Do We Have to Die? with Venki Ramakrishnan

Summary

StarTalk Radio: Special Edition – "Do We Have to Die?" with Venki Ramakrishnan

Episode Release Date: July 11, 2025

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Introduction

In this thought-provoking special edition of StarTalk Radio, host Neil deGrasse Tyson delves into one of humanity's most profound questions: "Do We Have to Die?" Joined by esteemed Nobel Prize-winning scientist Venki Ramakrishnan and co-hosts Gary O'Reilly and Chuck Nice, the conversation interweaves science, philosophy, and societal implications surrounding death and aging.

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Defining Life and Death

The discussion begins with exploring the fundamental definitions of life and death. Venki Ramakrishnan explains, “[00:07:04]... life, most biologists would define it as a system that can self-replicate and evolve” (00:07:04). He further distinguishes between various forms of death, emphasizing the biological perspective of an individual's irreversible loss of function:

“What we mean by death is the irreversible loss of that individual's ability to function as a coherent whole” – Venki Ramakrishnan (00:08:24).

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Cellular Mechanisms of Aging

Ramakrishnan delves into the molecular underpinnings of aging, highlighting the roles of DNA damage, epigenetics, and protein degradation. He elaborates on how cellular components, especially proteins and mitochondria, deteriorate over time:

“As we get older, the quality of the proteins deteriorates. They're not made at the right time and the right amount, they start aggregating” – Venki Ramakrishnan (00:17:28).

The conversation touches upon the evolutionary reasons for aging, explaining that many biological mechanisms beneficial early in life can contribute to aging later on:

“Evolution only cares about fitness now. At the same time, resources are limiting. So you have to select...” – Venki Ramakrishnan (00:35:05).

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Potential Interventions in Aging

A significant portion of the episode focuses on scientific advancements aimed at mitigating aging. Ramakrishnan discusses cellular reprogramming, particularly the groundbreaking work on Yamanaka factors, which can revert differentiated cells to pluripotent stem cells:

“If you were able to introduce those four factors, you could take a fully differentiated cell and make it go backwards in development” – Venki Ramakrishnan (00:26:23).

He also explores the concept of caloric restriction and its biochemical mimicry through compounds like rapamycin, which has shown promise in extending lifespan in animal models:

“Rapamycin was found in the soil of Easter Island... if you give rapamycin to mice, they lived a bit longer and seemed a bit healthier” – Venki Ramakrishnan (00:43:24).

Ramakrishnan remains cautiously optimistic, acknowledging the challenges in translating these findings safely to humans:

“I think it's promising. But there's a lot of work to be done before it's ready for primetime” – Venki Ramakrishnan (00:30:55).

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Societal Impacts of Extended Lifespans

The panel shifts focus to the broader societal implications if humans achieve significant lifespan extensions. Ramakrishnan warns of potential demographic shifts, such as aging populations with lower fertility rates, leading to economic and social challenges:

“Imagine a society where there's very little turnover. Same people are living longer and longer. Very, very slow turnover” – Venki Ramakrishnan (00:60:07).

Neil deGrasse Tyson muses on the philosophical aspects, pondering the meaning of life in the absence of mortality:

“If the knowledge of death is what brings meaning to being alive, then to live forever is to live a life with no meaning at all” – Neil deGrasse Tyson (00:69:16).

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Ethical Considerations

Ethics surfaces as a critical theme, particularly regarding the disparity between individual desires for extended lifespans and the collective good of society. The conversation underscores the tension between personal benefits and societal sustainability:

“There's a conflict between what we as individuals want and what's good for society” – Venki Ramakrishnan (00:63:32).

Ramakrishnan stresses the importance of balancing healthspan (the period of life spent in good health) with lifespan, cautioning against extending life without ensuring quality:

“We want to stay healthy all your life and then suddenly crash and die. Nobody's shown that that can actually happen” – Venki Ramakrishnan (00:65:30).

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Conclusion

Wrapping up the episode, Neil deGrasse Tyson reflects on the personal significance of mortality, asserting that the inevitability of death imparts meaning to our lives and drives human ingenuity:

“Knowing that I will die gives meaning to every day that I'm alive... to love, to have new ideas, to make discoveries” – Neil deGrasse Tyson (00:69:40).

The hosts agree that while the pursuit of extending healthy lifespans holds promise, it must be approached with careful consideration of both scientific feasibility and ethical ramifications.

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Notable Quotes

• Venki Ramakrishnan (00:08:24): "What we mean by death is the irreversible loss of that individual's ability to function as a coherent whole."

• Venki Ramakrishnan (00:17:28): "As we get older, the quality of the proteins deteriorates. They're not made at the right time and the right amount, they start aggregating."

• Venki Ramakrishnan (00:26:23): “If you were able to introduce those four factors, you could take a fully differentiated cell and make it go backwards in development.”

• Venki Ramakrishnan (00:43:24): “Rapamycin was found in the soil of Easter Island... if you give rapamycin to mice, they lived a bit longer and seemed a bit healthier.”

• Venki Ramakrishnan (00:60:07): “Imagine a society where there's very little turnover. Same people are living longer and longer. Very, very slow turnover.”

• Neil deGrasse Tyson (00:69:16): “If the knowledge of death is what brings meaning to being alive, then to live forever is to live a life with no meaning at all.”

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Final Thoughts

StarTalk Radio's exploration of death and aging with Venki Ramakrishnan offers listeners a comprehensive look into the biological, technological, and ethical dimensions of extending human life. The episode underscores the delicate balance between the allure of longevity and the complexities it introduces to both individuals and society at large.

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Keep Looking Up!

Transcript

[Chuck Nice]

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[Neil DeGrasse Tyson]

Why are you bumming us out with a topic on why we die?

[Gary O'Reilly]

Because we have a Nobel prize winner as our guest.

[Neil DeGrasse Tyson]

Dude, we have a comedian. It's a happy show.

[Chuck Nice]

It is a happy show because we're not talking about me dying on stage for once.

[Neil DeGrasse Tyson]

Coming up on StarTalk, how and why we die. Welcome to StarTalk, your place in the universe where science and pop culture collide. StarTalk begins right now. This is StarTalk. Neil DeGrasse Tyson, your personal astrophysicist. This is Special Edition, which means we've got Gary O'Reilly.

[Chuck Nice]

Gary.

[Gary O'Reilly]

I'm Neil.

[Neil DeGrasse Tyson]

Hey. And we got Chuck. Nice.

[Chuck Nice]

Hey. Hey.

[Neil DeGrasse Tyson]

Okay, what's happening? And Special Edition specializes in all science that matters to the human condition.

[Venki Ramakrishnan]

Yes.

[Neil DeGrasse Tyson]

And today's topic is no exception.

[Chuck Nice]

No.

[Neil DeGrasse Tyson]

And may I give the title of it?

[Gary O'Reilly]

Please do.

[Neil DeGrasse Tyson]

Why We Die.

[Chuck Nice]

Dun dun, dun.

[Neil DeGrasse Tyson]

Why We Die. Well, I have no expertise in that other than simply being alive.

[Chuck Nice]

Right.

[Neil DeGrasse Tyson]

But I fear death because I'm born knowing only life.

[Chuck Nice]

Wow, look at that.

[Neil DeGrasse Tyson]

Yeah, I got that from a movie. Okay.

[Chuck Nice]

That's.

[Neil DeGrasse Tyson]

Okay.

[Gary O'Reilly]

So Lane and I are our co producer on this.

[Neil DeGrasse Tyson]

Lane, our LA producer for StarTalk. Yes.

[Gary O'Reilly]

We have long wanted to investigate this Subject matter.

[Chuck Nice]

You want to investigate it. But not firsthand.

[Neil DeGrasse Tyson]

No, no, firsthand data.

[Gary O'Reilly]

More an observation. More an observation. So if you put it this way. Humankind has for millennia asked, why do we die? Followed by well, why can't we live forever then? And then?

[Neil DeGrasse Tyson]

It's kind of the same question.

[Gary O'Reilly]

Yeah, but different people. So has evolution programmed us to expire on a certain date? Could we extend the game? Cheat death? Play God? If you wish? Millions? If not, billions are spent annually on anti aging, be it research or products.

[Neil DeGrasse Tyson]

Billions of dollars.

[Venki Ramakrishnan]

Yes.

[Gary O'Reilly]

And so how close are we to unlocking the mystery of death? So no surprise that the research into proteins is proving to be the key to this mystery.

[Chuck Nice]

So the building blocks of life may hold the key to death.

[Venki Ramakrishnan]

How about that?

[Chuck Nice]

Wow.

[Neil DeGrasse Tyson]

Ooh, good sentence there.

[Chuck Nice]

Yeah, very good, Chuck.

[Neil DeGrasse Tyson]

So we have the world's expert on this very subject.

