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BIO Magazine - Meet Bill Andrews: The Man Who would be Immortal Ιούνιος 2015
Ιούνιος 2015 No32

BIO Interview

Meet Bill Andrews: The Man Who would be Immortal
Meet Bill Andrews: The Man Who would be Immortal

Dr. Bill Andrews is deadly serious. He wants to live forever, and he's definitely not crazy. The more you know about him and his quest the more you realize he's actually on to something really big.

The founder of a research company in Reno, Nevada, called Sierra Sciences , Andrews has a Ph.D. in Molecular and Population Genetics. He's been in the biotechnology industry for 28 years, and as Director of Molecular Biology at the Geron Corporation from 1992 to 1997, he was one of the principal discoverers of the components of human telomerase, an enzyme that makes telomeres grow. In 1977, Andrews was awarded 2nd place as "National Inventor of the Year" and he is the named inventor on 35 U.S. issued patents related to telomerase.

To understand why Andrews should be taken seriously, you first need to know a few basics about telomeres. Once considered nothing more than a relatively long strand of "junk" DNA at both ends of every chromosome in the human body, we now know telomeres are vitally important. When chromosomes divide and multiply, instead of losing DNA that matters, chromosomes only lose some of the telomere's DNA.

With each and every replication of our DNA, part of the telomere sequence is chopped off. This is how nature protects the DNA in a chromosome. Today, scientists can measure the age of cells by the length of the telomere--the cells in infants have long telomeres, the cells in adults have shorter telomeres. When telomeres become too short (less than 5,000 "base pairs") cells can no longer divide. Then one of two things happens; the cell either enters a state of paralysis called "senescence" or it simple commits suicide (apoptosis) and dies.

Thus, telomeres are the biological clocks of aging. Because they get shorter and shorter as cells divide, people cannot live beyond a theoretical limit of 125 years. No matter how well you take care of yourself, what you eat, how great your genes are, or how lucky you may be--it is thought impossible to live longer. Indeed, the longest "confirmed" human life span in history belongs to a woman named Jeanne Calment (pictured here) who died on August 4, 1997, at the age of 122 years, 164 days.

Bill Andrews, and many other biologists and gerontologists, however, beg to differ. They point out that the telomeres in our reproductive cells don't get shorter, because if they did, they would yield embryos as old as we are. So much cell division takes places in the womb, our children would be born much older than us. However, reproductive cells are essential immortal. Their telomeres remain nice and long.

The reason reproductive cells are immortal is they produce the telomerase enzyme which in turns lengthens telomeres as soon as they are shortened; it's as though every time the "telomere clock" inside reproductive cells ticks once, telomerase pushed the hands of the clock back one tick.

It turns out that all of our cells have the potential to produce telomerase, it's just that the genetic code for doing so is repressed. If we could find a way to turn this gene on, then the telomeres of all our cells would grow and we could live much longer than 125 years. We could even theoretically become younger again.

Sierra Sciences, which Andrew started 11 years ago, is on a mission to find what he calls "telomerase inducers," chemicals or drugs that activate the telomerase gene. As of this writing, the company has screened over 240,000 compounds and actually found 813 telomerase inducers. None of them are yet powerful enough to make telomeres grow at a rate which would reverse the age of cells, but Sierra Sciences is currently screening 4,000 compounds a week. It seems quite possible they will find the one they are looking for or they will find a why to boost the potency of one of the inducers they've already found.

Andrews, himself, is on a personal mission to live for a very long time, if not forever. He knows the day is coming when we can actually stop the aging process and even reverse it (the age of human stem cells have already been reverse in a test tube) but he doesn't know exactly when this will occur. It could be ten years from now or up to fifty years. Therefore, he is doing everything he can to stay as healthy as possible for as long as possible. This includes a special diet, taking supplements, daily meditation, and exercise, a lot of exercise. An experienced ultra-marathon runner, Andrews has run in over 100 races 50 miles of longer.

If it is possible for people to break through the 125 year barrier and live an indefinitely long life, I'm betting on Bill Andrews to be the first person to do this. To find out more, I recently drove from my home in Berkeley, California, to Reno where I visited the Sierra Sciences headquarters (picture here), talked to the people in labs and interviewed Dr. Andrews, which turned out to be one of the most fascinating interviews I've ever conducted.


The highlights of the interview with Bill Andrews, conducted on June 8, 2010, follow (questions in italics):


What came first, Dr. Andrews, your interest in telomeres or your interest in anti-aging?

