While we all know our chronological age — the number of candles on our last birthday cake — that number isn’t as important as our biological age. It reflects the amount of wear and tear currently on our body, and Dr. Morgan Levine, a leading researcher in the science of aging, has spent her career developing ways to measure it.
Levine argues that we generally underestimate the amount of influence we have on how our bodies age. Many assume their health outcomes are fixed by genetics, but biology tells a much different story. By understanding the mechanisms of aging, we can make meaningful lifestyle changes that could not only extend our lifespan, but also increase our healthspan.
0:00 The science of aging
2:14 How we measure age: Biological versus chronological
3:58 What aging looks like across species
4:45 Aging beneath the surface
5:55 Can we measure aging?
9:39 Slowing aging to extend health
13:33 How we measure age: Epigenetic
15:36 From molecular errors to systemic decline
19:48 Intervening in aging without over-optimizing
24:00 Is aging a disease?
26:31 How disease happens
29:39 The power of lifestyle
30:48 Can we reverse aging?
32:45 Reprogramming cells to a younger state
35:53 Why measuring age changes how we treat disease
40:15 How nutrition enables longevity
41:42 The science behind caloric restriction
44:40 What diet research really suggests
50:20 Living better, not just longer
The below is a true verbatim transcript taken directly from the video. It captures the conversation exactly as it happened.
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 started when I was quite young because my father was fairly old when I was born. He was in his mid-50s, and I became very aware of the aging process from a young age. At a time when most kids weren’t contemplating their parents’ disease risk and mortality, it was something I was always concerned about. When I 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. This discovery really drove me to work on the science of aging.
My current research focuses on trying to quantify or measure aging. Can we take all of the cellular and molecular changes that people have undergone and give them a sense of how they’re doing in terms of the aging process? Are they aging slower than we would expect, or faster than we would expect?
We all age, but we don’t all age at the same rate. My lab is interested in whether we can put a number to that, can we measure how fast or slow a given person might be aging. We think this is critical because it probably has implications for future disease risk, remaining life expectancy, and other aspects people care about in terms of their health.
I think a lot of people don’t realize how much power we actually have over our aging process. Many people assume their life expectancy or risk of diseases like cancer or heart disease is due to genetic or inevitable. But we have much more ability to modulate those risks, or at least the timing of when diseases might occur. By helping people understand the biology of aging and why it matters for disease, we think this can empower people to take meaningful steps to slow aging and increase what we call health span—their time of life expectancy free from disease.
Most people think of age or aging in terms of chronological time. We all know how many years we’ve been alive, and we usually measure our aging in terms of that time—months, days, and years since we were born. We put a lot of emphasis and importance on this measure, but this isn’t the number that counts. The reason we’ve become so fixated on chronological age is because it’s tied to what we consider the biological aging process.
Over time, living systems like humans or any other organism degrade and become less functional. We think of this as the biological aging process. How are our cells functioning worse than they were before, and how have our bodies changed over time? The important thing is that, unlike chronological time, this process is potentially malleable.
We know this from looking at different species. 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. Even among humans, you can look at two people who are 50 years old chronologically, and they may not look the same in terms of overall health status or overall aging rate. So it becomes important to understand the biological aging process, how far we’ve each diverged over time, and what this might mean for our future health.
There’s a debate in the field about whether aging is universal and whether every organism actually ages. Most scientists think aging is a universal feature of living systems, and that living systems inherently change and decline over time. But some organisms do this at such a slow rate—what we call negligible senescence—that we can’t observe aging in those systems.
To tell how fast different organisms are aging, we look at what we call survival curves. Do we see an increased risk of mortality in a population as a function of time? We think of that as the overall rate at which a species, animal, or plant is aging.
When we think of changes associated with old age, we think of functional changes—things we can see in ourselves and in the people around us. This includes how fast you can run or walk, your ability to go upstairs, or how much energy you have. We also think about wrinkles, graying or loss of hair, and the diseases that manifest with aging. But these aren’t where aging starts. These are the emergence or manifestations of aging.
We think aging starts at a much lower level, at the molecular and cellular level. If I ask someone how old they are, their immediate response is usually the number of candles they blew out on their last birthday, or the number on their driver’s license or passport. That number doesn’t hold much meaning except that it happens to be correlated with biological aging, which is what we really care about.
Biological age refers to the degree to which your biology has changed over a given amount of time. We think these changes are maladaptive and lead to more dysfunction, more decline, and ultimately more disease. A major focus in the science of aging is being able to quantify or estimate this process—whether we can measure biological age.
