The quest for a youth pill -

The quest for a youth pill

Why scientists think they have one, and why you can’t get it


Jodi Hilton/Getty Images

Award-winning journalist David Stipp has been writing about science and medicine since 1982, first at the Wall Street Journal and then Fortune magazine. In his new book, The Youth Pill: Scientists at the Brink of an Anti-Aging Revolution, he explains that slowing down aging is no longer a fantasy. After centuries of such anti-aging “remedies” as injecting minced dog testicles, scientists have recently discovered compounds that could dramatically extend human longevity and health.

Q: What’s the brass ring in anti-aging research?
A: The near-term, totally feasible prospect scientists are working toward is the development of a safe drug that delays by seven or eight years the onset of diseases associated with aging. The goal is to slow the rate of aging and postpone all the bad stuff: Alzheimer’s, cancer and heart disease are the three main killers, and then there are lesser diseases, from osteoporosis to cataracts. A true anti-aging drug would also extend maximum lifespan.

Q: As you explain in your book, scientists already know how to do all that in animals: cut their caloric intake by a third and they live 30 to 40 per cent longer than animals on a regular diet.
Calorie restriction (CR) revs up antitoxin defences, and that’s probably at the heart of why it has been shown, very robustly, to work across a wide range of species. The theory behind it is that if there’s less food, animals eat whatever they can get, including poisonous stuff. The only way you’re going to survive that is if you’ve got all these forces in play that fend off free radicals and everything else that basically makes you get old and sick. You can’t look at CR without thinking, “Evolution has built this mechanism into the genome.” From a natural selection point of view, it makes a great deal of sense to install a special device in the genome of many animals that would let them go into slow aging mode when food is scarce: they can hunker down and wait until the famine’s over to reproduce, therefore improving the chances their genes will be carried on.

Q: Doesn’t CR make them less healthy?
The opposite seems to be true. One study of rhesus monkeys showed those on CR had greater lean muscle mass, significantly less age-related brain atrophy, half as much cancer and half as much cardiovascular disease as those on normal diets. And when pathologists examined the tissues of calorie-restricted rodents after death, in a fourth to a third of the animals, there were no visible signs of severe age-related diseases. It’s as if they lived to ripe old ages then suddenly dropped dead without any terminal decline at all.

Q: Does CR work in humans?
It hasn’t been proven, so it’s not a sure bet, but it seems to me that it should work given everything we know about what it does in other species. However, it’s very tricky to get all the nutrients you need, and there are risks. CR affects fertility, for one. The first downside is hunger. I tried CR and lasted a little over two days. I couldn’t get any work done. I was thinking about food all the time.

Q: I guess that’s why scientists are focusing on finding compounds that mimic the anti-aging effects of CR, minus the unpleasantness. How promising is resveratrol, a compound found in red wine and peanuts, as a CR mimetic?
The most exciting data come from two studies of rodents on high-fat diets. The decline normally associated with that kind of diet didn’t happen to the mice on resveratrol: their livers didn’t get filled up with fat, their hearts seemed to be protected better. Several other studies suggest that high doses of resveratrol can cause formation of new mitochondria, which are these little power plants in all of our cells. There’s a lot of previous research suggesting that your mitochondria getting flaky is at the very root of what makes you get old—maybe not the whole story, but a very major part of it. So if resveratrol causes formation of mitochondria, it’s probably what accounts for those videos we’ve seen of mice on high doses being able to run on treadmills a whole lot faster and farther than mice that haven’t taken it. The implication is that even if resveratrol doesn’t extend lifespan, it might extend health span.

Q: Does resveratrol extend the lifespan of mice on normal diets?
In a 2008 study, no. But there were some signs that resveratrol was slowing aging, so the conclusion from that study was that it might be a “partial” mimic of CR.

Q: In the new issue of Nature, there’s a study saying it may boost memory and learning ability, which would have applications in Alzheimer’s research.
If you look at the literature, there are still, all the time, promising findings coming out that suggest anti-aging benefits from this compound.