I can remember when I was around 10 years old, my father, who realized I was very interested in science, said, "when you grown up why don't you become a doctor and cure aging?" He used to tell me all the time he doesn't understand why "no one has cured aging yet" and you know, I automatically thought of aging as a disease. (Bill is pictured here with his dad, Ralph, who is 83)

I became obsessed with this idea of curing aging and all through high school, college, graduate school everyone knew that that was my mission in life. It was only after I got into anti-aging research that I found out the whole idea of aging as a disease is a concept that very few people understand.

You had quite a career going at the biotechnology company, Geron Corporation. You were one of the inventors of the year and you had quite a lot of patents. So why did you leave and start Sierra Sciences?

I was afraid I would wake up 20 years from now and nobody did this. I went to Geron because their mission was to find a way to turn on telomerase to expand lifespan. After we cloned the telomerase gene, we did 2 experiments. We put it into normal cells and showed it could stop the aging process but we also took the anti-sense of telomerase and showed it could kill cancer cells, very quickly.

So Geron, even though their name comes from the word "gerontology" chose to go after cancer because the investors realized, and they were correct in this, there was a quicker return on investments doing cancer research.

I was a little stunned by, a little upset about it. I'm very interested in cancer research but it seemed like enough people were already doing cancer research and not enough people focused on aging. So I left and created Sierra Sciences to continue the work on telomere biology and telomerase to control the aging process.

My big fear was, if I didn't, as I said before, I'd wake up 20 years from now and find out that nobody even tried.

What lead you to believe telomeres are the key to all this? Some people say, 'sure, they are biomarkers of aging, but they probably don't cause aging.'

As long as I've been interested in aging I've been wondering why would environmental effects cause aging? I'm sure they do play a role in aging but if they were the only thing or the main thing causing aging we would see people in different environments aging at different rates. This told me there is some kind of clock ticking inside of our cells and what was that, what possible clock do we have and what kind of clock could explain why cats have a maximum lifespan very different from humans?

I was baffled by this for many years. I started attending anti-aging conferences, always keeping an eye out for something that could be this clock.

And then, about 15 years ago, I listened to Calvin Harley, the Chief Scientific Officer of Geron Corporation speak at a conference in Tahoe City at the Granlibakken Resort. He started explaining how telomeres shorten when cells divide and how there was a correlation between the telomere length and the age of a person.

I found myself sitting there nodding my head, thinking "this is it. This guy has figured it out." Of course, other people working with Cal figured it out too including Nobel Prize winners Elizabeth Blackburn and Carol Greider, but then it was all new to me.

I made an effort to meet Calvin as he was walking off the stage after his talk and simply said to him, "Calvin, I want to work with you. This is what I want to do."

Two weeks later I was working at Geron Corporation on this mission.

Amazing, and you've been at it ever since.

Yes, indeed I have, and to get back to answering your question, why do I believe telomeres are the key to aging. At that time it was the only explanation that I could come up with. I just knew this was it, but of course since then there has been an overwhelming amount of research showing that telomeres play a role in aging. And ever since we lengthened telomeres by putting telomerase into cells, that's been the real coup de grâce. We proved that by lengthening telomeres, we can actually make cells younger.

There is some concern that in lengthening telomeres you might also cause people to get cancer. Or suppose somebody already has cancerous cells, wouldn't you be inducing the telomeres of the cancer cells to grow as well as the normal cells?

That's a very good question. Nobody has shown today whether telomerase increases or decreases the risk of cancer. I think there is overwhelming data showing it is actually going to decrease the risk of cancer. There are still people who believe the opposite, for legitimate reasons, but I think they are getting fewer and fewer.

But you didn't say, "Will telomerase cause cancer," you said, "Will longer telomeres cause cancer," and I don't think most people believe that. I believe if you make telomeres long that will decrease the risk of cancer and just about everything else, everything bad for you.

Short telomeres are bad. Short telomeres will cause cancer, so keeping the telomeres long will prevent that cell from becoming a cancer. It is well known that a cell requires 8-to-10 mutations before it can become a cancer. I believe that most of those mutation are induced by short telomeres. So keeping telomeres long is a way to prevent cancer, and it can also help fight the cancer.

Another thing some people are saying is that moles and polyps increase the risk of cancer. They are precancerous but when you look at the size of a polyp or mole you can estimate it to be approximately 10-to-the-7th cells (10 7 ) . It takes about 30 cells divisions to make cells this big. So, if you have a single cell that has lost growth control but still is not yet a cancer, the telomeres will get really short because of all the cell division.

The reason moles and polyps are precancerous is because of their short telomeres. By turning on telomerase, you can lengthen those telomeres and therefore decrease the odds that they are going to cause the other mutations that cause cancer. By having a telomerase inducer, moles and polyps can grow and keep their telomeres long.

