Human Organ Transplant Drug Slows Aging In Mice Reporting in the journal Nature, scientists write that rapamycin, an immunosuppressant drug currently used in human organ transplants, boosted the life span of old mice. Study author David Harrison discusses the findings, and the implications for human longevity.
NPR logo

Human Organ Transplant Drug Slows Aging In Mice

  • Download
  • <iframe src="" width="100%" height="290" frameborder="0" scrolling="no" title="NPR embedded audio player">
  • Transcript
Human Organ Transplant Drug Slows Aging In Mice

Human Organ Transplant Drug Slows Aging In Mice

  • Download
  • <iframe src="" width="100%" height="290" frameborder="0" scrolling="no" title="NPR embedded audio player">
  • Transcript


This is SCIENCE FRIDAY from NPR News. I'm Ira Flatow.

Let's go back now about 40 years. Scientists isolate a new antibiotic, that's nothing new. They've been finding them for years. But this one, this one is found in a soil sample from Easter Island of all places. So, they name it rapamycin, after the Polynesian name of the island Rapa Nui. And what was it doing in the soil. Well a bacterium in the soil there uses the compound to fend off competing bacteria and fungi. And since it's discovery, rapamycin has turned out to be a great help to humans as well. The drug acts as an immunosuppressant.

They give it to people who have organ transplants that help the body from rejecting the organ transplants of a donor organ or bone marrow, stuff like that. But a study in the journal Nature this week suggests that rapamycin has another effect, prolonging life, in mice at least. When scientists gave the drug to old mice, that in human terms would have been eligible for social security, the mice had a 28 to 38 percent increase in lifespan. How did that happen? What does it mean for we human beings? That's what we're going to be talking about for the first part of this hour. Our number 1-800-989-8255. You can tweet us. Tweet sign is @scifri. Let me introduce my guest. David Harrison is professor at the Jackson Lab, that's a very famous mouse research institute at Bar Harbor, Maine. He joins us by phone. Welcome to SCIENCE FRIDAY, Dr. Harrison.

Dr. DAVID HARRISON (Professor, Jackson Lab): Thank you.

FLATOW: This is - was - dramatic results. They weren't just maybe results. These are very dramatic results.

Dr. HARRISON: We were surprised that how strong the effect was, considering how late it was done. It's important that, at this point, I point out that this is a big NIA program, not just me.

FLATOW: Mm-hmm.

Dr. HARRISON: But three co-equal PIs myself, but also Miller(ph) in Michigan and Strong(ph) at Texas and also Nancy Nadeau(ph) at the NIA. If I just may say another proof thing about it: For people who have compounds that they think have a good strong scientific reason for being tested for anti-aging effects in mammals, check out the Web site to send the article. We're still collecting compounds, we're still doing tests. So far, we've completed lifespans only on the first set of eight compounds and rapamycin has been the only one that was really effective. But we hope to find more.

FLATOW: And, oh, so you're collecting compounds, that's good to know. Let's also, let's talk about rapamycin because you, it almost was sort of an accident at the time of life of the mice, right?

Dr. HARRISON: That's correct. Rapamycin, we were testing because of its beneficial effects on lifespan in simpler, shorter lived organisms, yeast models and also fruit flies and nematodes. But when we aspired to put it in the mouse food we found it was destroyed by the palating process. And Strong of Texas developed an encapsulation method. Unfortunately it took about a year to develop, develop and prove it and make sure everything was working properly. And so the mice which we intended to start at approximately eight or nine months of age were...

(Soundbite of laughter)

FLATOW: Pretty old ones.

Dr. HARRISON: 20 months of age.

FLATOW: 20 months.

Dr. HARRISON: That's equivalent to about 60 in human terms. And so the question was should we even bother to use them. Well, you know, we'd already spent almost all the money on the experiment just getting them to 20 months of age. So we did use them and it turned out really to our gratification that this is a large effect. The 28 percent, 38 percent increases that you gave, that was the increase from 600 days of age.


