Is Aging Reversible? A Scientific Look with David Sinclair | David Sinclair | TEDxBoston

Summary

The speaker discusses the revolutionary advancements in aging and longevity science, suggesting that humans can potentially live beyond 150 years. He introduces the idea that aging is a reversible condition tied to changes in the epigenome, which controls gene expression. By reprogramming genes and using compounds like NAD boosters, researchers have reversed aging in mice and even regrown damaged nerves. The speaker envisions a future where age reversal will extend not just physical longevity, but also cognitive function, reshaping human life and health in unprecedented ways.

Takeaways

• 🔬 Aging science has made revolutionary progress over the last 25 years, changing the way we think about longevity and aging.
• 📅 The speaker believes that the first person to live to 150 years old has already been born, and recent advancements make even longer lifespans plausible.
• 👨‍👦 The speaker contrasts the fates of his grandmother and father: while his grandmother aged traditionally, his father is thriving at 82 due to advancements in health and longevity practices.
• 🧠 The speaker argues that aging should be treated as a medical condition, not a natural and unchangeable process.
• 🧬 A new theory of aging centers around the epigenome, which controls gene expression and loses its effectiveness over time due to 'scratches' that accumulate, similar to a scratched CD.
• 🔄 Sirtuins, a group of genes that sense environmental stressors like fasting and exercise, play a crucial role in defending against aging by maintaining the epigenome.
• 🧪 Experiments in mice have shown that it's possible to accelerate aging by damaging the epigenome, but also to reverse aging by resetting it.
• 🐁 Mice treated with NAD boosters or sirtuin-activating molecules demonstrated improved health, including cardiovascular rejuvenation and extended vitality.
• 🔧 The Yamanaka factors, which can reprogram adult cells into a younger state, have been used to successfully reverse aspects of aging in animal models, like nerve regeneration.
• 🔮 The speaker envisions a future where humans can regularly reset their biological age, potentially reversing age-related conditions and radically extending healthy life spans.

Q & A

What is the main focus of the speaker's field of study?

The speaker's field of study focuses on Aging Science and Longevity Science, which aims to understand and potentially reverse the aging process, moving beyond just treating diseases commonly associated with aging.

Why does the speaker avoid the term 'anti-aging'?

As a scientist, the speaker avoids the term 'anti-aging' because it is not commonly used in the scientific community. They focus more on the biological understanding of aging and longevity rather than the commercialized notion of 'anti-aging.'

What is the speaker's prediction about human longevity?

The speaker predicts that the first person to live to 150 years has already been born, and new developments in the last five years suggest that the potential for human longevity could extend even further, with no clear limits in sight.

What personal experiences shaped the speaker’s perspective on aging?

The speaker was raised by their grandmother, who lived through World War II and the Great Depression. Their grandmother's difficult aging process, contrasting with their father’s more successful aging due to modern science, influenced the speaker’s passion for improving human longevity.

How does the speaker challenge conventional views on aging?

The speaker challenges the conventional view that aging is a normal, inevitable process by arguing that aging should be treated as a medical condition, just like cancer or heart disease, and that efforts should be made to extend healthy life.

What are the three main biological defenses against aging mentioned by the speaker?

The three main defenses against aging are MTOR (responding to fasting), AMPK (responding to low energy and lack of sugar), and sirtuins (responding to adversity, exercise, and fasting). These defenses help protect and maintain the body's health.

What is the Information Theory of Aging?

The Information Theory of Aging suggests that aging is caused by the gradual loss of the body's ability to properly read and maintain the epigenome, which controls how genes are expressed in different cells. Aging is compared to scratches on a compact disc that disrupt the ability to play music correctly.

What role do sirtuins play in the aging process according to the speaker?

Sirtuins are a group of genes and proteins that protect the body by maintaining the epigenome. When activated, they help repair and defend against damage caused by aging, potentially slowing or even reversing some aspects of the aging process.

