Longevity for Plastic Surgeons

Late winter, he presented a paper on therapeutic management of oxidative stress at the National University of Singapore, which is what kind of came across my desk. And I thought, well, that seems like very interesting stuff and something that a lot of people would be interested in. So I asked Corey if you would come and let us know what that's all about and let him take it from here. So thanks very much for coming, agreeing to come early in the morning, and we're happy to have you here. Corey, thank you so much. Thank you so much. So thank you so much, Mitch. It's a real honor and a pleasure to present to my own faculty following the theme that Dr. Mankilow spoke about just a few weeks ago of standing on the shoulders of giants. I certainly have a lot of people to thank, including Drs. Mankilow and Brown and a slew of others who have supported my professional and personal development. I also want to take a moment to acknowledge my father who was a vascular surgeon at Mount Sinai Hospital. Later in his career he had health issues that ultimately resulted in him having to retire. Over the following seven years, his health declined and he eventually died at the age of 72. Knowing what I know now, I look back at that and I recognize that it was a predictable event and things could have potentially been handled differently, which is certainly part of my interest in the longevity space. I started with an undergrad in physiology, which is how humans function. My surgeon scientist program was in biomed engineering and stem cell science when I entered practice. I shortly thereafter started doing some clinical research on reactive oxygen species which is the nidus of this presentation. In 2019 I read a book called Lifespan by Dr. David Sinclair who is a geneticist at Harvard. Since then I started getting involved in associations and societies in longevity medicine to further my personal interest. In 2023 I co founded and I'm Chief Medical Officer for Healthspan Digital, which is a B2B longevity as a service company. In the same year I was able to attend the first annual roundtable on Longevity clinics at the Buck's Institute of Research on Aging, which is outside of San Francisco. In 2024, we were successfully able to launch longevity clinics in Dubai, Athens and shortly coming to Toronto. Also earlier this year I was able to speak at the first annual conference at the National University of Singapore at the center for Healthy Longevity. Also the presentation that was denied us for this talk this morning. This is a picture of my wife Stephanie and I. We occasionally work with a photo and I put it up both because I think it's really cool And I love being involved in stuff like this. But also as a reminder that I pay gratitude to many people, including those who help me boost onto the shoulders of the giants that I stand upon. Also, Stephanie serves as a central motivating factor for my personal journey in longevity. And as you'll see shortly, motivation when it comes to longevity is the most important thing. So I will never be an old man. To me, old age is always 15 years older than I am. So the first concept of longevity medicine is physician, heal thyself and teacher, teach yourself. You need to have an alignment of your practice and life. You certainly can't preach being healthy to patients if you don't do it yourself. Further, you need to use the self directed learning that you learned in medical school because there is no central textbook or curriculum and the pace of change of information is so great that there is no single source that can be relied upon. Now we all have an idea of what getting old means. It's declining cognition, frailty, medications, and ultimately an institutional death. But aging varies both in terms of how you appear, your endurance, your functional abilities and your strength. So we might ask the question, what is the pattern? What is aging? And if you look at animals across the biomass, there's certainly a wide range. And there's no specific pattern, neither in size nor vertebrate, invertebrate, nor land versus water. In fact, if you looked at rodents, there's a wide range there as well. A mouse would live an average of four years, where a naked mole rat can live upwards of 30. There is certainly no consistency. The average life expectancy in the United States over the past 150 years has steadily increased. Although interestingly, in the past few years that's gone down. If we look over a longer time horizon, over the past 100,000 years, our life expectancy has actually tripled. Now our global population is aging, and that's true of every country. Right now, 10% of the global population is over 65. That'll be 16% by 2050 and a quarter of the population by 2100. We have an imperative to understand the aging process and manage it because we are going to start seeing global health care crises. Old age is like flying a plane through a storm. Once you're bored, there's nothing you can do. As a pilot, I certainly respect the need for flight planning so that you can avoid storms. And I think the same applies to life planning. Let's start with some definitions. Lifespan, quite simply, is the duration of life. Healthspan is a little bit more difficult to define. In fact, in the literature, there's over 300 definitions. One that's used often is the time until onset of your first chronic disease. Now, this is not a very good definition because 75% of us will have one chronic disease by 65, 50% of us will have two, and 25% of us will have three chronic diseases. So healthspan in a more granular form certainly can be cut short by tragedy. But