How Real Science Unlocks Aging, Healthspan, and Longevity Secrets

Do you want to live forever? Or at least live longer or better? Well, the scientific and social media spaces around longevity and healthspan, they're among the fastest growing in the world. And one can understand why. Most of us, if not all of us, want to know how to live longer or at least better. Well, in what's to come, I promise you to dig into the fascinating new science around healthspan and lifespan with depth and nuance. We're going to cover data published in top science journals around Lifespan, healthspan, aging and exercise, omega-3 fats, biological age, plasma transfers, inflammatory signaling, and more. This is a compilation episode. It's part of a new series on my channel where I pack together high-yield content on a topic so you can watch it like a movie or listen to it like a podcast. Let me know what you like and what you didn't like or don't like because your time is precious. Now let's get you some more of it. It's not how old you are, it's how you are old. I can't think of a better quote to encapsulate the results of the brand new study that I want to share with you today. It's a one-of-a-kind study that took 139 adults spanning ages 20 to 93, including active and inactive participants across this broad age spectrum. And it asked the question: What are the relative effects of aging and exercise on body composition and muscle function? The results? Surprisingly uplifting. But there's one big problem with aging in muscles that even exercise can't fix. And another new study just found a way to reverse that problem too. I'm going to break this all down in this video. Now let's get to the results. One of the most fascinating findings was how closely the profile of the oldest active group mirrored that of the youngest inactive group. For specifics, comparing active individuals over age 70, average age of 76 years, with inactive individuals in their 20s and 30s, average age of 30. Their body compositions were nearly identical. They were within 0.1% body fat of each other, 27.2% versus 27.11%, and within 0.2% lean mass of each other, 69.7% versus 69.9%. It's rather eerie how closely matched the body compositions of an active 76-year-old is compared to an inactive 30-year-old. Functionally as well, more active older individuals were fitter—no surprise—but again, for some tests it was impressive how closely matched the average active 76-year-old was compared to the average inactive 30-year-old. And I will emphasize and heavily caveat average. We're not talking about ultramarathoners or obsessive gym rats here. For the oldest age group of active individuals, the average total physical activity was 6 hours per week, which isn't too bad, including 3.5 hours of aerobic exercise and 2.5 hours of resistance training per week, in addition to 5,250 steps per day. By comparison, inactive individuals across all age groups exercised only about 30 to 40 minutes per week. However, another important caveat to these data is even in active older adults, the proportion of time spent resistance training or weightlifting was far lower than aerobic activity time, especially in the 40 to 69-year age groups. For example, in active adults ages 60 to 69, aerobic training time per week was 300 minutes. Vs. only 70 minutes per week spent resistance training, including weightlifting. This is a really big deal because the propensity to build and maintain muscle mass does decline with age when not prioritized as part of a healthy lifestyle. Yes, aerobic activity like running, swimming, and biking, they're great, but it's a big disservice to overlook the importance of resistance training and especially weightlifting, especially as you age. Muscle mass is in fact one of the greatest predictors of longevity and healthspan. Muscle isn't just for flexing, it's for longevity. Not only does muscle tissue combat frailty, but muscle is a critical endocrine organ, meaning it secretes hormones into the blood. Hormones like irisin, which protects against neuroinflammation, increases levels of brain-derived neurotrophic factor, which itself is key for the effects of exercise on neurogenesis, the growth of new neurons, and on cognition. And irisin may reduce your risk of cognitive decline and dementia. This is a hormone secreted by active muscle tissue that protects the brain. And indeed, having more muscle increases this neuroprotective irisin, as well as other muscle-derived hormones broadly classed as myokines, which are muscle hormones, that can signal directly to the brain to improve brain health. So in a nutshell, your muscles literally signal to your brain with hormonal chemicals that protect the brain. Think about that the next time you're doing a squat, which is a butt exercise that's also a brain exercise. Quite literally. Muscles, they're also your biggest sink for blood glucose, helping to maintain healthy blood sugar levels, which has a positive knock-on effect for your blood vessels and brain health. So zooming out, the keep it simple, stupid line here is don't forget resistance training and weightlifting as you age. You're spotting your future self. Don't let them down. There are, of course, many different approaches to resistance training and weightlifting, but generally 3 to 5 times per week for 30 to 60 minutes per session is probably sufficient to optimal for most people. It's important to focus on large muscle groups like the glutes, quads, back, chest, and core. And while I couldn't tell you my favorite exercises personally, How much weight would that actually carry? I'm not even 30. Instead, I want to invite you to tell me in the comments: 1. How old are you? And what is your resistance training or weightlifting plan? Learn from each other in our metabolic health community in the comments. I look forward to seeing what you share. Alright, with that important tangent hammered like a sledge on the tire, let's get back to the data from this paper. Specifically, I want to discuss an area where exercise does not protect your muscle from the ravages of time. And also, what might protect them. Muscles. Muscles depend on calcium. Calcium influx into muscle cells is what triggers a muscle contraction. But, more to the point, calcium influx into mitochondria within muscle cells helps activate energy production to fuel muscles. And the ability of muscle mitochondria to import calcium declines with age, in part due to a decrease in the expression of part of the calcium transporter complex in muscle mitochondria membranes. This decline in the ability of olde muscles mitochondria to import calcium can contribute to decreased muscle metabolic capacity, in an age-dependent manner that is sadly not prevented or protected against by exercise. However, another new paper, a fascinating paper that I reviewed previously on this channel, also revealed there's a natural compound or a group of natural compounds that can treat this muscle dysfunction. You need to check out that video in full, but Briefly, what they found in that paper was oleuropein, a compound found in olive leaves, holds tremendous potential to offset age-related muscle calcium dysfunctions by increasing the activity of mitochondrial calcium transporters. In fact, at least in animal models, olive leaf extract with oleuropein increased endurance exercise performance and even increased muscle mass, which is pretty incredible, right? Now, getting to my big picture takeaways from this and related research. The key lesson from this study is aging is not an inevitable poison to muscles. Yes, the years do take their toll, that's true. But like a well-maintained car, your meatbag machine, your body, can run well for a million miles if it's well maintained. Aging is inevitable, but how you age is largely within your control. I'll also emphasize consistency is key. Based on these data, you don't need to go crazy. Try to target 6 hours per week of dedicated exercise. In addition to getting daily movements, like trying to get more steps and trying to take the stairs rather than the elevator, I'll admit, some hypocrisy there, but in my defense, I do live on the 37th floor. And do not neglect resistance training and weightlifting. The study here showed a bias towards aerobic activity, but building and maintaining muscles gets harder with age. And the best way to ward off the myocyte grim reaper is to resistance train and weightlift consistently throughout the life course. Strong muscles aren't just for aesthetics; they improve insulin sensitivity, they support metabolic health, and even function as an endocrine, hormone-secreting organ that benefits the entire body, especially the brain. However, exercise alone, it doesn't solve everything. One challenge of aging is a decline in muscle mitochondria's ability to import calcium, which reduces their ability to fuel muscle contractions. But the exciting part is that new and emerging research suggests that natural compounds found in foods like oleuropein from olive leaves could help restore this metabolic dysfunction. New breaking research like this, which I'm going to keep covering on this channel if you subscribe, opens the door to potential interventions that go beyond exercise or synergize with exercise to actively support muscle metabolism at the cellular and subcellular levels. So, smash that subscribe button like it's your last rep, and let's keep lifting knowledge together. Hey look, I'm back and I changed. No, but in all seriousness, I'm just back to tell you that Professor Guzpelov, the senior author of this research, has gifted us an exclusive clip just for this video so you can hear from the horse's mouth. I asked him a few questions, Here's what he had to say. I hope you enjoy.