Q: In all the rodent studies, the dosage has been pretty high. Is it possible for humans to get a similar-sized amount of resveratrol just from some dietary changes?
No, you simply couldn’t drink enough red wine without pickling your liver. You’d have to take resveratrol supplements. But I want to stress that while the data on resveratrol are very exciting, its potential benefits haven’t been pinned down in human studies.

Q: Have there been any human studies at all on its potential anti-aging benefits?
Preliminary data have been reported from clinical trials on diabetics, and they have some anti-aging implications. There’s some early evidence that resveratrol can help diabetics keep their glucose down, which would have major long-term benefits in terms of heart disease, for instance.

Q: Are the scientists studying resveratrol so convinced it works that they take supplements themselves?
Some of them do. Personally, though I have made some dietary changes to try to get more of it, I do not. The dose, safety and efficacy haven’t yet been studied sufficiently for me to feel comfortable taking supplements. And I worry about just wasting my money.

Q: What are the safety concerns?
Some researchers feel it poses a risk of cancer, although the bulk of the science indicates that it can help prevent cancer. And like any agent, there’s the concern that if you take very high doses, you’re going to get strange, unexpected side effects.

Q: The most exciting drug you write about is rapamycin, which is already prescribed for humans, typically for transplant recipients. What do rodent studies show?
Last year, researchers reported that when 20-month-old mice—roughly equivalent to 60-year-old humans—started taking rapamycin, their life expectancy, from the time the drug was administered, increased by 28 per cent for males and 38 per cent for females.

Q: That’s even better than CR, right?
When CR is started at an advanced age it doesn’t have this kind of dramatic effect.

Q: Is there other good news about rapamycin?
A study reported in April showed that chronic, long-term doses prevented Alzheimer’s-like cognitive losses in a strain of mice that are prone to a brain disease resembling Alzheimer’s.

Q: In the anti-aging study, were the mice who got rapamycin healthier at the ends of their lives than those in the control group?
No, they died from the same basic range of diseases as the controls, but at a much advanced age. The basic conclusion you could draw is that it postponed the onset of their diseases of aging.

Q: Does anyone know what happens if you give rapamycin to even younger mice?
The U.S. National Institute on Aging is now testing three different oral doses of the drug for anti-aging effects in mice beginning at nine months of age, which for people would be like initiating doses at about age 30. It will take a couple of years to complete this study, maybe longer if the mice wind up aging extraordinarily slowly.

Q: Since rapamycin is already prescribed for humans, it seems like it must be relatively safe.
At the kind of doses transplant patients take, common side effects are that cholesterol levels can rise and rapamycin can cause inflammation of oral mucous glands, neither of which is considered very serious. It’s also been linked in rare cases to a potentially dangerous inflammation of the lung. At higher doses, it sometimes engenders serious side effects, such as suppression of blood platelets, which are needed to form clots when we cut ourselves. What I find most intriguing about the drug’s side-effect profile, though, is what it doesn’t do. Rapamycin supposedly helps prevent the immune system from attacking transplanted organs and causing them to be rejected. It stands to reason that an immune inhibitor should increase the risk of cancer. After all, one of our immune system’s main jobs is wiping out precancerous cells before they start multiplying out of control and forming tumours. But rapamycin does just the opposite—it has been shown to ward off cancer. This suggests that the main argument against the idea of trying rapamycin as an anti-aging drug—that it causes dangerous immune suppression—needs to be rethought.

Q: Is that the only barrier to clinical trials in humans?
No. The main barrier, as with all anti-aging research, is that there’s no funding. We’ve got ever more promising basic research and yet I don’t know of anybody funding clinical work on agents that will possibly slow aging.