generally, we think of health as a declining factor over our lifetime until our demise. The concept of health span is to try and maintain maximum health for the maximum amount of time and potentially increase our lifespan as well. Healthy longevity medicine is optimizing healthspan by targeting aging processes across the lifespan. It's not a question of quality versus quantity. It's a question of quality and quantity. That's what healthspan is. Now, there are certainly ways that you can shorten your lifespan. There are many stupid things that you might do that might terminally end you. But if we think of aging and the various models of aging and how we might manipulate them, there are certainly things that we can control. For the moment, I'm going to focus just on the genetic control theory of aging and genetics as it relates to aging. The roundworm can be mutated and extend its lifespan from two weeks up to 20 weeks. Surely through genetics, you would ask the question, can we do the same for ourselves? Yamanaka factors were elucidated by Yamanaka and Takahashi in 2006. These four factors are highly expressed in embryonic stem cells. Now, the Yamanaka transcription factors can convert somatic cells into pluripotent stem cells. To make this clear, you could take any single cell out of your body and revert it to an embryonic stage at a pluripotent stem cell. For this work, they won the Nobel Prize in 2012. David Sinclair in 2020, took three of these four Yamanaka factors and were able to manipulate and reverse age related blindness in a mouse glaucoma model, Something which would have previously been thought impossible. So it begs the question, when it comes to aerospace, we think of a concept of escape velocity. If you can accelerate away from the earth at the same speed you accelerate towards it, you can enter orbit or escape the earth entirely. And this is escaping gravity. So could we escape mortality? Can we anti age as fast as we're aging? So there was a concept of the longevity escape velocity. And at this point, we're extending lifespan. But in theory, at some point, we may be able to reach an escape Velocity where people could live potentially forever. There is a hypothesis that the first 1000 year old person will be born only 10 years after the first 150 year old. Now, the issue with this is that aging biology is extremely complex. This is a model that was released in 2019. The idea of altering certain genes and being able to affect this entire thing in a controlled fashion is actually quite a feat, and one which many people think is not possible. In addition to this, there are many strata of aging. The human biology that I just showed really only goes up to the cellular level to think about aging. Guido Kromer has published on the hallmarks of aging, which allow us a framework to think about how to manipulate aging. There are primary, antagonistic and integrative forms of aging. The primary forms are genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, and disabled macroautophagy. The antagonistic versions are the deregulation of nutrient sensiting, mitochondrial dysfunction, cellular senescence, and then the integrative ones, which affect everything, are stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. I'll talk about a few of these through the morning. The first one I'm going to talk about is epigenetic alterations. Now, genetics is the series or sequence of your genes, while epigenetics is the folding of your genes. In a single cell, there's 2 meters of DNA, but the nucleus is only 6 micrometers. And so that's the equivalent of taking 40 kilometers of thread and stuffing it into a tennis ball. So epigenetics is the selective folding of DNA. And this is extremely important because this controls your gene expression and cell type. So, for example, it defines what makes a skin cell versus a liver cell. Epigenetic aging has four main ways that it progresses, and there are things that can worsen it or make it better. For the moment, I'm going to focus on DNA methylation only. DNA methylation is when methyl groups are inserted along your DNA, and this affects the epigenetic and the folding. Steve Horvath, who's a geneticist at UCLA, in 2013 published on this, and he found that the CPG sites, which are sites that have a cytosine followed by guanine in the 5 prime to 3 prime direction, get methylated at various rates and in various sites. He took a large number of samples, arrays and tissue types and was actually able to show that DNA age could be correlated to age of the organism. And using 71 of these CpG methylation sites, was able to develop a predictive algorithm revealing the biological age. This is called the Horvath clock. Longevity medicine principle number two is biological age which is a measure of a functional age versus chronological age, which is a measure of your number of years alive. Now if your chronological age and biological age are the same, you're aging an average. If your biological age is less than your chronological age, you could say that you're doing pretty well. While if your biological age is greater than your chronological age, you would probably report that that patient appears greater than their stated. Now there are many biomarkers of aging and epigenomics are only one. There are several other ways that you can measure molecular levels and measure somebody's aging. There are also physiologic measurements such as functional performance and physical characteristics and digital information from wearables and non wearable technology. Now all of this information put together can give you a very reasonable dashboard on how