Many thanks, Nick, for featuring our work. I believe that our paper is important for several reasons. The first one, and it's not really a novel finding, but I think our paper strengthened the available literature showing that physical activity is effective at promoting physical function and performance across the human lifespan. I think this is a very important message for the general population, and it showcases that physical activity has beneficial effect even at advanced ages. The second reason why I think our paper is important relates to our finding on mitochondrial bioenergetics. So I'm sure many of your viewers heard about mitochondria, how important they are for cellular energetics, metabolism, and mitochondria are also involved in many other key cellular processes that are essential to our health. So there is this idea in the field that with aging, mitochondrial bioenergetics progressively declines, and it's often referred to as a hallmark of aging. And in our cohort of inactive participants, we did see a strong trend for a decrease in mitochondrial oxygen consumption, which was our surrogate to assess mitochondrial energetics in our paper, which is in line with what I just mentioned. However, when we looked at our cohort of active participants, we could not see such a trend. So the way we interpreted the data, or what I think the data means, is that people that stay physically active do not see a decline in their mitochondrial bioenergetics. So physical activity can protect mitochondrial bioenergetics across the human lifespan. So if you care about your mitochondria, which I believe you should, then Integrating physical activity into your daily life is essential. So the third reason why I think our paper is important, and this is one of the most novel aspects of the work, is that we, we found that with aging mitochondrial calcium retention capacity progressively declines, and this was not protected by physical activity. So just to be a bit technical here, what it tells us is that mitochondrial resilience to calcium stress decreases with aging. So if faced with a calcium stress, mitochondria from old skeletal muscle are going to be more likely to trigger the opening of the mitochondrial permeability transition pore. So this, this pore, its molecular composition is still debated today, but what we know is that if it opens, it can trigger the activation of signaling pathways known to result in muscle atrophy and weakness. And one of the The strength of our study is that we found that mitochondrial calcium retention capacity was correlated in humans with markers of muscle mass, strength, and physical performance. So we believe that this may be an important mechanism here. And the fact that we saw this occurring in both inactive and active participants was for us very interesting because physical activity has many benefits, but it does not stop aging. So the fact that we saw that in both inactive and active participants of the cohort of active and inactive participants is to us suggesting that this may be a primary mechanism driving aging in skeletal muscles. So you asked me to touch on how important muscles are for longevity and healthspan. And I can tell you that this is— there is a lot of data in this field. And where the data is, is the strongest is that there is overwhelming evidence that muscle health is essential for healthy aging. We know that the aging-related loss of muscle mass and function increases your risk of fall fractures, you are more at risk of losing your independence, and it's generally negatively impacting the quality of life of afflicted individuals. There is some data that suggests that muscle health is also linked with longevity. So I think thinking about preserving your muscle health as you age is critical. You also asked me what I believe the next research questions are coming from this paper, and I have many here, but I will just highlight two. So the first one is this decline in mitochondrial calcium retention capacity that we saw. Is that something that is restricted to muscle, or is that happening in other tissues and organs? So in other words, is that a mechanism that could also be involved in the aging of other tissues and systems in the organism? The second question, it's kind of obvious with our findings, but it's, can we develop a treatment that could target the mitochondrial calcium handling, the functioning of the mitochondrial permeability transition pore, or the consequences of the opening of this pore? To improve muscle mass, strength, and physical performance, and thereby improving the quality of life of older adults.

What if you could slow aging for less than a dollar per day? And what if the alternative was spending millions of dollars on personalized high-tech protocols like the internet's famous self-proclaimed immortal centimillionaire Brian Johnson. Would you rather take the shortcut or the scenic route to longevity? Well, a new study just dropped in the journal Nature Aging, and the findings might surprise you. They definitely surprised me. Let's break it all down. But first, an introduction to Brian Johnson for those of you who are not familiar with this man. The longevity science field The longevity space is blossoming, with influencers exploiting the niche and making some hard-to-believe claims like that they're aging at two-thirds the rate of a normal person, or that they're having a birthday every 21 months, or that they're— and this is a quote— "the healthiest person on the planet." Of course, I'm talking about the famous Bryan Johnson, the centimillionaire who made his fortune founding and selling Braintree Venmo for $800 million, and who has turned his life into a case study in anti-aging. Honestly, on balance, I like Bryan's Do Not Die movement, particularly insofar as it challenges status quo thinking. That's something we have in common. And in long form, I actually think he's quite a thoughtful character. And is certainly a master of attracting social media attention, as is demonstrated by this video where I'm using him as a hook. So I guess kudos to him. Anyway, we're going to return to Bryan and his calendar-corrupted 21-month birthday, but first I want to frame the discussion with data that may be directly relevant to your health. This new research I mentioned that I want to discuss in this video was published in in Nature Aging and included an analysis of 777 people from the DOHEALTH trial who were randomly assigned to a protocol consisting of omega-3 supplementation at 1 gram per day, vitamin D supplementation at 2,000 international units per day, or a simple at-home exercise program, 30 minutes, 3 times per week, or various combinations of these protocols. So, in total, we've got 8 different groups battling it out for longevity, placebo included. The researchers of this study sought to assess how each intervention or their combinations impacted biological age or rate of aging over a 3-year time period. And to do so, they used 4 separate epigenetic aging clocks called PhenoAge, GrimAge, GrimAge2, and DunedinPACE. They chose to use 4 clocks because they appreciated the limitations of this technology at the present day, so they wanted to look for consistent results across the 4 clocks. Good on them, right? Now, I want to give insight into how these aging clocks were invented and why one is different from the others. 