How does the speaker describe the potential to reverse aging?

The speaker describes the potential to reverse aging by resetting the epigenome, essentially ‘polishing the CD’ to restore the original information and function. Experiments in mice have shown that it is possible to reverse aging in organs such as the eyes and brain, leading to restored function.

What are the implications of the speaker's research for the future of human health?

The speaker believes that the future of human health lies in controlling aging itself. By resetting the aging process and maintaining a healthy epigenome, humans may one day be able to significantly extend both lifespan and healthspan, potentially slowing or reversing aging-related diseases.

Outlines

00:00

🧬 The Revolution in Longevity Science

The speaker, representing the field of Aging Science, shares groundbreaking insights into the progress made in longevity research over the past 25 years. He confidently claims that the first person to live to 150 years has already been born, highlighting how recent advancements have expanded the horizon beyond even that. He emphasizes that these technologies will benefit not just future generations but also those born in the 20th century. The narrative becomes personal as he recalls his grandmother's struggles with aging and his father’s thriving health due to scientific progress. He stresses the importance of focusing on facts rather than internet misinformation.

05:02

📉 Debunking the Antioxidant Myth

The speaker addresses misconceptions about aging, specifically criticizing the belief that antioxidants are the key to extending lifespan. He explains that free radical damage is only part of the equation and introduces three primary defense mechanisms against aging: MTOR, AMPK, and sirtuins. These genes respond to fasting, low energy, and stress to protect the body and promote longevity. Sirtuins, in particular, help regulate the epigenome, a key element in controlling the body's aging process.

10:04

🎶 Aging as Scratches on the Epigenome

Using an analogy, the speaker explains the concept of the epigenome by comparing it to a compact disc (CD) and its scratches. Just as a scratched CD causes music to skip, the epigenome, which regulates gene expression, gets disrupted over time, leading to aging. These disruptions cause cells to lose their identity and ability to function, resulting in diseases and frailty. He posits that aging is driven by these epigenetic changes and proposes the possibility of reversing them by resetting the epigenome to its youthful state, like polishing a scratched CD.

Keywords

💡Aging Science

Aging Science, also called Longevity Science, is the study of how to extend human lifespan and improve the quality of life during aging. In the video, the speaker presents it as a rapidly advancing field with the potential to dramatically extend human life, possibly to 150 years or more. He emphasizes that aging itself should be viewed as a medical condition that can be managed or even reversed with new scientific discoveries.

💡Epigenome

The epigenome refers to the collection of chemical modifications and structural changes that affect how DNA is read and expressed, without altering the DNA sequence itself. The speaker likens it to the 'reader' of a CD, controlling which genes are turned on or off in different cells. According to the Information Theory of Aging presented in the video, aging is caused by disruptions or 'scratches' in the epigenome, and the ability to 'polish' or reset these marks could reverse aging.

💡Sirtuins

Sirtuins are a family of proteins that play a critical role in regulating cellular health, aging, and longevity by responding to environmental factors like exercise and fasting. In the video, the speaker highlights sirtuins as one of the body's natural defenses against aging. Activating them through lifestyle changes or supplements like NAD boosters can potentially extend lifespan and reverse certain aspects of aging.

💡NAD (Nicotinamide Adenine Dinucleotide)

NAD is a crucial molecule that helps fuel sirtuins and other processes involved in cellular repair and metabolism. It declines with age, but the speaker explains that boosting NAD levels with supplements can activate sirtuins and promote healthier aging. The video shows that giving NAD boosters to mice rejuvenates their cardiovascular systems, making them physically younger.

💡Information Theory of Aging

The Information Theory of Aging is the idea that aging is caused by the loss of information in the epigenome, akin to scratches on a CD that cause the 'music' (the body's cellular functions) to skip. The speaker argues that by resetting the epigenome, it may be possible to reverse aging. This theory shifts the focus from merely preventing damage like free radicals to preserving and restoring the instructions that guide cellular health.