well you're aging. This company called Longevity AI based out of Tel Aviv, Israel is a platform which uses AI and integrates all of this information and is able to identify the pace of aging of individual organs as well as long term risk of various diseases including diabetes and cardiovascular disease, as much as 10 years or more away. So longevity medicine principle number three is polyomics, which is the use of all of this data. And this medicine is data driven and you use biological age to gauge how well someone is doing and how well treatment is doing. This is the concept of precision medicine which is tailored to the individual person and not just used on a generic population based method. Moving on to loss of proteostasis, this is proteomics. Proteomics involves the measurement of human blood proteins. Tony Weiss Corre in 2023 published this paper looking at proteins from very specific organs across 5600 adults in the human lifespan and in 11 major organs was able to estimate organ age reproducibly. Now this is important because he actually also identified that 20% of us have one organ which is aging much faster than the rest. So you have a 1 in 5 chance that one of your organs is much older than you are and a 1.7% chance that several of your organs are doing that. Now this is important because this confers a 20 to 50% higher mortality risk. For example, heart aging results in a 250% increased risk of heart failure and brain and vascular aging. Predict Alzheimer's disease. Again, this is 10 years or more away that this can be predicted. Furthermore, organs act as a system. It's not just a single Organ that's aging. So if one of your organs is getting older faster, it affects all of the other organs as well in the system. And the course of this is predictable. Again, going back to the strata of aging, individual organs and organ systems are complex. Again reminding us that manipulating specific genes genes is a rather simplistic way of trying to reverse aging. Moving on to cellular senescence. This is a fun and interesting concept. In cellular senescence, cells irreversibly stop dividing without undergoing cell death. But they secrete paracrine and endocrine pro inflammatory factors, things that are extremely harmful. Senescent cells are colloquially called zombie cells, and the reason for this is because they're extremely harmful to things around them, and they actually convert other adjacent cells into senescence. And in fact, they secrete substances that cause senescence in other organs as well. Now, going back to skin, since we are plastic surgeons, your skin has senescent cells in it which result both from chronological and photo aging. And in fact, one hour in the sun will increase the number of senescent cells in your skin. Measurably, skin senescence has been related to skin cancer. Also systemic immunosenescence, cardiovascular risk. It inhibits neurogenesis in your hippocampus, it activates your adrenal axis, and in animal models has been shown to directly affect longevity. So on come the drug category senolytics such as dasatinib and fisetin. These selectively eliminate senescent cells and have a potential anti aging role. So of interest, fisetin is one of the things that I take in my personal stack. Beauty and health, I believe, have bidirectional causality, meaning the appearance and health of your skin most certainly affects the rest of your body just as much as the health of the rest of your body affects the appearance and health of your skin. So the concept that beauty is only skin deep is false. And I would say that beauty is healthy. Moving on to dysbiosis, your intestinal microbiome is the collection of bacteria that you have in your gastrointestinal tract. This has actually been related directly to neuropsychiatric disorders such as epilepsy, pain, neurotransmitter levels, depression, and also to nine different skin disorders, including psoriasis, acne and skin cancer. Furthermore, it has been elucidated that there is a skin gut brain axis where the microbiome of your skin and your gut relate to both of those organs and your brain in a triad which exists in very careful balance. So longevity medicine principle number four, bacteria are Kind of like animals. You need to be careful with wild ones like group A strep. But your microbiome bacterias are much more like pets. And I would suggest that you feed them well, which I'll speak about in a few minutes. Now, you know you're getting old when all the names in your black book have MD after them. We have all become accustomed to the idea that with age we get disease and we try to establish health by reversing that. But is health just the absence of disease? So longevity of medicine concept number five, traditional health care is really more like whack a mole medicine, which means it's kind of like sick care. We wait for something to be broken and then we fix it. Where true health care is preventive, where we would maintain or even promote health. So Vito Kromer also has published on the hallmarks of health. Things that are signs of physical and mental fitness coupled to normal functioning of all organs and measurable. These fall into spatial compartmentalization, maintenance of homeostasis and responses to stress. There are eight factors and I won't go through them all. But he more recently published in 2024 putting psychosocial adaptation at the center of this and found that in fact psychosocial adaptation relates to every other hallmark of health. The conclusion he drew from that is that mind and body are one, meaning the health of your of your mind and your psychosocial status is directly related to