There are three major advantages to quantifying aging. The first is understanding the science of aging—why systems age, what leads to it, and how to intervene. The second is that it provides an endpoint for clinical trials or other research that is trying to intervene in the aging process, to determine whether those interventions are successful. The third, which most people care about the most, is that it gives individuals an understanding of their overall health and is important for risk stratification.
Risk stratification means understanding who may be more at risk of developing age-related diseases. From there, people can work with a physician or reassess lifestyle and behavioral factors to see whether they can slow that process and monitor it in real time. There isn’t one right way to do this, and different types of data can be used.
Some approaches use functional abilities or the number of diagnosed diseases as indices of how much someone has changed over time. Another concept is what we call phenotypic age, which reflects changes at a physiological level. These are measures you typically get during an annual doctor’s visit through a blood draw. These measures capture organ function, including liver and kidney function, metabolic health, lipids, and to some degree inflammation and immune profiles.
When we put these together, we can generate an overall number that shows on a holistic phenotypic level, compared to other people their age. This gives us an idea of how different organ systems are working together to produce overall health. There are also more specific ways to measure aging at the molecular or cellular level, where we diving into on variables that may represent where aging actually be starting.
We think these measures are important because they capture physiological changes that precede the dysfunction seen arising in disease. We think it’s predictive of future risk of disease and it’s close enough to disease that it’s actually going to tell you how you’re doing.
On average, we expect people to gain one year of phenotypic age for every year of chronological age. If you measured yourself every year on your birthday, you’d expect it to increase by one year every year. Ideally, though, phenotypic age would increase more slowly than chronological age, which we think of as a deceleration or a slowing of the aging process.
There’s no right or wrong age to start measuring phenotypic age, we always say it’s never too late. Some people think they’re already too old or already have a disease, so it may not be worth it. But we find there’s still a lot of malleability in phenotypic aging throughout the entire lifespan.
People of any age can monitor this, and you’re are already getting these measures during your annual doctor visits. It’s relatively easy to input these values into an algorithm to generate an additional variable beyond what doctors usually look at. Typically, doctors focus on whether biomarkers are in an abnormal or high-risk range, but there’s a whole spectrum on how your physiology is behaving. Even if you haven’t crossed a high-risk threshold, it’s valuable to know whether you’re closer to it than expected for your age or how quickly you’re approaching it. This can give you additional information beyond traditional risk measures.
Because of how phenotypic age and other biological age measures were derived, the average person will have a biological age that matches their chronological age.
In a population, you’d expect a normal distribution, with most people are predicted around the same phenotypic age as they are chronologically. But we know there’s also spread on either side. For instance when we look at the U.S. population, the standard deviation is about five years. While there are extreme outliers who appear 10 or even 20 years older or younger than expected, most people fall within plus or minus five years of their chronological age.
If you’ve already had an annual blood test, you can likely calculate your phenotypic age for free. Online calculators list the nine biomarkers needed, which are publicly available. You can input values from recent lab tests and receive a phenotypic age estimate for you. So if you get regular physicals, this is something you can already do. If not, you can visit a physician or a lab offering blood-based tests for relatively little cost. Over time, you can modify behaviors and see whether those changes are reflected in your biological age year to year.
Aging is the biggest risk factor for most diseases people worry about, including heart disease, cancer, and diabetes. Scientists think that instead of treating each disease individually, if we slow the rate of aging and physiological decline could prevent or lessen the impact of many diseases. The isn’t just giving people a longer life, but a healthier and more functional one for as long as possible.
People in the field have come up with what we might call hallmarks of aging. One of these hallmarks that my lab in particular is very interested in is this concept of epigenetics. Epigenetics might not be a term that everyone’s familiar with. We all know genetics, our sequence of DNA that gives rise to our different genes. But epigenetics is what I like to think of as the operating system of the cell. It’s what gives each cell its different defining characteristics in phenotype.
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. It gives them their overall function and structure. The epigenome is something that has been studied in science for quite a few decades now, but the program or system itself is so complex that we’re only just barely starting to understand the meaning of many of these changes that we see.
The epigenome is usually written in chemical modifications. There are different forms of these. The one that is studied perhaps the most in aging, or at least in terms of trying to quantify aging, is DNA methylation. Basically, DNA methylation is a chemical tag that’s added to specific parts of your genome. You have A, C, G, and T, and DNA methylation is added when you have a C next to a G.
When it’s added, it closes off that part of the genome. The genome folds in on itself and that part is no longer accessible. This is how cells know which parts of the genome to access and not access, and this is different for all the different cell types.