💡Epigenetic Reprogramming

Epigenetic reprogramming refers to the process of resetting the epigenome to a more youthful state. The video discusses research using a subset of Yamanaka factors, a group of genes that can reverse cellular age without turning them into stem cells or tumors. This method was shown to restore vision in mice by repairing damaged optic nerves, providing evidence that age reversal may be possible.

💡DNA Methylation

DNA methylation is the addition of methyl groups to DNA molecules, which influences gene expression by turning genes on or off. In the video, the speaker explains that changes in DNA methylation can be used to measure biological age. This pattern of methylation, which accumulates over time, serves as a biomarker for aging and could potentially be manipulated to reverse aging.

💡Biological Age vs. Chronological Age

Biological age refers to how old a person's body and cells function, whereas chronological age is simply the number of years a person has lived. The speaker argues that biological age is a more accurate measure of a person's health and longevity. He mentions that biological age can be determined by examining DNA methylation patterns, and that resetting the epigenome could lower a person’s biological age, extending their healthy lifespan.

💡Yamanaka Factors

Yamanaka factors are a set of genes that can reprogram adult cells back to a pluripotent stem cell state, which can develop into any type of tissue. The video describes how researchers used a subset of these factors, specifically Oct4, Sox2, and Klf4, to reverse aging in mice without causing the cells to revert completely to stem cells. This breakthrough opens the possibility of resetting cellular age and treating age-related diseases.

💡Xenohormetins

Xenohormetins are molecules produced by plants under stress, which can activate similar stress responses in animals that promote longevity. The speaker explains that these molecules can mimic the beneficial effects of exercise and fasting, and that they are being studied as a way to activate sirtuins and slow down aging. An example given in the video is resveratrol, a compound found in red wine that may have anti-aging properties.

Highlights

The speaker claims that the first person to live to 150 years has already been born.

Advances in longevity science may extend human life well beyond 150 years, benefiting those born in the 20th century.

Aging is described as a medical condition, and efforts should be made to treat it, similar to combating diseases like cancer or Alzheimer's.

The speaker introduces the concept of the 'Information Theory of Aging,' suggesting aging results from disruptions in the epigenome.

Sirtuins are identified as genes that help the body fight aging by responding to environmental stressors like fasting and exercise.

The speaker presents a theory that aging is caused by scratches in the epigenome, similar to scratches on a CD that disrupt the ability to read it properly.

Research demonstrates that by activating sirtuins, it is possible to slow aging and rejuvenate organs such as the cardiovascular system.

A study in mice shows that accelerating aging by disrupting the epigenome results in rapid aging, but the process can be reversed using specific gene therapy.

The concept of 'resetting' the age of an animal, including restoring the function of the nervous system in mice, is presented as a key discovery.

The speaker discusses a breakthrough where neurons in a mouse's damaged optic nerve were rejuvenated, showing age reversal in practice.

The potential to reset the human brain's age is mentioned, with early experiments showing improved learning and cognitive functions in aged mice.

The ability to measure biological age through changes in DNA methylation is highlighted as a major advancement in understanding aging.

NAD boosters and molecules derived from plants are discussed as tools to activate sirtuins and extend lifespan.

The speaker envisions a future where humans can continually reset their age, potentially leading to significant life extension.

The speaker predicts that biological advancements in age control will define the 22nd century, similar to how technological innovations have shaped the current era.

Transcripts

Transcriber: Matheus Guimarães Reviewer: Sakunphat Jirawuthitanant

So I stand here as a representative of a field

called Aging Science, Longevity Science.

Some people call it anti-aging. We don’t use that as scientists.

But what has happened in the last 25 years is nothing short of revolutionary.

And thank goodness, I come from Harvard Medical School,

or what I’m going to tell you tonight

you would find extremely difficult to believe is true.