Q: Why aren’t pharmaceutical companies all over this?
There’s no economic incentive. A single drug in clinical development generally costs around a billion dollars, from the very beginning to the end. A pharmaceutical company can only afford to spend that kind of money on trials of something it knows it can sell as a prescription drug, with a pretty high profit. The issue here is that you can’t sell something as a prescription drug unless the Federal Drug Administration recognizes that there’s an indication for it. And the FDA does not consider aging a disease, so it wouldn’t give regulatory approval to a prescription drug used to treat aging.

Q: But since rapamycin is already prescribed, wouldn’t clinical trials testing anti-aging benefits in humans be less expensive?
Somewhat, because we have a pretty good handle on its side effects—though not a great handle, because the research has been done on people who are extremely sick, transplant patients, not healthy people. So there would still be substantial costs and again, even if you had that money, you could never sell rapamycin as a prescription drug for aging.

Q: Why isn’t the nutraceutical industry doing the research?
The profit margin on supplements simply isn’t big enough to support the clinical research you’d have to do to prove that something works in humans. First off, there’s a tough scientific nut to crack. Nobody is going to fund a study that goes on for 50 years, to see whether a drug actually does extend human lifespan. So scientists need to develop “biomarkers” of aging, which basically indicate how fast a person is going downhill. If reliable biomarkers were developed, then you could do fairly short trials. It would be the same logic used when testing cholesterol drugs to prevent heart attacks: you don’t wait 20 years to see whether heart attacks are really averted—at this point you basically just see whether LDL cholesterol has been lowered, and say, “Okay, that’s our proxy for lower heart attack risk, the drug works.” You could do the same thing with the biomarkers of anti-aging if scientists had them.

Q: Are there any ideas about where to start looking?
Yes. The longest study on the effects of aging is the Baltimore longitudinal study, which has been going on for decades. A few years ago, they looked at the people who lived the longest, and one thing that jumped out in the research, so it might be correlated with a long healthy life, is low insulin levels. Insulin tends to rise as you get older, regardless of your diet, regardless of whether you’re prone to diabetes. But apparently people whose insulin stays very low, youthfully low, tend to live a long time. There’s a lot of other science that would suggest that indeed, low insulin is closely associated with slow aging. So one biomarker might be just to look at insulin levels over time among the people taking a drug that supposedly slows aging. If it keeps insulin levels down, that would be one indicator it works—though obviously you’d need more. Establishing reliable biomarkers would take a lot of research, and unfortunately right now that research isn’t being done. We need someone with very deep pockets, such as the U.S. National Institutes of Health, to step forward to sponsor it.

Q: How much is the U.S. government currently spending to research the biology of aging?
In recent years, the National Institute on Aging has spent about $200 million annually, which is about one-fifth of its budget. But much of that is spent on studies about specific diseases rather than on research about the fundamental study of aging. In contrast, the National Cancer Institute’s annual budget is about $5 billion.

Q: Why haven’t anti-aging researchers been more successful at marshalling resources?
In a nutshell, the world of medical science doesn’t recognize what’s happened in the research on gerontology. Partly it’s because the anti-aging field has historically been an area rich with snake oil and con artists, and partly it’s because aging is extraordinarily complicated—so much so that unlike diseases, many biologists felt that figuring out exactly what was driving it was a hopeless cause. To a large extent, that’s how the FDA and many physicians still think about anti-aging research. People just don’t know how far the science has come and how promising it is.

Q: How far away do you think we are from human studies on drugs like rapamycin?
It’s very hard to answer. If you could successfully lobby Congress for increased funding—not necessarily for clinical research but for the basic research on biomarkers, which you’d need first—I would think you could hope to be in clinical trials in 10 years. In the best of all possible worlds, I would not be surprised if within 20 years there were some pretty well-established agents on the market that could slow aging. Whether we’ll get there in that time frame is anybody’s guess. It all depends on the politics.

Q: Aside from the cost, why would politicians oppose anti-aging research?
There’s great concern that anti-aging drugs will lead to drooling, demented seniors littering the landscape. But the interventions known to reliably slow aging in animals don’t prolong a period of terminal decline. At worst, they merely postpone it.

