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Reported April 3, 2010

Beating Your Genes -- In-Depth Doctor's Interview

Lewis Lipsitz, M.D., director of the Institute for Aging Research at Hebrew SeniorLife in Boston, Mass., determines fact from fiction when it comes to "aging remedies."

Is there a magic pill to help people live younger longer?

Dr. Lewis Lipsitz: I think everyone wants a magic pill. In fact, it was once William Osler, in the turn of the 20th century who said the thing that distinguishes man from the animals is the desire to take medications. Everyone looks for a magic pill, but in fact, there probably is not a single intervention that will help people live longer and better. We are talking about a poly pill, however, something that might have multiple components – vitamins and other types of interventions – that actually has been shown to prevent disease and prolong successful life.

What would the poly pill be?

Dr. Lipsitz: Scientists are beginning to understand a number of interventions that might prevent disease in late life. One of the perhaps most important vitamins in our diet is vitamin D. We’ve always known vitamin D as the vitamin that builds strong bones, but we also know now that it builds strong muscles, may have a role in improving the functioning of our brain, prevents falls, and may even prevent some cancers, so in my poly pill, I would definitely put a good dose of about 1000 units of vitamin D. In addition, we’re beginning to understand that some of the drugs called ace inhibitors are helpful in remodeling the heart and blood vessels and can help prevent the development of atherosclerosis and complications, such as strokes and other things, so we might want to sprinkle a little bit of an ace inhibitor. We know that it’s important to reduce cholesterol, even below levels that were thought to be normal, so we might put a little bit of statins in our pill to reduce cholesterol. Also, an aspirin a day has been shown to prevent heart disease in older people, so we might add an aspirin to our pill. Each of these interventions affects different systems, and that’s why one single intervention is not likely to influence the multitude of things that happen as we get older.

When you talk about this poly pill, is it something that scientists are currently developing?

Dr. Lipsitz: I think that many pharmaceutical companies are beginning to experiment with combinations of things that might go into such a pill.

There are some people that are taking hormones, thinking that that will allow them to live younger longer. Are they effective?

Dr. Lipsitz: One has to be very careful with hormones. Hormones are very, very important components of our body. If they’re deficient, it is often important to replace them. People who have low thyroid activity, or hypothyroidism, need to replace their thyroid hormone, but there are other hormones that naturally wane with age – estrogen, for example, in women. We used to think that by replacing estrogen, we would rejuvenate women, and lo and behold, we found the opposite. We actually created more heart disease, blood clots, and cognitive impairment than we prevented, so we have to be very careful. There was a time when we thought we should supplement everybody with growth hormone until we discovered that it caused a variety of problems, from pain in the feet to changes in the composition of the body that were actually detrimental rather than helpful. I think that we should look at hormones as important to restore to the level that they should be at, at a given age, but not to use excessively. They can be dangerous.

What are your thoughts when you hear, for example, that a man is using a growth hormone found in a pregnant woman’s urine, and he’s injecting it into himself?

Dr. Lipsitz: I think that those types of behaviors are dangerous. I think it’s not growth hormone, but probably a drug called Premarin, which is from pregnant horse urine, and that’s in estrogen. Again, estrogen, while previously thought to be beneficial, has actually been shown to be detrimental when used in those medications in older age.

What would you say to the people out there that think hormones could be their magic pill?

Dr. Lipsitz: I would say stay away because of the potential dangers and toxicity of many of these hormones when used in excessive doses.

Is it just that we don’t know enough, or do we know now that they’re dangerous?

Dr. Lipsitz: I don’t know which one you’re talking about in particular, but growth hormone does wane with age, but replenishing it can be dangerous. Estrogen, as we’ve just spoken about, wanes after menopause, but again, replacing it can be dangerous. Other hormones are beneficial, so if somebody’s low on thyroid, of course, we want to replace that to a normal level.

Can rapamycin add decades to your life?

Dr. Lipsitz: I think that again, that’s a bit of an exaggeration, at least with the current state of knowledge. Rapamycin is a very exciting new development in animals. We know that there are certain pathways – this happens to be called the Mtour pathway that mediates a number of different functions in the body. Rapamycin, by inhibiting those pathways, can actually extend the life span of animals, but we do not know if that really works in humans. As you know, animals are different than humans, and it would be an extrapolation that goes beyond the science to now start having humans take these medications.

What is rapamycin?

Dr. Lipsitz: Rapamycin is actually used for cancer chemotherapy. It’s not something that you would use in a healthy individual, but it is an enzyme inhibitor of a particular biochemical pathway in the body.

What are people thinking the hopes might be with it?

Dr. Lipsitz: They’re hoping that the same result can be obtained in humans as is obtained in animals, and that is an extension of life span, but again, that’s far from being proven. One would actually have to give this to people as they age, which would take many, many years, many, many individuals, and would have potential toxicities that would perhaps be more dangerous than beneficial.