your physical well being and aging. So why don't we talk about how we can actually maintain that? I'll talk about the four pillars of longevity. I won't get into biohacking except to say that it does work. 10 minutes a day in a sauna will elevate your growth hormone by 400% and cold plunging will activate something called hormesis, which is a stress response that is very positive for you. There are also lots of supplements and I will touch a little bit about that. The four pillars of longevity are exercise, diet, sleep and social connectivity. With regards to exercise, this gentleman is Dr. Kenneth Cooper. He's currently 93 year old and still runs the Cooper Clinic where you can go and get cooperized. He was the original person to look at VO2 max and the effects of exercise on human physiology and aging. He also is the person who invented the term aerobics with his book in 1968. As he says, we do not stop exercise because we grow old. We grow old because we stop exercising. He would advocate for at least 30 minutes of high intensity physical activity every day to maintain your endurance and well being. It's not just about endurance and aerobics, it's also about muscle mass. In fact, the amount of your muscle mass directly relates to your cognitive ability. Muscles in fact are an endocrine organ and secrete over 30 hormones which directly affect your brain and your cognitive ability. My best advice would be lift heavy things. With regards to diet, I personally recommend a whole foods plant based diet which is something I followed for the past seven years. This will make sure that you get enough fiber, which is exactly what your gut microbiome requires. Most of us don't get enough of this and it causes a lot of diseases. It's interesting to think that in Africa, a place where we think of a poor diet, because they have high fiber and low animal protein intake, they don't suffer many diseases like gastric cancers and gout and things which are related purely to our western diet. Plants also contain phytochemicals which can directly fight many diseases including cancer. And plants and things that grow from the ground have signaling which actually change your neural network. Your thinking, your cognitive status is actually changed and enhanced by signals gained from food that you eat locally. Of course this is lost from both animal proteins and processed foods. Also, I'll share with you my personal observation during surgery and the effect on tissue. Since becoming plant based. Myself I've noted my patients diets and I can say that those who follow a plant based diet have better quality of tissue. The planes dissect more easily, the tissue holds sutures better and it bleeds less. There are a few movies on Netflix. If you're interested in following up on this, I highly recommend having a look and pursuing your own interests in diet. With regards to animal protein there is certainly an impact on the environment and Dr. Mantelo shared that with us a few weeks ago noting that cows produce methane, which is a significant contributor to bio to greenhouse gases. And in fact a paper out of the Weizmann Institute in Israel noted that there is 94% of non human biomass being livestock. And this is certainly a huge impact on our globe. So that's one reason that you might want to decrease your animal protein. Another one is for your own personal health. Animal protein contains high amounts of branched chain amino acids, leucine, isoleucine and valine. Now these are actually extremely harmful. They've been linked to oxidative stress and systemic inflammation, also heart disease and type 2 diabetes. Branched chain amino acids affect many key signaling pathways in your biochemistry and aging and they activate this thing, mtor, which is the mammalian target of rapamycin and in activating it, it actually controls multiple aging processes. By eating animal protein which contains these essential amino acids, you are actually directly poisoning and harming yourself and causing aging. In particular, it affects the epigenetic aging as mtor is one of the key elements of repair. With regards to diet. Many people would look at the caveman diet and say, well we've evolved eating meat. I think this is very short sighted because hominids have been around for 6 million years, primates for 50 million years and life for 4 billion years. Most of our biochemistry relates to that and is built upon what we evolved billions of years ago. The idea that the last fraction of a percent of our evolution is actually what should guide what we eat is shortsighted and foolhardy. I'll also point out that one of the things that we evolved along this timeline 2.5 billion years ago is an enzyme called superoxide dismutase, which I'll speak about more later. So with regards to diet, my best advice to you is eat less and eat more things that grow from the ground. Now the last point in the pillars of longevity is around social connectivity. This is Dr. Dean Ornish who is well known for his lifestyle as treatment methods. He published this book Love and survival and among other things pointed out that people who go into a nursing home die six years earlier than matched controls. He also points out that people suffering from loneliness and depression have a three to time tens greater risk of premature death. So he put this into practice in the heart trial in 2001 and using just lifestyle interventions was able to increase coronary blood flow on PET scans. After five years with just lifestyle changes, 99% of patients stopped or reversed their disease. And there were two and a half times more cardiac events in the control group. The