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The Curious Case of the Backwardly Aging Mouse
ScienceNOW ^ | 29 November 2010 | Jennifer Carpenter

Posted on 12/04/2010 10:06:50 AM PST by neverdem

Enlarge Image
sn-aging.jpg
Golden years. Mice without active telomerase (right) look much older than those with the enzyme (left).
Credit: Mariela Jaskelioff/Harvard Medical School

In F. Scott Fitzgerald's short story, "The Curious Case of Benjamin Button," an old man gets younger with each passing day, a fantastic concept recently brought to life on film by Brad Pitt. In a lab in Boston, a research team has used genetic engineering to accomplish something similarly curious, turning frail-looking mice into younger versions of themselves by stimulating the regeneration of certain tissues. The study helps explain why certain organs and tissues break down with age and, researchers say, offers hope that one day such age-related deterioration can be thwarted and even reversed.

As we age, many of our cells stop dividing. Our organs, no longer able to rejuvenate themselves, slowly fail. Scientists don't fully understand what triggers this, but many researchers suspect the gradual shrinking of telomeres, the protective DNA caps on the end of chromosomes. A little bit of telomere is lost each time a cell divides, and telomerase, the enzyme that maintains caps, isn't typically active in adult tissues. Another piece of evidence: People with longer telomeres tend to live longer, healthier lives, whereas those with shorter telomeres suffer more from age-related diseases, such as diabetes, Alzheimer's, and heart disease.

Several years ago, Ronald DePinho, molecular biologist and director of the Belfer Institute of the Dana-Farber Cancer Institute, and colleagues at Harvard Medical School in Boston genetically engineered mice to lack a working copy of the telomerase gene. The animals died at about 6 months—that's young for mice, which usually live until they are about 3 years old—and seemed to age prematurely. At an early age, their livers and spleens withered, their brains shrank, and they became infertile. By early adulthood, these mice exhibited many of the maladies seen in 80-year-old humans.

DePinho says he wondered what would happen to the aging process in these mice if they suddenly began making telomerase again. "Would [we] slow it, stabilize it, or would we reverse it?" He and his colleagues genetically engineered a new batch of mice with the same infirmity, but this time they added back a telomerase gene that became active only when the mice received a certain drug. The researchers kept the gene off during development and let these mice prematurely age, as the previous ones had. But then at 6 months, the team switched on the telomerase gene.

The burst of telomerase production spurred almost total recovery. The rodents became fertile, their livers and spleens increased in size, and new neurons appeared in their brains, the researchers reported online yesterday in Nature.

The ability to reverse age deterioration in the mutant mice indicates that the cells that divide to replenish tissues don't simply die when their telomere clock expires, says DePinho. They apparently persist in a dormant state from which they can be revived. "One could imagine applying this approach to humans," he says, focusing the therapy on specific tissue types such as the liver, where telomerase is thought to play an important role in regeneration after damage by hepatitis, parasitic infection, and alcoholism.

K. Lenhard Rudolph, who studies stem cell aging at the University of Ulm in Germany, says that the results are encouraging for people with diseases that cause accelerated aging, like progeria, because the mice in this study were rescued despite already suffering from the effects of chronic disease. "It is a proof of principle that telomeres are at work here."

Drug companies and researchers are seeking ways to restore, protect, or extend a person's telomeres, but the jury is still out on whether such interventions can slow the symptoms of aging, let alone reverse them. Telomere investigator Maria Blasco of the Spanish National Cancer Research Center in Madrid cautions that DePinho's experiment shouldn't raise people's expectations of antiaging therapies just yet. "This study uses genetically modified mice," she says. "What remains a very important question in the field is can you delay aging in a normal mouse?"

DePinho agrees with those concerns. He also warns that his approach has potential drawbacks, as increasing telomerase activity beyond its natural levels can cause cancer. Still, that may not be an insurmountable problem if telomerase levels can be carefully controlled. DePinho notes that the mice in his study, whose telomerase activity was returned to a natural level, didn't develop tumors.