[Chuck Nice]

Wow.

[Neil DeGrasse Tyson]

And this is Venki Ramakrishnan. Venki, welcome to Stark Talk.

[Venki Ramakrishnan]

Thank you.

[Neil DeGrasse Tyson]

Excellent. And you are now based in Cambridge.

[Venki Ramakrishnan]

Yes, England.

[Gary O'Reilly]

Say it.

[Neil DeGrasse Tyson]

I knew you had to do that.

[Venki Ramakrishnan]

Wasn't really necessary.

[Gary O'Reilly]

It's always bash a Brit day here.

[Neil DeGrasse Tyson]

Yeah, yeah, it is. It is. But we do it lovably.

[Gary O'Reilly]

We do.

[Neil DeGrasse Tyson]

Yeah. So you run a small group, but used to be bigger. Cause you're winding down in your career. A program leader at the mrc.

[Venki Ramakrishnan]

That stands for Medical Research Council Lab at Cambridge.

[Neil DeGrasse Tyson]

Yes, yes. And it specializes in bio molecular biology. Molecular biology.

[Venki Ramakrishnan]

So it's the MRC Lab of Molecular Biology.

[Neil DeGrasse Tyson]

Okay. Okay.

[Chuck Nice]

Our name is what we do.

[Neil DeGrasse Tyson]

But that's like the least of your resume here. So in 2009 you were awarded the chemistry Nobel prize.

[Chuck Nice]

Wow. Why are you wearing it under your shirt right now?

[Venki Ramakrishnan]

No, no.

[Chuck Nice]

Cause that's serious blame. Honestly.

[Neil DeGrasse Tyson]

Go to the club.

[Chuck Nice]

Yeah. I would be like the Flavor Flav of Nobel prize winners. I would never take it off.

[Neil DeGrasse Tyson]

So, former president of the Royal Society, Very important.

[Gary O'Reilly]

That's a deal.

[Neil DeGrasse Tyson]

Organization that basically the first, we think, the first in the world to organize the ideas and publications of scientists.

[Chuck Nice]

Wow.

[Neil DeGrasse Tyson]

To make it a clearinghouse of peer.

[Venki Ramakrishnan]

Review, first peer reviewed papers. Also it advocated evidence based science in the 17th century at a time when authority mattered a lot. And they said authority doesn't matter, beauty doesn't matter. It's evidence that matters.

[Chuck Nice]

Yes.

[Neil DeGrasse Tyson]

Very enlightened and important posture. And then you got knighted in 2012. That's three years later. And do they knight with an actual sword?

[Venki Ramakrishnan]

Yes, but I think it's blunt.

[Chuck Nice]

Well, let's just hope you don't want.

[Neil DeGrasse Tyson]

Them to Slip up if there's a little sort of jiggle in the wrist.

[Chuck Nice]

We wanted to make him a knight. It turned into an execution.

[Gary O'Reilly]

Who was on the other end of the sword?

[Venki Ramakrishnan]

Yes, it was Princess Anne.

[Neil DeGrasse Tyson]

Oh, cool, cool. We love Princess Anne. Yeah, that'll work.

[Chuck Nice]

Yeah.

[Neil DeGrasse Tyson]

Yeah. Also you have a book. It's your second book, first one, a few years back, the Gene Machine. But what we're especially interested in now is why We Die. And give me the subtitle of that book, why We Die.

[Venki Ramakrishnan]

It's called the New Science of Aging and the Quest for Immortality.

[Neil DeGrasse Tyson]

Well, let's dive right in because you are our world's expert in this. And before we can define death, I guess we should kind of define life and then learn what it is that ceases in life that then brings death upon it.

[Venki Ramakrishnan]

Well, defining life is very hard. It's, you know, you could almost say, quote Justice Potter Stewart as. I can't define it, but I know.

[Chuck Nice]

When I see it.

[Neil DeGrasse Tyson]

Spoken of, maybe you don't know pornography, because that's America, that he said that of pornography.

[Venki Ramakrishnan]

But fact is life, most biologists would define it as a system that can self replicate and evolve. And at least in our world, it's carbon based. But when we talk about death, it's a little complicated because there are many different kinds of death. You can have societies dying, cities dying, nations dying. You can have companies dying. But what we're talking about is the death of the individual, which has a. The organism of an individual. Animal or organism. And there's a peculiar paradox there, because while you're alive, I mean, right now, millions of cells and you're dying, you don't even notice that. Okay, that's cell death.

[Neil DeGrasse Tyson]

Why you gotta tell me that right now?

[Venki Ramakrishnan]

No, they need to die in order to. In order to keep you alive.

[Neil DeGrasse Tyson]

That's how he got out of that. Thank you.

[Chuck Nice]

Dead cells.

[Neil DeGrasse Tyson]

So to make room for the new cells.

[Venki Ramakrishnan]

To make room for new cells, actually, during development. Cells will die at precise points during development. They've done their bit and then they have to get out of the way.

[Neil DeGrasse Tyson]

When you say development, you mean embryonic development.

[Venki Ramakrishnan]

Embryonic development. Correct. At the same time, when you die, when you say a person has died at the point of death, most of you is still alive. That's why you can donate organs.

[Chuck Nice]

Right.

[Venki Ramakrishnan]

Okay.

[Gary O'Reilly]

And there's the other side of the paradox.

[Chuck Nice]

Interesting.

[Venki Ramakrishnan]

So what do we mean by death by death? Okay, you're gonna have. By the way, since you're an astrophysicist, you're gonna have Death of the universe as well. And there's a book coming out on that or has come out. So the question is, what do we mean when an individual dies? What we mean is the irreversible loss of that individual's ability to function as a coherent whole. So that means that person can no longer exist as a unit. And that's what we mean by death.

[Chuck Nice]

Are you talking physiologically? This person cannot function as a unit because there are people who experience brain death or to an extent. And they keep them on a respirator because a family member says, I don't want them to die.

[Neil DeGrasse Tyson]

So there are two examples coming out of Chuck's point. You can be brain dead, but sustained on a respirator. So all your organs are working. Or you can be body dead, I suppose. And in the limit, it's like your brain in a jar or whatever.

[Venki Ramakrishnan]

That's more like a quadriplegic, what you said can't happen because if your body's dead, then it can't feed nutrients to the brain to keep it alive. The brain is the biggest consumer of resources. Resources. So coming back to your point though, about brain death, etc. That's interesting because it used to be that if your heart stopped beating, that was the moment people said, you're dead.

[Chuck Nice]

Right.

[Venki Ramakrishnan]

Then they found out that actually even if your heart stops beating, they can resuscitate you. But then they decided, okay, when you no longer have brainwaves and your brain has irreversibly stopped, that's brain death. And there's an interesting case, states in the US used to have different definitions of death. And there was a case where somebody died in California, but her relatives wouldn't accept it. And by New Jersey laws, she was not dead. So they moved the body to New Jersey and she was maintained, as you say, on some sort of artificial device. And then eventually she died. But this is slightly getting semantic because most people agree that there's a point when the body cannot reverse itself and get back to being alive.

[Neil DeGrasse Tyson]

Yeah. But that's a statement of the limits of medicine in the day today. Right. So I remember, I mean, I read this, that one of the definitions of death is if you do not fog a mirror held up to your mouth.

[Venki Ramakrishnan]

Yeah. And I'm thinking, that's respiratory.

[Chuck Nice]

That was a long time.

[Neil DeGrasse Tyson]

I'm thinking, you know, I'm glad that's not when I'm alive. I mean, I'm just thinking, thank you for.

[Chuck Nice]

Right, thanks for not being alive back then. Cause I'm a light sleeper.

[Neil DeGrasse Tyson]

Okay. So that tells me that however real our current definitions feel about when someone dies could be modified in the near or distant future.

[Venki Ramakrishnan]

Absolutely. And neither birth nor death are very clearly defined. And I've pointed this out that they're both somewhat fuzzy. I mean, when is it that you actually. Are you at birth? And that's the whole argument about abortion and all of that is just about that. And similarly, the point of death is also when are you.

[Chuck Nice]

Yeah, that's wild. Yeah.

[Gary O'Reilly]

So the bit in between is aging.

[Venki Ramakrishnan]

The bit in between is aging. And unfortunately for us, the little bit.

[Neil DeGrasse Tyson]

In between your whole life.

[Gary O'Reilly]

I may have downplayed that bit.

[Chuck Nice]

Okay.

[Venki Ramakrishnan]

And in fact, you. You start aging even in utero.

[Gary O'Reilly]

Interesting.

[Venki Ramakrishnan]

From the time you're conceived, you know, you fertilized eggs starts to California.

[Chuck Nice]

Is that why all children are born looking like old men?