Dr. HARRISON: If you use the most rigorous method looking at the total lifespan, to the maximal lifespan, the age of 90 percent mortality, when only 10 percent are alive, then the effects are, of course, smaller because you're looking at the percentage of the whole lifespan not since 600 days.

FLATOW: Right.

Dr. HARRISON: Males it's 9 percent, females 14 percent.

FLATOW: Mm-hmm.

Dr. HARRISON: But these are still very...


Dr. HARRISON: ...large increases by comparison with what one would expect from curing diseases in people.

FLATOW: All right, if this were equivalent to people with a lifespan of 70, you've increased it over 14 percent, you're talking almost 80 years old.


FLATOW: Wow. And…

Dr. HARRISON: It's approximately a 10-year increase in lifespan for healthy people. And it's a healthy lifespan. It's important to remember, these are mice. These mice don't need to go to in the hospital and have IV feeding or any fancy stuff...

FLATOW: Right.

Dr. HARRISON: ...they basically are humanely euthanized when they become seriously ill. So as the mice are living, they're alert. They're paying attention what's going in around them. They're able to stand up and use their strong jaws to chew on those hard pellets to get their food.

FLATOW: Mm-hmm.

Dr. HARRISON: And they keep themselves reasonably well groomed.

FLATOW: So let's not jump too quickly to humans then.

Dr. HARRISON: Oh, well I'm jumping - I'm being anthropomorphizing and saying the mice are in pretty good shape during the time that they're living if they get - to a condition in a human where they'd have to go into an intensive care or even a nursing home. We would probably humanely euthanize them.

FLATOW: Mm-hmm. How does - do we know how it makes them live longer, what it does?

Dr. HARRISON: That's a very important thing. We know that rapamycin acts on the TOR pathway. TOR is simply meaning target of rapamycin. This is an important one of many important biochemical pathways in mice and in people and for that matter in fruit flies and nematodes and yeast. So in this important pathway we know what the specific enzyme that's targeted. And we know the by targeting that enzyme, by reducing the function of that enzyme, protein synthesis is reduced and so proliferation is reduced. And we also know, because this is used in people, rapamycin is used in people as a drug to prolong organ grafts, to reduce or prevent rejection of organ grafts, we know that it has anti-immune effects.


Dr. HARRISON: We don't know however were those anti-immune effects the reason that they live longer or was there - were there are effects. Rapamycin, as I say, it reduces protein synthesis generally. It's important in pathways.


Dr. HARRISON: That we - that have a lot of effects on the different physiological systems and the next step here is to test which physiological systems…

FLATOW: Right.

Dr. HARRISON: …being changed. That may actually be the key changes that are increasing the lifespan.

FLATOW: Are there enough people who are organ recipients, who take this drug that you could get a population and see if they're living longer?

Dr. HARRISON: Very good question and my answer is I don't know.

(Soundbite of laughter)

Dr. HARRISON: Of course it's not, it's not population that's healthy obviously they had their organ transplant. So it would take sophisticated medical statisticians and demographers, but I'm hoping that people who are capable of doing this have an access to the data are looking right now to see if human beings who've been taking rapamycin for other purposes for long periods of time are showing any potential anti-aging benefits, which would be of course a reduction…


Dr. HARRISON: …in risk of death from a wide range of things other than what's wrong with them.

FLATOW: Well, the thing is, you know, we talk about expanding life and if you cure one disease then another disease is going to get you.

Dr. HARRISON: Exactly.

FLATOW: Is that what is happening here or not happening.

Dr. HARRISON: Well that's a very good point. A characteristic of aging is that vulnerability to most causes of death increases exponentially. That means in people, your chances of dying of a wide variety of things double every eight or nine years, after age 30. And what seems to be happening here is that we're protecting against a wide variety of different causes of death. Now, how do I know this? Because we're using mice that die of a wide variety of different causes of death. They're intentionally genetically highly diverse. In that case, maximum lifespan integrates all the different causes of death. So if we increase maximum lifespan, they didn't die of a large variety of these things. We postponed death from a large variety of things and that's what makes us think we may have, in rapamycin, a drug which actually retards basic mechanisms of aging.