TOPICS: Culture/Society; News/Current Events; Testing
KEYWORDS: adultstemcells; regenerativemedicine; telomerase; telomere; telomeres

1 posted on 12/04/2010 10:06:53 AM PST by neverdem
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To: neverdem

because the world needs younger mice.

heh.


2 posted on 12/04/2010 10:09:57 AM PST by GeronL
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To: Coleus; Peach; airborne; Asphalt; Dr. Scarpetta; I'm ALL Right!; StAnDeliver; ovrtaxt; ...

regenerative medicine ping


3 posted on 12/04/2010 10:11:47 AM PST by neverdem (Xin loi minh oi)
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To: neverdem

This should really ruin social security.


4 posted on 12/04/2010 10:15:50 AM PST by americanophile
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To: GeronL

I don’t see this as a positive for life on Earth. With the exception of cancer-like situations and car accidents...they’d be no life decrease. The population on the Earth in 300 years with this around would be a serious issue. Social Security? Well....we could make a rule that you could never retire, and you’d just keep working for the next 3,000 years. Maybe that’s the one positive if there were any.


5 posted on 12/04/2010 10:16:31 AM PST by pepsionice
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To: neverdem

Let’s hope they perfect this AFTER George Soros dies.


6 posted on 12/04/2010 10:17:15 AM PST by Hardastarboard (Bringing children to America without immigration documents is child abuse. Let's end it.)
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To: pepsionice

I doubt we would live for 3,000 years, at least with the same body. If the world were run properly (i.e. capitalism, free markets) we could support and feed a lot more people.


7 posted on 12/04/2010 10:19:18 AM PST by GeronL
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To: americanophile

Don’t you worry — our benign government will find a solution for it.


8 posted on 12/04/2010 10:22:52 AM PST by 353FMG (Soon, the peoples of the West will have to choose between ISLAM and their country.)
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To: neverdem

But they artificially aged the mice first, why???

Will these ‘younger’ mice actually have longer life spans than a normal mouse, or were they simply able to undo what they had done?

I can make someone healthy by ceasing to poison them, but that doesn’t make me a healer.


9 posted on 12/04/2010 10:23:35 AM PST by SampleMan (If all of the people currently oppressed shared a common geography, bullets would already be flying.)
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To: neverdem

Logan’s Mice


10 posted on 12/04/2010 10:24:41 AM PST by headstamp 2 ("My Boss is a Jewish Carpenter")
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To: neverdem

Hmmm.....
I’m opening me up a telomerase store....
Oh...and maybe a website....
oh, oh, oh, e-bay auctions once a day!!!!


11 posted on 12/04/2010 10:34:26 AM PST by G Larry (When you're right, avoid compromise!)
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To: americanophile

If that is the case then those who accept it will have to be prevented from collecting it.Perhaps insted of age it should be based on condition instead?Just a thought....


12 posted on 12/04/2010 10:37:36 AM PST by chris_bdba
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To: chris_bdba

Let’s try that again....If that is the case then those who accept social security can’t be alowed to take the drug.Perhaps social secuirty should then become conition based instead of age based?Just a thought...


13 posted on 12/04/2010 10:40:03 AM PST by chris_bdba
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To: neverdem

The people from Ork can explain how it works.


14 posted on 12/04/2010 10:43:30 AM PST by Jack Hydrazine (It's the end of the world as we know it and I feel fine!)
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To: SampleMan

It seems they were exploring the effects of Telomerase generally.

They created the defective mice to see what would happen, and that was interesting in itself, as they needed to create methods to manipulate the gene.

Then they did the reverse experiments to see what effects restoring Telomerase would have, the important point being that aged tissues are not permanently degraded and can be made to “come back”.


15 posted on 12/04/2010 10:46:45 AM PST by buwaya
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To: neverdem

16 posted on 12/04/2010 10:57:48 AM PST by SERKIT (TSA-Form 2 Lines: Irradiation or Humiliation)
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To: neverdem
Leave it to Harvard to take one step down the other brick road.

Hugh Downs, in 1998 reported on 20/20

The news is now out and it is astonishing," said Hugh Downs, co-host of ABC-TV's 20/20 program on January 16. "Researchers have discovered the mechanism that makes us age, and they claim they can slow it down."

