TOM BEARDEN: Let's talk about genetics and aging. How did you first become interested in this subject?
STEPHEN HELFAND, University of Connecticut professor: I became interested in aging, I'd studied a number of other fields, developmental biology and neuroscience and I watched as we made enormous progress in development and, and in neuroscience by using an approach called genetics which is where one can utilize the ability to alter genes one at a time and then see how that changes in that particular gene can affect a physiological process.
So I began to understand that aging, as far as I understand it, is not well understood and that many people spent many years trying to understand it, and we're sort of at an impasse because it's such a complicated biological process that, it's hard to understand the physiology of it and what genetics allows you to do, or at least some of the modern approaches of using mutations, single mutations that we can create in model organisms and then study, it allows us basically an unbiased, or the nonbiased approach to try to see how genes and particular protein products affect a complicated biological process.
It was enormously successful in understanding how development works. How you go from a single fertilized egg to a mature individual and it's been very successful in understanding some of the underpinnings of the genetics behavior.
So a number of years ago, about 10 or 12 years ago, I kind of recognized the possibility that we could use all of these techniques that have now come into fruition, the really great techniques that weren't available earlier to, to, to try it on this same, you know, a very difficult process.
TOM BEARDEN: What do you mean by aging? How do you define that?
STEPHEN HELFAND: OK, that's a very good question. Aging is hard to define and when I have to give seminars I start out by the fact that it is difficult to define aging. Now, one way to define aging, it would be to say processes that change over time in an organism.
Now, Sir Peter Metawar had pointed out that in the English language, there is no word for aging that is devoid of the negative consequences of that. So a fellow named Tuck Finch, a number of years ago has proposed that we use age related changes as a general feature and that those things that are deleterious to our health or age might be considered senescent phenotypes.
Now even there, even though that sounds like a nice way of separating to it, it's kind of problematic and that is because how do you define a senescent phenotype? How do you know, so (inaudible), the way of just, the definition for senescence would be a phenotype, a change in the animal over time or age, that leads to the animal's functioning in the next interval being lenient, allowing it or forcing it to have a higher mortality rate would be a way of defining it. So something that changes you that makes you more likely to die in the next interval would be sort of a senescent change.
Now, the problem is that those senescent changes are context-dependent, and kind of what I mean by that is if you take somebody like me who's a short little guy, who can't run very fast and as I get older I run even slower and maybe you put glasses where I can't really see and you put me out in the African sofauna, some 10-to-20,000 years ago, as I lose a couple of steps I'm going to be in a lot of trouble in that context.
But if you take me now and you make you a CEO of a major corporation in New York City, I could run the world. So what are senescent or deleterious changes with age in one context may not be the same in another context. So that become problematic.
The other thing is that we have phenotypes that don't, that are clearly things that we recognize as occurring with age, but may not lead to any deleterious effects. So gray hair would be one example.
So, and not only do we know about gray hair in general, but we also know that gray hair is part of the aging process in the sense that every culture has a term called premature graying of the hair, which means we much recognize that there should be a normal time for hair to gray and, but does graying of the hair lead to any increase in mortality? Now it wouldn't unless you live in a society where they kill people that get gray hair.
So there are all these changes that are taking place, some of which may actually be positive changes with age, and it's not clear which of these are deleterious and which of them are not. Some of them, it's obvious they may be deleterious, but in other ones it's not. So the problem is, it's hard to define the process of aging. It's what they call in medicine or in pediatrics the grandmother areas of affect. How do you know your grandmother? Well I've seen her before, but how do you describe her to someone else in a way that they would know, so it's hard.
So the next thing I think, I usually talk about or the way I think about it is instead of trying to find what aging is, one other way is to step back and see, well how do we measure. So by how you measure something often will help you understand what it is. And in aging at the moment, that's also a bit of a problem.