I’m on record saying that the first person to live to 150 years has already been born

and I already said that about five years ago,

and in the last five years,

something extraordinary has happened since

making me think that it’s not just 150 years.

All bets are off.

And that’s not just for somebody who’s born today

who will live definitely into the 22nd century,

where the technologies that they’ll have, we can barely even imagine.

Even 10 years from now, we can barely imagine.

But those of us who were born in the 1960s, like I was,

1970s, 80s and even those who are now just in their 20s

will benefit from this real major advance that I’m going to tell you about today.

This is also personal, it’s not just about technology.

In my family, I was raised by my grandmother predominantly.

My mother, also helped. She was working.

But my grandmother escaped Europe in the 1950s,

having lived through, as a young girl, the depression World War II.

She was from Hungary. It was a brutal time.

She escaped to Australia, where I got my accent;

and I came to MIT in my 20s.

But she raised me to believe

that humans can do better than we’ve done in the 20th century

And she said it’s partly my role to show humanity can be better than they are

and that’s what drives me every day I get up,

and my goal since I was really four years old

was to try and leave the world a better place.

And in my teens, late teens in college, I thought:

“Well, there’s this thing that happens to everybody called aging,

and it's 90 percent of all the sickness and suffering in the world.

But no one seems to care about it”

You go to your doctor and they say “That’s normal. You’re old.

You should be getting sick.”

And I said: “That’s not right.”

At any age, we should apply the same technology,

the same effort to make people live as long as they possibly can.

We fought against cancer, we fought against heart disease,

we’re fighting against Alzheimer’s disease.

What about aging?

And I refuse to believe that just because this is natural and common,

that we should regard it as something different from a disease.

In my view, in my world, aging is a medical condition.

You see behind me an image of my father, who, of course,

is the son of my grandmother who raised me.

My grandmother lived a very different life than my father.

My grandmother smoked, drank, did pretty much everything

that was not going to slow down the aging process.

She died like a lot of people do,

who lived through the 20th century in a frail state, demented in a slow decline.

It was very painful for her

and certainly painful for us as a family to watch.

My father, on the other hand,

has watched the science come out of this field

and done the right things that we’ll talk about later.

So at 82, he started a new career. He’s thriving.

He’s looking forward to the next 20 years of his life, if not longer.

This is what I want for everybody.

We can all do this if we just know the facts

and don’t pay attention to 99% of what’s out there on the internet

because it’s all wrong.

Speaking of wrong, we have a new theory of aging.

We used to think that antioxidants were the cure to aging,

and if you go to the supermarket, you’ll still get a lot of that bull.

It’s not true.

Antioxidants have been really unsuccessful

at lengthening the lifespan of anything, even a worm.

It doesn’t work that well.

The reason is that there’s much more going on than just free radical damage.

What we need to do is to tap into our body’s natural defenses against aging.

We have three main sets of defenses.

One is called MTOR, responds to fasting,

one called AMPK, responds to low energy and lack of sugar.

You want to keep your blood sugar levels low as possible without fainting.

And the group of genes that I work on are called the sirtuins,

they respond to all of the things that we do:

the adversity, the exercise, the fasting.

And this group of genes and these proteins

that the genes make, sense the environment.

And when times are thought to be tough and could threaten us,

they fight harder to keep our body safe, protected

and ultimately healthier and longer lived, even late in life.

And what they’re doing, these sirtuins, is controlling this structure here.

They’re doing a lot of things,

but the main thing I believe they’re doing to make us live longer

is controlling what we call the epigenome.

If you haven’t heard of epigenome, think of it like this: we have DNA.

I’m showing you as a blue strand. It’s digital information, ATCG.

There’s four bases. It’s base four. It’s not base two or binary.

The epigenome is not digital, it’s mostly analog.

And anyone who’s old enough to have had an analog device,

whether it’s a tape recorder, a record player or record,

these things get disrupted.

They get scratched.

It’s very bad, very poor at copying information.

And that’s true for the epigenome as well.