We also know that this epigenetic program, or DNA methylation patterns, are very remodeled with aging. Even though a skin cell should have a specific pattern, as people age, the pattern gets messed up. We think this gives rise to dysfunction in the skin cell, or they lose their essential identity, their ability to perform their specific task.
Every cell in our body has a very specific function, and this function is dictated by the epigenome. The problem is that with aging, the epigenome becomes remodeled either due to stress or random errors. What this produces is that each cell is going to lose its identity and not function in the way it was initially intended.
Over time, as more and more cells become dysfunctional, you can imagine how this produces dysfunction at the organ level and eventually at the whole system level.
One form of epigenetics is DNA methylation, which is a chemical modification to different places throughout the genome. 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 turn off regions of the genome.
Scientists have found that the pattern of these chemical tags changes quite dramatically with aging. Using machine learning and AI, we’ve been able to predict how old someone appears based on these patterns of chemical tags, or DNA methylation. This has come to be referred to as the epigenetic clock, which is a way to quantify biological age based on gains or losses in methylation at specific regions throughout the genome. We think that changes at this level, what we consider the molecular level, give rise to the changes we see at the phenotypic or physiological level. Over time, cells become less functional. They are less likely to represent what they were originally intended to do. We see this in many diseases. One instance is cancer.
Cells that have more rapid epigenetic changes may be more prone to being cancerous. My lab has shown that when you measure things like an epigenetic clock, it is highly accelerated in tumors compared to normal tissue. We also see that the 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 less prone to cancer.
Many people might be wondering how to get their epigenetic age measured or find out what the epigenetic clock says for them. Right now, there are direct-to-consumer products that can provide this. This is more expensive than regular lab tests because it relies on more advanced technology to measure these changes.
Typically, if you use a direct-to-consumer product to measure epigenetic age, this is done through either a blood or saliva sample. The question is whether that is a good proxy for how different systems or organs are aging overall, because epigenetic age can be measured in different cell types and organs.
That being said, epigenetic clock measured in blood has been shown to be a good predictor of remaining life expectancy and disease risk. Over time, these algorithms are going to get better at predicting aging overall using epigenetic measures.
A number of people have become interested in epigenetic clocks and have started to monitor their epigenetic age over time. Like measures such as phenotypic age or other biological age indicators, this gives people a way to track their aging process and figure out how they can change their health behaviors to try to optimize that.
For people who want to track epigenetic age at an n equals 1 or an individual level, we still don’t know exactly what changes in epigenetic age represent. If someone tracks it, changes something about their lifestyle, or adds a new regimen and then sees a change in epigenetic age, it’s not clear what drove that or whether it represents a true change in aging rate, versus phenotypic or physiological measures where we know a bit more about what those markers represent.
That being said, there is a lot of interest in the scientific community in figuring out what drives these epigenetic changes and how we can manipulate and intervene. We think the point of intervention may be better at this level, since we think aging starts at a molecular level, so understanding what drives changes in epigenetic age and what that represents functionally.
One exciting thing about epigenetic clocks is that they seem relevant to a wide array of diseases. They are implicated in cancer, where cells that appear more accelerated in epigenetic age seem more prone to cancer. We also see this in diseases like Alzheimer’s disease, diabetes, and some lung diseases. The remarkable thing is that this phenomenon is not disease-specific and may be a unifying driver of disease across the board.
The thing that is most exciting to me about studying the epigenome and the epigenetic clock is that this is a powerful tool for understanding cellular changes that may contribute to a wide array of diseases across different tissues. We see the same signature and the same phenomenon regardless of the cell types we’re looking at.
Another exciting thing is that this process seems to be something we can intervene in. We know that it goes both ways and may be amenable to being reversed. One worry I have with people constantly monitoring their biological age is that people will want to use this for biohacking. We can do this to a certain extent, but we need to remember that none of these measures are perfect. We haven’t perfectly measured biological age, and the measure you use might give different answers.
People shouldn’t over-optimize to a specific biological age measure. If the things you’re doing are good for health, like diet, exercise, sleep, and stress, and you see that reflected in your biological age, you can be confident that’s probably a real result.
The concern is that people will try therapeutics or supplements targeting one number, and that isn’t the goal. In the end, it’s important for people to realize how much power they have in impacting how they age and their risk of disease. Our risks of disease are not written in our genes. Yes, we will all age, and we’re not going to stop that, but the rate at which it happens and the length of time you maintain health and optimal functioning comes down to a lot of what you do in everyday life.
