The biggest myth about aging, according to science

Who's in the Video Morgan Levine Morgan Levine was previously a tenure-track Assistant Professor in the department of Pathology at Yale University where she ran the Laboratory for Aging in Living Systems. In 2022, she was[…] Go to Profile Part of the Series Full Interview Explore series

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Become a Member Login The biggest myth about aging, according to science “This will help people take meaningful steps to slow the rate of aging and increase what we call their health span or their kind of time of life expectancy free from disease.” ▸ 55 min — with Morgan Levine Description Transcript Copy a link to the article entitled http://The%20biggest%20myth%20about%20aging,%20according%20to%20science Share The biggest myth about aging, according to science on Facebook Share The biggest myth about aging, according to science on Twitter (X) Share The biggest myth about aging, according to science on LinkedIn Sign up for Big Think on Substack The most surprising and impactful new stories delivered to your inbox every week, for free. Subscribe

Most of us measure age by birthdays, but what if the number on your ID tells only half the story? 

Dr. Morgan Levine explores the hidden clock inside our cells, unraveling how the biological age that reveals how fast our bodies are really aging is calculated.

MORGAN LEVINE: My name is Dr. Morgan Levine. I study the science of aging, and my book is called "True Age." My interest in the science of aging probably started when I was quite young because my father was fairly old when I was born. He was in his mid 50s, and so I became really aware of the aging process from a young age. So at a time when maybe most kids weren't contemplating their parents' disease risk and mortality, it was something I was always inherently concerned about. And then when I actually went to college, I learned there was an entire scientific field focused on trying to understand the aging process and potentially even intervene in it. And this really drove me to work on the science of aging. So my current research really focuses on trying to actually quantify or measure aging. So can we take all of the cellular molecular changes that people have undergone and actually give them a sense of how they're doing in terms of the aging process? Are the aging slower than we would expect, or are they aging faster than we would expect? We all age, but we don't all age at the same rate. So my lab is really interested in can we actually put a number to that? Can we measure how fast or slow a given person might be aging? And we think this is really critical because it probably has implications for their risk of disease in the future, their remaining life expectancy and other things that we all care about in terms of our health. I think a lot of people don't realize how much power we actually have over our aging process. So a lot of people think, "Oh, my life expectancy or my risk of getting something like cancer or heart disease is due to genetics or it's just gonna happen." But we actually have a lot of ability to kind of modulate our potential risks, or at least the timing perhaps of when these diseases might occur. So by actually having people understand the aging process, the biology that goes into it and why that's important for disease, we think that this will actually help people take meaningful steps to slow the rate of aging and increase what we call their health span or their kind of time of life expectancy free from disease.

- [Announcer] "Chapter 1: How we measure age: Biological versus Chronological."

