Tuesday, November 30, 2010

Jumping Head First into the Fountain of Youth

Jumping Head First into the Fountain of Youth
Go on, it'll knock 50 years right off your age. (Photo by JB London)

I don't know if you noticed, but yesterday a study on telomeres and aging hit the news big time. Various media bought into the hype, claiming that aging had been reversed in mice. Daily Mail, for example, published a story that begins as follows (link):

Have they found the elixir of eternal youth? Scientists reverse the ageing process in landmark trial

The secret of eternal youth has been unlocked by scientists in remarkable research that paves the way for a ‘forever young’ drug. Lives could be longer and healthier, free from illnesses such as Alzheimer’s and heart disease, with skin and hair retaining its youthful lustre. Such a drug might allow men and women to have children naturally until they are a ripe old age.

The secret of eternal youth, huh? And just in case you missed what that would be like, the writer states:

The experiments mirror the plot of the film The Curious Case of Benjamin Button, where the lead character played by Brad Pitt ages in reverse.

Except, of course, that Brad Pitt was born as an old man and eventually turned into a fetus and died, which is not exactly the kind of eternal youth I'm looking for. As you might guess, the paper and its authors are slightly less modest about the results – but only slightly. Professor Ronald DePinho, who did the mouse experiments, says:

In human terms, it would be like having a 40-year-old person who looked 80-plus and reversing the effects to the levels of a 50-year-old.

Reporters obviously love statements like this, but the truth behind the hype is somewhat different. First, mice are not humans, so drawing conclusions about what results from mice would mean "in human terms" without actually replicating the experiments in humans can be misleading.

Second, and more importantly, the mice were not normal mice: they were genetically modified to have no telomerase – which, in simple terms, lengthens telomeres – resulting in prematurely short telomeres and thus premature aging. The authors then gave the mice a drug that kickstarted telomerase, and lo and behold, many of the signs of premature aging began to reverse.

Thus, this is very far from giving the same drug to a healthy person and making them live forever. The rejuvenation in this case applies to the damage caused by having artificially short telomeres, not to all the other kinds of damage that comes with aging. This is precisely why the mice given the drug "become normal", so to speak, but were not rejuvenated in the sense that the whole "fountain of youth" metaphor might suggest.

If this were truly a fountain of youth, the mouse would have lived exceptionally long – but they didn't. They lived as long as normal mice.

While I'm glad that the attitude of the media towards life extension seems to be positive and even optimistic these days, the people writing these articles don't seem to have much grasp of reality when it comes to anti-aging science. I don't claim to be an expert, but even a quick glance at the abstract of the paper (link) would have shown that this is not only "ten years away from being available for sale", it's simply not directly applicable to healthy people.

What I found encouraging, however, was that the mice given the drug not only stopped accumulating more damage, but that their organs did indeed begin to rejuvenate. I say encouraging because it shows that aging damage can be repaired and not only slowed down – which is a crucial difference, because for most of us alive today to make it past 120, it will have to be repaired and not just halted.

Another positive thing about the study is that the mice whose telomerase was reactivated did not get cancer. Since one of the purposes of telomere shortening is said to prevent harmful mutations from spreading, many people worry that boosting telomerase may increase the risk of cancer. It would be interesting to see what the same drug does to normal mice.

For more information on anti-aging and rejuvenation, see these posts:

Aubrey de Grey Interview in Wired.com
Russian Scientist Claims to Have Found Cure for Aging
How Do People Feel about Life Extension?
Anti-Aging in the Media: The Independent on Immortality

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5 kommenttia:

US_Taxpayer December 1, 2010 at 4:59 AM  

Great find, great article. Glad to have a skeptic on our side.

Jon December 1, 2010 at 8:08 PM  

I want to clear a few things up about this post.

First of all, the reason telomerase was disabled in these mice is that telomerase is usually active in mice, but is not active in human somatic cells. You have to disable telomerase in mice to make them age in a way that resembles human aging (with graying hair, frailness, spontaneous malignancies, shrinking organs, etc.). If you don't disable telomerase, mice don't really "age" - they just die from accumulated oxidative stress after a few years. A mouse that lives out its full lifespan will generally die looking like a young, but sick, mouse.

So, knocking telomerase out in mice is necessary to even give us a model to study. Certainly, there are animals that (like us) age through telomere shortening; they include dogs, cats, and horses. But it's incredibly time-consuming, expensive, and a publicity nightmare to perform scientific tests on those kinds of animals.

Second, the statement that the mice "lived as long as normal mice" is inaccurate. Dr. DePinho's team sacrificed the mice for study after four weeks; they were not allowed to live to their maximum lifespan. (For the same reason, Dr. DePinho cautions not to read too much into the fact that the mice didn't show evidence of carcinogenesis; they weren't alive very long. But, there has been absolutely no experimental verification of the theory that telomerase activation causes cancer, and it's looking more and more likely that it wouldn't).

It's very probable, however, that even if they hadn't been sacrificed, the mice would probably have only lived to a normal age or even shorter - because, essentially, they were both aging like humans and rapidly dying of oxidative stress like mice. Dr. DePinho's team appears to have reversed the human-like aging that was introduced into the mice, but they made no attempt to deal with issues of normal mouse mortality.

JLL December 2, 2010 at 1:25 AM  


Thank you for the corrections, I appreciate it. I'll edit the post later - meanwhile, a few questions, if you don't mind:

Do you have access to the full paper or where did you find out the mice were sacrificed after four weeks? It was repeated in several of the news articles that the mice lived normal lifespans, e.g.

Wall Street Journal: "The treated animals went on to have a typical lifespan, though they didn't live longer than normal mice."

The abstract doesn't mention anything about it, though.

Second, I'm a bit confused about what you mean by "aging" here. Why is accumulated oxidative stress not a kind of aging? How would you define aging so as to encompass the human kind of aging but not the mouse kind of aging?

I'd also argue it's a bit of a stretch to say that humans age through telomere shortening; I would say it's part of aging but certainly not the sole cause. Or are you saying that replenishing telomeres alone would make humans live forever?


Falco December 2, 2010 at 8:41 PM  

Nice article. Life extention research desperately needs more media attention. Thanks for that.

Aubrey de Grey, through the SENS Foundation, has mapped all the area's related to human aging. You can find a nice overview here:


Jeffrey Dach MD December 8, 2010 at 3:11 PM  

There is really no need for genetic engineerin­g to activate telomerase as was done in the Depinho mouse model. There is about 20 years of research on Telomere activation­. There are two receptors for estrogen on the TERT gene which controls this process. Whether you happen to be a human being or a mouse, the best way to increase telomerase activity, lengthen the telomeres and reverse aging is with the human bioidentic­­al hormone, 17-Beta-Es­­tradiol, also known as estrogen. In 1999, Kyo demonstrat­­ed that 17-Beta-Es­­tradiol activates telomerase via direct and indirect effects on the hTERT promoter region. This was confirmed in 2000 by Silvia Misiti and again in 2009 by Rodrigo T. Calado from the NIH.

A recent December 2010 study from Imanishi from Japan showed that 17-Beta-Es­­tradiol (estrogen) augments telomerase activity, thereby accelerati­­ng recovery after injury and reducing the effects of aging (reducing senescence­­).

Natural substances such as resveratrol, gingko and silymarin also activate telomeres.

For more see:


regards, jeffrey dach md

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