lifestyle intervention, vegetarian diet, aerobic exercise, stress management, smoking cessation and group psychosocial support. It seems very simple. Does it work for just the heart? Well, no prostate cancer. He did a study in 2005 and showed that over 12 months PSA is reduced and prostate cancer tumor size actually shrinks. By Dr. Ornish's estimation, our survival depends on the healing power of love, intimacy and relationships as individuals and perhaps even as a species. His advice, Eat well, stress less, love more and move more. Longevity medicine principle number six, lifestyle is unquestionably the most powerful treatment for healthy longevity. Now, blue zones, you might have heard of these. These are areas in the globe of the longest lived people. Dan Buettner recently made a documentary about this and focused on the benefits of exercise, diet and the community and social interactions that these people have, and pointed out that Singapore is the blue zone 2.0 because it's the only place where a blue zone has been manufactured and created that didn't exist before. The National University of Singapore actually has a place called the center for Healthy Longevity and that's where the conference was, which I attended and spoke at. I'll talk a little bit about supplements, nutraceutical, pharmaceuticals and some repurposed drugs. With regards to the repurposed drugs for anti aging, dasatinib, quercetin and fisetin, which I mentioned earlier, are senolytics. Rapamycin is also a potential target. And we often think of rapamycin as a chemotherapy agent and actually in lower doses it has anti aging capabilities. And there are a lot of people who are taking rapamycin on a regular basis as a part of their normal stack. Metformin is an interesting one and I'll speak a little bit about this. So a study came out in 2014 showing that diabetics on metformin actually lived longer than matched non diabetic controls. Metformin has also been shown to reduce the risk of diabetes, cancer, heart disease and cognitive decline. Metformin also, through mechanistic means, has been shown to affect every single hallmark of aging directly. And so I include metformin in my personal stack as well. At this point, as of October 1st, there are over 3,000 drugs that have been listed as potential anti aging related drugs. Of interest, all diseases run into one old age Longevity medicine concept number seven is inflammaging. Inflammaging is aging from chronic inflammation. Now interestingly, aging also causes chronic inflammation. And so you can see that this is a positive feedback cycle which is extremely harmful. Chronic inflammation is a central focus on our overall aging. Chronic inflammation affects every other hallmark of aging. And a primary driver of chronic inflammation are reactive oxygen species. These ROS reactive oxygen species, they show up in a lot of places in our biochemistry and they are immensely harmful to us. That was the nidus of the talk which I gave in Singapore, which I'm going to deliver to you now. I even wore the same suit so you could have the authentic experience. Also, I have to note, standing on the shoulders of giants, I was honored and a bit intimidated to be speaking on the same podium as Dr. Sinclair, just a couple of speakers after him. The talk I gave, which I'll give you now. Mellon derived superoxide dismutase oral biopolymer increases cellular and mitochondrial enzymatic antioxidant mechanisms. It's definitely one of the longest titles I've ever had for a talk. Of note, I am on the board of directors for iSocell, the parent company of the molecule I'll be speaking about. But to be clear, I am not paid by them. I have never been paid by them. I own no stock and no futures, nor do any of my family. So what I'm sharing with you now is of personal interest and I share it because if I keep it a secret and to myself I feel selfish and inappropriate. So I share this of interest. And also as I've mentioned before, I'm a co founder of healthspan Digital. The story begins with the Great Oxidation event which was 2.5 billion years ago. And it's when oxygen first began to accumulate in our atmosphere after photosynthesis evolved. Now, reactive oxygen species are balanced by antioxidant defenses. But if they're not, we exist in a state of oxidative stress. And reactive oxygen species come from outside sources, but also inside sources such as inflammation and also our normal biochemistry. Our mitochondria are energy plants that produce a ton of reactive oxygen species in our cells. Our own existence is actually harmful to us. Now, reactive oxygen species and oxidative stress have been linked to disease process in every single organ system, as well as directly to the epigenetics and genetics of aging. The thing that we evolved two and a half billion years ago that saved us from an extinction level event on Earth was superoxide dismutase. Superoxide dismutase is the enzyme which converts oxygen free radicals into hydrogen peroxide, which are then further reduced by catalase and glutathione peroxidase to water and oxygen. Now every living thing on this planet, eukaryote and prokaryote, produces one or more forms of this enzyme. Without it, we would die very quickly. If you eat antioxidants in your diet, such as in blueberries, the effect is minimal. And the reason is because it works in a direct effect. One molecule from your blueberry is going to annihilate one oxygen free radical and be destroyed in the process. While superoxide Dismutase will destroy 1 million oxygen free radicals in a catalytic mechanism before it's damaged and then recycled through autophagy. You can't of course