- Most people think of age or aging in terms of chronological time. So we all know how many years we've been alive, and we usually measure our aging in terms of that time, so months, days, years since we were born. And we put a lot of emphasis and importance on this measure, but actually this isn't the number that counts. So the reason we've become so fixated on this idea of chronological age is because it's actually tied to what we consider this biological aging process. So over time, living systems like humans or any other organism, actually kind of degrade and become less functional over time. And we think of this as kind of the biological aging process. So how are our cells functioning worse than perhaps they were before, and how have our bodies kind of changed over time? And the important thing is that, unlike chronological time, this is something that's potentially malleable. So we know this from looking at different species. So you can compare a 10-year-old dog to a 10-year-old human and clearly the rate at which their bodies have declined over that time is quite different. And we even know among humans, you can look at two people who are, say, 50 years old chronologically, and clearly they may not look the same in terms of their overall health status and overall aging rate. So really it becomes important to understand the biological aging process, how far we've each kind of diverged over time and what this might mean for our future health. So there's actually a debate in the field whether aging is universal and if every organism actually ages. Most scientists actually think that aging is a universal thing among living systems, and living systems will inherently change over time and decline. But some of them actually do this at such a slow rate, what we call negligible senescence, that we actually can't observe aging in those systems. So usually to kind of tell how fast different organisms are aging, we look at their, what we call survival curves. So do you see an increased risk of mortality in a population as a function of time? And we think of that as kind of the overall rate at which that type of species or type of animal or plant is actually aging. So usually when we think of changes associated with old age, we think of functional changes, so things we can actually see in ourselves and in the people around us. So we think of changes even in things like how fast you can run or walk or your ability to go upstairs or just how much energy you have. And then we also think of these in terms of the wrinkles on our face, graying, or loss of hair, and also, to some degree, the diseases that we actually see manifest with aging. But in reality, these aren't where aging is actually starting. These are what we would call the emergence or the manifestations of aging. We really think aging is starting at a much lower level, so at the molecular and cellular level. So if I were to ask someone how old they were, their immediate response is going to be however many candles they blew out in their last birthday. It's the number on their driver's license or their passport. And really this number doesn't hold that much meaning except that it happens to be correlated with this concept of biological aging, which is actually what we really care about. And what scientists mean by biological age is really the degree to which your biology has changed over a given amount of time. And we think these changes are gonna be maladaptive, they're gonna lead to more dysfunction, more decline, and ultimately more disease. A really important thing in the science of aging is being able to actually quantify or estimate the aging process. So this is really where we get into this idea of can we measure biological age. There's three major advantages that scientists have found for trying to quantify or trying to measure the aging process. So the first one is just understanding the science of aging, understanding the biology of why systems age, what leads to this and how to intervene. The second is it provides an endpoint for any clinical trials or any science that is actually trying to intervene in this process to say whether they were actually successful at doing so. And then probably the third, which most people might care the most about, is it actually gives people an understanding of their overall health and is important for what we call risk stratification. So understanding who might be more at risk of developing these different age-related diseases, and from there actually either working with a physician or reassessing your lifestyle and behavioral factors to figure out if you can actually slow that process and monitor it in real time. And there isn't one right way to do this. And you can imagine you can use different types of data to do this. So some people might actually just use your functional abilities or the number of diseases that you've been diagnosed with as kind of an indices of how much you've changed over time. Another concept is this idea that we call phenotypic age, which really boils down to kind of how you're changing on a physiological level. These are things that you would go to your physician for your annual appointment and probably are already getting measured