We have two basic ways in which we measure aging. One is the demographic or population based approach where what people do, what you're doing is you're taking a population of individuals, whether it's, whether it's plants, whether it's animals, whether it's humans and they all start as a cohort at some particular point at which they're born or they're adults, and then you follow them over time and you make a list of what they call a life table which is really calculating when they died, and, and then you, by based upon their time of death, you can create this survivorship curve where you start with 100 percent survivorship at the beginning and at some later point, no one's alive in that population.
And it turns out that the shape of this curve in a population that has optimal environmental conditions, will give you some very important information about, about the process that must be taking place in-between.
Now the problem with that on the other hand though is that it's not telling you about aging. The measure that you're making is of the death of an individual. So you're just looking at the age of death of individuals and based upon the age of death of individuals you're going back and calculating this process. But in fact, you're not looking at a dynamic process. You don't know why that individual died. You don't know how, what led up to the death of that individual. There's a single point which is death.
Now this is something that, that people recognized for many, many years and it's a valuable piece of information. The insurance companies for example are people that really want to know. They want to know in a population what, what are the chances of this group of individuals lasting for a particular time.
So as my dad explained to me, when you take out life insurance, what you're doing is the life insurance company is betting that you're going to live and, and you're betting that you're going to die and you usually hope they win that bet, I think. But in fact what you're, what you're really doing is it's a population statistical basis.
What we want to have is a physiological study, a way of determining not how old you are necessarily chronologically because, for example, some people who are 50 years old look 30, and some people who are 50 look 70. So there, there's this association sometimes between chronological age and physiological age which may be relevant for how long you're going to live.
What we like to know is, is what physiological changes take place and do they take place in a particular characteristic manner? So, at the moment, most people because of difficulties of measuring physiological changes, do in fact measure lifespan and, and conclude many important features based upon what the lifespan, but they're not necessarily looking at changes in the rate of aging.
TOM BEARDEN: Talk me through the methodology that you're using to investigate the world of genetics.
STEPHEN HELFAND: So we have a number of approaches that we're interested in using. The methodology essentially is that we are looking mostly at lifespans. So we take a cohort of fruit flies, so we have (scientific name) is a fruit fly, common laboratory organism, and of which an enormous amount is known genetically and molecularly and even behaviorally and in regards to aging.
In fact, fruisophola and it's related species have been used in aging studies since the 1915s to explain many important features in aging. But what we do is we grow a cohort of flies through their developmental period, usually all as a big cohort and at the time that they come out of their pupal case, they close into adult form and the adult form is what people are familiar with, this little flying insect that you find around your bananas, particularly in the summertime.
TOM BEARDEN: Or the lab.
STEPHEN HELFAND: Or in this lab, but they're not our flies. Well I guess some of them are flies, but we'll deny it if they get out of the room. They could come in with the bananas. Actually every summer we do have that problem because people bring in fruit and then they leave it in the trash and they colonize, or so we think, so when the secretaries complain somewhere else, we say they're not ours. And in fact, if you get rid of the garbage you do well.
So we take these flies as they come out of their pupal case, within just a couple of hours, because these, these organisms are basically partitioned morphologically. Anatomically two distinct parts of their lives. And what I mean by that is that when the egg is laid that's been fertilized, embryogenesis and the larval phases or maggot phases take place over a period of, of five to 10 days in which those guys are eating and growing.
Eating and growing but not reproducing. The fly that comes out from the pupal case after about a five day metamorphosis period, and that can fly around, within 12 hours or so at normal room temperature is capable of mating and putting off offspring.
So they're adults by all definitions that we can come up with. So the fly that, that flies around, we call the adult fly. And we take those flies and put them in individual vials, a certain number in a vial, males, in our case we allow males and females to stay together most of the time, and then we pass them every other day, sometimes every day, sometimes every other day to new vials so that their offspring don't arise and confuse us with who's the generation that's aging and who's a new generation.
And each day what we do is we then look at those flies that may have, that died. And that by going um, every day or every other day and passing them and checking who's dead, we create a life table ourselves which then generates a survivorship curve.
