The Science of Aging: Can You Teach an Old Cell New Tricks?

We've long thought that aging was just a part of life but now science is beginning to view aging as a disease that can be treated. This, as research on aging is exploding and some scientists speculate people could live 150 years or more.  Our aging expert, Dr. Kristin Slade, Associate Professor of Chemistry at Hobart and William Smith Colleges in upstate New York says, "We already know what is going on with aging at the people level, but I was determined to get inside the cell and discover what was going on at the molecular level.” Indeed, that could be the key to slowing down the aging process. She spoke before an audience at the Conference Center in Mountain Village, Colorado and the discussion was moderated by noted journalists Judy Muller and George Lewis.

Transcript

(OPENING THEME)

GEORGE LEWIS: From Telluride Science, it's science straight up. 

DR KRISTIN SLADE: Research on aging is just exploding. Scientists are making breakthroughs, 

GEORGE LEWIS: The science of aging. Can you teach an old cell new tricks? I'm George Lewis, and my cells are ancient. 

JUDY MULLER: Something else we have in common? I'm Judy Muller. Here's the question. Is aging just a fact of life, or should we view it as a disease that can be treated? Kristen Slade is a biochemist at Hobart and William Smith colleges in upstate New York, and she has been looking at how the cells in our bodies age, and whether that process can be slowed down. 

GEORGE LEWIS: Dr. Slade is one of the researchers who came to Telluride to participate in a series of scientific workshops put on by Telluride science. And for the benefit of the community, she shared some of her insights during a town talk in nearby mountain village. 

DR. KRISTIN SLADE: So when you think of aging, the good news is, in the last decade, there have been over 300,000 studies done on this topic, which is about the same as in the previous century. So the research on aging is just exploding. It's an area where people are very interested in science, scientists are making breakthroughs. 

JUDY MULLER: One of the scientists she talked about is geneticist David Sinclair of Harvard, who thinks that in the next half century, there will be treatments that may enable people to live as long as 150 years or longer, in good health. He has stirred up quite a debate in the science community. 

DR. SLADE: T  his is brand new, just out a few months ago. And the work of Dr. David Sinclair is very controversial. There are some some pros pros and cons. And I would say that at this point, we're gonna be hesitantly optimistic. But, the verdict is still out. 

GEORGE LEWIS: One of the areas that they're looking at is epigenetics, how our behaviors and our environment affect the way our genes work. Over time, our epigenetic information can get damaged. 

DR. SLADE: "W e are living organisms that have to adapt to new environments and unforeseen circumstances. And so adding in these chemical modifications that we call epi genetics, as opposed to genetics, that gives us a little bit more flexibility, and adaptability to pass on to offspring. However, you can think of this as kind of the analog equivalent. So those of you who have used records to listen to music, you know that if you've listened to it over and over and over, what happens it can get scratched, is not easy to copy. And so one of the theories of aging, called the information loss theory of aging, is that what's actually going on over time, is that we are losing these chemical modifications. And so that's equivalent to like scratching your record player or scratching your DVD. And so actually, we're at the point where if you wanted to, you can send your blood away for about $300 to get your epigenome read, and they will give you your biological age based on these clocks. 

GEORGE LEWIS:  That loss occurs to our aging chromosomes, the parts of ourselves that carry genetic information about how to duplicate those cells. At the ends of the chromosomes are protective layers called telomeres. They're kind of like the plastic tips at the ends of your shoelaces that keep them from fraying. 

DR. KRISTIN SLADE: So you started life as a single cell, one cell becomes two cells, two cells become four, so on and so forth. Every time we divide a cell, that cell needs to copy its DNA, so it can give it to so we have two copies of of that DNA. And the way the machinery works for copying that DNA, it can't quite get to the edge, the end. And so we lose a little bit of the telomeres. Every time you have the cells divide, and even after you've reached fully grown, you're still having cells divide certain types of cells divide even as we're sitting in this room. And so over time, it is known that your telomeres get shorter and shorter. And there's a specific short limit, that once the telomeres get below that limit, the cell goes into panic mode. It it doesn't know what to do and so it becomes a diffe rent type of cell. It's kind of panic.

JUDY MULLER:  L ike the scratched DVD that refuses to play, the panicky cells don't know how to duplicate anymore and turn into a zombie cells. More about that later. But researchers discovered that common pond scum, an organism known as tetrahymena has chromozomes that seemed to stay forever young. 