in a blood draw. So they're capturing things like functioning of different organs including our liver, kidney. They capture metabolic health, they capture lipids and to some degree they're also capturing things like our inflammation and immune profile. So when we put these all together, you can actually get an overall number or show on a holistic phenotypic level how you look compared to other people your age. They give us an idea of how your different organ systems are operating and kind of working together to give you your overall health. And then there are even more kind of specific ways you can do this on a molecular level or a cellular level where you're really diving into very specific types of variables that we think are where the aging process might actually be starting. And we think this measure of aging is really important because it captures the physiological changes that we actually think precede the dysfunction that we see arising in disease. So we actually think that it's predictive of future risk of disease, and it's also close enough or proximal enough to the disease that it's actually gonna be able to tell you how you're doing. So on average, we would expect most people would gain one year of phenotypic age for every one year of chronological age. So if you were to measure yourself every year on your birthday, we'd expect it to increase at one year every year. However, ideally what you would actually want to see is that your phenotypic age is increasing at a slower rate than your chronological age. And we would think of this as a deceleration or a slowing of the aging process. There's not really a right age or wrong age to start measuring your phenotypic age. So we also say it's never too late. So a lot of people think, "Well, I'm already too old, or I've already developed a disease, maybe it's not worth it to me." But we actually find that there's still a lot of malleability in terms of someone's phenotypic aging process throughout the entire lifespan. So we think that people of any age should actually be monitoring this, and you're probably already getting these measures when you go visit your doctor on an annual basis. So it's really easy to kind of put these into the algorithm and get one more variable beyond what your doctor's gonna look at. So typically when your doctor looks at your lab tests, they're gonna tell you if any of these biomarkers are in the kind of at risk or abnormal range. But that just gives you, we think of that as almost like there's high risk and low risk, but there's actually a whole spectrum of how your physiology is behaving. And there's a lot of information in knowing even if you haven't passed that high-risk threshold, are you close or are you closer to it than we would expect for your age, or how quickly are you approaching it? So this can give you additional information beyond these traditional risk measures that people look at. Because of the way phenotypic age or these other biological age measures were actually derived, the average person will have the same biological or phenotypic age as his or her chronological age. If you looked at a population, you'd expect to see a normal distribution where you find most people are predicted to be the same biological or phenotypic age as they are chronologically. But we know there's also spread on either side. And when we look at the average, for instance, United States population, we see that kind of that standard deviation or how much people kind of vary is around five years. Granted, you can get extreme outliers, so people who look 10 or maybe even 20 years older or younger than expected for their chronological age, but most people will fall in that kind of plus or minus five years of their chronological age. If you have already visited your doctor and you've got an annual blood test, you probably can get your phenotypic age test for free. So there are online calculators that list the nine biomarkers that you actually need to calculate your phenotypic age. These are freely available on the web. So all you would need to do is go and find your most recent lab tests, input the values and the algorithm will actually produce a phenotypic age measure for you. So assuming you are going and getting regular annual physicals with lab tests, this is something you can already do. And if not, you can visit your physician or something like a laboratory that offers a lot of these blood-based tests and get these for relatively little money. And over time you can actually try and modify your behaviors and see year to year if you're seeing that actually reflected in your biological age as you track it over time. Aging is the biggest risk factor for most of the diseases that people worry about, for things like heart disease and cancer and diabetes. And scientists actually think that rather than trying to treat each of those diseases individually, if we were to actually slow the rate at which people were aging and slow the decline in our different kind of organ and physiological systems, we could either prevent or perhaps lessen the impact of many of these diseases. So it's not just giving people a longer life, but it's keeping them healthy and functional for as long as possible.