As a physician, how does the thought of people trying to use rapamycin make you feel?

Dr. Lipsitz: As a physician, it scares me when people jump to conclusions about some of the basic fundamental studies. These studies are very, very important, and they give us clues as to what might later turn into important drugs or important interventions, but to jump to conclusions from an animal study to now a widespread use in humans has tremendous dangers. I would caution my patients against trying to jump on the bandwagon before something’s proven.

What is the key to old age?

Dr. Lipsitz: There is no one key to longevity or to a successful old age, but there are many contributors. Certainly, our genetic makeup is one important contributor to how we age, but it’s interesting that studies have suggested that genes play less of a role the older you get. If you think about it, our genes are very, very important early in life – they are actually evolved to be maximally effective in order to allow us to reach the age of childbirth. After we bear children, there is no pressure anymore to mutate genes to be beneficial, and therefore genes have less of a role in late life than they do in early life. Now certainly, those early life genes can set us up for atherosclerosis and heart disease and strokes and diabetes, so genes are important in the context in which we’ll age, but later in life, we can intervene with a variety of environmental and behavioral factors that can modify the effect of those genes. For example, exercise is perhaps the most proven intervention that can prevent cognitive decline, physical decline, and help prevent strokes and heart disease, and that becomes increasingly important as we get older, particularly since so many people become sedentary as they get older. We can intervene, and certainly, maintaining physical activity throughout life is important, and even 90 year olds can participate in a rigorous exercise program and improve muscle strength and function.

Is there anything people can do to sort of outlive their genes, so to speak?

Dr. Lipsitz: First of all, there is no guarantee that somebody who has had a relative with any of those conditions will develop them, and there are many things that people can do to try to overcome that genetic predisposition. For example, one thing that’s very, very important is just plain screening. If you’ve had a mother or a sister with breast cancer, it’s very, very important to do breast exams, to have mammograms, so that you can catch a cancer early and cure it. These are curable conditions in many cases. Also, if you’ve had a predisposition to high blood pressure or high cholesterol, you need to identify that and treat that early, and we now believe that the long-term treatment of high blood pressure will prevent strokes and heart disease and other adverse effects. The first advice I would give is to make sure that you are carefully screened for these conditions and at the present, you treat them early, so that you can experience a longer life. In fact, since the advent of anti-hypertensive therapy and anti-cholesterol therapy, stroke rates have been reduced in this country, so we can intervene early in life to have a better experience later in life. In terms of intervening later, we can actually promote exercise programs, nutritional programs, staying away from saturated fats, for example, can overcome the genetic predisposition that somebody might have later in life.

As far as popping a pill, that doesn’t exist currently?

Dr. Lipsitz: It’s curious. As I said, William Osler said at the turn of the 20th century that the thing that distinguishes man from the animals is the desire to take medications. Why is it that somebody wants to take an unproven medication like rapamycin and not exercise, or not reduce the saturated fat in their diet? I think that the tried and true exercise and diet, are in fact more beneficial than any of these other interventions.

Who will benefit from the current ongoing aging studies – is it the people in their 20’s, 30’s, 40’s, or 50’s?

Dr. Lipsitz: The wonderful thing about aging research and the whole field of aging is that everyone benefits. Certainly, if we can improve the lives of older individuals, their children will benefit by not having to bear the burden of caregiving later in life. Also, we can benefit older people by treating conditions in midlife. In fact, we geriatricians feel that perhaps the biggest bang for the buck is treating those people between age 30 and 60 by reducing their cholesterol, reducing their blood pressure, promoting healthy habits of exercise, nutrition and cognitive activity and engagement in life – social connectedness. These are things that are so critical to a healthy aging, and those interventions begin earlier in life.

If you had a crystal ball, and could look into the future, how long do you see before people will benefit from the research on aging?

Dr. Lipsitz: There has been a progressive improvement in lifespan and life expectancy over the past century, and I think we can continue to see those improvements into the future, so that generations from now, people will benefit. Let me give two concepts that I think are important to understanding this. One is the concept of lifespan, and the other of life expectancy. Lifespan may be pretty well fixed in the human species, and it’s probably about 100 years, maybe as much as 110, and then some exceptions – maybe 115 or 120 – but lifespan is going to be pretty fixed. Over the years, we may increase it incrementally by a year or two, but most species have a pretty fixed lifespan. However, life expectancy continues to increase until it reaches the lifespan. 100 years ago, a baby born could only expect to live on average to 47 years. Now, on average, a baby can expect to live to about 77 years, so that expectation, the life expectancy, has increased. What I hope will happen in a generation or two is that people’s life expectancy matches their lifespan, so that everybody can live out their entire lifespan, those 100 years, and then drop dead. What we hope is to square that survival curve, meaning everybody survives at a high level of function until they reach the lifespan, and then shortly thereafter, they die.