DR KRISTIN SLADE:  Dr. Elizabeth Blackburn wanted to know why. And so she spent early part of her career studying what is special about tetrahymena that they're immortal, and their telomeres don't get shorter. And it turns out that the answer is a protein. She named telomerase. So this is a protein that works to replace the telomeres in tetrahymena. 

GEORGE LEWIS: It's "T" time, are you following this? We're in Telluride, talking about tetrahymena pond scum containing terrific telomeres, because of telomerase, 

JUDY MULLER: Telomerase, a potential youth serum?  Naah, not quite. 

DR KRISTIN SLADE: Now, it turns out, we have telomerase too. But as we age, it gets turned off. So great, we've just solved aging, right? We just need to run out and buy a big bottle of telomerase. And we all stay young, right?Well, it turns out that this is a common theme in biology, we ourselves are well oiled machines. And so any little tweak you make, you're gonna have some unintended consequence. And so that's, you know, with drugs, you'll always have side effects. And so with telomerase, it turns out that this might actually be a defense mechanism by our body, because while it is bad to have two shorter telomeres, and that leads to aging, too long of telomeres actually results in certain very nasty forms of cancer. 

GEORGE LEWIS: So besides some TLC for our tired out telomeres, that challenge for science, treat the disease of aging without those deadly side effects.

DR KRISTIN SLADE: The aging community really is pushing for aging to be classified as a disease. And actually in 2019, the World Health Organization, first classified it as as a disease, and this this was a big step forward, 

GEORGE LEWIS: Does that imply it can be cured somehow someday? 

DR. KRISTIN SLADE: No, I don't I don't think it implies necessarily that it can be cured. But we were missing a big opportunity. But a lot of funding agencies are much more likely to to fund disease research than aging research, and his money. And his argument is that aging affects everyone. So isn't this something we do want to throw money at? And then there's the whole policy? So, you know, if there are pills available, then how do we know that they're safe to take? That's the FDA. And in order to get a drug past the FDA, you need to show that it does better than placebo? But what does better than placebo mean? It's easier for a disease to show, oh, I'm healing this disease. But if aging is not considered a disease, then how can you? How can you cure it? Or how can you use medication? So...

JUDY MULLER: Some of us are already aging.  So I mean, are there things that we can do at any age, to you mentioned meditation, lowering your stress levels, how you exercise? What else can we...

DR. KRISTIN SLADE:  So basically, the take home message is your mother was right, your grandmother was right, all the things that you were told to do, growing up, eating healthy. There's a lot of research on plant based diets, and versus meat based diets. But everyone agrees that that vegetables are good, and limiting the number of calories, getting a full night's sleep, not smoking, these are things that are actually shown to change that I was talking about the biological age and your scratch DVD. These are things that control that to areas that your mother may not have been correct about. And this is very, very new science. But I don't know about you, my mother always made sure I wore a coat. And it turns out that there's some some newer science that is showing that doing a little bit of stress to cells is good because it puts the right proteins on on high alert to to fix or shine up that scratch DVD. And one way to do that is sauna or hot or cold. So walking in a T shirt instead of wearing a coat. 

JUDY MULLER: So send the kids out in the snow?

DR KRISTIN SLADE:  So it's very it's very early on with with that research, but that's one possibility. And then the other one is skipping breakfast ever, you know, you said to have breakfast, but one of the areas of research that's really being studied is intermittent fasting. And so that's that's another thing that's that's been shown to positively slow down aging. 

JUDY MULLER: (asks audience) How many people are into intermittent fasting?  Hear? Ya see, I looked at it and I thought, wait a minute, you're gonna go from 5pm? To what? Before I can eat again? I don't know, it got it's a hard sell isn't it?

DR KRISTIN SLADE: It is a hard sell? And I that was my response as well. 

GEORGE LEWIS: There's an interesting number that among the areas of the United States with the longest lifespan, this County, San Miguel County, Colorado, has an average lifespan of 93.6 years. And I'm wondering, is that because everybody's outdoorsy and athletic? Or is it because there are a whole lot of affluent people who have access to better health care and better diet?

JUDY MULLER:  Just go raise that touchy... 