- [Announcer] "Chapter 2: How we measure age: Epigenetic."

- People in the field have actually come up with what we might call hallmarks of aging. So one of these hallmarks that my lab in particular is very interested in is this concept of epigenetics. And epigenetics might not be a term that everyone's familiar with. We all know genetics, so our kind of sequence of DNA that gives rise to our different genes. But the epigenetics is really what I like to think of as the operating system of this cell. It's what gives each cell its different kind of defining characteristics in phenotype. So even though the cells in your skin and the cells in your brain have essentially the exact same DNA, what makes them different is the epigenome. So it gives them their overall function and structure. And the epigenome is actually something that has been studied in science for quite a few decades now, but the actual program or system itself is so complex that we're only just barely starting to understand the meaning of a lot of these changes that we see. So the epigenome is usually written in kind of chemical modifications. So there's different forms of these. And the one that's actually studied perhaps the most in aging, or at least in terms of trying to quantify aging, is this concept of DNA methylation. So basically what DNA methylation is is it's just a chemical tag that's added to specific parts of your genome. So you have the A, C, G and T, and DNA methylation is actually added when you have a C next to a G. And the importance of this is when it's added, it actually closes off that part of the genome. So the genome kind of folds in on itself and that part is no longer accessible. So this is how cells know which parts of the genome to access and not access, and this will be different for all the different cell types. The other thing though is that we know this epigenetic program or DNA methylation patterns are very remodeled with aging. So even though a skin cell should have a specific pattern, as people age, the pattern actually gets messed up. And we actually think that this is giving rise to dysfunction in the skin cell or their losing their essential identity, their ability to perform their specific task. Every cell in our body has a very specific function, and this function is really dictated by the epigenome. The problem is that with aging, the epigenome becomes remodeled either due to stress or random errors. And what this actually produces is that each cell is actually going to lose its identity and not function in the way it was initially intended. And over time, as more and more cells become dysfunctional, you can imagine how this would produce dysfunction at the organ level and eventually at the whole system level. One form of epigenetics is actually called DNA methylation, which is just a chemical modification to different places throughout the genome. So you have A C, G and T as the different nucleotides in our DNA, and when you have a C next to a G, they can have this chemical tag that can basically turn off regions of the genome. So scientists actually found that the pattern of these chemical tags is changed quite dramatically with aging, and using things like machine learning and AI, we've actually been able to predict how old someone appears based on these patterns of these chemical tags or DNA methylation. And this has been come to refer to as the epigenetic clock, which is basically just a way to try and quantify biological age based on either gains or losses in methylation at specific regions throughout the genome. And really we think that the changes at this level, this is what we would consider the molecular level, are what are giving rise to the changes we see at the phenotypic or physiological level. So over time, cells actually become less functional. They actually are less likely to represent what they were originally intended to do. And we see this in many diseases. So one instance might be cancer. So cells that actually have more rapid epigenetic changes may be prone to be more cancerous. And actually my lab has shown that when you measure things like an epigenetic clock, we actually see that it's highly accelerated in tumors compared to the normal tissue. We also see that the different organs in our body that are more prone to developing cancer seem to be aging epigenetically at a more rapid rate than cells that are maybe less prone to cancer. Many people might be wondering, "How do I actually get my epigenetic age measured or find out what the epigenetic clock says for me?" And right now there are some direct-to-consumer products that actually can provide this. This is a lot more expensive still than going and getting your regular lab tests because it relies on much more advanced technology to actually be able to measure all these changes. So typically if you were to use a direct-to-consumer product to measure your epigenetic age, you would do this through either a blood or saliva sample. And the question is whether that's actually a really good proxy for how your different systems or organs are aging overall. 'Cause again, your epigenetic age can be measured within different cell types and organs. That being said, the epigenetic clock measured in blood has been shown to be a good predictor of things like remaining life expectancy and disease risk. And over time these algorithms are gonna get better and better at predicting things and capturing aging overall using epigenetic measures. A number of people have become interested in the field of epigenetic clocks and started to actually monitor their epigenetic age over time. And just like measures like pheno age or other biological age indicators, this can give people a way to kind of track their overall aging process and figure out how they can change their health behaviors to try and optimize that. For people who wanna track epigenetic age on what we call an n equals one, so an individual level, we still don't know exactly what changes in epigenetic age represent. So if you were to track it, change something about your lifestyle, or you know add a new regiment and then see it a change in your epigenetic age, it's not clear what drove that or if that actually represents a change in your aging rate; verse kind of the phenotypic or physiological ones where we know a little bit more about what these markers represent. That being said, there's a lot of interest from the scientific community in actually figuring out what drives these epigenetic changes and how we can manipulate and intervene, because we actually think the point of intervention is gonna be better at this level since we think aging starts at a molecular level, so to understand what drives changes in epigenetic age and what that really represents functionally. The one exciting thing actually about epigenetic clocks is they actually seem relevant to a wide array of diseases. So they are implicated in things like cancer, so cells that seem to be more accelerated in terms of their epigenetic age seem to be more prone to cancer. But we also see it in other diseases like Alzheimer's disease or diabetes or even things like some of the lung diseases that you see. So really the amazing thing is that this process or this phenomenon is not disease specific and actually might be a unifying driver of diseases kind of across the board. The thing that's most exciting to me about studying the epigenome and the epigenetic clock is that this is actually a really powerful tool to understand some of the cellular changes that we think are potentially contributing to a wide array of diverse diseases across different tissues. So we see the same signature and same phenomenon regardless of the cell types we're looking at. And then the other really exciting thing is that this process, again, seems to be something we can intervene in. We know that it goes both ways and that it actually is something potentially amenable to being reversed. My one worry with people constantly monitoring and tracking their biological age is that people are going to inevitably want to use this for biohacking. And I think we can do this up to a certain extent, but we need to remember that none of these measures are perfect. We haven't perfectly measured biological age, and also the measure you use might give you different answers. So I think people shouldn't over-optimize to a specific biological age measure. And if you know that the things you're doing are good for health, so again, these common things like diet, exercise, sleep and stress and you're seeing that reflect in your biological age, I think you can be confident that that's probably a real result. But the one concern is that people will go and try a bunch of therapeutics or supplements just targeting this one number, and really that's not the goal here. In the end, it's really important for people just to realize how much power they actually have in terms of impacting the way in which they're gonna age and impacting the risk of disease. Our risks of disease are not written in our genes. Yes, we will probably all age, and we're not going to essentially stop that, but the rate at which that happens and the length of time that you can maintain health and optimal functioning really comes down to a lot of what you do in your everyday life.