3 of the clocks, PhenoAge, GrimAge, and GrimAge2, were developed using data from a cross-section of individuals of different ages, and they predict a biological age that may be distinct from a chronological age, or age in calendar years. So, for example, if GrimAge2 says your biological age is 40, even though the world says you're 55 years old and you've had 55 birthdays, It means that your body looks 40 based on the measured biological markers. Hopefully that makes sense. So those were 3 in the clocks, but what about this last clock, Doomed In Pace? With Pace standing for Pace of Aging Calculated from the Epigenome. It's different. Doomed In Pace measures the rate of biological change, with a value of 1.0 indicating 1 year of biological change per calendar year. As opposed to the other clocks, which were developed by comparing people of different ages, Doomed in Pace was developed by following a cohort of individuals who were all the same chronological age and then measuring changes in biomarkers reflecting the health and integrity of different organ systems. Like the cardiovascular system, the renal or kidney system, the hepatic or liver system, the immune system, and so on, and then normalizing to 1 such that 1.0 indicates 1 year of biological change per 12-month calendar year. Now, of note, the famous biohacker Bryan Johnson has boasted a value of 0.64 to 0.66 as his DunedinPACE rate of aging score, suggesting he's biologically aging at 66%, or about 66%, or about two-thirds of the average person. Actually, on X, around this past New Year, he reported his own record DunedinPACE score of 0.57, which he claimed was a personal best, and that his birthday, as a function of that score, is every 21 months. Which is 12 divided by 0.57. I now interrupt this program to bring you more of this program, but in blue. After I recorded this video, Bryan posted that his new best DUNED in-pace score was actually 0.48. I find this interesting, but it's not clear to me if this is a result of an actual downtrend in his score, reflecting a true slowed pace of aging, which would be cool for him, a function of test variability and the fact that he has just more measures from which to choose and report, or finally, if he's modifying his protocols to optimize this metric, but without it translating to an actual slowing of his biological age. I'll have more to say later in this video, and forgive the jump cut to me in blue, but I thought it was only fair to steelman Brian's position. So, how do the interventions in this study compare? Well, daily supplementation with just 1 gram of omega-3 improved scores on 3 of the 4 clocks: PhenoAge, GrimAge2, and DunedinPACE. And the average improvement for the DunedinPACE score was -0.17 with a 95% confidence interval of -0.04 to -0.13. And if you take the lower bound of this confidence interval at 0.13, and we take 1.0 to be the normal pace of aging, this could suggest omega-3 alone at just 1 gram per day, which is lower than a lot of other trials, was lowering DunedinPACE's estimated rate of aging to 0.69, which is near many of Bryan Johnson's scores, despite the fact that he's invested million dollars per year in developing his personal anti-aging protocol. Not bad, right, for something you can buy at Costco instead of spending millions at a high-tech longevity spa. Admittedly, Bryan's most recent score, if taken to be true, is substantially below 0.69. More on that in a moment. But it remains true that even after years of investing $2 million per year in developing a personalized health protocol, Brian's scores were in range of the confidence interval for just 1 gram per day of omega-3 supplementation in a general population. And there's more. But how much confidence can you put in these numbers? And what do they really mean for you and for Brian? Well, strap on your scientist hat really tight for me because we're about to do some deep thinking. Which actually should be good for cognitive health, so you're welcome. Anyway, one question you should ask yourself is what population these clocks or calculators were developed in. The Doomed in Pace looked at individuals 26 to 45 years old. In my opinion, this limits the relevance of this score outside that range. And of note, Bryan Johnson is 47, which is just outside the range. Also of note, and as a little fun fact, Bryan Johnson was born August 22nd, 1977, which is less than 3 weeks after Tom Brady, whose birthday is August 3rd, 1977. So tell me in the comments, who looks younger and healthier? Anyway, comic relief and pattern interrupt to improve the average view duration on this video aside, it's worth noting that when Researchers take older individuals outside the age range I just mentioned, such as individuals in their 70s and 80s, and calculate their DunedinPACE scores. Those with higher scores, representing faster aging, are at higher risk for developing chronic disease and even death, which gives me some confidence in these scores. So, do I have confidence in these scores overall? Or otherwise put, Do I think they're actually useful measures? I do. I don't take the exact number, say Bryan Johnson's 0.57, as gospel, but I do think the scores are directionally useful. In other words, if you can lower your score over time, that probably predicts an improvement in your lifespan or at least your healthspan. It's kind of a gamification of anti-aging, and I think that's just fine. With that said, a final interruptive remark on Bryan's numbers. Because Bryan places so much stock in these values, assuming his public hyping of these values isn't just a PR stunt and represents his true feelings about the Pace of Aging Clock, it's possible that even if he is downtrending, this downtrend isn't actually linearly related to his actual pace of aging. There are many ways in medicine and science to hack biomarkers in manners that might not actually improve health, as I've demonstrated on more than one occasion. Although I don't think Bryan is eating Oreo cookies. But returning to the Nature aging data at hand, I would be skeptical that omega-3 supplementation can actually slow your biological rate of aging by a true 30%. Even if you are an omega-3 hyper-responder. However, I do believe omega-3 supplementation, especially in those with lower levels, can improve healthspan and even lifespan, consistent with these data. And if you want a little bit more on omega-3 and fatty fish, you can see this video. By the same token, I don't think Bryan Johnson's rate of aging permits him to actually have a birthday every 21 months. And based on his own rate of aging, he is certainly not the slowest aging person or healthiest man on the planet. Actually, here's another fun fact, in the Dune in Pace cohort, they had an individual with a pace of aging of 0.40, which blows Bryan Johnson out of the water. Now, maybe this person is a secret billionaire expending twice as much I'm Bryan on a secret health protocol that's not on the internet, but I doubt it. So what does all this really mean for you? Well, while Bryan Johnson's protocol certainly is fascinating, I have fun observing it myself, the reality is you do not need millions of dollars to take meaningful action on your health and even your longevity. Simple evidence-based interventions like omega-3 supplementation regular exercising, and optimizing a key nutrient, vitamin D, maybe sun exposure as well, can have measurable impacts on biological aging, at least given current tools. Now, does this mean omega-3 will slow your aging by 30%? Probably not. But it does suggest that small, consistent positive health habits can move the needle in meaningful ways. So, here are your actionable takeaways in my opinion. If you're not eating fatty fish rich in omega-3, consider doing so or consider supplementing with at least 1 gram, preferably 2, of omega-3 fatty acids daily. If you're curious about your own rate of aging, look into epigenetic aging testing. Take the results as directional, not definitive, and consider whether they're going to motivate you to make more positive behavior change or not. And if you're looking to optimize your longevity, focus on proven fundamentals before chasing extreme interventions and spending millions of dollars that you might not have. I certainly don't. So what do you think? Are we overcomplicating longevity? Or is Bryan Johnson onto something? Drop a comment below, and if you know someone who needs to hear this, send them this video they might just save a few million dollars. What if I told you that social stress doesn't just mess with your head, it damages your DNA and biologically ages you? That's not hyperbole, it's not exaggeration, it's based on science from new data published in the journal Nature Aging. And if you're like me, juggling a life full of psychological