TOM BEARDEN: And (inaudible) genes.
STEPHEN HELFAND: And we vary a number of different things. One of the things you can vary is environmental conditions. So the fly which is a cold-blooded organism, is very dependent upon its metabolism, based upon the ambient of the present temperature. So you can dramatically change the lifespan of the fly and all the physiological characteristics that are, go in tempo with that lifespan by changing temperature.
You can also change the lifespan of the fly with reproductive status as well as with we'll talk about I guess a little bit later by nutritional or calorie contents. But we all, what we really want to get at is to use genetics to understand this process. And what we want to do and we do, have done partly is in fact to take individual genes and alter them.
Now, often the term mutation is used, but in fact, the capability and for (scientific name) of the fruit fly field now, so we have such enormous control over the technology that we can actually take any gene and thus change its gene product by either increasing it in an animal, or decreasing it in the animal in any single set of cells, or group of cells at any time we want.
So, we could take one gene or a group of genes and alter them. But traditionally what one in the past has done and we still are partially doing, is essentially making mutations in individual genes and then looking to see whether that mutation has altered the lifespan of the fly. And preferably looking for those that extend it.
TOM BEARDEN: Which brings us to the question of caloric intake. How does that relate (inaudible)?
STEPHEN HELFAND: Calorie restriction which is a fairly well, is a common phenomena throughout the animal kingdom at least or actually (inaudible) as well, we find that, that under periods in which nutritional resources are diminished, the organisms in a variety of different ... organisms in a variety of different ways respond to that loss, that decrease in nutrition by altering their physiology in a way that tends to prolong their lifespan.
What they're probably doing from an evolutionary perspective is saying look, I shouldn't reproduce now. I should reproduce later. Now one of the byproducts of hunkering down and waiting it out is that you have to live longer in order to wait things out. So the phenomena is that when you withdraw calories from the organ -- many different organisms, it tends to extend their lifespan.
There are other phenotypes as well. What we discovered a couple years ago. First it was discovered mostly in other model org groups, such as yeast, the single-cell yeast, that there are a number of genes that directly seem to affect how calorie restriction may work.
For example there's an enzyme called RPD3 and an enzyme called SIR2, both of which change, basically remove acetyl groups, a group from a protein changing the confirmation of that protein and thus changing that protein's function.
RPD3 and SIR2, which are two, these two enzymes that we're talking about, when they interact say with histones, and histones are the proteins that help the chromodine structure help to maintain the chromodine structure, let me keep it in a tight form or a loose form, thus allowing that particular region of the genome, or that particular gene that's present in that place to either be expressed or not expressed.
So these particular enzymes are involved in modulating through both their effects on histones and their effects on other proteins gene regulation, in other words, what genes will be expressed at that time or not expressed at that time.
You can imagine if you're in an environment where you need to change your physiology in some dramatic way because of the nutrient sources that you're sensing, or lacking, what you'd like to do is change a lot of things in a characteristic altogether manner and one way to do that is to begin to stimulate some of these processes to change gene regulation in a conserved directed manner.
So what we have done is we've looked in the last couple of years, particularly based upon yeast studies and based upon studies in the roundworm C. elegans, the particular genes that they seem to show both extends lifespan and may do so through a calorie restricted manner, we've done the same thing with the fly.
One is we took this mutation called RPD3 which is a histone DS (inaudible), and in the yeast cell, when you decrease RPD3 activity, you both extend the lifespan of the mother cell in yeast and what we do is we do that in the fly and when we decreased RPD3 levels we extended the lifespan of the fly. So two genetically identical flies except for a mutation in RPD3 and one which decreased RPD3 led to a dramatic extension about 35, 40 percent in those flies that had a decrease in RPD3.
And then the next step that we did was, or the next kind of thing that we thought about is well, how is RPD3 extending lifespan and partially due to the effect that we were able to study it and we have studied it. We began to explore some of the three ways that we know that we can alter lifespan in the fly.