If that happens, are we equipped as a society to keep up with that?

Dr. Lipsitz: We’ll need a lot of societal changes in order to accommodate all those people who are living out their full lifespan, and this challenges many of the current social and policies that we have, for example, retirement. If everybody can expect to life to 100 years, why should we be forced to retire at 65? People can be productive far into late life, and we’re going to need to change our policies so people can continue in productive jobs until very late in life as long as they’re functional. We’ll have to change our notion of driving and education. Perhaps instead of bunching all the education in the beginning of life, people from age six to age 30, maybe we should spread it out throughout life and have jobs that change as people grow older. You retool at age 40, get a whole new profession for another 20 years, retool at age 60, have a new profession for another 20 years – it really challenges the way we organize our behaviors.

What do you think the risks are of longevity?

Dr. Lipsitz: People will argue, perhaps, that we can’t afford increased life expectancy. I think that the risks might be thought of as economic risks. How are we going to pay for all of these people? Certainly, if we have a large number of people who are disabled, the economic costs are huge, but if we have people who are healthy into late life, the productivity of those individuals is also huge. I think that we can expect a huge increase in our GNP and our ability to improve this world if we have older individuals whose knowledge and experience goes towards a variety of different business activities and social improvement activities, so I think there’s reason to be positive as long as we can maintain a healthy old age.

As a physician, how do you feel when you hear about some of the gimmicks that people are trying to tout out there to try to help you live longer?

Dr. Lipsitz: I think that everybody has their pet ideas and their fads. My view is that, as a physician, our approach should be evidence-based, and I would caution people about jumping on the newest bandwagon before an intervention is properly tested, which is why research is so critical. We really need to promote research in aging so that we can test these interventions and not release them for public use until they’re proven to be safe and effective. We’ve had so many drugs come out that have actually been toxic to anybody of any age. We’ve had fly by night interventions that have proven to be dangerous, and we don’t want people jumping on that bandwagon until they’re proven to be safe and effective.

Does it anger you to hear about laboratories that make it look like the research is better than what it is, and then they tout the products or promote them?

Dr. Lipsitz: Well, sure, I’m very upset by people who are disreputable, and in any field, whether it’s research or business or investments or anything else, and unfortunately, there are some folks who misrepresent their findings. I think that programs like this are good in that they’re educating the public about what is known and what is not known, what is effective and what is not, and I think that the press can perhaps do a better job of putting things in their proper perspective. Unfortunately, we are in a society that likes to jump on the latest finding as newsworthy, and promote it as the greatest new intervention before it’s time. I think we have to be very cautious about that, and not put investigators and others into a position where they feel compelled to promote their work in order to get funded or in order to get recognition. There’s a lot of pressure to get recognition, and at universities, it’s their whole promotion and tenure process, and that can sometimes force people to behave unethically. There’s a lot of pressure to get funding. Research is not funded adequately, so that can put pressure on people to represent their work with hyperbole, so that people think it’s better than perhaps it is. I think that those pressures sometimes drive people in the wrong direction, but in general, I think that scientists are ethical. I think that research is done in a way with many safeguards to make sure that patients are treated properly, and I think we’re all very cautious about promoting our work before it’s time.

To sum it up in a nutshell, what would you say to people who want to take steps to live younger longer, based on what we know?

Dr. Lipsitz: It may sound trite, but my advice to everybody is use it or lose it. If you’re sitting in front of your television watching this, get up afterwards and exercise. We live in a very sedentary society. After our childhood, we sit in lectures, we sit in front of the television, we sit in front of computers, and we don’t use our bodies the way they were intended to be used, and I think we should get in the habit of a daily exercise routine. It does not have to be going to a gym or joining a club. It can be walking to work instead of driving, using a bicycle, parking a distance away from where you’re going and walking, taking stairs instead of elevators, those are simple interventions that go a long way, and I think that use it or lose it is what I’d like everyone to take away.

What would be the downside to taking resveratrol?

Dr. Lipsitz: Resveratrol is relatively safe from what we know, but any medication can interact with other medicines, and people can develop allergies, and we don’t know if many of these compounds, after taking them for year after year, actually accumulate. We may later find out that there are adverse effects, so I would not encourage any of my patients to take anything that isn’t shown to be safe after many, many years of trials.

 

If you would like more information, please contact:

 

Scott Edwards

Media Relations

Hebrew SeniorLife (Harvard Medical School)

Boston, MA

Edwards@hrca.harvard.edu

 

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Read the full report Age Wave: Beating Your Genes.

 

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