eat the sod, it's an enzyme and it would be digested in your stomach. So the question is, can SOD be made orally bioavailable? And as you might guess, the answer is yes, it can. The sod is isolated from this melon just because it happens to have a very high concentration of the sod, but the source is really quite irrelevant. The sod is then encapsulated within gliadin on a molecular level, which is what protects it and allows the sod to be consumed. Now, a quick word about gliadin. It is a component of gluten. A dose of this gliadin sod biopolymer contains 30 milligrams of gluten, which is less than the recommended limit for a person with true celiac disease, which is 50 milligrams per day. However, the gliadin is absolutely essential because it's what protects the sod in the stomach acid and causes adherence to the walls of the small intestine. So I'm going to present on three papers about this molecule. The first is an animal study which had groups of control. The free sod, free gliadin, and then the biopolymer of the gliadin sod combined treated for 28 days. So the first thing is intestinal immunofluorescence confirmed that the biopolymer passed through the stomach undigested and did adhere to the intestinal walls, while the pure sod did not. Then measuring circulating levels of the SOD as of 14 days, the level was significantly increased and it maintained throughout the study. And this was an 89% increase. Additionally, there was concomitant increase of both glutathione peroxidase and catalase along with this, and these were all significant changes. The effect of this on oxidative stress was significant as well. The treatment group, when exposed to high levels of oxygen, had less cellular lysis, showing that the sod was there, functional and actually protected the cells. So the study showed gastric protection and intestinal adherence resulted in increased circulating and tissue sod, and also cellular protection of both hematocytes and hepatocytes. I did exclude the data from hepatocytes and mitochondrial protection just in favor of brevity this morning and simplicity. I thought the data was maybe a little bit overwhelming, but the data is there and does show those things. The next study I'll show is on experienced human scuba divers. And so these divers were pretreated for 14 days with either placebo or the biopolymer and then exposed to hyperbaric oxygen, which is an established oxidative stress model. So the first thing is Plasma Prostaglandin F2, which is a marker of lipid peroxidation and oxidative stress. After hyperbaric oxygen exposure, the placebo group increased, showing that they did have oxidative stress, while the biopolymer group showed no change from baseline and also that it was lower than the placebo group, confirming that their oxidative stress levels were in fact lower. A comet assay measures DNA tails and is a measure of actual direct DNA damage. And this comet assay showed that even before the patients were exposed to hyperbaric oxygen, there was a tendency for the treatment group to have lower tail moments because they had already been Pre treated for 14 days with the biopolymer and had some benefit at rest. But certainly after exposure to the hyperbaric oxygen there was a significant difference where the treatment group was protected and their DNA was saved from the oxidative stress. So this study showed reduced inflammation overall from oxidative stress in humans and a resultant DNA protection. The third study is a cardiovascular study which was done on asymptomatic humans with cardiovascular risk. They were all given diet and lifestyle counseling and then divided into groups of placebo and the gliadin SOD biopolymer and treated for two years. Now, the oxidative stress, the SOD levels, the superoxide dismutase levels increased and as of 270 days was significant and maintained throughout the two years. And Malandialdehyde is a marker of inflammation and this decreased as well and maintained throughout the study. Now, malandialdehyde is not just a marker of oxidative stress, but it itself is a direct toxic factor for DNA for Genesis. It actually directly harms your genetic sequence and so lowering this is actually a significant thing. Now, the clinical outcome of this carotid artery intima media thickness was measured using ultrasound and the control group intima media thickness increased despite their lifestyle changes while the treatment arm decreased. So what this showed was that the thickness of the artery wall was actually decreased or cardiovascular disease was reversed in the treatment group. I don't know that there's any pharmaceutical that could make this claim. So this study showed that there are increases in SOD in humans and also reduced systemic inflammation from the biopolymer and it was effective at a preclinical stage in subjects with cardiovascular risk and also demonstrated safety of the substance after two years of use. Now an important note that there is some utility of oxidative stress. For example, when we do exercise, some of the benefits we gain from it are from the hormones effects or the stress impact that it has on us and that's mediated through oxidative stress. There are Also some immune system mechanisms that we use that require oxidative stress and some chemotherapy agents that depend upon it to achieve their therapeutic endpoint. Also, hyperbaric oxygen is very beneficial, but some of the benefits that it derives are from oxidative stress that it causes. And so completely short circuiting oxidative stress would be a problem. However, it would be quite impossible to completely eliminate oxidative stress, even with the