Ambient temperature which didn't seem to be something that we could look at, sexual reproduction and we did look and these animals, what I didn't say earlier was that in the fruit fly, if you have the female not mate, it lives significantly longer than if it's mated. So one thing that you have to do whenever you have these interventions that seem to extend lifespan is to try to maybe look into and/or exclude whether it's not due to the fact that you're now shutting down fertility.
TOM BEARDEN: Excellent.
STEPHEN HELFAND: And so, we look at how many eggs it can lay and we found that with RPD3 there was very little decrease. And in addition, the males are perfectly normal, so the idea that this is a reproductive problem was, was less likely.
And the third thing that we were really left was, was this idea of calorie restriction. So if you take a normal fly, or sawfly and you, in its food that it's living in 24 hours a day anyway, and you reduce the amount of calories in that food, a variety of laboratories has shown that this extends the lifespan of the animal.
And you can do it in a dose manner so that as you reduce the calories of the food you get a longer and longer lifespan until you've gone too far and maybe they're slightly in a starvation mode.
So we took our RPD3 mutants, and one of the things we found was that if we look at a normal fly that we have calorie restricted, that we know will live longer, if we look at its activity of RPD3, we find that the level of expression of that gene is lower. It's about half or so, which was, which was what we were doing by our genetic manipulation.
So the normal animal under calorie restricted conditions appears to cause RPD3 to lower to about the same level that our mutation did. When we took our RPD3 mutation and we looked at its effect on lifespan under normal food conditions, and we looked at normal flies under calorie restricted conditions and then we looked at RPD3 mutants under calorie restricted conditions. And we found that the extension of lifespan with RPD3 was sort of similar to the extension that we saw of a normal fly and calorie restricted fly.
And if we put RPD3 and calorie restriction together, two different things, we didn't get an added effect. They didn't live any longer. So that it wasn't as, suggesting that the two may be in a related pathway. If they were completely unrelated, you would expect to find that they would add up and give you an extension and they didn't. That was the first clue.
Now the other part that was a clue to us of what genes might be involved in mediating how calorie restriction leads to this lifespan extension, was that in addition to looking at calorie restricted animals and looking to see what RPD3 levels looked like, we also, because it was a popular gene, looked at what SIR2 levels would do. Now SIR2 has been found in yeast and in C. elegans roundworm, that when you increase the level of SIR2, you extend the lifespan of both of those organisms.
So what we found in our normal calorie, a normal animal that's calorie restricted, we found that whereas the RPD3 gene was decreased, the SIR2 gene was actually increased. If we took our RPD3 mutation that's living longer, and we looked at SIR2, we found that it was increased there as well.
TOM BEARDEN: So they're working in tandem?
STEPHEN HELFAND: So we're not, we believe that they may be working in tandem, and that's the evidence that we've gotten most recently, which is if we take SIR2 itself in the fly and we caused the fly to increase its expression of its normal SIR2 gene, we can extend lifespan.
And the things that are interesting about it is that, the first thing we did is we used a technological approach that allowed us to, that permitted us to extend, to increase SIR2 levels in all cells of the body and, and that extended lifespan say 40, 50 percent.
And then we say, well what tissues might be more important? I mean and one way of asking that is where is SIR2 normally expressed? And when you, when you look, it appears that two of the tissues it's primarily expressed there in the brain, in the nerve cells of the brain and in the fat body which is part of the persofola, it's part of, sort of the equivalent of the liver or the fat cells.
And that's where SIR2 is normally expressed, so we then said, well what happens if we just restrict our increase or SIR2 expression to one of those tissues. And we have the capability of doing that using molecular approaches so that we increase it just in the nerve cells of the brain. And when we did that, we got almost as good an extension of lifespan. So SIR2, an increase to the whole body, or SIR2, an increase in only neurons, both extended lifespan. Now we also did --
TOM BEARDEN: It sounds as if what you're describing is that you're using manipulation of genes to activate what amounts to be it an ancient survival mechanism?