stress, you might be wondering, How can I, how can you, how can we fight back against the age-accelerant effects of stress? Stick with me because by the end of this video, I'll share 3 tips to help you turn these lemon of data into practical mind-hacking and biology-hacking lemonade, including a powerful randomized controlled trial-backed breathing technique that could take just 5 minutes per day and could help you combat the harmful effects of stress on your biology. And make sure to stick around to the end to hear directly from the first author, Dr. Carrie Lyons, herself. But moving on, I want to give you background on aging. Aging is complex, and there's no one easy way to measure biological age. It's a little bit of a fluffy term. However, certain hallmarks of aging like DNA damage, telomere shortening, and cellular senescence are widely recognized. Senescence is the focus of this paper, and it's a process by which cells age and permanently stop dividing. Senescent cells accumulate as we age and play roles in chronic diseases like heart disease and Alzheimer's disease, dementia. Now, while senescence does have some adaptive functions, I wanna put that out there, for our purposes, it's fair to call senescence a hallmark of aging. Now, senescence can be triggered by various pathological processes, including inflammation and DNA damage, which we'll also tap on later. And senescence can be measured using markers, like p16, which is the focus of this paper. And if you want to remember this, just imagine the stress of having a pissed-off 16-year-old kid. I don't know, I don't have a teenager of my own, but I can imagine it's stressful. Anyway, in this study, the researchers subjected mice to chronic social stress, or more specifically, chronic subordination stress. The experimental mouse is exposed to an aggressive, dominant mouse every single day. The human equivalent of chronic subordination stress, chronic social stress, will be like a bully at school, or an abusive parent, or a hyper-aggressive boss. And in just 4 weeks, the experimental mouse, the one that got bullied, exhibited increases in markers of senescence, predominantly p16, this marker I mentioned earlier. And this marker of senescence and biological aging accumulated over time, with levels getting to as high as 12 times that of control mice by 26 months of age in circulating blood cells, as you can see here. But if only it were just circulating blood cells. The researchers then found something really scary. The cell type most sensitive to stress-induced senescence were neurons in the brain. You can see that here. Red marks senescent cells, the p16-labeled cells, and you can see they're massively increased in mice subjected to chronic subordination, chronic social stress. That's the red bar. And they found evidence consistent with the hypothesis that the senescence and presumed biological aging were triggered by DNA damage, which can be measured by a marker called gamma H2AX. It's not very important, but that's what you see here, a massive increase in DNA damage in chronic subordination, chronic social stress. And and increase inflammation. So to summarize quickly, chronic social stress caused DNA damage and inflammation in association with increases in a marker of senescence and biological age, that p16 we talked about, and this occurred especially in the brain's neurons. Pretty scary, right? And it's also worth noting chronic social stress is also associated with overeating and weight gain, cardiovascular, neuroimmune, and metabolic diseases, including in humans. So the signs of biological damage tend to align with clinical hard outcomes. Stress is an age accelerator. In 5 words, that's the summary: stress is an age accelerator. And as a brief aside, a nuance note, there were other nuances in this paper— different senescence markers they used, like p21, SA-beta-Gal, etc., and different responses in different non-social stress models, potential sex-dependent differences, and so on. So if you want to read the paper, I always encourage it. But I'm going to put those aside for now because I want to discuss the "so what" and suggest practical solutions that don't involve quitting your job if your boss is a jerk. So combating stressors, tip 1: awareness matters. Awareness is the first step in adaptation. And now that you've watched this video, you have a biological handhold for awareness. I think even or especially when the data are scary, as they are here, I find awareness offers the motivation to seek change. Now, by way of a personal analogy, when I found out I carry not one but two risk genes for Alzheimer's disease, two copies of the APOE4 allele, at first I was honestly freaked out. Alzheimer's scares the shit out of me. Sorry. But then I realized this was always in me, but having the knowledge especially early on in life, it's a gift. It's the motivation and power to take every preventative action. In the end, you can achieve the best outcome in a given scenario. I can't change my genes, but I can change what I do in life and the impact those genes will have on manifesting into reality. And the same goes true for these data on stress and biological aging. So tell me in the comments, do you agree knowledge and awareness is power? Anyway, moving on. Combating stressors tip 2: a growth mindset. Stress is not all bad. Stress forces you to adapt. And the balance of research shows it's not about what the stressor is. It's about how you respond to the stressor. And if you can find a way to adopt a growth mindset in a situation, focus on the positives and focus on your purpose That's huge. Now you can skip forward to the next chapter if you don't want to waste time on me rambling about myself. But again, I'm going to share a little bit of a personal example in case that resonates with anybody. So as a personal example, I've been subject to academic harassment and academic bullying over the course of my still young academic career. I'm not going to share with you the specifics. That's not really important. But to me, this is worse than physical bullying. In a physical altercation, I can punch back if I need to, when I need to. But when someone exerts their academic seniority in a very hierarchical system, especially in medicine, to attack your career, hitting up the hierarchy can sometimes create more pain for you than for the aggressor. Now, the instance I have in mind, it tore me up inside, but ultimately I did find contentment in a growth mindset. Here I mean, I internalized the truth that the event as it transpired was initiated by an unforced error on my part. I think I did the right thing ethically, but I did it in a way that left me vulnerable to attack. In retrospect, that was dumb, but it taught me not to assume that others will play fair, and that was a valuable lesson about a harsh reality that I'll carry forward with me. The issue is now resolved. Thankfully, and I'm wiser for it. So I should be, and I am grateful for the experience. Also, I focused my energy on my purpose. I'm doing an MD-PhD. Actually, I'm a few months away from finishing it after 11 years of higher education, but I'm doing this for you because I love science, teaching, conducting research that can change lives. The practical value of Oxford and Harvard brands, an MD-PhD, those letters, it's immense. And I know I will soon be in a position to leverage those credentials for the greater good—this world's metabolic health. Now, to be clear, I am not saying letters and brands should be used as a lever for credibility. I am just acknowledging the realities of our social structure and being transparent that I will play the game that needs to be played in order to make metabolic health mainstream. And the only reason I'm verbalizing this to you now in a video is because I promise myself and you authenticity. So I like to take moments aside to present that to you. Anyway, now moving on, tip 3, moving back to the science, tip 3 for combating stressors is the physiologic sigh. And this might be the most practical of all. So try practicing a physiologic sigh for