- [Announcer] "Chapter 3: Is aging a disease?"

- There's a lot of debate in the scientific field of aging whether aging is actually disease that should be treated like we treat diseases. My personal take on it is that aging is not actually a disease in and of itself but it's the process that actually contributes the most to many of the diseases we care about. So that being said, I actually think we should intervene and try and treat or at least slow the rate of aging, but we shouldn't think of it as a disease 'cause there isn't a clear point where you say you have aged a specific amount that you now have a disease. And we are all aging from the time we're born to the time we die. And ultimately what's important is how do we slow this process in an idea that will prevent many of the diseases that people are actually trying to treat. A lot of people think the aging field is focused on this concept of immortality or curing death or curing aging. That is a little bit fringe to I think a lot of the science that's going on. And really what the field is focusing on is how can we prevent the diseases of aging and keep people healthy for as long as possible. And if that ends up increasing life expectancy, that's almost a bonus. But the goal is not immortality. Our bodies are set up to function in a very specific way. This is something we've evolved, but over time that function does decline. And this is what we actually see in terms of manifestations of disease, diseases really, once your body has reached a dysfunctional state in terms of one type of process. And the reason that our bodies actually get to that point is because of all the changes we think that are accumulating as a function of this aging process. Granted, there can be other things like an infection or genetic kind of predisposition that might give people a disease, but most of the diseases like cancer, cardiovascular disease, Alzheimer's disease are these progressive loss of function in our various systems that we think is directly driven by the aging process. So if we can actually figure out how to slow our aging rate internally, we think, and actually science has shown, that this will probably manifest in terms of our external appearance as well. Living systems are really remarkable. Through evolution, we've evolved to have this beautiful kind of coordination and specificity that kind of makes us who we are. So cells have specific roles, our organs are set up to function a specific way and this really gives us life. However, all of these things that are kind of determining the function of these organs and cells actually degrades with time. So we think of this as kind of the molecular changes that enable cells to function a certain way are rewritten with aging. And now cells actually lose their specificity, they become more dysfunctional. As you accumulate more dysfunctional cells in your tissues and organs, those organs are now not working the way they're originally intended to. And over time, as your organs start to dysfunction, you actually start seeing this at the whole body level. So we start seeing overall declines in our kind of bigger functional aspects. So just our ability to run for a bus, or our ability to hear our friend say something to us, these bigger functional attributes are actually degraded with time due to all these small changes that are accumulating at the molecular and cellular level. Living systems are also remarkable in that we're actually open systems, so we can take energy in from our environment and actually use that to sustain ourselves. So in general, non-living systems will kind of degrade in terms of this entropic change at a fairly constant rate. But actually our systems have adapted to actually have a buffer, resilience. We can use energy to maintain our kind of function and structure for much longer, but over time this will eventually get kind of overpowered and we will still see this kind of dysregulation and functional decline as we also see a loss of resilience. Aging is really personified by dysfunction, and we see a lot of this in the diseases that tend to arise with aging. So one great example is a disease like diabetes where we actually see dysfunction in terms of our metabolic health, where we get this accumulation of glucose throughout our circulation. But there are other diseases of aging that are also associated with dysfunction. So things like cancer are actually our own dysfunctional cells that are not behaving the way they were initially intended. Many diseases of aging can actually be attributed to dysfunction, decline in specific organ systems. So something like diabetes can be thought of as a decline in our metabolic system. Things like Alzheimer's disease are declines in dysfunction in our central nervous system. And another disease of aging called sarcopenia, which is actually the muscle wasting that we see with aging, can be thought of as declines in actually multiple systems including our metabolic system and also our musculoskeletal systems. Until the science actually up with drugs or treatments to actually try and target aging, lifestyle right now is actually our best ticket in terms of slowing our aging process. And this is really because, again, living systems are adaptive. We adapt to our environment, we adapt to the things we experience. So you can actually boost things like resilience through different lifestyle behaviors. So for instance, physical activity or exercise can actually increase our resilience and buffer us against further stressors down the road. We also know that different dietary regimens can actually increase our resilience as well and we think slow the aging process overall. And these aren't new things. These are things that we've been told about from, let's say, our mothers or grandmothers, you know, eat well, get good sleep, exercise, don't smoke. So these shouldn't be a surprise to people, but I think people don't realize how much these actually impact how fast they're gonna age and also their propensity for developing different age-related diseases.

- [Announcer] "Chapter 4: "Can we reverse aging?"

