00:00So, what are we talking about when we're talking about aging?
00:03What's happening inside our bodies as time moves on?
00:07And what's happening at a biological level and at a cellular level?
00:10Welcome to The Future You, a new series by Men's Health,
00:13where we talk to the leading experts in health and longevity
00:15to help you live longer and stronger.
00:17I'm your host, Rich Dormant.
00:19In this episode, we're talking with Dr. Nir Barzilai
00:21about the biology and genetics of aging
00:23and how certain drugs may extend a person's lifespan and healthspan.
00:27So, I want to start a little bit farther from there and I'll answer you.
00:32But aging has a biology, right?
00:34Everybody knows that.
00:36Everybody knows that you're younger than me.
00:39What people don't realize is that this biology drives age-related diseases.
00:47You think you're getting old, you're getting diseases,
00:50and then the disease makes you older.
00:52It's in part also true, but no, it's really the other way.
00:56Aging brings the diseases.
00:58So, for example, you can be born with a genetic change
01:04that will change something that's called ApoE gene, ApoE4 gene,
01:09and you'll have two copies that will make you high risk for Alzheimer's.
01:14You'll probably get Alzheimer's when you're 60 or 70 and die when you're 80.
01:18But when you're born, you're not demented.
01:22And when you're 1 year or 10 years or 20 years or 50 years, you're not demented
01:26because it needs the biology of aging to trigger those diseases.
01:31And I can go over other diseases and tell you the same story.
01:35So, aging causes the disease.
01:37But we know that aging is flexible.
01:41We, geroscientists around the world over years, have gone from hope to promise.
01:47We know that we can target the process of aging, delay it significantly,
01:53even stop and reverse it in some context.
01:56And we've done it in animals, and we've done it in humans.
02:00Now, to your question, you know, what is this biology?
02:06And I'll tell you really simply, we geroscientists agree on a concept
02:11that's called the hallmarks of aging.
02:14What are the hallmarks of aging?
02:15Something that goes wrong when you're old.
02:18And when you fix it, you can fix it in animal with genetic ways or with drugs,
02:24or in humans also.
02:26So, you target this hallmark, you reverse the aging,
02:32you extend the health span of the animals and humans,
02:36and you increase their lifespan.
02:38That's how you become a hallmark.
02:40Now, there may be 12 hallmarks like that,
02:43but the important thing is you fix one, you can fix the others.
02:48Most of the drugs that we're doing are doing that.
02:50So, you don't have to fix all of them at one time to get an effect.
02:56Maybe it's going to be better if you do that.
02:59But we have a biology, we have targets,
03:03and we can start dealing with it right now.
03:05And some of those targets, as you mentioned before,
03:08you're born with, and they're only activated or active over time.
03:12Some of them are just the natural process of aging.
03:14Things break down.
03:16Can you tell, a lot of people might have heard of a word like telomeres.
03:18Can you talk a little bit about the genetic influences of aging
03:23and sort of what happens on that genetic level
03:25that could impact or expedite aging?
03:28So, let's start with genetic stability.
03:32So, in each one of our cells, we have the same information, right?
03:37That's the DNA.
03:38That's our chromosomes.
03:39They come in each cell.
03:40In each of those cells, there are changes that happen with time,
03:44maybe with radiation, maybe with accelerate aging in other ways.
03:50And there's a lot of changes in the sequence of our DNA.
03:54And they're usually repaired.
03:56In every cell, we have hundreds of them now.
03:59I probably underestimated it.
04:01And they're going to be repaired.
04:02Naturally.
04:03Naturally.
04:03By your body's own mechanism.
04:04By our body's own mechanism.
04:07But this process is not 100%.
04:09And if you have more changes in the cells with time,
04:14then it's even less than not 100%.
04:18Okay?
04:19So, you start getting cells that are starting to get into trouble.
04:24And they can deal with the trouble.
04:27They can either die, commit suicide.
04:31It's called apoptosis in medical term.
04:34Or they can form to some other cells that are called senescent cells.
04:39Senescent cells just stop multiplying because, you know,
04:44something is wrong with them.
04:45And they stand there.
04:47And it's protective.
04:48It's good.
04:48Okay?
04:50Sometimes it's a way to prevent cancer.
04:52Okay?
04:53Because you don't know what those cells are going to be.
04:55Otherwise, they become senescent cells.
04:58Those senescent cells accumulate in our body.
05:01And then they become a problem, actually.
05:04Because they secrete lots of bad stuff.
05:07Okay?
05:07And they actually can cause cancer.
05:09Although they're protected in cancer, they cause cancer.
05:12So, one of the things we want to do with aging is to remove those cells.
05:16But back to the telomeres.
05:18The telomeres are in those chromosomes that I described,
05:22that are in every cell.
05:24Their end has a little straw-like thing that wraps around.
05:31But it gets shorter every time the cell divides.
05:35And there is a connection between how short are those telomeres being
05:40to what happened eventually to the cell.
05:43It will become senescent or it can die.
05:45So, the telomeres shortening could be part a reason for aging,
05:51not a major reason for aging.
05:53But it can also be a biomarker to tell you,
05:57hey, you know, your telomeres are becoming too short.
06:00And that means trouble.
06:04And you and your team are investigating different ways
06:06when you look at these hallmarks of aging that we can intervene.
06:09To your point, either arrest or, in some cases, rewind the damage that's being done.
06:15Correct.
06:16So, in our center, we are approaching basically all of those hallmarks of aging
06:22with drugs that could, in combination or not,
06:26change them and affect each one of those hallmarks.
06:30Now, this concept is really difficult for scientists to hear.
06:34Certainly, for you, I'm expecting, though I know you're really smart.
06:39But I'm pretending you're not.
06:43So, how is it possible, okay, that we have drugs, okay,
06:49that attacks all the hallmarks of aging?
06:53You know, who thought about it?
06:56And this is how you have to think about it.
07:01You take a cell or an organ or your whole body and you make it younger.
07:07By making it younger, you're making lots of changes
07:10that are really fixing a lot of the hallmarks.
07:13It doesn't mean that all those hallmarks are what this drug did.
07:18The drug did something that repair all of those hallmarks
07:23and has really effect on your health span and longevity.
07:26So, we are looking for drugs that are exactly that,
07:31that we can actually measure on a cellular level
07:34if they change the hallmarks,
07:35and then we can test them to see how they are doing in animals
07:38and then in humans.
07:39Okay.
07:40Let's get started.
07:41Okay.
07:44Let's see you.
07:46Um.
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