just 5 minutes per day. This is a structured breathing technique characterized by 2 stacked inhales, followed by a long exhale. So a 1-second inhale stacked by a quarter-second inhale, then a 2-second exhale. Like— This physiologic sigh form of breathing is actually a method that Andrew Huberman turned me on to. You may have heard him talk about it. And it's backed by science. In fact, in a randomized controlled trial published in Cell Reports Medicine, researchers—I'll tell you who those were in a moment—compared 3 forms of breathing: a physiologic sigh, box breathing, and cyclic hyperventilation, and they compared this to meditation. And in short, they found that the physiologic sigh performed best overall at increasing positive affect, reducing anxiety, and improving physiological markers like respiratory rate. Furthermore, the benefits of daily physiologic sigh for just 5 minutes per day accumulated as people engaged in the practice for more days. So now quoting from the paper, we, the research team, found that the cyclic physiologic sigh group had significantly higher increases in positive affect as compared to those in the mindfulness meditation group. Cyclic physiologic sighing also had a significant interaction with cumulative days on protocol compared with mindfulness meditation, suggesting Subjects, those engaged in physiologic size, benefited more from the exercise the more days they did it, an effect that was not observed in other groups. Now I want to pause for another brief aside, this one on Andrew Huberman himself. One thing I'll note is that Andrew Huberman was the senior author on this paper in Cell Reports Medicine, and I want to note that because you'll notice if you follow him, Andrew promotes a lot of research, but rarely if ever self-cites. Now, this is rare, especially given his position, where he does have the influence to crank up metrics on his own research. He can do that easily, but he chooses not to. And I don't think anyone else has ever before publicly observed this quirk in Hyunbin's character, so let me be the first, as I think it speaks to his honestly humble character, and that deserves credit, at least in my opinion it does. It's sometimes hard to know the authentic person behind the brand, especially when fame invites vicious attacks. Sometimes they're warranted, sometimes they're outright lies. And how are you, as a member of the general public, to know the difference? So take this observation for what it's worth. Again, I thought it deserves some credit, because I can't think of another single famous researcher who intentionally avoids promoting their own work. It's interesting, at the very least. Do you agree? Anyway, moving on and in conclusion, I want to end this presentation by speaking to a key question about resilience to consider as this research progresses. Now, it's highly likely there are differences in vulnerability to stress-induced senescence, the topic of this paper. And the flip side of this coin is resilience to stressors, biological resilience to stressors. But what makes one more resilient? Is it about psychology? Mindset? Or is it primarily metabolic? In fact, in this paper, they note that chronic social stress, the chronic subordination stress, activates known inflammatory pathways, like those stimulated by the NLRP3 inflammasome, which can be inhibited by practices like fasting or ketogenic diets, which generate the molecule beta-hydroxybutyrate, which inhibits the NLRP3 inflammasome. So in theory, certain dietary or lifestyle practices could build resilience to social stress in terms of senescence. My hypothesis is that lifestyle practices including diet, sleep, and exercise contribute to biological resilience to social stress. And this highlights their importance in our stress-filled world. Because honestly, stress isn't going away anytime soon. So now I'll ask you, What's your first step? Will you try a physiologic sigh, reevaluate your stress response, or focus on improving your sleep or diet? Take one small step today, and then another tomorrow. Your future self will thank you. And now, here are some thoughts from the first author of this paper, Dr. Carrie Lyons, recorded exclusively for you.

Thank you, Nick Norwitz, for reaching out about our research. The data from our study are exciting because they directly link psychological stress to promoting a fundamental aspect of aging, which is cellular senescence. For a long time, people have had the idea that intense stress accelerates aging, but we didn't really know what biologically was happening to cause this. The study that we recently published found that over time, stress, especially social stress, increases the abundance of senescent cells, and that the first systems where this can be measured are the brain and in circulating blood cells. While our studies were performed in mice, a large body of research has shown that social adversity affects health and lifespan across species, from mice to monkeys to dolphins to humans. In people, multiple types of social stress, including low socioeconomic status, loneliness, and caregiving for a chronically ill loved one, are associated with greater risk of developing aging-associated diseases. So we believe that we can learn a lot about human health in regards to social stress from animal studies like ours. For more on the topic of what seems to be an evolutionarily conserved relationship between social interactions, health, and aging, I'd point folks towards two review articles that I'll link for you. The first was published in the journal Science in 2020. First author is Noah Snyder-Mackler. The second I published with my group in 2023 in Neuroscience and Biobehavioral Reviews, and it negates the current evidence we have from human, animal, and cell studies showing a link between stress and aging. The other side of the coin of stress research is research into resilience. This research shows that having supportive social relationships predicts better health outcomes in humans and in other species. Additionally, when we talk about stress from a scientific point of view, we're thinking about challenges that the subject experiences as being both uncontrollable and unpredictable. Health studies in humans have shown that people who feel a strong sense of control in their lives, even if they are experiencing social adversity, don't have the same negative health outcomes as people who don't feel that sense of control. I mention this not as a personal admonishment to anyone to take control of their lives, but is something to be conscious of looking at our own feelings and how we make others feel through our interactions and through institutional and public policies, because I do think that social stress should be regarded as a public health concern. Underlying the negative effects of social stress on health, I believe that there are both psychological and metabolic components at play. I'll add that these factors likely interact with each other and could create a bit of a positive feedback loop or have a snowball effect. The next steps for our research can be divided into two main lines of inquiry. The first would look at interventions that promote resilience to social stress-induced senescence. One might be providing our stressed mice with positive, non-aggressive social interactions with other mice. In terms of interventions more focused on the metabolic side, my PhD advisor was always very interested in diet and specifically caloric restriction, while I've always been very interested in exercise given its demonstrated ability to improve both psychological health and metabolic health. Secondly, we would like to look more closely at the specific long-term health consequences of social stress-induced senescence. This could be accomplished by exposing mice modeling a certain disease, maybe atherosclerosis, sclerosis, maybe Alzheimer's disease, to social stress while giving them either a placebo or an agent to kill senescent cells, and then seeing how both the stress and then the removal of senescent cells affects their disease progression.