STEPHEN HELFAND: That's probably one way to step back and think about it. It looks like what we are in fact plugging into is something that's a remnant of, it's important in survival, that's right.
And we're utilizing it in not a survival mode, we're tricking the animal into thinking that it needs to go into a survival mode and the idea of, so calorie restriction creates this physiological changes, and what we're seeing is that some of the changes that it creates, that are particularly relevant to the lifespan extending part, which is what we tend to be interested in, include RPD3 and SIR2.
And so that, instead of the diversity of both positive and maybe negative effects that calorie restriction has in addition to the fact that it's very hard to actually calorie restrict oneself, at least for me, by looking at more downstream or the mediators of this otherwise complicated environmental process allows us to maybe intervene at those points so that we can by manipulating RPD3 or by manipulating SIR2 at least theoretically the possibility of getting the benefits of calorie restriction without some of the limitations of calorie restriction.
So what we did was to, in order to tie SIR2 to calorie restriction and had it already been tied in the yeast to calorie restriction (inaudible), we did similar studies as we do with RPD3 where we, well we actually do two things.
One is we took a normal animal and we showed that when you calorie restricted it extended its lifespan. And then we knocked out or we took an animal that had a mutation in SIR2 that prevented it from increasing SIR2 levels and we asked, can that animal, when calorie restricted, still respond by extending lifespan? And it cannot. So it seems as though when we block the ability of SIR2 to increase, we block the ability of calorie restriction to extend lifespan.
TOM BEARDEN: So is SIR2 the key to aging?
STEPHEN HELFAND: Well, I know people that would like to believe that certainly there's a number of pieces of data that suggest that SIR2 is one of the central regulators of this process and it actually has a number of features to it that, that would make it an important part of the process. I mean the things we know about, so these, what I'm describing are the actual studies. We changed SIR2, we can change lifespan. We prevent SIR2 from increasing, we can block the lifespan extension.
But SIR2 itself does actually have many of the features that you would want of a molecule that, that can sense how the environment is being hit and then, and then based upon that sense, actually react by changing gene regulation, a diversity of genes is the same thing. So, is it a central regulator? Well I don't know. You know I'm not so good at making those sorts of decisions, but I would say that it's a very, it's very likely to be something that we'd be very interested in.
TOM BEARDEN: Is it likely to be applicable to human beings?
STEPHEN HELFAND: Actually it does seem to be that it's likely going to be applicable to humans and why I say is that the SIR2 gene is present in humans and other mammals and there's actually more SIR2-like genes, so you have to figure out which one is the one you really want, but the reason why it is likely to be applicable or, or data that's (inaudible) applicable is that other individuals at the same time we were doing our studies on the fly to see whether SIR2 is involved in lifespan extension and whether it worked through caloric restriction, other groups were looking at molecules that affect the activity of SIR2.
So a couple of years ago, David Sinclair's lab at Harvard went in and examined are there small molecules which eventually could be used, used as drugs that effect the activity of SIR2 and about a year and a half ago or so, he published that in fact there are a group of small molecules that activate SIR2's desatilase activity, the activity that we think is important in this process. And one of those is, is a molecule that I usually mispronounce so I will call it resveratrol which is a small plant polyphenol present in red wine among other things. ...
And this molecule which some people think may be responsible for what's called the French paradox where the French don't necessarily eat the best of diets, but they have enough red wine around to offset that and make up for it. Anyway, this small molecule, he found activates SIR2 in both human SIR2 and also in yeast and went to show that resveratrol ... can extend the lifespan as it's measured in yeast.
So this past summer in collaboration with David and with Mark Kator at Brown, (inaudible), Regina and I went and studied does resveratrol affect the worm lifespan, the roundworm C. elegans' lifespan and in our case the fly.