- We actually think, as a science, whether we can actually figure out ways to slow or perhaps even reverse these biological changes that actually matter for the aging process. We don't know to what extent we can actually reverse aging in a whole body, although we do know that you can reverse the age of a cell. So this happens in development when you have two cells from a female and male that come together and produce an entirely new age-zero organism, even though they came from parents that perhaps were in their 20s or 30s or even 40s. And we've actually found that in science we can do this in a dish. So we can activate specific factors that can take, let's say, a skin cell from a 75-year-old and convert it back into something that's almost indistinguishable from a cell from an embryo. So we know that, at least at the cellular level, this is possible. The question is can you actually do that in an adult organism? For those of us that are actually old enough to get to go to our high school reunion, let's say your 20 or 30-year-old high school reunion, we know that if you were to go there, not everyone looks like they're at the same chronological age, even though they probably are. Some people look exactly like they did when you graduated high school, so they haven't changed since they were 18, whereas there might be other people who you don't even recognize. And you look at them and you think, "I can't possibly be that old, we haven't aged that much." So we know inherently that people don't all age at the same rate, and some of us are going to be faster agers and some of us are gonna be slower agers. And ultimately the question is how do you become a slow ager? Like many of the things we've talked about in terms of aging, the epigenome, again, is highly dynamic. These are things that can go, we think, in both directions. So you can increase epigenetic age, but we've also shown that you can actually reverse this in cells. So Shinya Yamanaka actually won the Nobel Prize for discovering four factors that, when you overexpress these in cells, it can convert an old cell or basically any cell type back into what looks like an embryonic stem cell. And later as scientists were actually applying things like the epigenetic clock to this data, we found that not only are you changing the cell type, but you're also erasing or essentially reversing all those epigenetic changes that we've actually used to try and quantify biological age. So then the question becomes how do you do this in a body? Can you actually what we call reprogram or program cells from an old epigenetic state back into a younger epigenetic state? And then the question becomes what does this actually mean for our physiology and our health? So some people might actually say that we have solved the aging problem with cells in a dish. We can age cells, and we can reverse their age and essentially reset them to an age zero. And then people are now trying to actually do this in an organism. So right now to start out, people are doing this in mice where again, in different mouse models, you can over express these four factors commonly referred to as Yamanaka factors. And the scientists have actually observed that the mice seem to have improvements in different functional outcomes and there perhaps might be an increase in life expectancy, although this needs to be followed up a little bit more. The most amazing thing about this science is that we always thought aging really happened in one direction, that these were just stochastic damage that you couldn't go back and fix because there was just so widespread and so much of it, and that the only thing you could really do was just slow the accumulation of this damage. But really what this reprogramming of the epigenome tells us is that this is a lot more kind of modifiable and elastic than we originally knew. So you can actually take a cell that has aged and is of a given type and completely change its state using just a few factors. And so this really opens up this whole idea of things like cell engineering. So how do we take cells and move them to states that we actually think more functional and healthier? And how do we figure out what types of states actually give rise to health and function in our different organ systems? And then once we know those states, can we move different cells into them? A lot of the changes that cells undergo with aging, including changes to the epigenome, actually give rise to some diseases like cancer. So the risk of cancer actually increases exponentially with age. And we think some of this might be due to the types of changes that are measured when we look at the epigenome. So one hypothesis is if you can actually remodel or reprogram the epigenome to a younger state, that you actually might prevent some of these cells from developing into cancers. Now that won't deal with some of the mutations that might proceed cancer, but actually a lot of mutations accumulate early in the lifespan. And the question is, what is happening with aging that is still later on pushing these cells to become cancerous? The epigenetic clock has been really remarkable in that it can actually track aging across a diverse array of cell types and organ systems. So you can use the same measure to track aging in your skin as you would use in your liver or in your blood. And more importantly, what we find is actually the difference between the age you get predicted based on the epigenetic clock and your chronological age holds biological meaning. And the reason we think it holds biological meaning is because it actually seems to be somewhat predictive or indicative of different kind of outcomes or diseases in whichever organ it was measured in. So when I measure epigenetic age in the blood, what we find is that that measure is actually predictive of things like remaining life expectancy or heart disease risk or diabetes. We've actually looked at epigenetic age measured in the brain, these are people after they've died. But what we find is that that seems to be correlated with the pathology associated with things like Alzheimer's disease. So we think even though we haven't proven that this is causally driving these diseases, it does seem to be a signature for the aging processes that seem to give rise to the diseases of aging. As we continue to develop and improve these epigenetic clock measures, they'll actually be highly useful for tracking things like aging and actually understanding things like disease risk. So the great thing is that epigenetic clock measures aren't just giving you a whole-body aging measure, but we can actually measure it in different subsystems and understand how people might be differently aging across different systems in their body. So some people might be more prone to metabolic aging, other people might be more prone to kind of inflammatory aging. And that profile, when you take it all into consideration, might give you a better idea of, one, the interventions or the lifestyle factors that you should actually implement in your life, or two, the specific diseases that you might be more or less at risk for. The reason why scientists are so excited about the idea of intervening in the aging process, whether it be slowing the aging process or reversing the aging process, is because we actually think that in doing so we can stop all of the different changes that are giving rise to the diseases that we care about. So rather than going after one disease at a time and having, you know, one type of science aimed at trying to cure cancer and another aimed at diabetes, if we actually could reverse or slow aging, we could basically eliminate diseases or at least postpone diseases across the board. Right now people are using the epigenetic clock as more of a diagnostic as opposed to a means to intervene. So people are using it as potentially one indicator of how they're aging overall. It's not a perfect indicator, and it's only capturing one facet of the aging process, but it can give people some indication of their health status and potentially their overall risk of developing different diseases of aging.