When I say fat, you probably think of a blob of amorphous jiggly tissue that contains stored energy or stored calories. But the fat or lipids that fills and fluxes through our bodies is is so much more complex, and there are thousands of different lipids, each with fascinating metabolic functions that we are still exploring. And a new paper in Nature Aging entitled A conserved complex lipid signature marks human muscle aging and responds to short-term exercise has discovered a lipid signature of aging as well as a simple way to reverse it. Now, to gain a better understanding of the lipid signature of aging, they started studied in model organisms, particularly mice, taking 10 different tissues— those you see here— from young mice, 3 months old, and old mice, 2 years old. And they identified over 1,200 different lipids, over 21 different lipid classes, and found that the top 10 lipids that were significantly enriched in most tissues in aging mice were all from the BMP lipid subclass. BMP stands for bismonoacylglycerol. Glycerol phosphate, and it's a complex lipid class implicated in neurodegenerative diseases, cancer, and other disorders. So in brief, they found that accumulating levels of BMP lipids constituted an aging signature in mice. But does this hold true for humans? To answer this question, the researchers took muscle biopsies, particularly muscle biopsies, from young 20 to 30-year-old or older 65 to 80-year-old human adults. And again, like in the mice, they found elevations of BMP lipids accumulating in the muscles as we age, as can be seen in this graph. Basically, the red dots here indicate lipids that accumulate with age, and those above the horizontal line in panel B are significantly enriched with age. And as you can see, there is a lot of BMP lipids. And now for my favorite question addressed by the study, and maybe your favorite question too, if I may be so presumptuous. Can you rejuvenate your aging lipid signature? Can you attenuate, decrease BMP levels? Or are we just stuck with an aging lipid signature no matter what? Well, the answer is yes. You might have gathered from the title, we can rejuvenate our aging lipid signature, reduce BMP levels with exercise. So in a study, they took 12 overweight older women who underwent a randomized crossover trial through 3 phases. Each phase lasted 4 days and there was a sedentary phase whereby women were sitting 14 hours a day, an exercise phase whereby they took one of those 14 hours and actually exercised vigorously during it, or moderate to vigorous exercise. So 13 hours sitting, 1 hour exercise. That was the second arm. And then they had a third arm whereby they were doing a little bit more standing and walking, but not vigorous exercise. And they wanted to see, would more standing or walking or more vigorous exercise reduce BMP levels, reverse the aging signature. And what they found was that moderate to vigorous exercise for just 1 hour a day for 4 days was able to significantly reduce BMP levels, reverse the aging signature, as seen here in this graph, which is super cool. Now, that said, these data do have some limitations. For example, in the human study, only short-term effects of exercise were examined. We don't really know what the chronic effects of exercise would be in chronic exercisers. I think overall the data are very strong that a routine, an exercise routine, is very good for healthspan and longevity, but we don't know what the effects on BMP levels will be. I speculate that the more you exercise over time, the lower your BMP levels will be, the more you'll rejuvenate your lipid signature. Also, we only have muscle biopsy data. It's harder to get data from, say, a liver biopsy in generally healthy humans. So We only have one tissue in older adults, although I would suspect this would generalize across tissues as we saw in the mice. It's also not clear whether the BMP accumulation, the aging signature, is a cause or a consequence of the physiology of aging. That still needs to be worked out. Nevertheless, I think these data provide interesting new evidence that exercise is anti-aging and that this is an added benefit of exercise that can be measured in the lipid signature of the lipids circulating around, fluxing through our bodies, which is super cool. So that said, I will leave you with one final question, and I want you to answer in the comments. What is your favorite form of moderate to vigorous exercise? And also, does this video change your perspective on exercise, and is it going to change your exercise patterns? Let me know. So this video was pretty short. I thought I'd take some time to tack on some rapid-fire bonus questions or Q&A about an exercise-related topic protein. So let's just dive into it, and you can let me know if you like this format and what questions you have, and if you want me to do another episode on protein or exercise and what topics I should cover therein. That said, let's go. How much protein someone should eat is a common question. The RDA, in my opinion, is very, very low at 0.8 grams per kilogram. I think that's way too low. From what I've heard from experts, 1.6 grams per kilogram will be sufficient for most protein needs. Now, if you go higher than that, there may be some benefits on things like satiety. You can play around with that. I don't think it's necessarily harmful, provided you don't have kidney disease, but 1.6 grams per kilogram should be sufficient for most purposes. Moving on, do you need to space protein throughout the day? The answer is no, not really. There might be a tiny, tiny edge to spacing protein if you're like a very high-level, say, bodybuilder, but in general, it's more about the total protein you eat over the course of the day. So you can block it into two large meals if you want. That's what I do. Now, as for plant versus animal protein, there's a lot of debate about this. People saying plant proteins are suboptimal, they have low bioavailability. I would say this is more or less a myth, but it's a myth based in some truth. As a class, plant proteins tend to have lower bioavailability than animal proteins and a slightly different amino acid profile. But the fact of the matter is there are plant proteins with high bioavailability, say soy protein protein has much higher bioavailability than, say, peanut protein. And also, bioavailability isn't as important if you're not like teetering around the RDA. If you're, say, eating 1.6 or 1.8 grams per kilogram of protein, then you'd be getting enough protein whether or not you're eating animal protein or plant protein. As for plant protein and amino acid composition, plant proteins can have a different amino acid composition, but all plant proteins— listen to me here— all plant proteins contain all essential amino acids. And if you're eating a diversity of plant proteins and you kind of sum the amino acid profile over the day, it's not that different from eating animal proteins. So if you prefer to eat plant proteins for whatever reason— I prefer animal proteins— but if you prefer plant proteins, then I say go for it. I don't think it's going to negatively affect your muscle building or athletic performance, and I hope that myth will die. Don't know if it will, but hope it does. Another question— this is more exercise than protein— relates to keto adaptation and how how long keto adaptation takes to get back exercise performance. And I would say it depends on the kind of exercise performance you're looking for. For steady-state cardiovascular exercise, generally about 6 weeks. After about 6 weeks, you'll have sufficient keto adaptation, fat adaptation on a strict ketogenic diet to recover your steady-state cardiovascular performance. Now, highly glycolytic activities, things like sprints, will take a little bit longer to recover because you want to recover your muscle glycogen stores, and that take many months, even up to a year. Now, the fact of the matter is we don't have great data on long-term keto adaptation and highly glycolytic activities. So there is a gap in the evidence base there. But I would say in general, for steady-state cardiovascular, 6 weeks. For highly glycolytic activity, it can take much longer, months to maybe even a year. And it's not even clear then if your full performance will be recovered. I have my opinions. I think it can be, but that's still in the realm of unknown. And then the last exercise-related thing I want to plug is on a video that I also just released on L-citrulline, an amino acid. So it does relate to protein. It was a super cool paper showing that L-citrulline can talk to osteocytes in bone and help coordinate bone's response to mechanical loading. So things like running or weightlifting, you know, go