GEORGE LEWIS: Yeah, I know, I know. That third rail? George, no, 

DR KRISTIN SLADE: that is a good question. And actually, that reminds me of a different set of, of research. Looking into trends, there are blue zones in around the world. And these are areas where there are higher population of centenarians or people over 100. And so there were some people that went part of this blue zone organization, and they went, and they wanted to find out what are the trends? What are these people doing? How can how can we live longer, and they found some trends, and one of them was to be more active, and they noticed that these people weren't being more active by going out and refreshingly exercising, but more just moving around throughout the day, and, and having to walk long distances, not owning cars, for example. So it doesn't have to be tied to socio economic, they also found that they had calorie restricted diets, some of them had a culture of what they call the 80%, or only only eat till you're 80% full and leave the rest. But a major part of it is going back to the telomeres in the mindset was community. And it all of one of the things all of these blue zones had and one of the things I've noticed since I've been here is the tight close knit community, and having a purpose in life, and having close friends, a lot of these blue zones have a higher number of lifelong friends than average people around the world. So there are a lot of those different trends that I think mirror, what's going on in some of these mountain towns in Colorado that have a long lifespan. 

JUDY MULLER: Well, Okinawa, Japan is one of those blue zones, and I'm wondering if it isn't fish diets, you know, the diet has to be, but when you say 80% full and stop. How I don't understand that, you know, how will I know when I'm 80%? 

DR KRISTIN SLADE: And it's it's a saying that they have in some of some of the cultures...

JUDY MULLER  Well, that's a silly saying.I would not be welcomed in that culture. (LAUGHTER)  Anyway. So I'm just curious as to this is outside your realm. This is sociology more, but if everybody well, first, let's start with how old do you think people will live to in a healthy way? Let's say 25,  30 years from now.

DR. KRISTIN SLADE:  Oh, okay. So actually, that reminds me of the second part of the question about David Sinclair, Dr. David Sinclair, being controversial. is, nobody knows that the answer to that, and he actually says that in the next 50 years, he thinks that there are people that will live to 150 or beyond.

JUDY MULLER:  But will they be happy? 

DR KRISTIN SLADE:  W ell, that isn't actually I was gonna say that that's what I think is more important is not lifespan, but healthspan. And so a lot of the research that that's being done is not necessarily to live longer, but to live better while while you're alive. 

JUDY MULLER: Okay, because when people live longer, it's going to have real impact on population, on jobs, on housing, food, in a world that's already in trouble. That's not your area. But do people ever raise this question? 

DR KRISTIN SLADE: Oh, yes, yes. And it's a concern. But they, the counter that I've seen to that is, we've had as a society, we've had one obstacle after another that we've had to overcome. And yet we come up with creative solutions. And so isn't this a good problem to hav e if people are living longer? Maybe we can come up with a creative solution on how to ....

GEORGE LEWISyou mentioned, you mentioned a test that people can get for 300 bucks to show how old their cells are? Oh, yeah. Why would I want to spend 300 bucks to find that?

DR. KRISTIN SLADE:   I don't know, I have not taken the test. So I'm with you on at this point, I don't see any any value in it other than the novelty factor. I do think that it can be useful over time, especially to scientists, as they're trying to to figure out the correlation versus causation. And I know we had talked before, you mentioned that AI is is an interesting tool, it's a big buzzword. And so this might be a place where AI can help out with the aging world, because if you do collect this data, that is something that machine learning can can look for those trends and, and deal with that loss of information and the epigenome, the actual patt erns of the DVD scratching, and those chemical modifications, 

GEORGE LEWIS: And can find the exact causes of  shortness of life or or more, longevity, through big data?

DR. KRISTIN SLADE: Find out more more information on it. 

JUDY MULLER:  I can imagine HAL,  big computer AI saying, I'm sorry, I can't answer that. 

GEORGE LEWIS: And, I'm pulling the plug on all of you right now.

JUDY MULLER: Scary, I noticed that one of the couple of the things that you can do, obviously his attitude adjustment buck up, Bucky. But as you're aging, sometimes the physical ailments are hard. I mean, I know a lot of people who meditate and I do and it works, it helps.But you know, when you're hurting.It's mind over matter gets harder. So, you know, have you looked at that at all?

And I think that's

DR KRISTIN SLADE: And I think that's where community comes in. We're having close friends, things to get up for in the morning. Active doesn't necessarily have to mean running marathons, it can just been going for a walk with a close friend, and being distracted by the great conversation and, and not feeling those aches and pains. And so I think each person has to find their way to do that.

GEORGE LEWIS: You mentioned that people live longer when it's when they're colder?

DR. KRISTIN SLADE: That that is that the verdict is still out on that. That is one theory that has been tested in mice. But one of one of the challenges with all of this aging research is that what models do we use? We've come a long way. 10 years ago, we were using lower level tetrahymena, and flies and worms. And now we have a lot more mouse models. But you know, there's ethical concerns with testing on humans. 

