Exploring the concept of aging and the variation in aging rates among individuals.

Introduction

Examining the importance of quantifying aging at the cellular or molecular level and its implications for health.

Quantifying the Aging Process

Introducing the concept of hallmarks of aging and their association with molecular and cellular changes.

Hallmarks of Aging

Exploring the role of epigenetics in aging and its impact on cellular function and structure.

Epigenetics and Aging

Discussing the epigenetic clock as a method to quantify biological age based on DNA methylation.

The Epigenetic Clock

Exploring the potential to reverse the age of cells through reprogramming the epigenome.

Reversing Aging at the Cellular Level

Highlighting the modifiability and elasticity of the epigenome in relation to aging.

Modifiability of the Epigenome

Examining the current use of the epigenetic clock as a diagnostic tool for aging and disease risk.

Using the Epigenetic Clock

Exploring the relationship between aging, disease development, and the potential for interventions.

Aging, Disease, and Interventions

Discussing the goal of postponing diseases rather than solving death through aging interventions.

Conclusion

- Aging affects individuals differently, with some appearing to age slower than others.
- Scientists are interested in understanding the molecular and cellular changes associated with aging.
- Epigenetics, specifically DNA methylation, is one aspect of aging that has been studied.
- DNA methylation changes with aging and can be used to predict someone's biological age.
- While reversing aging at a whole body level may not be possible, it is possible to reverse the age of individual cells.
- The epigenome plays a crucial role in cell function and identity, and changes to the epigenome can lead to dysfunction and disease.
- The epigenome is dynamic and can be modified, as shown by the ability to reverse epigenetic changes in cells.
- The ability to program cells from an old epigenetic state to a younger state has potential implications for health and physiology.
- The epigenetic clock is currently used as a diagnostic tool, but there is hope that intervening in the aging process could prevent or postpone age-related diseases.
- Slowing or reversing aging could potentially eliminate or postpone various diseases.
- While death may not be solved, the goal is to postpone disease and improve overall health.

Science can’t stop aging, but it may be able to slow our epigenetic clocks.

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Up next, Michio Kaku: How to reverse aging ► https://www.youtube.com/watch?v=DV3XjqW_xgU

What if we could slow down the hands of our biological clocks? This question underpins much of the research of Morgan Levine, who leads a research team at the life science company Altos Labs. 

Levine investigates the fascinating intricacies of aging, recognizing that it doesn't happen at a uniform pace for everyone. Central to her exploration is the concept of epigenetics — the factors that influence gene activity without changing the DNA sequence. Levine focuses on DNA methylation, a significant epigenetic change that occurs with aging, and the development of models called "epigenetic clocks" that can be used to predict biological age. 

While she acknowledges that it might be possible to reverse aging at a cellular level, Levine clarifies that the ultimate goal is not to "cure" aging or death, but to delay disease onset and improve healthspan.

0:00 Fast agers & slow agers
1:25 The hallmarks of aging
1:59 What is the epigenetic clock?
3:05 Can we ‘Benjamin Button’ aging?
5:22 The holy grail for scientists

Read the video transcript ► https://bigthink.com/series/explain-it-like-im-smart/epigenetics-and-aging/?utm_source=youtube&utm_medium=video&utm_campaign=youtube_description

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About Morgan Levine:
Morgan Levine was previously a tenure-track Assistant Professor in the department of Pathology at Yale University where she ran the Laboratory for Aging in Living Systems. In 2022, she was recruited to join Altos Labs as a Founding Principal Investigator at the San Diego Institute of Science. She currently leads a research group at Altos Labs working at the intersection of bioinformatics, cellular biology, complex systems, and biostatistics with the overall goal of understanding the molecular trajectories aging cells, tissues, and organisms take through time.

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Read more of our stories on aging: 
Aging gratefully: Will you be happier in old age?
► https://bigthink.com/neuropsych/happiness-old-age/?utm_source=youtube&utm_medium=video&utm_campaign=youtube_description
Blood test can calculate your true biological age
► https://bigthink.com/health/calculate-your-biological-age/?utm_source=youtube&utm_medium=video&utm_campaign=youtube_description
The brain undergoes a great “rewiring” after age 40
► https://bigthink.com/neuropsych/great-brain-rewiring-after-age-40/?utm_source=youtube&utm_medium=video&utm_campaign=youtube_description

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For those of us that are old enough to go to our 20 or 30 year old high school reunion, we know that if you were to go there, some people look exactly like they did when they 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.

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.

A lot of people are very concerned about the aging process because of what it does to our parents.

But actually, we know that aging starts on the inside.

So how can we actually quantify the aging process at either the cellular or molecular level?