And in all three cases so far, yeast, worm and flies, resveratrol when fed to the animals extends the lifespan of the animals, a modest 20, 25 percent and more importantly maybe, or we demonstrated that clearly in the fly, and I believe also in the worm, that lifespan extension is dependent upon SIR2's activity. So by removing SIR2 we block resveratrol's extension of lifespan.
TOM BEARDEN: So are we talking about treatment for aging here potentially? And if so, when?
STEPHEN HELFAND: We're talking about moving aging from a field where there is anti-aging phenomena that's not based on any rationale or I should say any good rationale basis. I mean yes, oxidation is something that's important and yes it's probably true that oxidation and aging go in hand and hand, and it may even be true that oxidation drives the process of aging, but in the many, many years that people have tried to use anti-oxidants to effect the process of aging, it has failed for the most part.
So, we are in fact seeing what you already specifically said, the idea that by understanding at least part of this ancient pathway of calorie restriction and understanding what are the biochemical and the molecular mediators of transforming a decrease in calorie content to an extension of lifespan, by having those players along the way available to us, we should be able to come together and develop a rationale, therapeutic approach.
As opposed to this being a completely pie in the sky many, many years away idea, yes I suppose that I would have to say based upon our work that in fact, we are moving either slowly or lurching towards reasonable intervention. As we talked about earlier perhaps is that it's hard to know how to study that in humans because of the length of the lifespan. And we need to develop ways of looking at that.
TOM BEARDEN: Are we talking, not only about -- maybe delay's the wrong word -- maybe making people, allow them to be healthier longer? Are we also talking about a significant longer lifespan itself if the projections that might be made do come true?
STEPHEN HELFAND: Yeah, I think we're talking about both. Yes, so if we're talking, so there's two things about this survivorship curve that I talked about before is there's a particular shape to it.
And many years ago, Fry explained that what we're doing in the United States and through both sanitation and good medical practices, what they call rectangularizing the curve, everybody's healthier, but the point at which they're going to die is still the same, that there's this idea of a species specific lifespan that you can't really get past. And in normal terms what a species specific lifespan means is that your dog only lives about 15, 20 years. It doesn't live 100 years.
That idea is based upon two things. One, the observation that your dog doesn't in fact live 100 years. But the scientific underpinning, at least as far as I see it, was based upon the measurement of survivorship data and taking survivorship data and the next derivative which is mortality rates. So by determining how people, how organisms die over time, you can determine whether the chances of you dying in the next interval is something that's going to increase or not.
And Benjamin (inaudible) back in 1825 who was an actuary, getting back to why life insurance companies are interested in this, in fact developed this idea which he called the law of mortality. If he looked at humans, which is what he was looking at, and he measured the rate at which you died as you got older, it increased in an exponential rate.
So, the idea being, and many people have looked since 1825, it's actually called Gompret's law or Gompret's curve, at many different organisms and many, or all of them up until quite recently were all thought to obey the Gompret's law in which then you could think mathematically speaking at least that since it's an exponential curve there's going to be some point where you hit 1.0 and nobody should make it past that and therefore maybe you can't live longer, unless of course you change the (inaudible) curve which you could do.
But a couple years ago, a group led by James Lapell, at the (inaudible) Institute in Germany and Denmark demonstrated in fact that the Gompret's law is not entirely correct. That in the elder, or in the older there is in fact a mortality deceleration. So in humans it doesn't occur until about 80 years which is why we may have missed it. And in fruit flies it occurs a lot earlier. ...
Back in the '90s, Jim Bopell led a group when he sat at (inaudible) Institute a group that quite international including people in the United States, Jim Kerry, Jim Kritsinger, demonstrated that, first in med flies that as they get older, there reaches a point where their mortality curve, instead of just constantly increasing in an exponential manner, actually kind of plateaus and actually they feel, actually they turn down.
So what that means, the reason we didn't see that before in human terms is that in humans it doesn't seem to begin to plateau until about 80 years of age and you need a large number of individuals to demographically demonstrate this, but with med flies and with tresopholine and the roundworms, you can get a large population and you can see this plateau.
