Key To Vitality May Be Found In Fruit Flies

CAVANAUGH: In is KPBS Midday Edition. I'm Maureen Cavanaugh. Fruit myself generally don't live having. They have to cram in all the joys of fruit fly life in about 30 short days. Not the fruit flies researchers at Salk institute have been working with. Some of those flies are living 50% longer than they would naturally. The reason for that life span could have big implications for hundred health. Leanne Jones is associate professor in Salk's genetics lab, and lead scientist on the fruit fly study. Welcome to the program. JONES: Thanks, Maureen, it's a pleasure to be here. Please call me Leanne CAVANAUGH: I certainly well, Leanne. If I'm correct, and if I say anything wrong through this, please let me know, okay? Scientists already know that restricting calorie intake can extend life spans in animal studies. That's the knowledge that is the basis for your fruit fly study; is that right? JONES: That's exactly right. And all of the organisms in which it's been tested so far, that's the case. And that was the starting point for my collaborator at UCLA. CAVANAUGH: Do we know what the relationship is between reduced calorie intake and an increased life span? JONES: There are numbers of scientists who are trying to get at this question. We have several ideas about certain genes and pathways that can be involved. But we don't know exactly what's happening. So that's one of the things that we're really trying to answer. CAVANAUGH: So to find out more about this connection between low calories and increased life spans, you started research with fruit flies. Why fruit flies? JONES: How much time do we have? I could probably spend the whole afternoon extolling the virtues of fruit flies CAVANAUGH: Please do! I'd love to hear it. ? JONES: It breaks down into several different categories. There are some practical, economic reasons why we use fruit fly, there are scientific reason, and there are specific reasons why my lab uses fruit flies. Very simply, they are small. I think most people know what the fruit fly looks like. We can grow a lot of them in a very small space. The food they eat is a mixture of corn meal and molaces, so it's very cheap or relatively cheap to feed them. We know all of their genes, which, from the genetic standpoint makes them incredibly useful. And many of those genes are actually shared with human beings. But what's nice is if the fly has one copy, then hundreds or mice which is another organism we use in laboratory to investigate these types of questions, if a fly has one copy of a gene, then sometimes the hundreds or the mice will have three copies. So if you really want to try and understand what a gene -- that's called redundancy from the scientific standpoint. You might be able to knock out a gene in an hundred cell, but there are other copies that can make up for that loss. In a fruit fly, they only have one. So we knock out that gene and we can start to understand what its function is without worrying about other genes that make up for it. CAVANAUGH: So it's less complicated to do the research then. JONES: Much less complicated CAVANAUGH: And yet there are apparently lots of similarities between fruit fly intestines and hundred intestines? JONES: Again, I could go on and on about the similarities. In short, the intestines are very similar. The structure is slightly different, but still, it's a tube made up of similar cell types, it's a very simple epithelium, but there are cells that serve a secretory function. One of my favorite examples I like to give people when they're trying to wrap their heads around how similar fruit flies are to hundreds is to ask someone to look at their hand. Autokind of hard to do over the radio. Look at your right hand, for example, and you see five digit, and your thumb is at the top, it's the shortest digit. And if you look at a fruit fly wing, they actually have five wing vains. The shortest is at the top, and the same genes and proteins that are involved in making sure that you only have five fingers insures that fruit flies have five wing vains that are spaced perfectly. If you can tweak this gene or pathway, then the fly has extra wing vains, and that would be a situation where hundreds might have polydactyly. So to me, that's a very visual, very specific example that shows you how similar things can be CAVANAUGH: I never knew! Now, in doing this research, let me go back, and we're doing the research to find out why a reduced calorie intake might lead to a longer life span in certain animal studies. And you're using fruit flies. You didn't restrict the flies' diet, right? JONES: Exactly. So that was part of the hypothesis that my collaborator had was that there was another phenomenon that accompanied the dietary restriction, which was an increased activity of these specific organelles in your cells, and the cells of your body called mitochondria. He fought if he could tweak a gene to artificially increase their activity, you might be able to get life span extension in the absence of the dietary restriction. So he began working, trying to test this hypothesis, and he was expressing this gene in the whole fly, and the flies weren't living longer. He expressed it in the brains of the flies. And the flies still didn't live longer. So he came to me and asked if we had any tools that he might use that -- in this series of experiments. So this is where we came into the study. He had already been working for about three years, I think. And then we came into the study about two years ago. Of a little more than two years ago. We were able to give him a tool that allowed him to express this gene and specific subsets of cells that were targeted to the intestine. So that's how we got brought into the work CAVANAUGH: So what happened to these fruit flies who had their genes boosted in their intestines? JONES: Well, as we said, what he first noticed, my collaborator at UCLA, noticed was that the flies lived almost first% longer in some cases. So you could see the control flies as they got older, they became less active, they would stay down at the bottom of their vile, we keep them in viles. Wouldn't move very much, whereas the ones that had the genes tweaked were still very active. They looked very young. So then we became involved in trying to understand what was happening at the level of the cells and tissues that might be leading to this increased life span CAVANAUGH: I want to invite our listeners to join the conversation because it would seem to me anyone who has been following this might have a lot of questions about this study and extending hundred life span. Give us a call at 1-888-895-5727. Now, one thing that occurred to me when I was reading through the very nonscientifically friendly press release that you had about this, why would intestinal tissue, why would revitalizing intestinal tissue affect the aging process? JONES: Well, I think that's one of the next big questions that we'd like to answer. Maybe if I can just take a step back. CAVANAUGH: Sure. JONES: The primary focus of my will be's work is to try and understand how these cells within our bodies that are called stem