[Neil DeGrasse Tyson]

Winston Churchill. So that's even earlier than a loaf of bread. Cause you know when a loaf of bread starts aging?

[Chuck Nice]

No.

[Neil DeGrasse Tyson]

Right. When you take it out of the oven.

[Chuck Nice]

Okay.

[Neil DeGrasse Tyson]

In that moment, it starts getting old.

[Chuck Nice]

Right?

[Neil DeGrasse Tyson]

Right.

[Venki Ramakrishnan]

But here, this is in the oven.

[Neil DeGrasse Tyson]

In the oven, you're getting old.

[Chuck Nice]

Look at that.

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[Chuck Nice]

Hey, this is Kevin the sommelier and I support StarTalk on Patreon. You're listening to StarTalk with Neil DeGrasse Tyson.

[Neil DeGrasse Tyson]

Forgive me. As an astrophysicist, I hear talk of cells, but then I also hear talk of proteins. So could you distinguish the two of them for me with regard to the role of aging?

[Venki Ramakrishnan]

So aging is. You can think of aging as an accumulation of damage and changes to our molecules, our cells, our tissue and entire organs and the body. And this aging occurs at every one of those levels. So if you think of the molecule that holds all the information necessary to make all of the other molecules in the cell, that's our genes, our DNA. So DNA can be damaged. It can also change, which is not exactly damaged, but it can be modified as we age, typically by adding chemical groups to it, often methyl groups.

[Neil DeGrasse Tyson]

It's gene editing.

[Venki Ramakrishnan]

It's epigenetics. It's not editing as such. It's not changing the bases, it's not changing the letters of the DNA.

[Neil DeGrasse Tyson]

That would be gene editing.

[Venki Ramakrishnan]

That would be gene editing. This is epigenetics, which means sort of on top of. Of genetics.

[Neil DeGrasse Tyson]

Like the epicenter of an earthquake is the point on our surface above where the right. Yeah.

[Venki Ramakrishnan]

And so you can modify DNA and that changes the way in which the program is expressed. So which genes are translated into protein.

[Neil DeGrasse Tyson]

So this is the plain God part, because now you are changing the.

[Venki Ramakrishnan]

No, we're not doing anything. This is happening. This is happening even in utero.

[Chuck Nice]

Experiential circumstances can change your epigenetics.

[Venki Ramakrishnan]

So it's part of. It's just part of life. And it evolved for probably a very good reason. Mainly it may have been of a cancer prevention mechanism. Early in life, we can get into why we have death from an Evolutionary point of view, but nevertheless, the DNA program itself ages. You know, damage and modifications change the nature of the genes that you're expressing. Then that results in the proteins which are encoded by DNA.

[Neil DeGrasse Tyson]

There you go.

[Venki Ramakrishnan]

These are the workhorses of the cell. They carry out all the function. They give the cell its structure. Almost everything you think of as a property of life, like vision or touch or, you know, or antibodies. They're all proteins, and they're all encoded by DNA. But as we get older, the quality of the proteins deteriorates. They're not made at the right time and the right amount, they start aggregating. You know, Alzheimer's is a case where proteins clump up together and form tangles. In the brain. Yeah, in the brain. So that also is a consequence of age. And as a result, things in the cell, larger entities like compartments in the cell, also start to age. One of them are mitochondria, which are. Mitochondria were actually bacteria that were swallowed up by a larger cell 2 billion years ago and then lived in symbiosis. And now today, mitochondria are specialized as the centers for energy metabolism. It's where oxygen is. Is used to burn sugar effectively and get energy out of it.

[Neil DeGrasse Tyson]

So it's that kind of chemistry going that far back that accounts for our genetic similarity to life forms that are nothing like us. Like the, you know, we're something like 25% identical genes to a banana.

[Venki Ramakrishnan]

Yes. Yes. All eukaryotes came out of that. Yes, out of that symbiosis.

[Neil DeGrasse Tyson]

Okay.

[Venki Ramakrishnan]

And so. So you can think of this as an ancient organelle that's now specialized. And because it's a center for oxygen usage, it can create what are called free radicals or reactive oxygen species, because these are partially reduced oxygen atoms, which are chemically very reactive. So you can have a lot of damage.

[Neil DeGrasse Tyson]

To be clear, if it's fully reduced, that means all the oxygen is where it becomes water. And then you can't. There's nothing else that can happen.

[Venki Ramakrishnan]

Carbon dioxide and water is what you get.

[Neil DeGrasse Tyson]

Yes, it's fully reduced, partially. It's basically activated. It's activated to do things.

[Chuck Nice]

And it does damage. Yeah, yeah.

[Venki Ramakrishnan]

And so it can cause damage. And mitochondria have preserved a little bit of their own genome. They used to have a much larger genome when there were bacteria, but now that genome has shrunk. In humans, they only encode 13 protein genes, but they're essential for the function of mitochondria and the mechanism to replicate that DNA, to copy that DNA as mitochondria divide, it's not as accurate as the mechanism for our own DNA replication. The more errors creep in. And so mitochondrial aging is a big problem with our aging is that the.

[Gary O'Reilly]

Single point of failure in terms of.

[Venki Ramakrishnan]

It's not a single point. I think aging.

[Neil DeGrasse Tyson]

Blame it on mitochondria.

[Chuck Nice]

Yeah. Aging is like a cascade failure.

[Venki Ramakrishnan]

But I do like to say that the reason my grandson has a lot more energy than I do is because he has much better mitochondria than I do.

[Chuck Nice]

Something's going on with the mitochondria for your skin, because your skin's perfect. I don't know how old you are, but, you know, clearly I look at your hair and I'm like, okay, this guy's old, but I look at your skin, I'm like, but he stole his skin off of a teenager.

[Neil DeGrasse Tyson]

I thought, black don't crack.

[Chuck Nice]

That's true. Black don't crack.

[Neil DeGrasse Tyson]

And then it goes.

[Venki Ramakrishnan]

You're absolutely right.

[Chuck Nice]

It doesn't make a difference.

[Venki Ramakrishnan]

It's the dark skin.

[Chuck Nice]

It's the dark skin.

[Neil DeGrasse Tyson]

Yeah, it's just melanin.

[Chuck Nice]

Yeah, that's just melanin at the end of the day.

[Neil DeGrasse Tyson]

Okay, so this reduced chemistry that makes it chemically active, that could not have been useful before Earth's atmosphere became oxygen rich. That's right.

[Chuck Nice]

And that happened because of the cyano. What?

[Neil DeGrasse Tyson]

Yeah. So cyanobacteria basically turned a carbon dioxide atmosphere into one that had a presence of oxygen. And then anything that needs oxygen can thrive, can now thrive, but it couldn't before then. So that helps age date or time date?

[Venki Ramakrishnan]

I should say it's about 2 billion years.

[Neil DeGrasse Tyson]

That helps time date these activities. Yeah.

[Gary O'Reilly]

Interesting watershed moment for.

[Neil DeGrasse Tyson]

Very good.

[Chuck Nice]

Yeah, look at watershed. I like that. That was good.

[Gary O'Reilly]

So there's something called senescent cells where they age and they secrete these sort of inflammatory compounds.

[Venki Ramakrishnan]

Yes. So senescent cells are another. I mean, I said you can have aging at every level. And aging at this at a cellular level is often due to senescence. And senescence is interesting. It may have evolved originally as an anti cancer mechanism or as a mechanism to get rid of defective cells. So what happens is, if a cell gets DNA damage, it has a number of enzymes to repair the damage, to sense and repair the damage. But if the damage is too extensive, then it triggers pathways to either kill the cell, commit suicide, or to send it into this state called senescence. That can also happen due to other kinds of stresses. What senescence cells do is they no longer function normally and they no longer divide, but they secrete inflammatory compounds. And the purpose is to signal to the immune system that there's something wrong here. Come and repair the damage around this site. Maybe it's a wound or a infection or something. Call the cavalry and. Exactly. Call the cavalry.

[Neil DeGrasse Tyson]

So it has utility.

[Venki Ramakrishnan]

It has until. It has utility early in life, until it doesn't. But later in life, you get too many of these events. Buildup of senescent cells, systemic inflammation which causes organ damage, more senescence. And so it's a big problem in aging.

[Chuck Nice]

Wow. Yeah. And that's why you see so many medical reports now that talk about the dangers of inflammation.

[Venki Ramakrishnan]

Absolutely.

[Chuck Nice]

Totally. Like, it doesn't make a difference what kind of inflammation. The idea is to eliminate inflammation as much as you can, no matter what.

[Venki Ramakrishnan]

Sure. And actually, people know, for example, in the COVID pandemic, the cause of death is often triggered by inflammation.

[Chuck Nice]

Right.

[Venki Ramakrishnan]

Not by necessarily directly by the virus itself.