- [Announcer] "Chapter 5: "How nutrition enables longevity."

- Nutrition science is actually something that people in the longevity and aging field have been very interested in. And actually for hundreds of years, people have been studying how our diets and the amount of food and types of food we eat seem to impact our aging. But the science is also really difficult because, at least in humans, it's hard to actually assign people specific diets and actually have them maintain those for a long enough time to study them in kind of this randomized clinical trial way. So usually what scientists end up kind of leaning on is what we call epidemiological or observational data. So they look at populations and they compare the diets that different people eat, and then they look at kind of the features of those people. Using things like biological aging or disease risk or life expectancy, do certain diets tend to correlate with certain outcomes? The problem with this is it's really hard to say anything about whether the diet is actually causing those things, and also people who tend to have healthier diets also have other health behaviors that go along with them. So figuring out exactly what components of diet matter is really difficult. The main dietary component that's actually been studied in the aging and longevity field is actually this idea of caloric restriction. So more than a hundred years ago, researchers actually saw that when they restrict the amount of calories that animals eat, they tended to live longer. And so this really sparked an entire field of studying this concept of caloric restriction. Caloric restriction isn't starvation, it's usually just about a 20% reduction in the overall calorie intake. And in a lot of different animal models, so anything from a worm, fly, mouse, people have seen that when animals are caloric restricted, they tend to live longer. One caveat though is that this actually may be different depending on genetics. So there was a study in mice that actually showed mice with different genetic backgrounds. Some of them benefited from chloric restriction, some of them had no effect, and then actually some of them did worse. So we actually think that the amount of chloric restriction our bodies can tolerate might be genetically determined and that actually this should be a more personalized regimen. When trying to figure out if something like caloric restriction is actually beneficial to the aging process in terms of slowing aging, one caveat is that humans today are actually not kind of at baseline. We're actually more prone to overeating. So some researchers have figured out that it might not be the caloric restriction that's actually the beneficial thing but the kind of tendency away from overeating. Even if you can't restrict your calories in terms of what's actually been studied in caloric restriction, just moving away from over consumption or overeating and being more in line with your actual caloric needs, based on your energy out, is probably gonna have a beneficial effect for most people. The discovery of caloric restriction was on accident. So the scientists weren't actually going in to try and study how diet was affecting aging and longevity. But they just happened to find that when their, in this case it was rats, were eating a lower-calorie diet, they tended to live longer. And after that was first discovered a few hundred years ago, people continued to study this, and it really became a big deal in kind of the 1970s and 1980s and moving even into today where people have tried to figure out what is the mechanism by which reducing your calories into this kind of minimal deficit produces a kind of extension in terms of life expectancy and healthy disease-free life expectancy. Diet is probably the behavior that's been studied the most in terms of trying to affect things like aging and longevity. So in animals it's shown to have a quite marked effect on life expectancy. But it doesn't mean that your diet has to be extreme. So when we say it's gonna have a big effect, this might just mean avoiding certain diets like overconsumption or eating a lot of things that we actually already know are bad for us and just maintaining a moderate diet that is in line with our energy needs on a daily basis. There are really three components of diet that seem to be impacting aging. So the first is how much we eat, the second is what we eat, and the third is perhaps when we eat. So in terms of how much we eat, a lot of science went into this idea of caloric restriction, but really, again, it's maintaining even a slight deficit to no deficit. So most of us aren't going to be able to maintain a 20% calorie deficit for our whole life. But as long as we can meet needs that are in line with our energy expenditure and we're not over-consuming, we think that's gonna have a benefit for overall aging in health. The other thing that's been studied is this concept of what we eat. So a lot of research has gone into whether things like a plant-based diet are actually beneficial to aging longevity, and there seems to be some evidence that a moderately low animal protein diets, so eating less animal products, more fruits and veggies, more whole foods is gonna be better overall. Also minimizing things like refined sugars and the things that we actually know are bad for our health. The third comes down to when we eat, and this is really a new field in kind of aging and longevity science. So again, most people aren't gonna be able to calorically restrict, but what scientists found is actually fasting can mimic some of the benefits that we've seen with caloric restriction. So if people can fast for, you know, a number of hours throughout the day, so perhaps minimize their eating to a small window, we think that this can actually recapitulate a lot of the benefits that we're seeing in the caloric restriction studies. So there's still some debate about when that window should occur. So some of the scientists actually pointing to front loading your calories, so eating earlier in the