Q: So as a society, we’d still have to pay for a senior who gets a disease, we’d just have to pay a few years later?
That may well be true. But isn’t that the whole point of medicine, to buy us more quality time?


The quest for a youth pill

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  3. I see no particular benefit to extending maximum life span.

    • What is your " maximum" life span?

    • You see no particular benefit from living longer?

      Is "not being dead" not a "benefit"?

    • I see no particular benefit to extending maximum life span.

      It's easy to be philosophical about the pros and cons of extending maximum life span…. until one starts thinking about one's own lifespan. Then the benefits become self-evident. As Lord K has already alluded to, the state of "undeadness" is a highly desirable one to be in.

    • It's been four days now. Are you still breathing?

  4. Why do many of our politicians go to the USA for health problems? a] because they can afford it, b] health care is in general better and available in its full spectrum. Not so in Canada by a long shot. In Ontario PET scans are not part of your health plan.Some cancer drugs,used in most countries in the western world and approved by Health Canada, are not available in Ontario.
    The point of the above is: If you have the money for first class health care,you will live longer, every else being the same.Would you not rather go to the Mayo Clinic for cancer treatment than to your local Health Care Center?
    Fund allocation is another problem.Some piggish people get their stomachs stapled.[Instead of their mouths]. Is overindulgence a disease?What germ or virus causes it?
    I suspect we spend more health care money on pregnancies and child birth than on cancer care. [Since when is a pregnancy considered a disease or illness?]
    Even if there were a drug that extended your life span,it would not be available to the common man,since it would bankrupt the pension plans in a few decades.
    In the meanwhile we can live our lives starving ourselves,hoping for less disease and a longer life.Is it really worth it? You decide!

  5. I live in NS. Am a 7 yr. survivor of Stage IV cancer. Have rec'd excellent and timely treatment, including a PET scan. Been through 2 chemo sessions and am still monitored via CT scans, etc. But, told hubby not sure I'd go through it again. I'm not worried about dying, even tho I'm only 62.

  6. The point really is having an extended "healthy" lifespan. I was born in February of 1932. Through ignorance and industry propaganda I discovered all the great new taste sensations and speedy ways to ingest the toxic elements that make up most of the convenience, snack, and 'treat' stuff that passes as food. Result? Digestive problems, constipation, diverticulosis, and finally a triple bypass in 1998. Have since come back to pretty robust health with very minimul medication by making changes in diet and using some breakthroughs in whole food technology. I look forward to an extended enjoyable lifespan. (am now 78) I try to spread the word and provide the means to help others by providing the information and back up research for anyone interested enough to look at The proof is there. Live longer, finish stronger.

  7. That was an interesting Q&A and people should check out David Stipps recent posts on resveratrol and David Sinclair. i've agreed with his reasoning since the Pfizer story broke and was surprised by those who claimed to be scientists who assumed Sinclair's work was all bogus, ignoring the 3000 studies showing efficacy with resveratrol. If resveartrol directly affected SIRT 1 but not the GSK compounds, then there might be a serious concern. That isn't the case, though.

    Still, I wonder why Mr. Stipps thinks youth pills are 10 to 20 years away when those in the field seem to expect them sooner.

    Westphal who cofounded Sirtis thought 5 to 7 years last year. This is what he said thin April:
    " Will Sirtris be successful? I don't know. It's still going to be very risky. But I'll be shocked if there are not drugs in the next 10-15 years that target gene that control aging.”

  8. I'm less concerned about how long I live and more concerned about the happiness I experience while I'm alive. I'd prefer not to take a pill for happiness when the people around me…family, friends, colleagues…are sources of so much joy.

  9. "Injecting minced dog testicles"? What on earth could that possibly do? And who volunteered for that experiment?

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  11. Sounds like we need to lobby the government to label aging a disease, so that pharma companies could sell a drug to combat it. Would everyone join a Facebook group demanding this, if I started it?