The 20/20 show went on to tell the story of an eye-opening breakthrough by a California-based company, Geron Corporation, which was trumpeted around the world. The breakthrough involves the extension of the life span of normal human dividing cells in vitro by the introduction of the enzyme telomerase. Telomerase prevents telomere shortening, a process that has been described as the molecular clock that triggers senescence.

Telomeres are segments at both ends of gene-carrying chromosomes in the cell nucleus that maintain the integrity of the chromosomes. Normal dividing cells grow old and sluggish. Eventually they stop dividing because they lack telomerase to keep their telomeres from shortening, which weakens their chromosomes. Cancer cells, on the other hand, which have a plentiful supply of telomerase, continue dividing indefinitely, but are abnormal. The continuous, rapid division of abnormal cancer cells is a lethal process that leads, if unchecked, to the death of the organism.

"We believe that telomerase therapy will provide ground-breaking advances within the next 5 to 10 years for the treatment of the diseases of aging."

The treatment hasn't been implemented because of the societal implications.

17 posted on 12/04/2010 11:07:24 AM PST by Young Werther ("Quae cum ita sunt" Since these things are so!)
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To: pepsionice
I don’t see this as a positive for life on Earth. With the exception of cancer-like situations and car accidents...

...and heart disease, diabetes, communicable diseases...and murder and war. Extending the human lifespan isn't conferring immortality.

they’d be no life decrease. The population on the Earth in 300 years with this around would be a serious issue.

I don't believe so - raising children costs quite a bit of time and money no matter how long we live. Few people are going to look upon 300 years of healthy adulthood as an opportunity to spend 300 years making the sacrifices needed to raise children. Even in our world today, as life expectancy climbs towards 100 in the West, the birth rate is falling, not rising.
18 posted on 12/04/2010 11:09:10 AM PST by AnotherUnixGeek
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To: neverdem
Fortunately these sorts of experiments never result in unintended consequences.

(Young mouse mutation monster on left communicates its displeasure at being created to Will Smith)


Frowning takes 68 muscles.
Smiling takes 6.
Pulling this trigger takes 2.
I'm lazy.

19 posted on 12/04/2010 12:59:38 PM PST by The Comedian (Government: Saving people from freedom since time immemorial.)
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To: buwaya
Then they did the reverse experiments to see what effects restoring Telomerase would have, the important point being that aged tissues are not permanently degraded and can be made to “come back”.

But curiously, they didn't just start with old mice. I infer from this that it doesn't work on normally aged mice. Otherwise, why wouldn't that have been done?

So this study is opens a window to another window.

20 posted on 12/04/2010 2:14:23 PM PST by SampleMan (If all of the people currently oppressed shared a common geography, bullets would already be flying.)
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To: neverdem

The Chinese herbal “medicine” derived from astragalus root is reputed to have anti-aging effects. I believe the Chinese name for it actually means “hair stays black” or something along those lines. Maybe it has some effect upon telomerase.


21 posted on 12/04/2010 2:50:06 PM PST by RegulatorCountry
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To: 353FMG
Don’t you worry — our benign government will find a solution for it.

Nothing a few world wars can't take care of.[/sarcasm]
22 posted on 12/04/2010 3:19:00 PM PST by Sparticus (Tar and feathers for the first dumbass Republican that uses the word bipartisanship.)
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To: neverdem

Thanks for the ping.

Very interesting article...


23 posted on 12/04/2010 4:34:24 PM PST by Dr. Scarpetta
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To: SampleMan

They found a tool whereby they could manipulate Telomerase in the lab, this was the gene they were playing with.

They don’t seem to be able to reverse the Telomerase setting of a normally aged mouse as yet.

But if they figure out how to do this at some point, this experiment shows what can be achieved.

One step at a time.


24 posted on 12/04/2010 8:57:29 PM PST by buwaya
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To: neverdem

Man I wish they’d hurry up with this stuff, I’m not getting any younger.


25 posted on 12/05/2010 10:26:03 PM PST by bogusname (Banish All Liberals)
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