[Chuck Nice]

By the virus itself.

[Neil DeGrasse Tyson]

It's our reaction.

[Chuck Nice]

It's the reaction. So it's the cytokine storm that was created as a reaction to the virus itself.

[Neil DeGrasse Tyson]

Cytokine.

[Chuck Nice]

Cytokine.

[Neil DeGrasse Tyson]

Please explain.

[Chuck Nice]

Cytokines are. If I'm not mistaken, or we can get him to. Oh, can you answer that? Yeah. Because I'm not an expert, I'm not.

[Venki Ramakrishnan]

An immunologist.

[Chuck Nice]

But, yeah, the cytokines are what's released when we respond to what our body thinks is an attack on us. And.

[Neil DeGrasse Tyson]

And sometimes it can open. It goes in overdrive, and it goes.

[Chuck Nice]

In overdrive, and, you know. Yeah.

[Gary O'Reilly]

Are we anywhere close to being. Or is this the epigenetics thing where we can deal with these senescent cells?

[Venki Ramakrishnan]

No, but there is a new field emerging, which is cellular reprogramming.

[Chuck Nice]

Ooh, yeah.

[Venki Ramakrishnan]

Yeah, that sounds sexy. To explain that if you start from a single fertilized egg, it divides into many cells, becomes something called a blastula or a blastocyst, and then it divides further and further and then forms specialized stem cells. And each of those specialized stem cells give rise to certain kinds of tissues. So some stem cells will only generate cells of the blood system, including white blood cells, red blood cells, and so on. That used to be thought of as unidirectional. You can't go backwards. You can't go back from a skin cell back to a fertilized egg or an early embryo. But that turned out not to be true. Okay. And actually, it was done in a natural way when Dolly the sheep was cloned, but actually, even earlier, when John Gurdon Cloned the skin cell of a frog and cloned an entirely new animal from it.

[Chuck Nice]

Wow.

[Venki Ramakrishnan]

And that meant that somehow these marks on the DNA had been erased or changed.

[Neil DeGrasse Tyson]

Just historically, that completely changed the public dialogue about our source of stem cells.

[Chuck Nice]

Right.

[Neil DeGrasse Tyson]

Because we only were getting them from.

[Chuck Nice]

Aborting fetuses from fetuses from fetuses.

[Neil DeGrasse Tyson]

And so that was a complicated ethical issue for many people.

[Chuck Nice]

Right.

[Neil DeGrasse Tyson]

And then once this. That blew open that whole field.

[Venki Ramakrishnan]

Right. Well, that wasn't Garden and Dolly the sheep and others, but it was actually Shinya Yamanaka, a Japanese scientist, who showed that if you were to introduce just four factors. These are genes for proteins that regulate other genes.

[Chuck Nice]

Gotcha.

[Venki Ramakrishnan]

If you were able to introduce those four factors, you could take a fully differentiated cell, like a skin cell or a heart, liver cell or a heart cell, and you could make it go backwards in development all the way back to what's called a pluripotent stem cell. Pluripotent means it can make any tissue. And so that eliminated the need for what you said, which is he not.

[Gary O'Reilly]

Putting no veil for that as well?

[Chuck Nice]

He better have.

[Venki Ramakrishnan]

He and John Gurdon shared a Nobel Prize. And here's an interesting thing. John Gurdon's paper, for which he won the Nobel Prize, was published the year Shinya Yamanaka was born.

[Gary O'Reilly]

No.

[Chuck Nice]

Wow.

[Venki Ramakrishnan]

That's how. That's how far apart they are in the age.

[Chuck Nice]

And all that time, all that work, and then he just comes along and takes credit for it. Look at that. Would you look at that?

[Gary O'Reilly]

We've had sort of variations of this with David Sinclair, who we've had a guest, as a guest, took mice that were blind.

[Chuck Nice]

Correct.

[Gary O'Reilly]

It sounds like a nursery rhyme.

[Chuck Nice]

Three of them. Don't start.

[Neil DeGrasse Tyson]

You did it, didn't you? Somebody had to go there. You did go.

[Gary O'Reilly]

Go and turn them into sight. Cured their blindness.

[Chuck Nice]

Yeah.

[Gary O'Reilly]

So, I mean, if that's the case, how far away from.

[Venki Ramakrishnan]

I would say it's early days. Okay.

[Gary O'Reilly]

I can tell you that I'm aware that this has happened. And then my question is just the distance between this and doing other things on a grander scale. Mice are one thing. Larger primates.

[Venki Ramakrishnan]

Yeah. And curing blindness, it's a little further.

[Chuck Nice]

Down the line, is what you're saying. It's a little. But the idea is we do have. Would you say we now have a. Not a blueprint, but maybe a template that we know we can take these programming cells and use them to maybe change our makeup?

[Venki Ramakrishnan]

I think the biggest use of that is in something Called regenerative medicine, where if you want to replace tissue that normally can't be replaced, for example, damaged heart muscle and heart attack, or pancreatic tissue, which has been destroyed and you have diabetes or cartilage, for example, osteoarthritis. Very good.

[Chuck Nice]

Absolutely.

[Venki Ramakrishnan]

And maybe one day, I'm hoping, even hair. So if you can.

[Chuck Nice]

It looks good on you. Though very few people can pull this.

[Venki Ramakrishnan]

Off anyway, so if you can do that. Regenerative medicine is a huge area of research, and they're making good progress in some things.

[Neil DeGrasse Tyson]

Just to be clear, I've always been disappointed in humans for not being able to regenerate limbs the way newts do.

[Venki Ramakrishnan]

Exactly. That's because newts have stem cells all over.

[Chuck Nice]

All over their body.

[Venki Ramakrishnan]

All over the body.

[Chuck Nice]

Their whole makeup.

[Venki Ramakrishnan]

Yeah. It's spread out throughout. And so they can. Or starfish.

[Neil DeGrasse Tyson]

We're old enough to remember reading biology books, Humans are the top of the evolutionary. Back when we spoke that way, unless.

[Chuck Nice]

You lose an arm.

[Neil DeGrasse Tyson]

Unless you lose.

[Chuck Nice]

Then.

[Neil DeGrasse Tyson]

I went through the list of all the other animals that do things way better than we do, and I quickly re.

[Gary O'Reilly]

Yeah, it's not a short list.

[Venki Ramakrishnan]

It's humbling to know that we have about the same number of genes as a worm or a weed.

[Chuck Nice]

Right. So, yeah, there you go.

[Gary O'Reilly]

Put us in that place.

[Neil DeGrasse Tyson]

Yeah.

[Venki Ramakrishnan]

Anyway. But going back to stem cells, the thing with aging is, can you take a fully grown or an aged individual, apply these kinds of factors, and get their tissues or their stem cells to be regenerated? Because one problem with aging is that our stem cells also age. They decline in number and in quality. So if you were able to take. Use a method that would somehow either rejuvenate tissue or actually regenerate stem cells, that would be a big thing. And people have done experiments to do this kind of thing in mice. And they say that the mice. I mean, the papers report that the mice look healthier, they seem younger by many criteria, and so on. But how to do this safely?

[Neil DeGrasse Tyson]

And the bald mice, did they get hair back?

[Venki Ramakrishnan]

No, but their fur looked better.

[Neil DeGrasse Tyson]

Oh, okay.

[Chuck Nice]

That's not bad.

[Venki Ramakrishnan]

So the question is, how can you do this in humans in a way that's safe, that doesn't cause cancer, that is at the right dose, and so on, and that's a big challenge. So I think it's promising. But like many of these things, you know, the aging field, I should say, is full of hype. Okay. And it's very promising, but there's a lot of work to be done. Before it's ready for primetime.

[Gary O'Reilly]

Are we at this sort of Frankenstein moment? I mean, you've done a Frankenstein show before with, Let me get his name right, David Andreas. You know, the cells. You've said there can be death to the organism, but cells will remain alive. And now we've got the Yamanaka factors. Are we getting to that thing when we can create, or are we just fantasy talking here?

[Venki Ramakrishnan]

You mean create a new individual or the same individual?

[Gary O'Reilly]

Well, the same individual.

[Venki Ramakrishnan]

You could certainly clone yourself. That's theoretically and practically possible. They've cloned all kinds of mammals. There's no reason why they can't clone a human being. Except that all countries have decided that's a bad thing to do.

[Chuck Nice]

A bad thing to do.

[Venki Ramakrishnan]

But that's not the same as rejuvenating the same individual.

[Chuck Nice]

Right, right. Which, by the way, for selfish purposes, rejuvenation is a hell of a lot better than cloning, because that clone is not me.

[Venki Ramakrishnan]

Exactly. People forget that.

[Neil DeGrasse Tyson]

Yeah, yeah. There's all these fantasies in the multiverse where you have an infinite number of possible molecular outcomes of all organisms. They're imagining themselves in another universe, in a way, being reincarnated and living forever. It's like, no, that's a different person.

