Revolutionary new medicines may soon be able to slow and even reverse the aging process. Scientist and author of “Ageless: The New Science of Getting Older Without Getting Old” Andrew Steele explains how and why we age, and traces the exciting new medical research. KCRW’s Jonathan Bastian talks with Steele about the quest for life-extending drugs and hears why aging is currently our greatest humanitarian crisis.
KCRW: What drew you to the subject of aging?
Andrew Steele: “I actually changed careers because of a graph. I started out as a physicist, and I was coming to the end of a PhD in physics when I saw the graph of how likely you are to die depending on how old you are. It's quite a morbid reason to change your career, I guess.
What you notice is that this graph is an exponential increase. So your risk of death doubles about every seven or eight years as a human being. That means that I'm in my 30s, so I've got something like a one in 1000 chance of not making my next birthday. But that carries on doubling and doubling. Tt doesn't go very far for a few decades. But then at a certain point in life, maybe in your 60s, 70s, or 80s, those numbers start to get big.
So if you're lucky enough to make it to 80, your odds of death that year are about 5%. And if you make it into your 90s, your odds of death in any given year are about one in six. That's life and death at the roll of a dice. As a human, you can look at the exponential increase as, ‘That is terrifying, I've got this wall of mortality coming at me.’ But as a scientist, you look at that, and it's just fascinating. Because human bodies seem to go wrong in such a coordinated way.
And it doesn't matter much about your genetics, your social background, or your history. This seven or eight year doubling in mortality actually applies across human populations across the world and across the span of time. And so you know, given that our bodies go wrong in this synchronized way, perhaps there's some underlying process, namely the aging process, that causes that to happen. And if we can understand and intervene in that process, think of all the suffering we could avert.”
Why do you say that being able to treat aging is one of the greatest, if not the greatest, medical revolutions?
“We've got to reimagine our approach to aging. And the reason for that is I think a lot of us just think of it as this inevitable process. It's something that happens to us, it happens to our pets, it happens to our farm animals. It just seems to be something that inevitably happens to everyone we know and care about throughout our lives. But actually, aging is responsible for this enormous quantity of death and suffering. All the biggest killers in the modern world, like cancer, heart disease, dementia, can not only take your life toward the end of your life, but can also remove a lot of independence.
We're at this fascinating and exciting time in the history of medicine where we're starting to get these hints that we can slow and even reverse the aging process in the lab. We've got dozens of different ways that we can slow and reverse aging in cells in worms, flies, and even mice. ... And what this does is it basically makes these animals younger for longer, and puts off the frailty, the cognitive decline, and these diseases all at the same time. And that's why I'm so, so excited about this idea, because it's got such huge potential to make you want to extend what's called ‘healthspan’ — not just how long we live, but how healthy we live as well.”
On the other hand, are we talking about disrupting what's been considered a natural process in the cycle of life for as long as we've known of human existence?
“I think a lot of people do think like that. But actually, the current life expectancy of about 80 years in most rich countries in the world is a surprisingly recent phenomenon. Life expectancy, even just a couple hundred years ago, was maybe 30 or 40 years old. And that's because there were huge numbers of infectious disease deaths, particularly in children and babies. And what that meant was that there was only about a 50/50 chance of making your 20th birthday. And if you then made it to 20, you did have a reasonable chance of making it into what these days we’d call ‘old age,’ maybe your 50s or 60s, perhaps even your 70s.
And now we've largely beaten that back. We've got this new, seemingly natural frontier of aging. I think we're gonna look back on this period of time, perhaps in a few hundred years … once we've cured aging, [and] we're gonna see this [time] is just as barbaric as the huge numbers of deaths from smallpox and tuberculosis seem to be to us looking back at the past.”
Will that mean we have to expand our idea of what it means to live a long life or a normal life?
“I think that's exactly right. It's really interesting to look at what public opinion is on this. There are surveys that asked people, ‘How long would you like to live?’ And the answer that most people give is normal life expectancy in their country, plus about 10 years. And that's because everyone wants to have a good innings. You want to live a decent amount of time. But we've got this sort of normalized expectation of life expectancy at the moment. And that's just baffling to me, because life expectancy in the countries in the world that have the highest life expectancy has been going up by about three months per year, every single year, since the middle of the 19th century.
And what that means is that we've effectively doubled what it means to be human. And at the same time, we've got this sort of mass normalization of what the current number happens to be. Even if we just extrapolate that fairly linear, continuous incremental of progress into the future, then kids born today are going to be easily living into their hundreds. And obviously, if we can come up with some more exciting treatments for the actual biology of aging that I talk about in the book, then who knows what the upper limit is?”
