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Michael Fossel, Ph.D., M.D.

is, not only not much, but to the extent you’ll be able to, it’ll be too late for most of the children that you know. The life span is about twelve and a half years, and that’s a pretty narrow research horizon. 

The other question is what can they teach us about normal aging? I find that the most effective point. The most promising way to look at almost any research question is to ask yourself, where are the outliers? Where are the anomalies? Where are the exceptions? To understand aging I think there’s a certain benefit from just looking at normal human aging. But I think you learn a lot more by looking at organisms that either don’t age, age slowly, age quickly, or age in a peculiar fashion. 

Now, the latter two are true of progerics. They age quickly, but they age in a peculiar fashion. Not all of the body seems to age. In fact, you could reasonably ask whether this is aging at all. Is it accelerated aging? Is it aging? Does it tell us anything? I think the answer is it does. I think what you’re seeing in the arterial supplies in the skin and the joints in the bones reflects, if not real aging, at least something that can offer us a great deal of insight into aging. Whereas, if you’re looking at the immune system, or the nervous system, frankly there’s very little it can offer us–except, again, as an anomaly. Why is it that the arteries of these children seem to show rapid aging, and the brain cells don’t? Again, it’s the anomalies, I think, that can teach us more than just the routine humdrum process.

David: How is cellular aging related to the bodily symptoms of aging that ultimately lead to disease and death?

Michael: To put it bluntly–and again, there’s a certain inaccuracy in saying this, but just by saying it this way, I think it prompts a great deal of both insight and appropriate criticism–I think the answer is that all aging is cell aging. Organisms age, and if you look at an organism aging, what you’re really looking at is organ aging and tissue aging. And if you look at organ aging and tissue aging, you look at cellular aging. The human body is composed of cells, and while it’s appropriate to keep in mind the gestalt involved, the real process occurs not only at the cellular level, but between cells. It’s like looking at society. Society isn’t a thing, it’s a collection of individuals. It’s not only the individuals, but the way they interact. It’s the same thing here. If you really want to understand a society you want to understand the individuals. If you really want to understand aging you want to understand how the cells are effected.

David: What do you think will be the best way to reset gene expression in elderly cells and  increase telomere length?

Michael: The quick answer is that the best way to reset gene expression is to increase telomere length. But the best way to increase telomere length is to use one of three process. One is something that we’re technically capable of now–although we haven’t tried it yet in human volunteers–is to insert a new hTERT gene that’s turned on. That can and has been done in the cells, and has been done in reconstituted tissue. 

The second way, which is much more elegant, is simply to turn on and off the existing hTERT gene in human cells. That process has been looked at, and we’re very close, tantalizingly close, but to the best of my knowledge it hasn’t been accomplished yet. 

The third approach would be to put in hTERT. That is, essentially, to put telomerase into the cells, and that was regarded as technically impossible, perhaps, as late as five years ago. Now it looks like it’s probably possible, but, again, to the best of my knowledge hasn’t been accomplished. 

If, right now, what I wanted to do was to run a study trying to use telomerase, or telomere maintenance approaches, to correct, say, osteoarthritis, I would try insertion of a new hTERT gene into the cells of human joints. It’s not the most elegant approach, but it’s the process we’re most able to perform right now technically.

David: Does the enzyme telomerase actually reset telomeres back to their youthful lengths, or simply prevent them from getting any shorter with each cell division?

Michael: The simple answer is both. In the hematopoietic cells in your bone marrow the latter is what happens. That is, you use recurrent and well-controlled telomerase expression to almost maintain the length of your hematopoietic stem cells. This is a very delicate, very carefully crafted process, but the end result is that over the, say, hundred years you might live, you don’t lose much in the way of hematopoietic stem cell potential for division. You more or less maintain telomere length during your entire lifespan. You certainly don’t shorten it as much as would be expected otherwise. Telomerase can not only be used that way, but it can be used to reset or relengthen telomeres.

David: What possibilities do you foresee for using some form of telomerase suppression as a treatment for cancer?

Michael: Certainly to me, I think it’s probably the most interesting and tantalizing approach to controlling cancer now. The reason I say that is that it’s probably the most universal approach. You remember back when I was talking about interventions in aging, and I said the question is, where’s the most effective single point of intervention? With joints, for example, you could replace them, or you can try to use something to control inflammation and so forth. And the same thing in cancer. There are lots of approaches, some of which may be very effective with particular cancers, in particular patients. But if you’re looking for an overall single approach, I think the most promising one is probably control of telomerase expression and function.

David: How long do you think it will be before the first telomere therapies become available?

Michael: I think that you’ll see the first human trials within ten years. Having said that, the telomerase trials in terms of cancer are already in progress now. But if you’re looking at using telomerase to, in effect, control or reverse aging pathology, I think you’ll see the first human trials within ten years. We almost began that about two years ago. We had a donor who wanted to underwrite the whole process, but they pulled out, actually the night before they were to sign the final financial contracts, or we’d probably be in progress now. So it depends. It depends on the market. It depends on people’s beliefs. And it certainly depends on whether this entire approach is accurate or not.

David: Is there anything that people can do now, say with nutritional therapies or caloric restriction, that can reduce telomere loss, and possibly help to slow down or reverse the aging process?

Michael: I think the answer to that parallels the question that you would have asked in 1953 or 1952 with regard to polio. What can we do to prevent our children from having polio? And you would get the same sort of answers. You need to have a healthy diet, avoid swimming pools, avoid people with polio, and keep an eye out for other risk factors. This is the same thing that you could have said in, say, 1870, with regard to tetanus. How do we prevent lockjaw (that is, tetanus)? The answers are similar. You certainly want somebody who’s relatively healthy, and avoids skin breaks that are near horse manure and so forth. 

But as far as therapy goes for either of those, on those two dates, the answer was pretty dismal. I think the same thing is true of aging. The best you can do is hope to ameliorate your current gene expression. If you want to avoid heart disease as an aging process there is lots of advice I could give you. Your grandmother probably gave you similar advice. Just as your doctor certainly gives you advice now. But the truth of it is, that’s all it does. It ameliorates the risks you have from gene expression. People who have bad genes tend to get bad atherosclerosis. That’s not to say they should smoke and not exercise and so forth. No, they should certainly follow standard, appropriate medical recommendations. But the real answer is, if you want to make a significant change in the outcome of that pathology, you’re going to have to do something more dramatic and fundamental, like effect telomere expression.

David: Are you referring to the aging process in general, or telomere loss specifically?

Michael: They’re closely linked, and you’re right, it sort of depends on what you’re addressing, which one you want to focus on as you’re answering the question. As I said before, my primary interest is the pathology. I’m not interested in wild intellectual discussions about aging and disease. No, I’m interested in people who actually have disease, and where we can intervene. So when you ask questions like that, I tend to magnetically home back to specific diseases, like osteoarthritis and so forth, and bring it back to what I see as practical intervention, rather than far-flung discussions, like aging in general. But no, in one sense, it’s all one process. Aging and age-related diseases are very entangled with one another.

David: How long do you think its possible for human life span to be extended?

Michael: I think that using the sort of approaches that we’ve been talking about in this conversation we can probably extend the lifespan well into the several century range. Could be more. My usual answer to that is the human lifespan becomes either

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