[Chuck Nice]

That's just a different person in a different timeline.

[Venki Ramakrishnan]

And by the way, these transhumanists, people who think that they're gonna dump their brain into a computer and then maintain their consciousness, a simple question to ask is, what if you make two copies of it? Which one's the real you? And you immediately have a paradox.

[Chuck Nice]

Absolutely.

[Gary O'Reilly]

The copies that you make will be of you, of that moment, but in your timeline are still proceeding. They would be stuck.

[Neil DeGrasse Tyson]

You still get to go to the beach and have friends. And your brain in a jar does not. Right.

[Chuck Nice]

Oh, gosh.

[Neil DeGrasse Tyson]

Or your brain in a silicon chip.

[Gary O'Reilly]

This is you from whenever it was you created it.

[Neil DeGrasse Tyson]

So I heard long ago, and I checked it out, and I think it's true that all mammals live for about the same number of heartbeats, except for humans, who live two or three times that. Except if you go back far enough in time, when we were just living in caves, we were right with all the rest of the mammals. So, first, is that true? Second, there are animals, not mammals, that live much longer than we do. I'm thinking of the Galapagos tortoise, for example. So do you guys study other animals to get insight?

[Venki Ramakrishnan]

So. So there is a whole field devoted to looking at lifespan of different species. And you are right that at Least among mammals. Jeffrey west, who's written a book called Scale, shows that the number of heartbeats is roughly the same. That has to do with the fact that smaller animals have a higher metabolic rate, they have a faster metabolism, and they almost need to. Because their surface to volume ratio is larger, they dissipate heat more.

[Neil DeGrasse Tyson]

We did a whole explainer on surface to volume ratio.

[Venki Ramakrishnan]

And so they need to maintain a higher metabolic rate. That's one of the reasons.

[Neil DeGrasse Tyson]

Well, that's only one of the reasons why they have higher heart rate. That's not a reason why they should die sooner.

[Venki Ramakrishnan]

Ah, the why we should die sooner has an evolutionary explanation, and that is evolution doesn't care how long you live. It only cares about fitness. Fitness in the biological sense is the likelihood that you're going to be able to successfully pass on your genes.

[Neil DeGrasse Tyson]

And people always misinterpret that as being physically fit or stronger or whatever.

[Chuck Nice]

Survival of the fittest. I'm in great shape.

[Neil DeGrasse Tyson]

Yeah. Darwin should have found a different word.

[Chuck Nice]

He should. Yeah.

[Venki Ramakrishnan]

So evolution cares about fitness now. At the same time, for most of our history, and certainly the history of all other species, resources are limiting. And so you have to select, do you put more of your resources into maintenance and repair of the individual animal, or do you put it into growth and reproduction? There's always a balance if you have limited energy. So in the case of a mouse, which lives about two years in the wild, there's no sense in having a mouse live for 40 years because long before that it's going to be eaten. Exactly. You beat me to it. Or it'll die of starvation or drought or something. And so in the case of a mouse, evolution has favored selection of a species that grows very quickly and reproduces prolifically. That's a mouse. If you get to a large animal, like a bowhead whale, let's take even bigger than an elephant. They can live for two, 300 years, and they have a very, relatively slow metabolism. An even slower metabolism is not a mammal, but it's still a vertebrate called The Greenland shark. 700 years into that. Yeah. A vertebrate living for 700 years, very slow metabolism.

[Neil DeGrasse Tyson]

Wait, wait, wait, wait, wait. How do you know that? We didn't even have marine biology 700 years ago.

[Venki Ramakrishnan]

So they can do things like carbon dating and then look at.

[Gary O'Reilly]

They cut one open, it was 700 rings inside. I mean, you've got on.

[Chuck Nice]

Okay, I'm just.

[Neil DeGrasse Tyson]

I'm just weird.

[Gary O'Reilly]

No, no. So you've got the mayfly, lives a day.

[Venki Ramakrishnan]

Mayfly Lives a day.

[Gary O'Reilly]

Exactly right. And then between that, you've gone from there to a Greenland shark and your Galapagos.

[Venki Ramakrishnan]

And there are actually other animals that are thought not to even age biologically.

[Gary O'Reilly]

What's the immortal?

[Venki Ramakrishnan]

Like the hydra and the immortal jellyfish? These things.

[Neil DeGrasse Tyson]

But there's an actual animal called the hydra.

[Venki Ramakrishnan]

Yes.

[Chuck Nice]

Awesome.

[Neil DeGrasse Tyson]

Not just in.

[Chuck Nice]

Not just in G.I. joe.

[Venki Ramakrishnan]

No.

[Chuck Nice]

Oh, no.

[Venki Ramakrishnan]

Marvel.

[Chuck Nice]

No, no, no.

[Venki Ramakrishnan]

In mythology.

[Chuck Nice]

Oh, you mean the real hydra. Yes.

[Venki Ramakrishnan]

This is a freshwater small animal, and they're full of stem cells, so they're constantly regenerating themselves. But if you followed an individual, it would also age, only very slowly. It's just in the wild, it dies for other reasons before actually aging. So there's a whole range.

[Neil DeGrasse Tyson]

So humans might be the only species that dies of natural causes in the world. I mean, if you want to think about it that way.

[Venki Ramakrishnan]

Possibly. Possibly.

[Neil DeGrasse Tyson]

You know, we're apex predator.

[Venki Ramakrishnan]

Yeah, yeah, I think that may be true. In fact, there's a book written by Stephen Ostad called Methuselah Zoo where he talks about all these animals and he.

[Chuck Nice]

Talks about Methuselah Zoo. Love it.

[Venki Ramakrishnan]

And it's a great book.

[Neil DeGrasse Tyson]

So that reminds me, because Methuselah's the oldest person in the Bible, right? In the. In the. In the Old Testament Bible, the oldest star we know of in our galaxy is called Methuselah.

[Chuck Nice]

It's called Methuselah. Yeah.

[Neil DeGrasse Tyson]

Right. So Methuselah had a lot of influence.

[Chuck Nice]

Yeah. And that star, too, is lying about its age.

[Gary O'Reilly]

Who knew that?

[Venki Ramakrishnan]

Anyway, in this book, he points out Methuselah Zoo. In Methuselah Zoo, he points out how all these species have such different lifespans, and it's because of this evolutionary selection. But it's actually worse than that. The fact is, evolution will select for things that help you early in life, even if they cause a problem later in life. So many of the things that cause aging are related to growth, for example, or to cancer prevention, prevention of. Or senescent cell creation. These things all help us early in life, and they're a problem later in life. But evolution doesn't care what happens to you later when you're not making babies. Right, Exactly.

[Chuck Nice]

Because that's the whole deal.

[Gary O'Reilly]

So what helps us survive in infancy and then go on to reproduction is the key component of our decline and demise.

[Venki Ramakrishnan]

Not always. Not everything. But there are things that happen to us early in life that are selected for early in life that cause aging.

[Chuck Nice]

So the real deal is just keep having babies your entire life and then you'll never age. However, you will eventually kill yourself because of these kids.

[Venki Ramakrishnan]

So we're an outlier. We're an outlier. We live about twice as long as twice as we would based on our.

[Neil DeGrasse Tyson]

Size, but only post caveman life. Right.

[Venki Ramakrishnan]

Because 40,000 years.

[Neil DeGrasse Tyson]

Exactly. So only, I mean, half of everyone died by 30. And so we're not 2x other mammals @ our size. Right?

[Venki Ramakrishnan]

Yeah. And one last thing is there's a group of animals, mammals, the bats, they live much longer. They're about the same size as a mouse in terms of mass, your fleet or mouse. They live about 10 or 20 times as long as a mouse. And the reason is they can fly around. So that means two things. They can escape predators more easily, and they can also forage over a much wider area for food. And when they roost, they roost in the ceilings of caves. So they're not as accessible.

[Gary O'Reilly]

They've been designed to survive longer.

[Venki Ramakrishnan]

And so there. It's worth it for evolution to make them live longer because they'll still keep producing more babies.

[Chuck Nice]

Yeah. So you gotta be Grandpa Munster is basically the deal.

[Neil DeGrasse Tyson]

Grandpa from the monsters.

[Chuck Nice]

The grandpa from the monsters. If you want to live long, sleep hanging upside down, away from predators.

[Gary O'Reilly]

So if we're looking at aging, we all do it can't help it, more or less. What have been the attempts to reverse the aging? I'm not talking potions and lotions here. So let's go through the laundry list. The sort of young blood transfusion.

[Chuck Nice]

Oh, yeah.

[Gary O'Reilly]

How successful has that been?