cells, how they're different for most of the other cells in our bodies. And stem cells, I know people probably have heard about stem cells in certain contexts, but these are different in the fact that they are the cells to help maintain our tissues. So there are stem cells within our skin, blood, within our intestine that maintain the intestinal epithelium. And so what we were able to do in this study, it appears, is to delay the effects of aging on the stem cell population within the intestine. So what we're trying to understand now is exactly what it is that's happening when -- as I said, at the level of the cells in the tissues. So then the other questions that we could ask, does tweaking this gene in stem cells of another tissue have the same effect? Or is the intestine really the most important organ in this situation? CAVANAUGH: To be clear, in tweaking the stem cell of fruit flies' intestine, you didn't change anything else about the fruit fly, right? It was just the cells in the intestine. And that caused, it would seem, the fruit flies to have this increased life span. JONES: Right. So if we just kind of work through it, for all of the other scientists out there , we tried to door as many controls as possible to make sure that we were only targeting expression to the stem cells and progenitor cells within the southwestin. What happens, it appears that what would normally happen with increased age in the intestine, all of that is being delayed. One of the things that starts to happen with age normally is that the intestinal epithelium starts to break down. One of the things that our intestines does is serves as a barrier. There are bacteria, toxins that are in our intestine. So if the epithelium barrier breaks down, that can start to leak out. So by delaying the aging of the stem cells, we delayed the aging of the tissue, and that probably was the reason why the flies were living longer. As I said, now we have all of these questions to ask about why that was actually happening and if the stem cells in the intestine are really the only stem cells in which this can happen. CAVANAUGH: It's fascinating, even to someone who doesn't understand it. Let me invite our callers to call in at 1-888-895-5727. %F01 NEW SPEAKER: I'm just wondering on a planet of 7 billion human beings when we're over-fishing the oceans and using all of our natural resources, we're worried about research that would extend hundred life when we're already at what seems to be maximum capacity of a population CAVANAUGH: Fair enough, John. JONES: It's a great question, John, and it allows me to make a point that I think is very important, which is that the goal of most aging retcher system not to extend life span. I can't think of many people who would want to live to be 100 and 50 and be bedridden for 70 years. That's absolutely not the goal. What our goal would be is to increase the health of people for as long as we are alive Fthat makes sense. So what we may be able to do with this research is by preserving the stem cell function, if you'll allow me to kind of think ahead a number of years, if we are able to preserve stem cell function and preserve tissue function, then that could delay the on set of many aging related diseases. So things like cancer, things like Alzheimer's or other neurodegenerative diseases, Parkinson's, all aging is the highest risk factor for the on set of all of these diseases. If we can delay the aging process, it's not necessarily to make people live longer. What it is is to delay the on set of many of these aging related diseases. Does that make sense? CAVANAUGH: It does make sense, but indeed if we didn't die of an aging related disease, what would we die of? JONES: It's actually -- there are people who have really kind of looked at what people are dying of more now. Now we die of cancer. Before a number of years ago, people weren't dying of cancer. It's because we live long enough to develop cancer in some cases, of course. That might be an experiment that someone else can do. I don't know that I'm going to be around long enough to do that. CAVANAUGH: Well, you alluded to something, though, doctor Jones. You alluded to the idea that this research is going to be going on along the lines of, what did you say? Stimulating stem cells? JONES: Well, what we'd like to do is to really understand whether or not manipulating the gene's function in different stem cell populations provides the same benefit. So if some of the other work that we've done in our lab is really suggesting that stem cells age very differently. And so my prediction would be that this isn't going to be the way to delay aging of every single stem cell population am we're working on flies. We could take these types of experiments and translate them into other model systems like mice which are more similar to human beings, and see if the results hold true there. There's still a lot of work to be done CAVANAUGH: Would it make any sense for people just to reduce their calorie intake? Would that -- do you have to do that so drastically that it wouldn't be feasible to try to keep yourself healthy and Alive longer if do you that? JONES: Well, there are actually people who are doing this to themselves. So there are groups of people who are going through a dietary restriction regime. So I think technically it's defined as 60% of what your normal caloric intake would be. So there are people who are doing this. I know that they -- there may be some kind of benefit in years, in many, many years in advance -- in the future. But I don that they're not necessarily that happy. There are other side effects that are becoming more prevalent that I think are inhibiting their ability to really enjoy what might be an extended life span. CAVANAUGH: Yes, a bland diet, no desert forever. Yes, I can see that. Is the ultimate goal, do you foresee, perhaps some sort of a drug? JONES: The protein that's encoded by this gene could certainly -- could certainly something that could be a drugable target. As I said, I think before we think of it as a cure-all, what we would like to do again is just try and understand how we can modulate or regulate the aging of stem cell, and what benefit that provides to each of the tissues that are maintained by stem cells. In humans there are stem cells that maintain a lot of tissues, our skin, our blood, spermatogenesis is maintained by stem cells. Muscles are maintained by stem cells. And each of these populations behaves very differently. I just think it'll take some time to try and understand what's the gene we need to tweak in each of these different stem cell populations to maintain their activity for longer and in order to maintain the issues and the O begans for longer, and again, as I was trying to explain to John, which might lead to a healthier life CAVANAUGH: Now, I want to tell everyone the study is published online in cell metabolism. I've been speaking with Leanne Jones, associate professor at Salk's genetics lab, and lead scientist on the fruit flies study at Salk's genetics lab. And thank you very much for explaining this to us. I really appreciate it. JONES: It was my pleasure, Maureen.