Copying epigenetic information doesn’t work that well.

What is the epigenome?

It’s the structures that wrap up the DNA

and say that this gene A should be on in a brain cell,

but in the liver cells should be off.

And this gene B should be off in a skin cell, but should be on in a kidney.

That’s the epigenome.

And largely it’s due

to the three dimensional structures of the folding of DNA

and these sirtuins that defend us are called silent information regulators.

That’s what sirtuins actually stand for: SIR.

And “tu” is the number two for the first gene in yeast

that we showed extended lifespan,

way back in Lenny Guarente’s lab at MIT in the 1990s.

But here’s the analogy that the DNA is the digital information on a compact disc.

Those of us who are old enough know what that is.

For the youngsters, this is what we used to store 20 songs on.

It was great technology.

That’s your genome, the digital information. The epigenome is the reader.

It can read different songs depending on different parts of the body

in different cell types.

But what I believe is causing aging is the skipping of those songs,

skipping of the reader.

And what makes songs skip? Scratches.

So aging is essentially scratches on a compact disc that makes the music skip

and eventually cells, by reading the wrong genes,

skipping the wrong genes, lose their ability to fight against disease.

They lose their function.

We get dementia, we get heart disease, we get cancer, we get frailty.

That is aging.

So with this new theory of what I call the Information Theory of Aging,

we can perhaps test this by testing if epigenetic changes cause aging.

And if that’s true,

is it possible to reset these structures back to being young?

Is there a backup copy of the epigenome?

In other words, can you polish that CD and get back the original music of our youth?

Before I go on I want to point out

something really important in this structure.

It’s not just the proteins that wrap up the DNA

but the modifications that are on the DNA itself.

Chemical additions called methyls,

Methyls are carbons with three hydrogen.

They’re very simple.

And cells add them as we’re developing in the womb to say, all right,

that cell that’s come from stem cells should be a neuron

for 80, 90, 100 years in the brain.

And this one should be a skin cell.

These marks, called methyls, dictate the production of 26 billion cells.

Many of them have different functions in the body,

even though they have the same set of instructions encoded in the DNA.

What’s been found since 2013,

Steven Horvath and his colleagues discovered that by reading

the changes over time of these DNA methylation marks on the DNA

that are attached to the letter C in the DNA, not the A, T or G,

you can estimate somebody’s biological age, because it’s reproducible.

We’re all aging due to the same mechanisms

and that there’s a pattern that occurs from conception very rapidly

until we’re born and then slows down,

and then is linear throughout our lifespan.

We can measure that clock.

I can take your blood, I can take your skin, any part of your body,

and I can run that through a DNA sequencer to measure the methylation,

there’s thousands of them.

And putting that into a machine learning derived algorithm,

I can tell you your actual real age, not your chronological age.

I mean, birthdays? Who cares?

Number of times the Earth went around the Sun. That’s not your real age.

What your real age is, is these changes to the epigenome,

that determine how old you really are.

So the question is if we tweak the epigenome, if we scratch that CD,

if I’m right about the Information Theory of Aging, what do we get?

We’ll get accelerated aging.

This is a mouse. That’s the control in my lab.

So we tweak this mouse in every other way, except scratch its CD.

At the same time, we took a sibling born at the same time,

and we for three weeks accelerated the scratches on the CD.

We disrupted its epigenome and the cells started to lose their identity.

The mouse didn’t feel it.

It’s like getting an X-ray, you don’t feel that,

but what happened 10 months later was we got an old mouse.

This isn’t just a mouse that looks old.

This mouse is 50% older than its sibling, even though it’s genetically identical.

These are twins born at the same time.

One is old and one is not.

We can drive aging as fast as we want forwards.

Then the question is, if you can give something, can you take it away?

And if I’m right, the answer is yes.

First of all, let me show you about a minor tweak to age reversal.