We think this is really critical because it probably has implications for the risk of disease in the future, their remaining life expectancy, and other things that we all care about in terms of our health.

Ultimately, the question is, how do you become a slow ager?

What scientists think is that there are actually changes at the molecular or cellular level that will differentiate how quickly people will age and how they actually look on the outside.

So people in the field have come up with what we might call hallmarks of aging.

So what are these different changes that we see tracking with aging and also linking to the manifestations that all of us recognize as a part of the aging process.

1 of these hallmarks that my lab in particular is very interested in is this concept of epigenetics.

We all know genetics, so our sequence of DNA that gives rise to our different genes.

And 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.

It gives them their overall function and structure.

1 form of epigenetics is called DNA methylation.

Scientists found that DNA methylation 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 DNA methylation.

And this has been referred 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.

We always think of the movie Benjamin Button where he aged in reverse.

I don't know if scientifically that is possible, especially at a whole body, whole organismal level.

Although we do know that you can reverse the age of a cell.

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 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.

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.

Shinya Yamanaka actually won the Nobel Prize for discovering 4 factors that can convert an old cell 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 essentially reversing all those epigenetic changes that we've used to try and quantify biological age.

We always thought aging really happened in 1 direction and that the only thing you could really do was just slow the accumulation of this damage.

But really what this reprogramming of the epigenome tells us is that this is a lot more modifiable and elastic than we originally knew.

So The question becomes, how do you do this in a body?

Can you actually program cells from an old epigenetic state back into a younger epigenetic state?

What does this actually mean for our physiology and our health?

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 1 indicator of how they're aging overall.

It's not a perfect indicator, but it can give people some indication of their health status and potentially their overall risk of developing different diseases of aging.

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.

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 1 disease at a time and having 1 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.

So Are we gonna solve death and will the epigenetic clock help us get there?

My thinking is that we probably will not solve death and this actually shouldn't be our goal.

What our hope is is that this will just postpone disease, but we're not going to quote cure aging or cure death overall.

Get smarter, faster with videos from the world's biggest thinkers.

To learn even more from the world's biggest thinkers, get Big Think Plus for your business.


Speaker 0: Can you actually reverse aging? For those of us that are old enough to go to our 20 or 30 year old high school reunion, we know that if you were to go there, some people look exactly like they did when they 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.

A lot of people are very concerned about the aging process because of what it does to our parents. But actually, we know that aging starts on the inside. So how can we actually quantify the aging process at either the cellular or molecular level? We think this is really critical because it probably has implications for the risk of disease in the future, their remaining life expectancy, and other things that we all care about in terms of our health. Ultimately, the question is, how do you become a slow ager?

What scientists think is that there are actually changes at the molecular or cellular level that will differentiate how quickly people will age and how they actually look on the outside. So people in the field have come up with what we might call hallmarks of aging. So what are these different changes that we see tracking with aging and also linking to the manifestations that all of us recognize as a part of the aging process. 1 of these hallmarks that my lab in particular is very interested in is this concept of epigenetics. We all know genetics, so our sequence of DNA that gives rise to our different genes.

And 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. It gives them their overall function and structure.

1 form of epigenetics is called DNA methylation. Scientists found that DNA methylation 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 DNA methylation. And this has been referred 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. We always think of the movie Benjamin Button where he aged in reverse.

I don't know if scientifically that is possible, especially at a whole body, whole organismal level. Although we do know that you can reverse the age of a cell. 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 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. And the epigenome 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. Shinya Yamanaka actually won the Nobel Prize for discovering 4 factors that can convert an old cell 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 essentially reversing all those epigenetic changes that we've used to try and quantify biological age. We always thought aging really happened in 1 direction and that the only thing you could really do was just slow the accumulation of this damage. But really what this reprogramming of the epigenome tells us is that this is a lot more modifiable and elastic than we originally knew. So The question becomes, how do you do this in a body? Can you actually program cells from an old epigenetic state back into a younger epigenetic state?

What does this actually mean for our physiology and our health? 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 1 indicator of how they're aging overall. It's not a perfect indicator, but it can give people some indication of their health status and potentially their overall risk of developing different diseases of aging. 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. 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 1 disease at a time and having 1 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. So Are we gonna solve death and will the epigenetic clock help us get there? My thinking is that we probably will not solve death and this actually shouldn't be our goal.

What our hope is is that this will just postpone disease, but we're not going to quote cure aging or cure death overall.

Speaker 1: Get smarter, faster with videos from the world's biggest thinkers. To learn even more from the world's biggest thinkers, get Big Think Plus for your business.

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The science of super longevity | Dr. Morgan Levine