There’s a lot of debate in the scientific field of aging whether aging is a disease that should be treated like we treat diseases. My personal take on it is that aging is not a disease in and of itself but it’s the process that contributes the most to many of the diseases we care about. That being said, I 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 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 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 see in terms of manifestations of disease, diseases once your body has reached a dysfunctional state in terms of one type of process. And the reason that our bodies 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 predisposition that might give people a disease, but most of the diseases like cancer, cardiovascular disease, Alzheimer’s disease are progressive loss of function in our various systems that we think is directly driven by the aging process. If we can figure out how to slow our aging rate internally, 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 coordination and specificity that 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 determining the function of these organs and cells degrades with time. We think of this as the molecular changes that enable cells to function a certain way are rewritten with aging. And now cells 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. Over time, as your organs start to dysfunction, you start seeing this at the whole body level.
We start seeing overall declines in our bigger functional aspects. So our ability to run for a bus, or our ability to hear our friend say something to us, these bigger functional attributes are 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 open systems, so we can take energy in from our environment and use that to sustain ourselves. So in general, non-living systems will degrade in terms of this entropic change at a fairly constant rate. But our systems have adapted to have a buffer, resilience.
We can use energy to maintain our function and structure for much longer, but over time this will eventually get overpowered and we will still see this 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 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 our own dysfunctional cells that are not behaving the way they were initially intended. Many diseases of aging can 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 the muscle wasting that we see with aging, can be thought of as declines in multiple systems including our metabolic system and also our musculoskeletal systems.
Until the science comes up with drugs or treatments to try and target aging, lifestyle right now is our best ticket in terms of slowing our aging process. This is because, again, living systems are adaptive. We adapt to our environment, we adapt to the things we experience.
So you can boost things like resilience through different lifestyle behaviors. So for instance, physical activity or exercise can increase our resilience and buffer us against further stressors down the road. We also know that different dietary regimens can 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, eat well, get good sleep, exercise, don’t smoke. These shouldn’t be a surprise to people, but I think people don’t realize how much these impact how fast they’re going to age and also their propensity for developing different age-related diseases.
We think, as a science, whether we can figure out ways to slow or perhaps even reverse these biological changes that matter for the aging process. We don’t know to what extent we can reverse aging in a whole body, although we do know that you can reverse the age of a cell.
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 found that in science we can do this in a dish. 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. We know that, at least at the cellular level, this is possible. The question is can you do that in an adult organism?
For those of us that are old enough to get to go to our high school reunion, let’s say your 20- or 30-year 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.”
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 going to be slower agers. 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 reverse this in cells.
Shinya Yamanaka 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 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 reversing all those epigenetic changes that we’ve used to quantify biological age.
Then the question becomes how do you do this in a body? Can you reprogram cells from an old epigenetic state back into a younger epigenetic state? And then the question becomes what does this mean for our physiology and our health?
Some people might say that we have solved the aging problem with cells in a dish. We can age cells, and we can reverse their age and reset them to an age zero. People are now trying to do this in an organism. Right now to start out, people are doing this in mice where, in different mouse models, you can overexpress these four factors commonly referred to as Yamanaka factors. The scientists have observed that the mice seem to have improvements in different functional outcomes and there 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 happened in one direction, that these were just stochastic damage that you couldn’t go back and fix because there was so widespread and so much of it, and that the only thing you could do was slow the accumulation of this damage.
But what this reprogramming of the epigenome tells us is that this is a lot more modifiable and elastic than we originally knew. So you can take a cell that has aged and is of a given type and completely change its state using just a few factors.
And this opens up this whole idea of things like cell engineering. So how do we take cells and move them to states that we think are more functional and healthier? How do we figure out what types of states 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, give rise to some diseases like cancer. So the risk of cancer 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.
One hypothesis is if you can remodel or reprogram the epigenome to a younger state, you might prevent some of these cells from developing into cancers. Now that won’t deal with some of the mutations that might precede cancer, but a lot of mutations accumulate early in the lifespan. And the question is what is happening with aging later on that is still pushing these cells to become cancerous?
The epigenetic clock has been remarkable in that it can track aging across a diverse array of cell types and organ systems. You can use the same measure to track aging in your skin as you would use in your liver or in your blood.
More importantly, what we find is the difference between the age you get predicted based on the epigenetic clock and your chronological age holds biological meaning. The reason we think it holds biological meaning is because it seems to be predictive of different outcomes or diseases in whichever organ it was measured in.
When I measure epigenetic age in the blood, what we find is that measure is predictive of remaining life expectancy or heart disease risk or diabetes. We’ve looked at epigenetic age measured in the brain after people have died, and what we find is that it seems to be correlated with pathology associated with Alzheimer’s disease. 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 give rise to the diseases of aging.
