seem to be the best way to go. They don't have any electrophilic toxicity. They have a therapeutic plateau instead of a therapeutic peak, so you don't have to worry about the effect dropping off over a certain level. They reduce cholesterol production. They can dramatically reduce cytokine storm related to viral illnesses like COVID, as I mentioned. Um they activate SERTUAN genes, and they are really the new wave in Nerf2 activation, the carnosic acid-based ones. So what I would just like to say in conclusion is I've been involved with the nerf 2 pathway for now 15 years. I've seen nerf 2 activators come and go, I've seen good ones, I've seen bad ones. But really, it's the carnosic acid-based nerf 2 activators that seem to be the ones that are going to give you the most benefit today. Um there are nerf 2 activating drugs, but honestly, when they've compared the nerve 2 activating drugs like dimethylfumarate to some of the more natural plant-based nerve 2 activators, the plant-based nerve 2 activators had more of an effect on activating nerf 2. So I'd encourage all of you to activate your nerf 2 and live as long as you can. So thank you very much.

SPEAKER_00 44:56

Well, that and that concludes our event. So we're gonna pick these numbers out and see who picked the almonds and they'll get their bottle of Grandevity. But you're all winners tonight, so are you ready to optimize your health and embrace healthy aging? Meet Longevity Synergy from Grandevity, a daily supplement designed to tap into key biochemical pathways for vitality.

SPEAKER_01 45:26

With a powerful blend of natural ingredients including Gota-Cola, green tea, resveratrol, and others, Longevity Synergy activates Nerf 2 to bolster your antioxidant defenses, regulates mTOR for balanced metabolism, and kicks your AMPK into gear for effective energy management. Plus, it enhances sertuans for cellular repair and helps preserve vital telomeres. Each ingredient works synergistically to target the 12 hallmarks of aging, promoting cellular renewal and overall wellness.

SPEAKER_00 45:57

Join the movement toward a healthier future. Visit GrandevityLife.com and take the first step toward unlocking your vitality. Don't wait. Order now and thrive. Thanks so much for joining us on this episode of Age Gracefully. We hope you found valuable insights and inspiration to help you embrace the journey of aging with grace and vitality.

SPEAKER_01 46:31

Remember to subscribe to our podcast and share it with your family and friends. And don't miss our monthly giveaway, a complimentary bottle of Grandevity. To be eligible for the drawing, sign up for our newsletter at GrandevityLife.com forward slash contacts.

SPEAKER_00 46:47

Aging is not something to fear, but a beautiful journey to cherish. You have the power to shape your health and well-being. Until the next time, take care of your body and soul and keep striving for your best life. This is Veronica Gordon, signing off from Age Gracefully. This information is not intended as a substitute for professional medical advice, diagnosis, or treatment. Always consult with a qualified healthcare professional before making any changes to your health regimen or starting any new treatment. Do not disregard or delay seeking medical advice based on something you hear in this podcast. Your health is personal, and the information provided here may not be suitable for everyone.