enzymatic mechanism. And moreover, there have been a series of studies done on the substance and 40 of them are on humans, all of which have shown positive beneficial effects on a wide range of organ systems. And so from this I would conclude that this biopolymer has been shown to increase health span. My conclusion for the conference was to humbly submit this biopolymer to the longevity community for further investigation and clinical application. Now, we are plastic surgeons, so I do want to bring it back for a moment to the skin. So this is a cross polarized image from a Vectra Canfield imaging system. This is my wife, Stephanie, and this is her at zero and again at six weeks, showing the impact on inflammation and redness of the skin. I've done a study on this, it was published in 2016 in PRS and it did show clinically significant reduction in erythema. This is another one of our patients shown at 6 and 12 weeks with measurable decrease in her inflammation in the skin. And so longevity medicine principle number eight. I really believe that health and beauty are in fact the same thing. So I would say beauty span and healthspan are synonymous. So up until now I've spoken about longevity for plastic surgeons. And so these principles are practice on yourself, direct your own learning. Biological age is measurable and controllable. Polyomics guides precise treatments and can be used to change your dashboard and the aging of your organs and yourself. Your microbiome is a part of you. I would suggest you treat it well. Lifestyle is by far the most powerful treatment that we have, and reactive oxygen species are the principal driver of inflammaging and also something that can be controlled and managed to and finally that health and beauty are one and the same. Now, after finishing my thoughts on longevity for plastic surgeons, how about plastic surgeons for longevity? Well, I personally think that the aesthetic world is a gateway for patients into health. And I believe that on the whole we should be correcting the course of the cosmetic industry, which I believe has distorted the concept of beauty. And I think it's up to us to realign beauty standards. Moreover, I think that we should be Redirecting patients from piecemeal reactive treatments to precise and preventive treatment, and adopt a more holistic approach to beauty through health. We've always been leaders in surgery and medicine, and I think that this is an area that requires us to do the same. If we're going to enter this field, we need to consider some of the ethics of longevity. So, for example, there's certainly a question if longevity increases could result in two tier aging and a greater disparity between the rich and poor. And while this is possible, the general ethos in the longevity community is to democratize the longevity principles and share it with public health care systems as able. Hopefully this is something that can be avoided. A question of would an indefinite life lose its meaning? While that might be true, it's also true that if someone is granted greater capabilities over their lifetime, they could give a greater functional contribution and have a better sense of of purpose and motivation in life. Also, a longer life would result in greater care of the environment. As Dr. Semple pointed out at our last rounds, if we lived as long as trees, we would certainly have a very different perspective on the environment around us and what we would do to care for it. I can't help but note that while love confers longevity, longevity induces stewardship. There's something that I do, and this is a plug for a place called the Weizmann Institute and one of the ways that I personally steward the environment. I sit on the board of directors for Weizmann Canada promoting this institute. They have partially or completely developed seven of the top 10 pharmaceuticals currently available globally. They consistently rank in the top 10 global research impact by the Leiden Institute, including this past year. And the Weizmann Institute is located in Rehoboth, Israel. I was very fortunate to be able to carry out some research there before starting my undergraduate career. And it is truly a spectacular place. One of their flagships is the Institute for Environmental Sustainability. One of the things they've engineered is colored cotton which can produce T shirts, which avoids the need for 2,700 liters of water which are required for each individual dyed T shirt. They've also engineered bacteria that digest plastic, biodegradable plastic, intelligent solar power, cloud science, and much, much more. This is something that I feel very strongly about because I believe that their motto of science for the betterment of humanity is one which will help to save our world. As Winston Churchill said, we are happier in many ways when we are old than when we were young. Young. So wild oats, the old grow sage. And so I put this up, both because it's a fun picture. And I would also ask that you not be too critical of my sutures. This picture was taken before loops were invented. But moreover, you know, it's an interesting thing to think that surgery is only 200 years old. The first operation in the ether dome was done in 1821. And so it has taken 200 years for us to reach the current state that we're at in surgery. But pace of change is exponential, and the longevity space has developed only over the past decade. And I would say that in the next 10 years, it will revolutionize how healthcare is delivered. And I would say it's important for us to be a part of that, both for our personal well being and also as clinicians. Thank you so much.