FLATOW: Wow, that's - that would be something. A fountain of youth in the soil of Easter Island.

Dr. HARRISON: It's not exactly the fountain of youth. I mean 10 years is nice. What we hope is that this is just the foundation of setting up a whole range of different treatment, different anti-aging treatments, that will be synergist and effective and maintain health. Because really, when you think about it, the human lifespan, you spend the first, like, 30 years getting started. Then after about 30 more years, you begin to decline in health.

FLATOW: Tell me about it.

(Soundbite of laughter)

FLATOW: So you're not even talking about it - not fighting disease, heart disease, cancer or things like that. You're increasing just longevity, which fights all those diseases at once, if I hear you.

Dr. HARRISON: Exactly right because all the things that double, all the chronic diseases that double every eight to nine years, if you can alter aging, successfully (unintelligible) aging, you extend the healthy lifespan really much more effectively than success in preventing one disease.

There's actually a statistic that people, if you're protected from all atherosclerosis, which is a common cause, most-common cause of death, of all cancers, which is the second-most-common cause of death in the aging human population, if you prevent all those deaths, your average increase in lifespan will only be about 10 years, roughly the same as the effect here of rapamycin alone.

And so why is that? Well, it's because as you get older, your chances of dying of every other problem - diabetes, osteoporosis, organ failures of any organ, Alzheimer's and Parkinson's Disease and so forth - double every eight to nine years. And so the benefits of curing those major things isn't as large as you might expect. On the other hand, success in retarding aging would extend health life-spans very effectively because it would retard all the - or a large, large subset of specific diseases.

FLATOW: Now what do you need to do to advance this to where we might find it helpful to people?

Dr. HARRISON: Oh, the first thing is exactly what you suggested, and I hope that's going on now. People need to look and see if there's any strong evidence in human beings already taking the stuff.

The second thing is also, I know it's going on now, and that is in mouse models to look for what may be the basic mechanisms. I mean, is this stuff, for example, by slowing cell proliferation, is it protecting the stem cells against running out of proliferative capacity? By reducing immune response, is it protecting against the chronic inflammation, which may cause the danger? By reducing cell proliferation, is it protecting against a wide variety of cancers? We just don't know yet.

FLATOW: What's to prevent people, since this is a commonly available drug by prescription, from people going out and finding it and taking it themselves now?

Dr. HARRISON: I hear rumors that there are people doing that, but I'm not. I mean, I'm - I'll tell you why I don't do it. I'll put it in a personal way. At 67, I wish I was as healthy as I was when I was 40, just like all of us who are getting older. I don't take it for the following reason.

I know rapamycin has strong biological effects. And when you have something with strong biological effects that are both harmful and helpful, and in order to take it to do something like an anti-aging treatment, you have to make sure the balance of benefit is stronger than the deleterious effects.

Since I don't know what the optimal dose will be, I don't know what the optimal schedule of doses would be, I don't know what kinds of markers to test to make sure it's helping me in anti-aging and make sure it's not hurting me in other ways. I fear the chances of it doing harm is actually greater than the chance of it doing good, so I'm not taking it, and I would advise that of other people, as well.

FLATOW: David Harrison, thank you very much for taking time to be with us today, and good luck to you. We'll be following this research.

Dr. HARRISON: Thank you.

FLATOW: Dr. Harrison is a professor at the Jackson Laboratory and Research Institution in Bar Harbor, Maine. We're going to take a short break, and we're going to talk about food. David Kessler is here. He's going to talk about his new book. Stay with us. We'll be right back after this break.

(Soundbite of music)

FLATOW: I'm Ira Flatow. This is SCIENCE FRIDAY from NPR News.

Copyright © 2009 NPR. All rights reserved. Visit our website terms of use and permissions pages at for further information.

NPR transcripts are created on a rush deadline by Verb8tm, Inc., an NPR contractor, and produced using a proprietary transcription process developed with NPR. This text may not be in its final form and may be updated or revised in the future. Accuracy and availability may vary. The authoritative record of NPR’s programming is the audio record.