The biggest myth about aging, according to science

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 and molecular changes that people have undergone

and actually give them a sense of how they're doing in terms of the aging process

Are they 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

the 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 going to 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 healthspan or their

kind of time of life expectancy free from disease. Chapter 1, How We Measure Age, Biological vs. 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 on 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 going to be maladaptive. They're going to 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 been diagnosed with as kind of an indices of how much you 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 going to 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 will 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 is going to look at

So typically, when your doctor looks at your lab tests, they're going to 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

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 the cell. It's what gives each cell

its different kind of defining characteristics and 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 just a chemical tag that 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 and 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, you know, 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 they're 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

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

Over time, cells actually become less functional. They actually are less likely to represent what they were originally intended to do

We see this in many diseases. 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. Because 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 going to 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 want to track epigenetic age on what we call an n equals 1, 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 add a new regimen

and then see a change in your epigenetic age, it's not clear what drove that, or if that

actually represents a change in your aging rate, versus 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 going to 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 reflected 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 going to 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

Chapter 3. Is aging a disease? There's a lot of debate in the scientific field of aging

whether aging is actually a 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 because there isn't a clear point where

you say you have aged a specific amount that you now have a disease. And we're all aging from the

time we were 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. Disease is 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 were 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 comes 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

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 going to age

and also their propensity for developing different age-related diseases. 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 are 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 going to 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 overexpress 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 It would 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 are 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

precede 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. 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 this 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 longevity field is actually this idea of caloric restriction. So more than

100 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 caloric restriction. Some of them had no effect

And then actually some of them did worse. So we actually think that the amount of caloric 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 studying caloric restriction, just moving away from overconsumption 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 actually going in to try and study how diet was affecting aging and

longevity, but they just happened to find that when they're, 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

that'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 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 overconsuming, we think that's going to have a benefit for overall aging and 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 diet, so eating less animal products, more fruits and veggies, more whole foods is going to 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 going to 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 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 science is 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 to stress 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 healthspan. So lifespan, again, is just the time you've been alive between birth and death

And what scientists think healthspan is, is the time you're 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 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 because 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 want to 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 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 really, how do we make sure that everyone can have as healthy and long a life as possible