As we continue to develop and improve these epigenetic clock measures, they’ll be useful for tracking aging and understanding disease risk. So the great thing is that epigenetic clock measures aren’t just giving you a whole-body aging measure, but we can measure it in different subsystems and understand how people might be aging differently across systems in their body.
Some people might be more prone to metabolic aging, other people might be more prone to inflammatory aging. And that profile, when you take it all into consideration, might give you a better idea of the interventions or the lifestyle factors that you should implement, or the specific diseases that you might be more or less at risk for.
The reason scientists are so excited about intervening in the aging process, whether slowing or reversing it, is because we think that in doing so we can stop the changes that give rise to the diseases we care about. Rather than going after one disease at a time, if we could slow or reverse aging, we could eliminate diseases or at least postpone them across the board.
Right now people are using the epigenetic clock more as a diagnostic as opposed to a means to intervene. People are using it as 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 their risk of developing different diseases of aging.
Nutrition science is something that people in the longevity and aging field have been very interested in. And 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 assign people specific diets and have them maintain those for a long enough time to study them in this randomized clinical trial way. So usually what scientists end up leaning on is what we call epidemiological or observational data.
They look at populations and they compare the diets that different people eat, and then they look at 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 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 been studied in the aging and longevity field is this idea of caloric restriction. So more than a hundred years ago, researchers 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.
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 may be different depending on genetics. So there was a study in mice that showed mice with different genetic backgrounds. Some of them benefited from chloric restriction, some of them had no effect, and then some of them did worse. We think that the amount of chloric restriction our bodies can tolerate might be genetically determined and that this should be a more personalized regimen.
When trying to figure out if something like caloric restriction is beneficial to the aging process in terms of slowing aging, one caveat is that humans today are not at baseline. We’re more prone to overeating. So some researchers have figured out that it might not be the caloric restriction that’s the beneficial thing but the tendency away from overeating.
Even if you can’t restrict your calories in terms of what’s 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 going to have a beneficial effect for most people. The discovery of caloric restriction was on accident. So the scientists weren’t going in to try and study how diet was affecting aging and longevity.
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 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 minimal deficit produces a 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 going to have a big effect, this might just mean avoiding certain diets like overconsumption or eating a lot of things that we 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. 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 going to 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 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 going to be better overall. Minimizing things like refined sugars and the things that we already know are bad for our health.
The third comes down to when we eat, and this is really a new field in aging and longevity science. So again, most people aren’t going to be able to calorically restrict, but what scientists found is that fasting can mimic some of the benefits that we’ve seen with caloric restriction. If people can fast for a number of hours throughout the day, so perhaps minimize their eating to a small window, we think that this can recapitulate a lot of the benefits that we’re seeing in the caloric restriction studies. There’s still some debate about when that window should occur.
Some of the scientists 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. We’re not sure if that would have the same benefit as doing it earlier.
The idea of why things like caloric restriction or fasting might improve our aging process and increase our health is because we think this evokes this idea of hormesis in our bodies. What hormesis refers to is a mild stressor that 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, makes our bodies more robust and we think more resilient against a lot of the changes we see that increase with aging.
What we eat may also change depending on who we are. We 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. People who are older and more prone to things like muscle loss or weakness might need more protein than people who are younger, where science has shown that a low-protein diet might be beneficial.
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 keep track of a lot of these health indices, things like our biological age measures to see how our diet is affecting us.
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. As people get older and might be more prone to things like weakness or muscle wasting, they might 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 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 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. What matters to most people is quality of life.
We all want to maintain our health and our functions and be able to enjoy the things that make life worth living. So really what aging science is about is not just prolonging life at all cost, but 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?
We think if we intervene in the aging process itself, that we can delay all of the things that people are scared about when they think of aging. 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. Lifespan, again, is just the time you’ve been alive between birth and death. What scientists think health span is is the time you are alive in a more healthy functioning state. 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 this idea of the health survival paradox that we see between men and women. 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.
On average, women tend to spend more time in some of this age-related disability than men do. Some might argue is that a better life because they’ve lived longer? Or would you want maybe a shorter life but more free from these diseases of aging?
In thinking about how we 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 compressing the timing of disease into this really short window, as opposed to having it earlier in life and surviving 20, 30 or 40 years with these diseases of aging?
We think this is possible because you can look at centenarian populations and see that they tend to compress the timing of disease into the short window right before death. They’re spending the majority of their life in a much more healthy state.
What we want to do is figure out how we can make 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 don’t want to increase what we call health disparities.
Right now, even though the average life expectancy in the population is just under about 80 years, we want to 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 how do we make sure that everyone can have as healthy and long a life as possible.