[Venki Ramakrishnan]

It's not incredibly successful, but the science underlying it is solid. If you connect an old rat with a young rat, by that, I mean you connect them so that their blood.

[Chuck Nice]

Systems are sharing the same circulation system.

[Venki Ramakrishnan]

Exactly. Then it turns out that the old animal benefits from the blood of the young animal, but even more so, the young animal suffers from the blood of the old animal.

[Chuck Nice]

Wow.

[Venki Ramakrishnan]

And so this means there are factors in blood that change as we age.

[Neil DeGrasse Tyson]

There's such a thing as old blood.

[Venki Ramakrishnan]

Exactly. Or young blood. And that's why I call it vampire blood. So that's the science and the research is now about finding out what these factors are, what they do. And once you know that, you might be able to figure out whether you can use them to our benefit. But people have not waited for that. What's happened is the very first time these people from Stanford Rando and others published this, they got creepy phone calls from rich people asking, like, Keith Richards, and companies started sprouting up getting blood from young Donors and extracting the plasma and setting them up at $8,000 a pint or something to rich old people. And one of them, the fda, wanted to shut it down. And then they sprouted up under a different name. The whole thing was like the Wild West. But there's real science under it. And that's an ongoing area.

[Gary O'Reilly]

Okay. Stem cells. We've kind of addressed as to how you could, through the Yamanaka factors, dial up, dial down.

[Venki Ramakrishnan]

And that's. I would consider that Yamanaka.

[Neil DeGrasse Tyson]

What is the Yamanaka factor?

[Gary O'Reilly]

The Oscar winning. Where he sort of.

[Neil DeGrasse Tyson]

Oscar winning.

[Gary O'Reilly]

Yes, Oscar winning. He was a bloody good actor. Unbelievably good actor. Nobel Prize.

[Neil DeGrasse Tyson]

Okay, that guy. Right, that guy.

[Chuck Nice]

Thank you.

[Gary O'Reilly]

Okay, the Nobel Prize.

[Neil DeGrasse Tyson]

Get your prizes straight here. Okay.

[Gary O'Reilly]

The calorific restrict or caloric restriction. Restriction.

[Venki Ramakrishnan]

Yeah.

[Gary O'Reilly]

So basically, fasting.

[Chuck Nice]

It is.

[Venki Ramakrishnan]

It is. So lots of experiments, starting in mice, but now also in flies, worms, even in single celled animals like yeast. If you reduce the amount of calories, it turns out that you can. The animals live longer. But more importantly, older animals start resembling younger animals in terms of their physiology and their biomarkers. And so the question is, can you mimic caloric restriction? And it turns out that there are many important biochemical pathways that are affected by caloric restriction. One of them is the IGF1 insulin growth hormone factor.

[Neil DeGrasse Tyson]

Just to be clear, what you're saying, you wouldn't have to imitate calorie reduction. You could just consume fewer calories. So what you're trying to do is we can still eat our cheeseburgers and the blueberry pie dessert, and then you hijack what would be the starvation mechanism biochemically.

[Venki Ramakrishnan]

Exactly.

[Chuck Nice]

That's intermittent fasting.

[Neil DeGrasse Tyson]

Yeah, but I don't have to fast.

[Venki Ramakrishnan]

Is this the gop?

[Chuck Nice]

Yeah. The whole point is not to fast, just to restrict. Yeah.

[Neil DeGrasse Tyson]

No. Did you get what I just said?

[Chuck Nice]

No, what he's saying.

[Neil DeGrasse Tyson]

That's why I paused on it saying.

[Gary O'Reilly]

Have your cake and eat it.

[Chuck Nice]

So you have your cake and eat it too.

[Venki Ramakrishnan]

Yeah.

[Chuck Nice]

Yes, but explain your point again. Cause I missed it.

[Neil DeGrasse Tyson]

Okay, so the point is what he said. He just slipped it in.

[Chuck Nice]

Right.

[Neil DeGrasse Tyson]

But I caught him. Okay. He's saying fasting will prolong your life.

[Chuck Nice]

Absolutely.

[Neil DeGrasse Tyson]

So can we find a way to mimic the biochemistry of that in your body?

[Gary O'Reilly]

We can.

[Neil DeGrasse Tyson]

And the word mimic in that sentence means still eat the cheeseburger, but do what the fasting would have done to your biochemistry. I see.

[Chuck Nice]

What? Yes.

[Neil DeGrasse Tyson]

Have your cake and eat.

[Chuck Nice]

But you're doing it Artificially is what you're saying.

[Venki Ramakrishnan]

In my book, I call it eating your blueberry pie and ice cream and. And getting the benefits of ice cream.

[Neil DeGrasse Tyson]

And still getting the benefits.

[Chuck Nice]

Wait, so have we done this?

[Venki Ramakrishnan]

No, there are. There are some.

[Chuck Nice]

Okay.

[Venki Ramakrishnan]

No, no, I'm. I'm not working on it.

[Chuck Nice]

He's like. He's out this game.

[Venki Ramakrishnan]

I should say.

[Chuck Nice]

He was like.

[Venki Ramakrishnan]

Did you see.

[Neil DeGrasse Tyson]

Yeah, the way.

[Chuck Nice]

The way he just went like this. No, no, no, not me.

[Neil DeGrasse Tyson]

They keep trying to keep me working.

[Chuck Nice]

I'm telling you right now, I'm out.

[Gary O'Reilly]

But if you do know how to do it, tell Chuck because he'll set up a company.

[Venki Ramakrishnan]

Certainly lots of companies. That's a problem. So, anyway, one of the drugs that does this is called rapamycin. It's the darling of the anti aging research community. Easter Island. Yes, Easter Island.

[Neil DeGrasse Tyson]

Somebody's got to connect these.

[Chuck Nice]

Yeah, Rapamycin. Okay, let's.

[Venki Ramakrishnan]

So rapamycin was found in the soil of Easter island from bacteria in the soil of Easter island that produce this compound, which turns out to be an antifungal compound. And then they found out that it may have some properties against cancer. And then eventually they found out that it actually is an immunosuppressor, and that's what made it get FDA approval as an immunosuppressive drug. Then much later, it was found in a completely different place. It was found that it shuts down a major pathway in the cell, and that pathway is related to the. It's a pathway that senses nutrients, so it's related to caloric restriction. People then said, okay, let's see what happens if you give rapamycin to mice and so on. And mice lived a bit longer. Seemed a bit healthier. However, rapamycin is an immunosuppressive drug, so it's going to make you more prone to infections like steroids. And it has other side effects as well. So the question they have is, can you adjust the dosage so you get the benefits against aging without the problems of immunosuppression and so on? And that's still, you know. Jury's still out on that.

[Chuck Nice]

Yeah.

[Neil DeGrasse Tyson]

Okay. Now, there's also relativity where you can slow down time for yourself.

[Gary O'Reilly]

Oh, well, that's going into space, though.

[Neil DeGrasse Tyson]

Yeah, well, Right.

[Venki Ramakrishnan]

That's one way to defeat aging. Right.

[Neil DeGrasse Tyson]

However, you are still aging in your own body one second per second.

[Chuck Nice]

Right.

[Neil DeGrasse Tyson]

The difference is all your friends are aging faster than you.

[Chuck Nice]

Much faster.

[Neil DeGrasse Tyson]

Right. So you're not gonna live older than you would have as an organism.

[Venki Ramakrishnan]

Right.

[Neil DeGrasse Tyson]

You'll just live longer than everybody else.

[Chuck Nice]

Exactly.

[Gary O'Reilly]

Isn't that the.

[Neil DeGrasse Tyson]

And then when you return, all your friends would have been dead.

[Chuck Nice]

They'll be dead.

[Gary O'Reilly]

The Kelly twins. They did the experiment.

[Neil DeGrasse Tyson]

Oh, yes, yes. We had one of them on, on this program.

[Gary O'Reilly]

Yes.

[Neil DeGrasse Tyson]

Scott Kelly, astronaut who went up.

[Chuck Nice]

That's right. And his brother stayed here.

[Neil DeGrasse Tyson]

Brother stayed here. They're identical twins. And you can calculate how much younger one would have been like a fraction of a second. They weren't.

[Chuck Nice]

That's what he gained. He gained half a second. Huh.

[Venki Ramakrishnan]

Does it show?

[Chuck Nice]

So basically. Basically, yeah. Excellent.

[Neil DeGrasse Tyson]

I don't remember the fraction, but it was. They were not going so fast that the speed of light.

[Gary O'Reilly]

Sibling rivalry.

[Neil DeGrasse Tyson]

Yeah.

[Chuck Nice]

The most expensive anti aging regimen ever.

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[Venki Ramakrishnan]

We're really doing this, huh?

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[Venki Ramakrishnan]

Bye bye Truckee.