There are studies that show telomeres in polyps and moles are long but someone as experiences as me in measuring telomere length knows it is very difficult to do this accurately. A lot of time in these papers I believe people really didn't have a good way of measuring telomere length. And the same thing goes true for measuring telomerase activity. Now then if a mole or polyp already has telomerase activity then an inducers is not going to effect that cell in any way.

There is at least one paper that came out in 2002 suggesting telomerase can cause other activities like transformation of cancer into tumorigentic cells but I think they didn't have the whole story--there are a lot of missing links here. So right now if I had cancer I would be taking as much telomerase inducer as possible.

I believe a telomerase inducer will help you fight cancer. If you already have a cancer, taking a telomerase inducer it's is not going to help your cancer cells stay immortal, but it will boost your immune system. When the telomeres in immune cells get really short they loose the ability to fight. But if you take a telomerase inducer, you can keep the telomeres in your immune cells long and maintain the ability of your immune cells to fight the cancer.

The immune sytem is actually pretty effective at fighting cancers. This is one of the reasons cancers are a lot more prevalent in the elderly because older people have shorter telomeres in their immune cells.

(editor's note: New study published in JAMA validates some of the points Dr. Andrews makes above concerning telomere length and cancer. Click here to see the JAMA article .)

At Sierra Sciences you've screened hundred of thousands of compounds looking for telomerase inducers, and you've found quite a few of them. But you haven't yet found one that is powerful enough to induce immortality and achieve what you are really looking for. What happens next if you find the compound that will cause cells to actually become immortal?

Years ago people were telling us it is impossible to find a telomerase inducer and I think that is part of the reason we have no competition. Nobody else has decided to make the effort to look for a telomerase inducer.

We found our first drug to induce telomerses 2 1/2 years ago and we sent it to all the people who had told us it was impossible and had them test it. Sure enough, they all came back and said "Wow, it works!" They didn't understand why it works but it does work.

Since then we have gotten up to 39 different families of drugs or chemicals that induce telomerase and we're up to about 12% of what we need, or think we need, to make human cells immortal. And actually that is pretty high because we think it won't be too much harder, using structure activity material relationship activities and learning the mechanisms of action of these drugs, to figure out ways to make these chemicals more potent. But at that point we then have to go through FDA trials and that is going to require up to 12 years to get something to the market.

We think we can get this into the pet market earlier.

Oh really, amazing.

Our colleagues at the University of Texas at Southwestern and the University of Edinburgh have found cats, dogs and horses all age by telomere shortening, even though mice don't and other rodents don't. We think we can sell our telomerase inducers to the cat, dog and horse markets. Many of the owners will buy a lot of it to extend the lifespan and the healthspan of their pets. Unfortunately the people who love their mice and their rabbits won't benefit because these animals age by different mechanisms.

We also see earlier opportunities in the stem cell market. Recently, we coauthored a paper with Mike West at BioTime Corporation showing that induced pluripotent stem cells have shorter telomeres than you would like. So, let's say you want to take cells from an elderly person and induce them to become pluripotent stem cells and then put them back into a person. Well, they are not going be as effective because the telomeres in older stem cells are short. So, I think a telomerase inducers is going to be very, very useful for that whole market.

And there's a few other research markets where telomerase inducers will be useful, but even more exciting is the possibility of fighting life threatening diseases, some of which could be FDA fast tracked. For sure, this would include progeria, a disease where kids age very rapidly age and die before they are 20. Our company is very interested in that disease even though we don't see it ever making us any money. I can tell you every employee here would feel great self-satisfaction knowing we'd come up with a way of helping these kids even though there is only 15 in the world at any one time. Helping them to live a normal life would be wonderful.

There's also the immune systems of AIDS patents. When a person first gets infected with the AIDS virus the immune systems puts up a pretty big fight. Ultimately though it is unsuccessfully because of the fact the AIDS virus is pretty much inside the immune cells. So in this effort to fight off the virus the telomeres of the immune cells get really short. This is why back in the early 80's when AIDS was first discovered doctors were surprise to find these AIDS patents had no T cells. It's because the telomeres got short and essentially the immune cells died of old age.

We believe a telomerase inducer will keep the immune system alive. Rita Effros, the UCLA immunologist, is doing work right now with some of Geron's telomerase inducing compounds to actually follow through on this possibility. So that's another market where I think we can probably get fast tracked by the FDA.

So there is a lot more to your efforts than just the single goal of immortality?

The goal is not to just make us older, the goal is to make us healthier. When I'm 140 years old, I want to look and feel like a 24 year old. The goal is not to extend lifespan, the goal is to extend healthspan.