Why do we age? What's going on in our bodies that we start to get sick and old?
“In the book, I break it down into 10 hallmarks of aging. … They're basically the fundamental underlying biological driving forces behind aging. If you think of something like cancer, heart disease, or even just frailty or gray hair, these are the end stages of aging. If you think of aging as a disease — which some people do, I'm not so sure — those are the symptoms of aging.
What we want to know about the causes, and the causes are on everything from the smallest to the largest scales in your body. On the very, very small scale, as you go through your life, your DNA, the genetic instruction manual at the center of every one of your cells, accumulates damage that can turn to mutations, and that can cause your cells to misbehave. Scaling up a little bit, those kinds of effects can cause the cells themselves to age. It’s something called a senescent cell, which is a cell that's basically itself old. And then on an even larger scale, there can be dysfunction in whole systems caused by these smaller scale changes. So it's this combination of different factors … that combines together to cause everything from cancer to heart disease to wrinkles and gray hair.”
How are scientists working on aging targeting parts of the body or the way our system works?
“The most exciting intervention that I've read about is the targeting of senescent cells. One of the ways they can become senescent is damage to their DNA. And that can mean the body effectively slams on the brakes and tells them to stop dividing. Another thing that can happen is they just divide too many times. Our cells are constantly dividing in our body. Places like our skin and our intestines are being refreshed every few days, and sometimes, again, our body just slams on the breaks.
Both of these are because the body is basically protecting against the risk of cancer. Cancer is a cell that gains the ability to divide an infinite number of times. And the way it gets that is mutations to its DNA. So if you've got a lot of mutations, or you divided suspiciously many times, it's better to stop dividing. And what would happen in a young person is that the immune system comes and clears up these aged cells. And basically, there's no problem.
But as you get older, you get more DNA damage, your cells are divided more times, and your immune system is getting less effective. And what that means is that you start to accumulate these cells. And these cells are thought to be a smoking gun, often found at the sight of a whole range of different age related problems. This can be from cancer to heart disease to cataracts. And so the idea is that we can get something called a SenOlytic drug, which is a drug that specifically kills the senescent cells, while leaving the rest of the cells in the body intact. And what scientists have done is designed these drugs. They're given them to mice aged about 24 months.
Now, mice have much shorter lifespans than humans. So 24 months is about 70 in human years. So that means they've accumulated a lot of these senescent cells. And if you clear out those senescent cells, it seems to basically make them biologically younger. They live a little bit longer, which I guess is a good start. But they don't just live longer, sort of in geriatric ill health staggering on. They're protected from a whole range of diseases, like cancer and heart disease. All kinds of different things.
And it's not just the diseases. These mice are less frail. They can run further and faster on a little mouse treadmill that they're using in these experiments. They're more curious. If you get a mouse that's been treated with these SenOlytic drugs and put it into a new environment like a maze, it'll behave more like a young mouse. It will try and explore in a new environment where an old mouse might be more anxious and less willing to explore.
And honestly, these animals, they just looked great. … They've gotten better fur, they've got thicker, plumper skin. So what this really shows us is that these senescent cells are behind a whole range of different problems in aging, from very serious diseases to more cosmetic features. And so the dream would be, can we get some of these drugs given to people and stop them from getting old, and some from getting ill in the first place?”
How far away is a drug like that from making its way into mainstream medicine?
“One of the reasons this is so exciting is that the answer is not very far. We've already got 20 or 30 companies that are trying to turn this from something that works in mice in the lab to something that works in the clinic in people. And the way this is going to happen at first is these companies are primarily targeting diseases where we know that, at these ages, senescent cells are a specific problem. And these are things like lung fibrosis, which is a disease that you very commonly get at an old age.
If these treatments prove effective, you know that you sort out the problem. But more importantly, if they prove safe, then we could imagine starting to roll them out into people preventatively, because the most important thing is that these drugs don't have any severe side effects. If you're going to give them to people who are ‘healthy’ at the moment, the only thing that's wrong with them is maybe they're 50 or 60 years old and they've accumulated a lot of senescent cells, you want to make sure this drug isn't gonna do anything bad to them while preventing these diseases.
The first clinical trial started in 2018. There are a lot of these trials ongoing now. It could only be a few years, but we're starting to see these in the clinic for specific conditions. And then it's just a matter of, how safe are they? How effective are they? How confident are we to get them out to the general population? It could certainly be something that happens in the next 10 years. This isn't pie in the sky theoretical biology.”