do leg day, you really want your bones to remodel properly when you mechanically load them, and L-citrulline potentially can augment that effect, making your bones stronger in response to exercise. If you don't know who this man is, his name is Brian Johnson. He's a tech multimillionaire who started Braintree, which acquired Venmo and then was acquired by PayPal for $800 million, and he made off like a bandit. And now he's devoted his life to a prolonged n=1 experiment where he's trying to reverse aging, or maybe more accurately achieve aging escape velocity. I'll speak a little bit more about Bryan and my opinions on him at the end of this video. But he did go viral for this one stunt where he was taking blood donations from his 17-year-old son and then giving blood donations himself to his older father. The results of that experiment were kind of interesting. Bryan abandoned it in the past, but I predict he might pick it it up again in the future, and I'm going to tell you why again at the end of this video. But anyway, when I first saw this headline about Bryan taking blood from his son, I thought to myself, like everybody on the internet, wow, this guy is a lunatic. And quite honestly, the article that I saw was behind a paywall, so I didn't end up reading it until recently. But now I'm going to eat a slice of humble pie because I just read a paper that came out in Nature Aging that blew my mind and that Bryan Johnson is going to love. Stick around, you're gonna love it too. The paper I want to cover is entitled "Small extracellular vesicles from young plasma reverse age-related functional declines by improving mitochondrial energy metabolism," and it describes how these little packages in your blood, small extracellular vesicles or SEVs for short, can transfer metabolic youth. Isn't that exciting? Now let's not waste time and dig straight into the data. They started their experiments by looking at the chronic effects of transfer of young mice SEVs from young mice, 2 months old, to old mice? What are the long-term chronic effects? And the first obvious question is, is there an impact on longevity? And the answer is absolutely, without a doubt. Here are the survival curves, and what you see in red is the survival curve for the older mice given the young SEV injections weekly. And what you see is a 12.4% improvement in median survival, 34.4 4 months in the mice getting the young SEV injections versus 30.6 months in mice getting the PBS control injections. PBS just being the control, the details of that aren't super important. Now another question is, well, was healthspan improved? And again, the answer is a shocking yes, or a consistent yes. You can see that just phenotypically in the mice. The mice getting the SEV injections from the young mice just have a glossier coat. They look healthier and younger. And they actually did an objective analysis called a frailty index, which is kind of looking more at biological age versus chronological age. And what you're looking at here in Figure C is the frailty index for the young mice in blue. So blue is young mice throughout the paper, and then the older mice with the control injection in white, and then the red is the older mice with the young SEV injection. And what you can see is the frailty index for the older mice given the young SEVs comes back down to a level that's similar to the young mice in blue. And I'm really emphasizing the colors because This is the color scheme they carry throughout the paper, which makes the data very easy to interpret. So I'm gonna show you several graphs, and every time what I want you to look for where there's the blue, white, red is the blue is always young mice, the white is always older mice that are controls, and the red is always gonna be the older mice with the SEV injections or something equivalent. So what you're gonna look for is does the red, the older mice given the young SEVs, come to approximate or come closer to the blue, which is the actual young mice? As compared to the white, which is the older control mice. Hopefully that makes sense. They also measured a ton of other parameters. For example, in male mice, looking at testosterone, sperm quality, and fertility, all of which went up dramatically. So for example, for fertility, young males produced 8 pups per litter, whereas older males produced 4 pups per litter. But when the older males were given injection of the young SEVs, they again produced 8 pups per litter, which I think is super cool. And there were improvements in things like VO2, improvements in locomotion, how much the old mice moved around, which again returned to near young mice level, and improvements in bone density. And now this is crazy, there were changes in the brain with injection of the young SEVs into the older mice decreasing loss of cortical and hippocampal volume. The brain was protected from atrophy. In this study, in addition to looking for chronic benefits of young SEV treatment, they looked for acute anti-aging benefits by injecting older mice 7 10 times with young SEVs over just 2 weeks, and then tested for things like improvements in memory. And what they found were significant improvements in memory in things like the Morris Water Maze test and other functional tests of memory. And again, I can go through the methodological details, but really what you're looking for, as I explained before, is you have the blue, which is the young mouse, the white, which is the older mouse, and then what happens when you give the older mouse young SEVs? That's the red column. Does it approach the level of the blue, the young mouse? And yes, indeed it does. There are functional improvements in memory with acute treatment of young SEVs in older mice, showing an acute benefit in addition to a chronic benefit of these young SEVs from young mice, which is super cool. And they looked in the tissues of these mice for biomarkers of aging. So for example, one is called senescence-associated beta-galactosidase, which you can see here in blue. And basically the idea is with aging, there's going to be accumulation of this aging marker and the anti-aging signature would be a decrease in the blue. And you see that here, it's actually very obvious. So the far left is the young mice, the middle column is the aged mice that are controls, and the right column is the aged mice that get the young SEVs. And what you're looking for is in the far right column, the old mice with treatment, do they have a decrease in blue again towards the young mouse phenotype? And it's very, very obvious that they do. So you can look at any row, any tissue, but spleen for example. You see the young mice Not much blue. The aged mice, tons of blue. But then when you give aged mice the young SEVs in the far right, the blue starts to go away. And this was just one aging marker, the senescence-associated beta-galactosidase. But they looked at many other aging markers too, such as p21, p16, reactive oxygen species production, AGE generation. And basically you saw this consistent pattern whereby even acute treatment with just 2 weeks of young mouse SEV reversed aging biomarkers in addition to improvements in functional tests and things like memory and exercise patterns. So again, they're showing there's the chronic benefit of young SEV treatment, but there's even an acute, really potent benefit of young SEV treatment, which is absolutely shocking. They then went a step further to look at the heart of metabolism, mitochondria, the powerhouse of the cell, because in large part, aging is a process of accumulating metabolic dysfunction. So it would make sense that in aging mitochondria and their functionality is impaired, and this could potentially be reversed with SEV treatment from younger mice. What did they find? Well, Figure 4 as a composite shows you the answer, and the answer is again a resounding yes. There's an anti-aging effect on mitochondria whereby in aging mitochondrial activity like complex 5 ATP synthase activity goes down, ATP production goes down, mitochondrial DNA content— yes, mitochondria have their own DNA— goes down,, and mitochondrial number can also decrease. And all these things, all these features of mitochondria, were reversed, were improved with young SEV treatment, which is really astounding. And here, here's something that is super cool. Because SEVs aren't actually that species-specific, you should be able to not just take young mouse SEVs and give them to old mouse— old mice, I guess that's the plural— and improve old mice health, old mice mitochondrial function. You should be able to do the same thing with young human SEVs transferred to old mice. And indeed, they show they can do that. They show they can take SEVs from