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[Neil DeGrasse Tyson]

Hello, other truckee.

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[Neil DeGrasse Tyson]

So, as you surely know, in physics we speak of this thing called entropy, where left to itself, a system will always degrade to lowest energy, highest disorder.

[Venki Ramakrishnan]

And the key is left to itself.

[Neil DeGrasse Tyson]

Yes, yes. So we can create any manner of complexity on Earth because we're not a closed system. We're open to the sun. So the sun is gaining entropy by helping us out. Eventually it's gonna die and nothing's gonna help it.

[Chuck Nice]

Right?

[Neil DeGrasse Tyson]

Right. So do you guys in molecular biology think of entropy?

[Venki Ramakrishnan]

There's no question that entropic forces exist. But of course, living systems all use external energy to keep it alive. And part of the energy is used to do this maintenance and repair of the damage. But it's not perfect. And so eventually, even if you keep repairing DNA damage, repairing cells, getting rid of defective cells, all of that stuff which takes energy, it's not perfect. And eventually the system gradually decays. But it means it decays at different rates for different species.

[Neil DeGrasse Tyson]

Interesting. Or different parts, different systems, even within your own body.

[Venki Ramakrishnan]

Oh, that's something that you. Very interesting. So if you were to people were to analyze your different organs, they'd find that they all had different ages.

[Chuck Nice]

Yes.

[Venki Ramakrishnan]

To say someone's biological age is another.

[Neil DeGrasse Tyson]

Different ages mean different time distance from its birth to its death.

[Venki Ramakrishnan]

Correct.

[Neil DeGrasse Tyson]

Right. Because obviously it's all physically the same age.

[Venki Ramakrishnan]

Chronologically it's the same age.

[Neil DeGrasse Tyson]

Yes.

[Chuck Nice]

But physiologically they're different ages. But it doesn't make a difference. Cause if I got an old heart and a young pancreas, I'm still gonna die.

[Neil DeGrasse Tyson]

With by a heart issue.

[Chuck Nice]

With by a heart issue, yes.

[Neil DeGrasse Tyson]

So that was always what I suspected, that people who live very long, all of their organs somehow are aging at the same rate physiologically.

[Venki Ramakrishnan]

Well, I don't know if that's true, but maybe they're still aging differently. But the lead organ, the organ that's aging fastest is. Is still slower than other people, Right?

[Neil DeGrasse Tyson]

Right. If they die, it's not gonna be from that. So given what you just said, I didn't Put two and two together here until just now. In the second law of thermodynamics, one of its stipulations is if you have sort of usable energy over here and you convert it into another kind of energy over here, there's always energy losses. Always. That's why you cannot make a perpetual motion machine. And so the body is all about converting energy of one kind into another. You have chemical energy in food and you turn it into ATP. Yeah, exactly. Remind us about that. We all learned it in biology class. The ATP cycle, is that right?

[Venki Ramakrishnan]

ATP is adenosine triphosphate. It's a molecule with high energy bonds. So you can think of it as a universal currency. Just like in our world, electricity is the universal currency. So you use everything converted to electricity, then you can use that for everything. And so the body uses it so you can think of it as a kind of storable form of energy that it can use.

[Neil DeGrasse Tyson]

Right. But it's taking energy from what? It's taking energy from one thing and converting it.

[Venki Ramakrishnan]

Typically in our case, we're getting it from carbohydrates and by burning carbohydrates.

[Neil DeGrasse Tyson]

So it's chemical energy.

[Venki Ramakrishnan]

It's chemical energy. So that energy is used to make ATP.

[Neil DeGrasse Tyson]

Got it. And anything else we make in our body to maintain our body temperature because we're warm blooded to move. So it goes to thermal energy, kinetic energy and the like.

[Venki Ramakrishnan]

And most of those things involve ATP and electrical energy.

[Chuck Nice]

Right. For your brain and your heart and signaling and all that.

[Neil DeGrasse Tyson]

So I'm just saying, every time you convert from one form of energy to another, you're getting less energy than you started with. So there is a decay in there eventually.

[Chuck Nice]

Interesting. Yeah.

[Neil DeGrasse Tyson]

So you describe this sort of implicit value of death to a species because it doesn't need you after a certain point of your fertility. We're beyond that now and we're what we call civilized. And so there are people who want to do anything they can to stay.

[Chuck Nice]

Alive for as long as they can.

[Neil DeGrasse Tyson]

To stay alive for as long as they can. And you're in that business scientifically. What is the ethics?

[Venki Ramakrishnan]

I should say my own lab has never worked on aging. I went from zero to expert in one book.

[Neil DeGrasse Tyson]

Oh, okay. Okay.

[Venki Ramakrishnan]

My lab works on protein synthesis, which is a central component of aging. I don't actually do aging research myself.

[Neil DeGrasse Tyson]

Okay, but surely you've thought about the ethics of it. Yeah, why wouldn't you?

[Venki Ramakrishnan]

Oh, definitely, yeah.

[Neil DeGrasse Tyson]

Yes, yes.

[Venki Ramakrishnan]

And I also have no skin in the game, so that's okay.

[Chuck Nice]

Well, that Means we can get a very, a truly objective, other than beautifully soft skin. Right, I missed that one.

[Neil DeGrasse Tyson]

I don't want to be ahead of you.

[Chuck Nice]

That was a good callback. I like it.

[Gary O'Reilly]

Chemical laws, biological laws, any in the way to stop us going from where we are now to potential immortality?

[Venki Ramakrishnan]

Right. So there are two issues. One is, is aging programmed? I mean, are we all programmed to die? Yes. No. Because evolution doesn't care about.

[Chuck Nice]

It doesn't care about us dying.

[Venki Ramakrishnan]

So there are genes that affect aging, but those genes don't exist in order to make us age. They were selected for some other reason, but they happen to cause us to age. So now that we understand some of the biology of aging, you ask, can we extend that?

[Gary O'Reilly]

Yes.

[Venki Ramakrishnan]

And there's no. There are no physical or chemical laws that say that we have to die at 120. I mean 120 is about the record for humans. Very few reach that.

[Chuck Nice]

And by the way, whenever you see 120 year old, they're like, I am ready to go.

[Venki Ramakrishnan]

Oh, I'm not sure.

[Chuck Nice]

Not all of them, but yeah.

[Venki Ramakrishnan]

There's a woman, Jeanne Calmont, who's a record holder at 122.

[Gary O'Reilly]

She was the smoker and drinker.

[Venki Ramakrishnan]

She used to smoke and drink into her hundreds. And reporters after a while used to gather at our house every birthday. And one of the reporters said, well, see you next year, I hope. And you know what she said?

[Chuck Nice]

What?

[Venki Ramakrishnan]

She said, sure, why not? You look pretty good to me, so. But there's no physical or chemical law that says, you know, at 120, you gotta go, you gotta go. There are species, as I said, that live 700 years. Vertebrates, of course, the question is, can we change our biology to make us live much longer and still keep us humans. You don't wanna be a very slow metabolic animal like a Greenland shark. You still wanna be human and you wanna live much longer. Now there are people, I would say at the one end of the anti aging research community, including perhaps somebody you've had on your show, who think that it is possible you can just keep extending life and that'll buy you enough time to do more research and you'll.

[Neil DeGrasse Tyson]

Extend more life and eventually there's a generation that would reach the escape velocity exactly where the prolonging of your life is one year per year and then you live forever. Yeah.

[Venki Ramakrishnan]

Now I'm highly skeptical, as are most scientists in this field, because aging is a multifactorial process. And to be able to do this in a way that's safe. That's efficacious. That actually works. I think it's going to be very, very hard. Yeah, but there's not impossible.

[Neil DeGrasse Tyson]

The Google software that uses AI for folding proteins, which won a Nobel Prize, if memory serves, won't that solve all your protein folding problems?

[Venki Ramakrishnan]

No, this is different from. I think AI will have a big influence on biology, and maybe one day it will help with things like aging.

[Neil DeGrasse Tyson]

One day, 18 months from now, sometime.

[Chuck Nice]

In the distance, in the future, distant future of AI. What time is it?

[Venki Ramakrishnan]

Okay, let's say I'm highly skeptical, but there is no physical law. But I'd say there's also no physical or chemical law that says you can't colonize other galaxies or even Mars. And so why would we want to? You know, whatever Elon may say, it's not gonna happen tomorrow. So I think.

[Chuck Nice]

And I think we should get down here. Kind of worked out first. I'm sorry. But yeah, why don't we make this place habitable?

[Neil DeGrasse Tyson]

All right. So what happens the day we as chiefs Escape velocity? What happens to civilization?

[Venki Ramakrishnan]

I think before that, a number of things will happen. For example, more people may live to be 100 or well into their 90s or early hundreds. That itself will cause a huge shift in society. For example, fertility rates everywhere are dropping, dropping. And so what you're going to have is.