day and trying to fast throughout the day. But we're also not sure, for a lot of people it's easier to do the opposite and have just a dinner and calorically restrict early. So we're not sure actually if that would have the same benefit as doing it earlier. The idea of why things like caloric restriction or fasting might actually improve our aging process and increase our health is because we think this kind of evokes this idea of hormesis in our bodies. So what hormesis refers to is a mild stressor that actually makes our bodies more resilient and robust distress over time. So having these short-term mild stressors, whether it be fasting or whether it be a small caloric deficit, actually makes our bodies more robust and we think more resilient against a lot of the changes we see that increase with aging. So what we eat may also change depending on who we are. So we also know that our genetics might determine what we should be eating and how much, but also our age might change what we should be eating and how much. So people who are older and more prone to things like muscle loss or weakness might actually need more protein than people who are younger, where science has actually shown that a low-protein diet might be beneficial. So it's important to keep in mind that these things aren't set in stone and really need to be considered on a personalized basis. It's not that easy to figure out what the optimal or ideal diet is for each of us. We don't know exactly how things like genetics are going to predispose people to different diets, but one way to do this is to actually keep track of a lot of these health indices, things like our biological age measures to actually see how our diet is affecting us. So if you were to completely change your diet or introduce something like intermittent fasting, do you see that reflected in your measures? The other things are just functionally how you're feeling. So as people get older and, again, might be more prone to things like weakness or muscle wasting, they might actually want to increase things like protein in their diet to make sure they're maintaining some of these functions that they might see declining with time. As we move forward in the science and actually develop more of these biomarkers of aging, I think this will really start to accelerate our understanding of how diet impacts the aging process. But for now, what we can say is that probably the best advice is to not eat too much and try and maintain kind of a whole foods organic diet with not too much animal protein in it. People have been really consumed with the idea of immortality and aging for a very long time. But the question is, is a longer life truly a better life? And in some cases, perhaps yes, but not always. So really what matters to most people is quality of life. So we all want to maintain our health and our functions and be able to enjoy the things that actually make life worth living. So really what aging science is about is not just prolonging life at all cost, but actually prolonging healthy life. So can we delay the onset of disease? Can we delay the onset of functional decline and keep people healthy and functioning for as long as possible? So we think if we actually intervene in the aging process itself, that we can delay all of the things that actually people are scared about when they think of aging. And that's really the goal. We want to increase quality of life and maintain that over time. And if that produces a longer life, that's an extra bonus. But that's not the ultimate goal. We know that there is sometimes a disconnect between this concept, what we call lifespan and health span. So lifespan, again, is just the time you've been alive between birth and death. And what scientists think health span is is the time you are alive in a more healthy functioning state. And that's really what we're trying to optimize. But sometimes we see a disconnect or discordance between these two features. So one example is actually this idea of the health survival paradox that we see between men and women. So on average, women across the world tend to live longer by a few years than men. But women are also more prone to some of the diseases we see with aging. So things like arthritis, Alzheimer's disease. And really on average, women tend to spend more time in some of this age-related disability than men do. And some might argue is that a better life because they've lived longer? Or would you actually want maybe a shorter life but more free from these diseases of aging? In thinking about how we actually want to intervene in aging and what we want to be the outcome of our science, this really comes down to this concept that we call compression of morbidity. So the idea is, can we push the onset of disease and disability as far away so that right before you die, you're really compressing the timing of disease into this really short window, as opposed to kind of having it earlier in life and surviving 20, 30 or 40 years with these diseases of aging? And we think this is possible 'cause you can actually look at centenarian populations and see that they actually tend to compress the timing of disease into the short window right before death. So they're spending the majority of their life in a much more healthy state. And really what we want to do is figure out how can we have this possible for everyone so that we can remain healthy, functioning and happy with good quality of life for as long as possible. Another really important thing to keep in mind, in terms of longevity science, is that we actually don't wanna increase what we call health disparities. So right now, even though the average kind of life expectancy in the population is just under about 80 years, we wanna make sure that we can get everyone to a longer and healthier life and not just have interventions or therapeutics that help richer or more affluent people get there. And really how do we make sure that everyone can have as healthy and long a life as possible.

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