The idea that Gomperts and exponential rates lead you to have a species specific lifespan may now be not entirely true which steps back to the question of in fact can you extend the lifespan, not just extend the healthy portion of the lifespan.
And there's a bit of a debate on this, but the data actually suggests that, and have been published, that in fact just like with the patent office in feeling like we'll never have another invention heretofore, almost anytime some has said we've reached the maximum human lifespan, it's been surpassed within five years
And due to communications, some of the earliest times that that claim has been made, it was surpassed before it was even said but the people didn't know about it. So, if you do look, and I'm not an expert in this field, in demography and population and census, the centenarian group is growing at a very high rate in developing countries.
So the idea that you could extend the healthy portion of a lifespan and also the maximal lifespan I think is entirely possible. In fact, that's what's extended in calorie restricted mice and rats. They, they extend both their health and the actual longevity itself.
TOM BEARDEN: I know it's not your field, but have you given much thought to the potential sociological implications of a much longer life population, a much healthier population?
STEPHEN HELFAND: It's not my field, but yes I have. I mean, we are often asked that question. Now I, a couple of different thoughts on that. One from a sort of maybe practical perspective, if the population lives longer it's like, so the question is, will we bankrupt Social Security in the practical sense. Well, people will work longer. Many of these, maybe people don't want to hear that, but people will be healthier and longer, so many things will scale out so that the period in which you can be happy and healthy and working will be longer so you can be productive for longer.
I think there actually, from a philosophical perspective, there could be some real benefits to that and, not just philosophical, but for a real benefits and this is getting a little bit off the focus here now, but I've kind of been impressed in my life that as people get older they do change their feelings about a lot of things. They temper a lot of the passions that they may have had earlier, both positive ones and negative ones.
And I believe that occurs through experience and you can't provide experience to a baby. I mean they have to have it. So maybe if we have an older population that has had some of these experiences, maybe what we'll have is more wisdom that we have now. I mean that instead of it just being older people, we'll have older people with more wisdom and that'll help.
The other thing is that as in all things, when we're still developing them, we're not sure what we're going to make of them. I mean, and that is up to society to do and not really up to the scientists at all. I don't think that's just a cop out, I mean it's just the fact that what scientists think they're developing and how they like to see it be used is not often the case of how it is used. I mean politics and economics usually drive what's going to happen.
The other part is that if the example of mature populations in any case, that as people can be more stable, know that they can live longer, know that their children are not going to die in infancy, they begin to have less children. Maybe we'll end up stabilizing everything so that it's not like people will continue to have hundred, you know 10 children and all, everyone's going to live longer. Maybe we'll scale everything down in some proportional way. I suspect that we will.
TOM BEARDEN: If the ancient defense mechanism in the flies cause this organism to have children later in life because that's the point of let's not reproduce right now, would the same thing happen in humans or is it too early for that now?
STEPHEN HELFAND: Would it still happen in humans? Well, if what we're saying is that we're just changing the proportions of a period of time so that menopause would presumably happen much later, meaning in average, so yes. You would expect that you could have children later.
But it might not feel later cause you might feel younger. It's sort of like the Star Trek episodes where you know it depends on the speed at which you're living, you know, just those parallel universes where everyone's living in microseconds you just hear them as a fly in the ear, but for them it's a full lifespan, so it may not be much of a problem I think. We'll adapt. There'll certainly be growing pains and bumps I suspect. But this catastrophe that we're going to overpopulate the world with the elderly, it's extremely unlikely to be the outcome of what would happen.
TOM BEARDEN: How long before a viable treatment might be available?
STEPHEN HELFAND: Yeah I don't even begin to think about that but you know viable, one could say right now, but the point is how do we know? Because the ability to know whether that particular intervention will in fact have an effect, unfortunately due to the process of aging itself will take a hundred years unless we can come up with some reasonable way of looking at physiological age in a short period of time to demonstrate whether we've actually slowed it or not.