human beings given to old mice and recapitulate the anti-aging effect. Isn't that cool? I'll actually read that section from the paper. Behavioral tests revealed that young human SEVs efficiently ameliorated cognitive deficits and improved endurance exercise capacity in aged mice. This was supplement figure 13B. In young Human SEVs also significantly accelerated ATP production from mitochondria, stimulated complex V ATP synthase activity, and increased mitochondrial DNA content in the hippocampus, the brains, and muscles of aged mice. Isn't that freaking awesome? But now, here's another question, one that's probably been bugging you throughout this entire video. What is the magical anti-aging substance in these little packages that are floating around in your blood? What's inside them? And what the scientists identified is the active component, or at least one of the active components, is something called microRNAs. So you may know that DNA is generally transcribed into RNA, and then RNA is generally translated into protein. But that refers to messenger RNA, which is coding RNA, meaning the RNA codes for protein. But not all RNA actually codes for protein. There are non-coding RNAs, including microRNAs, which are regular they can regulate the production of other proteins, but they themselves are not turned into proteins, but they are metabolic regulators. And indeed, they found in the study that there were specific microRNA signatures of young SEVs that differentiated them from old SEVs, and that these young SEVs were the active components inside the SEVs that transferred the anti-aging effect. So you actually see that here. One thing I really want to draw your attention to between E and F is E is mice, F is humans. And what you see is the signature, the young microRNA signature, is the same between them, where the young microRNAs— I think it's actually in red— are the same 3. The same 3 are the anti-aging mRNAs between humans and mice, suggesting this is all pretty conserved, or consistent with the idea that it's all pretty conserved. Now, among the targets of these microRNAs was something called PGC1-alpha. PGC1-alpha is master regulator of mitochondrial biogenesis. So you can see how this puzzle is starting to fit together. And what you see is with treatment with young SEVs or treatment with these microRNAs, PGC-1α levels and activity were boosted. So now we have this picture whereby the young SEVs are carrying a particular cargo, these microRNAs, which are positively affecting metabolism, in part through positively affecting the master regulator of mitochondrial biogenesis. Autophagosis to improve overall metabolism and have this massive anti-aging phenotype. Now, PGC-1α isn't the only target, and it's not the whole picture, but you can start to see how the picture starts to puzzle together. Isn't that beautiful? And it makes a lot of sense. I want you to pause for a minute and think about this, because the biological cascade, as I've explained it, as these data have shown, makes sense. But then you juxtapose it to something that on the surface sounds crazy, like a tech billionaire taking blood from his 17-year-old And you see that headline. I saw the headline. I'm like, this is nuts. But then you have to eat your slice of humble pie when the paper comes out and it's like, wait a minute, there's biology here. There's data here. There are things that we didn't understand. I love that. I love being wrong. I love feeling like, Nick, you idiot. Like, how did you not think deeper about this to begin with? That's the way I'm feeling right now. I hope you're feeling that way too. I love that feeling. Now, in closing, I actually want to return to Bryan Johnson and my thoughts on him. I said before before, when I first saw the coverage on him, I thought he was probably a little bit cuckoo and maybe needed to find another life purpose and something to do with his hundreds of millions of dollars. I've changed my tone. I actually think, upon thinking more about it, that he and I are probably a lot alike. What he's doing, which I think is absolutely fantastic, is taking his money and doing a rigorous and public open science n=1 experiment for the benefit of the world. I love to do it, I just don't have hundreds millions of dollars and the free time to do it on scale like he does. But in retrospect, I really admire what he's doing with his open science. And when you actually sit down and get to listen to him speak, he's a pretty rational guy. I first heard him speak in long form on Trevor Noah's podcast, which I'll link below, and it was a fantastic discussion. Him talking about just his observations on human behavior and his philosophies about health. One of the things I actually got out of the conversation is I was fully convinced that what he's doing, which is a very rigorous, probably intimidating protocol for most people, he genuinely loves it. He loves what he's doing, and it's a way for him to enjoy and engage in life and is not actually restrictive to him, which was a mental shift for me about how different people live their lives. I also thought he was actually really funny. I thought he had a great ability to laugh at himself, which I really respect. And, um, one other thing that that we do share is we both love dark chocolate and macadamia nuts, but he keeps his calories tightly locked in apparently to 1,977. So I'm pretty sure I outeat him in terms of macadamia nuts at least. But that aside, I thought it was a great conversation. I actually think he's a pretty interesting, open-minded, and science-forward guy. And in terms of his Young Blood experiment, it was quite interesting. The way he explained it was he abandoned it because he wasn't seeing clinical benefits. In himself, getting the transfers from his 17-year-old son. But actually, what I didn't realize upon first looking at the coverage, literally just looking at the headline, I was being pretty superficial, was the origin of that experiment actually had to do with his father, who had been a heavy drug user and had had obesity and was approaching potentially the end of his life. So Brian had offered to his father to do a plasma transfer to him to give his father benefits. And then in addition, his His son volunteered, wanting to make it a, you know, son, father, grandfather family activity with multi-generational plasma transfer, which actually to me as a total dork sounds really fun. Bryan didn't see benefits from his son, potentially because Bryan's biomarkers were already so tuned in and he already probably had the phenotype, at least a metabolic phenotype of a young adult. But his father had massive improvements. If I'm recalling correctly, I think it was a like 25% 5-year decrease in aging, um, like velocity rate or something like that. You can listen to the podcast with Brian and Trevor because he brings it up there. But bottom line, his father actually appeared to benefit. And what's more, while Brian may not have benefited potentially because his phenotype, his metabolic profile was pretty tuned in, I wonder— I hope he comes forward and gives his impression of these new data because they were just doing plasma transfers. But now if we understand the active component these small extracellular vesicles in the plasma that are exerting the effect, I wonder if he's gonna extract and concentrate or bioengineer super anti-aging SEVs for his personal use. And then maybe there's a trickle-down or a scale-up effect whereby they become commercially available. I would certainly be interested, and I will donate as well if anybody wants to take from me as a subject. You know I like n=1 experiments. But anyway, with that, I hope you found this video really interesting. I generally think, to be perfectly honest, the anti-aging science is kind of hooey, and maybe I should change my tone on that. I do think that reading this paper really caused a cognitive shift in me, and these data I found really compelling and exciting, even if they're not all human data. I think, you know, we have a gut reaction to some things we hear about anti-aging, and there have been some cases of anti-aging science fraud, and people look at Bryan Johnson and just kind of laugh at him. But I think having an open mind about these kind of things and acknowledging that, you know, we laugh at some human strongly held notions from 50 years ago, to be humble and think, in 50 years, what are we going to laugh about? In 100 years, what are we going to laugh about? Weirdly enough, reading papers like this do help me acquire that philosophical perspective. I thought you found this interesting. I really love this video— sorry, I love this paper. I hope you love this video, and I hope you have a good day. Okay.