[Neil DeGrasse Tyson]

It's an aging of the population.

[Venki Ramakrishnan]

Yeah. Society where there's very little turnover. Same people are living longer and longer. Very, very slow turnover. To me, that means a less dynamic and less vibrant society. If you look at the history of science or any fields, even literature, people have done their most creative work when they're young. And it's not just about physiological age. When you're young, you're looking at things fresh. You're not as opinionated, you're not dogmatic. And that allows you to think out of the box.

[Neil DeGrasse Tyson]

You have to convince the old people that they're less useful to society. How do you.

[Venki Ramakrishnan]

Well, that's. Well, one of the reasons I'm retiring is because I decided four or five years ago to close down my lab. It's going to happen late this year. It's partly because I do believe that when you've had your time, you know, you should step aside and let younger people carry on.

[Chuck Nice]

Carry on.

[Neil DeGrasse Tyson]

When Einstein was given the option to be operated on, basically on his deathbed, he said, no, my work is done.

[Chuck Nice]

My work is done. Yeah. I would have said, what kind of doctors are you? Save me. Thank you.

[Gary O'Reilly]

What you were talking about is inverting the population pyramid. So it goes from a small peak of aging population to a rather large one and less young people. We are basically diving down a drain here.

[Neil DeGrasse Tyson]

But what it would be, it would be more stable the whole time.

[Venki Ramakrishnan]

More stable. Stable thing would be good. But if the turnover is very slow and people just live for very long, I mean, as people get older, they accumulate power, they accumulate wealth, they accumulate influence. And of course the three go together. And that then means that it's harder for younger people to gain entrance, to gain entrance, to make it and so on. That's a real problem.

[Neil DeGrasse Tyson]

Cultural fact.

[Chuck Nice]

Yes.

[Venki Ramakrishnan]

And that's a, that's a.

[Chuck Nice]

And you're, you're, that's a real problem. That's. We're seeing that right now in a certain party in America where they're like, yo, everybody who is in charge is 80 years old. Get out of the way. Because we have a different way to do things and we want to get to it.

[Venki Ramakrishnan]

And so I think societies would be more stagnant and less dynamic and less creative. People will always throw exceptions at me. Oh, so and so was so brilliant late in life. But those are exceptions. You know, that's not what you plan a society around. But here's the problem. If somebody gave you a pill and said this is going to give you 10 extra years of healthy life, Nobody wants to be sick for 10 years of extra healthy life. Would you take it? I know I would.

[Chuck Nice]

Yes.

[Venki Ramakrishnan]

Okay. Almost all of us would. And this is the conflict between what we as individuals want and what's good for society. And that's because at the end of.

[Neil DeGrasse Tyson]

Those 10 years, if you're given the option again, you'll probably say yes again.

[Venki Ramakrishnan]

Exactly right, Absolutely.

[Chuck Nice]

Especially if it's healthy life.

[Neil DeGrasse Tyson]

So that thought experiment takes the larger question down to its individual parts and you realize people really do want to live forever.

[Chuck Nice]

They do. Well, because.

[Venki Ramakrishnan]

Yeah, they do. Because this is, as you say, the only life we know. It's our existence. We fear the loss of existence.

[Chuck Nice]

And that's, that's, you know, there's, I mean, I'm about to get philosophical. The great thing about death is that when you look at it full on and embrace it for what it is, it allows you to wake up and treat each day as something special. Because you know this thing is going to be over if you take that away. You know, I don't give a damn.

[Venki Ramakrishnan]

People have said that, that having a finite life gives you the drive, the incentive to accomplish things. Otherwise there's always Tomorrow.

[Chuck Nice]

There's always tomorrow.

[Venki Ramakrishnan]

Okay, so that is true. But at the same time, there's an old joke. Who would want to live to be 100? And the answer is always someone who's 99. So you may be philosophical about death in the abstract, but you don't want to die next year.

[Chuck Nice]

Well, no, you're absolutely right. I don't want to die, period. You know, because my life is pretty damn good. So, you know, as long as.

[Neil DeGrasse Tyson]

And we're not talking about people who are so mortally injured or ill that death feels like an escape. We're talking about someone who's fully.

[Chuck Nice]

Who's vibrant.

[Neil DeGrasse Tyson]

Vibrant, yes.

[Venki Ramakrishnan]

There's also one aspect of aging research. If you ask most of them, they'll say, except for some of these outliers, they'll say, oh, we're not about extending lifespan. We're about increasing health in your life. And the idea is that you stay healthy all your life and then suddenly crash and die. And there's a poem called the One Horse Open. Shay.

[Neil DeGrasse Tyson]

I just learned about that poem. It's the horse that the carriage was.

[Venki Ramakrishnan]

Perfectly designed so that it wore out all its parts wore out equally exactly.

[Neil DeGrasse Tyson]

At the same time.

[Venki Ramakrishnan]

And one minute the farmer was riding along, the next minute he was on the ground surrounded by a bunch of debris because his whole carriage had collapsed. Now, that's what people are asking when you say we're going to compress the period of morbidity in old age and we're just going to suddenly decline and die. Nobody's shown that that can actually happen.

[Chuck Nice]

Apple is working on it, believe me.

[Venki Ramakrishnan]

Nobody's shown that. So if they increase our health span, it's equally possible that they may extend health span.

[Neil DeGrasse Tyson]

Good phrase, not lifespan. Healthspan.

[Venki Ramakrishnan]

Yeah, but if they do that, if they keep us healthy in old age, it's equally possible that they extend our lives too, and that eventually we still have that slow.

[Neil DeGrasse Tyson]

You still have the.

[Chuck Nice]

You just reach a point where now I'm 108 and it's all falling apart, but I'm not gonna die tomorrow. It's still gonna be a slow Mars deaths five years from now. Yeah, yeah.

[Neil DeGrasse Tyson]

Of course, if we live forever, we need to find another planet because the population will continue to rise and we will outstrip the resources of Earth and possibly Mars, Venus, and any place else.

[Venki Ramakrishnan]

We search for that isn't quite true.

[Neil DeGrasse Tyson]

For example, okay, if birth rate went to zero, then it's not a problem.

[Venki Ramakrishnan]

Exactly.

[Neil DeGrasse Tyson]

But who wants that?

[Venki Ramakrishnan]

Well, first of all, you're not gonna have complete Immortality, you're going to have extended lifespan. So the birth rate simply has to fall in accordance with how much you've increased your lifespan.

[Neil DeGrasse Tyson]

There you go.

[Venki Ramakrishnan]

And in fact, if you look at Korea, South Korea, it's happening anyway. It's happening. People are living longer, and yet the population's going down. It's going down.

[Neil DeGrasse Tyson]

So venky. This conversation has been delightful and illuminating and enlightening.

[Chuck Nice]

I can't wait to die.

[Gary O'Reilly]

You're gonna have to.

[Neil DeGrasse Tyson]

And after we're done with this episode, he's gonna whisper to us that he's 150. On this topic of why we die, we covered so many nuances of it, I'm left with very little to offer as a cosmic perspective. What I will say is that, speaking for myself, I, at this stage in my life, value the knowledge that I will die because that gives meaning to every day that I'm alive, knowing that there's one fewer days left in my future to love, to have new ideas, to make discoveries, to embrace all that it is to be alive in this world. If you look at it mathematically, if the knowledge of death is what brings meaning to being alive, then to live forever is to live a life with no meaning at all. If you can just put off to tomorrow what you could have done today, will I think this on my deathbed, If I'm offered a pill that can make me live another 10 years, when I'm on my deathbed, would I take that pill? I don't know. Kind of easy to talk about death when I'm pretty sure I'm not near it in this moment. But I will say I reserve the right to revisit the option of living a little longer when I'm on my deathbed. But for now, knowing I'm gonna die is what's keeping me going. And that is a cosmic perspective. Chuck, good to have you, man.

[Chuck Nice]

Always a pleasure, Gary.

[Gary O'Reilly]

Pleasure, my friend.

[Neil DeGrasse Tyson]

All there. This has been StarTalk Special Edition, why we die. Until next time. Neil Degrasse Tyson, your personal astrophysicist. Keep looking up.

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[Chuck Nice]

Edu.

[Venki Ramakrishnan]

What does possibility mean to you?

[Neil DeGrasse Tyson]

Um, that's a hard question.

[Venki Ramakrishnan]

Something that you can strive for.

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I'm able to do anything I set my mind to. You're confident in yourself and you believe in yourself.

[Venki Ramakrishnan]

Stuff that you could achieve. I feel at Sarah, anything is possible.

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When you're more confident.

[Neil DeGrasse Tyson]

Shoes are a huge part of that.

[Chuck Nice]

They are the most important part of my style.

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