We found these sirtuins can defend against aging,

but they can also reverse aspects if we activate them,

either giving them molecules from the plant world,

that plants produce when they want to slow down their aging process

and survive.

We call these xenohormetins.

We have drugs that have been in development.

We have more that are coming.

We have one in particular that’s of interest and it’s called NAD booster.

NAD is a fuel for the sirtuins, whereas resveratrol is the accelerator pedal.

So giving the fuel to these mice, I’ll show you what happens.

One of these mice has been on the sirtuin activating molecule

called NMN: Nicotinamide Mono Nucleotide.

Hopefully you can guess which of them has been rejuvenated from an old state.

These are really old mice.

They are almost two years of age,

and only one of them has been drinking NMN in the water.

If you pick the mouse on the right, you’d be wrong.

(Laughter)

It’s the mouse on the left, obviously.

And we published in the Journal Cell in 2018 that this is possible,

to rejuvenate the cardiovascular system of mice

and make it younger, through the sirtuins.

We know it works for this sirtuins because, if we delete those genes,

you don’t get this effect on these mice here.

But that was just the beginning, that’s 2018.

We’re now in a world where our technology makes this pale by comparison.

We now have the ability to reset the age of an entire animal,

leading to one day being able to reset the entire age of our bodies.

What did we do?

We really stood on the shoulders of a scientist,

Shinya Yamanaka, who won the Nobel Prize in 2016

for discovering a set of embryonic genes

that could take an adult skin cell from any of you,

and turn it into a pluripotent stem cell

that could be made into any other type of tissue,

and we can do that in the lab.

High school students can do this by putting in the six Yamanaka genes.

Now we found that if you put in a subset of three of them Oct4, Sox2 and Klf4

short for OSK, we could take the age of the body of a mouse backwards,

but not so far that it would become a stem cell or a tumor.

This was published in December 2020.

It made the cover of Nature Magazine,

and the title on the magazine was Turning Back Time.

This is one of the pieces of data from that paper. We did three things.

The first was to damage an optic nerve in a mouse,

and you can see on the top image that the crushed nerve is dying.

That orange stain should extend all the way to the brain on the left.

But in the reprogrammed eye where we injected those three genes

and turn them on for three weeks, we could make those neurons grow back.

We measured those neurons and they were literally half the age

that they were three weeks ago.

And young nerves, as you might know, grow back. Adult nerves do not.

So this was the first indication that we were on the right track.

We also could see that those structures, the epigenome,

those scratches on the CD, they went away.

We can also grow human tissue in the lab.

We don’t know yet if this works in humans, but we can model it in the dish.

These are human pluripotent stem cells

that have been engineered into little mini brains.

On the left of this image, you can see these are little organoids.

These are quite similar to human brains. They have electrical activity,

and on the right is the electrodes that we put the brains on.

We can measure that. We think they dream.

They have thoughts,

and we can also age them using our technology of disrupting the epigenome.

And now we’ve shown that if you reset the age of those little brains,

they get their ability to think again.

The electrical activity comes back.

Does this mean one day if we reverse the age of the brain,

you’ll get your memory back?

Possibly. We’ve done this now in old mice.

We can rejuvenate their brains, take their brains back to half their age,

and they get their ability to learn again.

So you might say, well, sounds great,

but how long is this going to be before we have it?

And my hope is that we’re at a turning point in human history

as important as flight and Silicon Valley and energy and crypto.

The 22nd century is going to be about biology

and the ability to control your age and the rate of aging

and slow down not just body aging and heart aging, but even brain aging.

With these tools and age reversal tools

that are just coming along will radically change the arc of our lives

in a way that we can barely even imagine,

and where we can reset our age by a couple of years,

which is now being published, that’s been done by Greg Fahy and colleagues.

If we do that every year, even just set your age back one year every year,

what happens?

Things then get really interesting.

And that’s the world that we have to stay alive to be able to witness.

And if we all do the right things, we will witness that.

Thank you very much.

(Applause)