I keep a list of all the different diseases related to telomere shortening and this list has gotten to way over 100 different diseases that humans suffer from that are controlled by telomere length. That includes cardiovascular disease, cancer, which we just discussed, macular degeneration, osteoarthritis, osteoporosis, and some more recent data is showing a big correlation between Alzheimer's disease and telomere length. Keeping telomeres long could prevent Alzheimer's or could stop the progression of Alzheimer's if a person is diagnosed with it.

Even if telomeres didn't have anything to do with lifespan people would live longer because the number one cause of death is heart disease and cancer. If we can decrease that significantly we are going to increase the average lifespan and healthspan of humans.

When you are a centenarian, you obviously plan to be different from today's centenarians. You say you want to run a 7-minute mile when you are 130 years old.

I'm an ultramarathon runner. I've been running ultramarathons since 1986 and almost all ultramarathon runners have their biography written to a website, run110.com. If you read my bio, which has been there unchanged since 1997, it says my ultimate goal is to run the Western States 100 mile race when I'm 100 years old and I plan on have my father, who will be 125 at the time, crew for me. ( link to Bill's bio )

That was my first bold statement. And yes, my most recent bold statement is I'm going to feel like we succeeded in what we are doing when I run a 7-minute mile when I'm 130 years old or when somebody else does before me.

Is there an existing record for 100-year-olds running the mile or a marathon?

I know there have been 90-year-olds who have run a marathon, but I don't think there is a record for the marathon at 100. But I think it will happen before I get a shot at it because there are number of older athletes doing supper well running ultramarathans and marathons.

You invest a lot of time running and working out and I know you also invest a lot of time in your scientific pursuits and running this company. So, I'm wondering how do you manage your time?

That's a very tough thing to do. I am very eager to live forever and I have to really exercise a lot of discipline in order to do that. I sacrifice my social life but I feel that what I lose in a social life right now I'm going to make up 10 fold more after I have a cure for aging and figure out a way to extend my lifespan.

I think when you are 130 and can run the mile in 7 minutes, you'll have a lot of friends and fans. Can you imagine? (laughter).

Yes, I can imagine. As I said, I'm eager to live forever and I know I'm never going to live forever, I'm going to die early, if I don't keep fit and stay in shape. There is a lot of supporting data that has come out in just the last couple years showing that good health, physical and mental health help keep your telomeres long.

Put differently, being unhealthy both physically and mentally accelerates telomere shortening by creating stress inducing free radicals. Free radicals actually clip DNA telomeres making them shorter and also causing tissue damage thereby inducing cell division to repair that damage. Whenever you induce cell division you get telomere shortening.

Studies have been published in two major publications in the last year showing endurance athletes have longer telomeres than people who aren't as athletic or who are sedentary. Obesity has been shown to affect telomere length and lack of omega-3 fatty acids and vitamin D have been shown to affect telomere length.

Everytime I hear or read about something new I include that in my regimen. I exercise, try not to get obese, and take my omega-3 and vitamin D.

But then on the mental side it has been shown that people who have a lot of mental stress have shorter telomeres. Elizabether Blackburn has published some great papers finding people who are caregivers for Alzheimer's patients have shorter telomeres because they are clearly under a lot of stress. So meditation might be something that can prevent telomere shortening.

Even pessimism, people who are pessimistic have been shown to have shorter telomeres. If you ask a person a question like do you think you will live to be 100 and they say "no" they probably won't because thier telomeres are going to be shorter. But if they answer "yes" the probably will because their telomeres are going to be longer.

So, I try to be very opltimistic, not pessimistic. I try to cause everybody else to have stress, not me.

Do you meditate and if so, how often?

Yeah, I meditate ... I've gone to meditation people and they tell me I already meditate.

From the running?

Well, running and I learned a long, long time ago, maybe when I was back in high school, I just go into a self meditation type mode and it helps a lot. Every time I get on an airplane as soon as I'm sitting in the plane, everything is ready and the plane starts to move, I always fall asleep and I usually sleep through the whole flight.

What's more important, diet or exercise?

Clearly exercise. I'm trying to figure out if there is a diet that could keep your cardiovascular system strong without exercise. However, I think you cannot separate one from another because if you ate at Burger King three meals a day and ran 10 miles a day you are still going to get cardiovascular disease and die.

Nobody has ever asked me that question. One thing I will mention is antioxidants clearly prevent telomere damage. A lot of fruits, particularly blueberries, contain a lot of antioxidants.

Is there anything else you'd like to include in this inteview?

Just that bad things happen when telomeres get short and so, let's keep them long.


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