JUDY MULLER: So basically, this, in summation, we should aspire to be pond scum. And,

and, and have a good attitude about it. 

DR. KRISTIN SLADE: That's pretty much summarized right there.

GEORGE LEWIS: Don't worry, be slimy?

DR. KRISTIN SLADE: Don't worry, be slimy.

GEORGE LEWIS: Well, okay, are we about ready for q&a from the audience? 

JUDY MULLER: If you're a scientist in the audience, and you want to ask a question, make sure all of us can understand it. 

AUDIENCE MEMBER: I am a scientist, but like not this kind of scientist. So I was wondering, different types of cells divided at different rates. And if telomeres are shortening, do they shorten at the same rate? Or do you see wrinkles before you see like cognitive degeneracy, or degeneration? Yeah. Does that how do we see different signs of aging at different rates? Because to me, your shorten at different rates? 

AUDIENCE MEMBER: Okay. 

DR. KRISTIN SLADE: Certainly, so different types. I mean, that's one of the things that that makes this challenging. And, and the same thing with telomeres, they're they're going to shorten it at different rates, not only in different cell types, but also in different individuals as well. 

SECOND AUDIENCE MEMBER: Can you talk about the role of insulin or insulin spikes in the aging process, particularly because we have a diabetic or an epidemic of insulin resistance? 

DR. KRISTIN SLADE: Yes, that's a great question. There's a lot of ramifications of of having insulin spikes, because it does stress your cells and also having what what that means is that you have high glucose so a sugar in your in your blood, that can can do damage, all of those hallmarks are interconnected. And so, insulin resistance is known to cause further epigenetic loss, and it can it can lead to other ramifications as well. So I have not looked at whether that's linked to telomere shortening but I would not be surprised if it was linked to that as well. 

GEORGE LEWIS: Kristin, can I ask you what initially got your interest in science fired up? What made you decide to want to become a scientist? 

DR. KRISTIN SLADE: I you know, I think I was always I mean, I think there's a little bit of scientist in all of us. Children are extremely curious. And I think that's the number one trait that you need to be a scientist. And I know my parents tell stories of me just ask you following them around the house asking question after question of but why is this happened? But why? Why that and why that. And I didn't get that necessarily in science classes in my K through 12. Training. Because, unfortunately, the way my school was taught, and I think that this is, sadly, very common, science was taught kind of as this is the list of facts, and you memorize them, and you go spit them back. And so it wasn't when I went to college actually went thinking I was going to be a math major, because I liked the puzzle puzzle solving. And it wasn't until I got to college, and saw the the creativity aspect that there is creativity in coming up with ways to design experiments and ask the right questions. And that's when I really got pulled into science.

JUDY MULLER:  A question that I had had on my list was what are zombie cells because I heard that brought up.

DR. KRISTIN SLADE: Scientists call these senescence cells. And so I indirectly referenced them in my talk, when I said that when you get to a certain limit with the shortening of the telomeres, those cells go into panic mode. And that panic mode is cell senescence or zombie cells. And they're often the lay term is zombie cells, because they don't die. But they no longer perform their proper function. And they don't copy themselves, they don't reproduce. And so they're kind of sitting there. And they're doing worse than that, because they excrete nasty chemicals that communicate with the surrounding cells and have very bad downstream ramifications. So one consequence, for example, is some senescence cells. If you've heard the term, this terms become more popular with COVID cytokine storms, so they can release these chemicals that lead to chronic inflammation. And they send out signals other surrounding cells to to have damaging effects as well. 

JUDY MULLER: Oh, boy, really glad I asked. Between the pond scum and this...

GEORGE LEWIS: Night of the Living Dead cells. 

JUDY MULLER:  Well, I think that's about all the time we have, isn't it? Yes. Think s. Yes, so let's give a big hand to Kristin. Thank you. (applause)

GEORGE LEWIS: That's it for this edition of science straight up. Our podcast was recorded live at the conference center in Mountain Village, Colorado, our audio engineer Neil Deichmiller. 

JUDY MULLER: Mark Kozak is executive director of Telluride science. Cindy Fusting is executive manager. Annie Carlson runs donor relations. And Sarah Friedberg is lodging and Operations Manager. For more information and to hear all our podcasts, go to Telluride science dot o RG. I'm Judy Muller. 

GEORGE LEWIS: And I'm George Lewis inviting you to join us next time on science straight up. (CLOSING THEME)