Aging Mice Rejuvinated

Mice - Not related to the story, I just like the picture...

Mice - Not related to the story, I just like the picture...

Original image

From the “WOW” department.

Telomeres are the controls on gene lifetime. As cells divide, the telomers on the end of genes get shorter. Eventually they cause the cell to no longer divide, the cell is aged, and with it all the rest of the organism.

These folks gave a drug to some mice with artificially shortened telomeres and reversed several symptoms of aging.

Yeah, a thousand and one reasons why it might not work out as well in people, but… The potential of this is astounding…

From:

http://online.wsj.com/article/SB10001424052748703785704575642964209242180.html

The study was published online Sunday in the peer-reviewed journal Nature.

“These mice were equivalent to 80-year-old humans and were about to pass away,” says Ronald DePinho, co-author of the paper and a scientist at Dana-Farber Cancer Institute in Boston. After the experiment, “they were the physiological equivalent of young adults.”

The institute is a teaching affiliate of Harvard Medical School. The first author of the study is Mariela Jaskelioff at Dr. DePinho’s lab.

I have no idea if the original Nature article is available or behind a paywall. Somehow I think this is going to be a big big deal…

The researchers had devised an estrogen-based drug that would switch on the animals’ dormant telomerase gene, known as TERT. The drug, in the form of a time-release pellet, was inserted under the skin of some mice. A similar pellet without the active drug was given to a separate group of control mice.

A month later, the treated mice showed surprising signs of rejuvenation. Overall, their telomeres had lengthened and the levels of telomerase had increased. This woke up the dormant brain stem cells, producing new neurons. The spleen, testes and brain grew in size.

In addition, key organs started to function better. The treated mice regained their sense of smell. The male animals’ once-depleted testes produced new sperm cells, and their mates gave birth to larger litters. The treated animals went on to have a typical lifespan, though they didn’t live longer than normal mice.

The reversals of age-related decline seen in the animals “justify exploration of telomere rejuvenation strategies for age-associated diseases,” the paper concludes.

The biggest question here is raised by that line about “didn’t live longer than normal mice”. Does this drug reverse normal aging? Or does it only fix the artificially induced aging in these mice?

One worry is cancer. Tumors somehow turn on the telomerase gene, allowing cancer cells to divide continuously. Up to 90% of human cancers require certain levels of telomerase to do so. Indeed, many researchers are trying to deactivate telomerase as a cancer-fighting strategy.

Still, turning on telomerase for controlled periods of time might be useful. The strategy might one day have a role in treating rare genetic disorders that are linked to telomeres and cause premature aging, such as Werner’s syndrome, according to Dr. DePinho.

The telomerase technique may also be relevant for people who age normally—provided it is clear that prolonged telomerase reactivation doesn’t trigger tumors in later life.

Pardon me, but if I’m 75 and miserable with maybe 3 years lifespan ahead of me and I can take a drug that makes me, oh, like 40 again (but I die of a rapid cancer in 5 years) I’m more than willing to make that deal.

Statistically, people with longer telomeres in their blood cells have an increased number of healthy years beyond the age of 60, Dr. DePinho said. And those over 60 with the shortest telomeres have higher rates of diabetes, cardiovascular disease and Alzheimer’s.

Dr. DePinho said the next step was to try the technique on normally aged mice to see whether it can slow, halt or reverse signs of aging in them.

Write to Gautam Naik at gautam.naik@wsj.com

I found this article in “Nature News” but I’m not sure if that is “Nature” or not…

http://www.nature.com/news/2010/101128/full/news.2010.635.html

It has a link to a ‘full article’ which requires payment here:

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature09603.html

so I presume the “Nature News” is the freebee teaser publication…

It has the following abstract:

Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice

Mariela Jaskelioff1, Florian L. Muller1, Ji-Hye Paik1, Emily Thomas1, Shan Jiang1, Andrew C. Adams2, Ergun Sahin1, Maria Kost-Alimova1, Alexei Protopopov1, Juan Cadiñanos1, James W. Horner1, Eleftheria Maratos-Flier2 & Ronald A. DePinho1

Belfer Institute for Applied Cancer Science and Departments of Medical Oncology, Medicine and Genetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
Division of Endocrinology, Diabetes & Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA

Correspondence to: Ronald A. DePinho1 Email: ron_depinho@dfci.harvard.edu

An ageing world population has fuelled interest in regenerative remedies that may stem declining organ function and maintain fitness. Unanswered is whether elimination of intrinsic instigators driving age-associated degeneration can reverse, as opposed to simply arrest, various afflictions of the aged. Such instigators include progressively damaged genomes. Telomerase-deficient mice have served as a model system to study the adverse cellular and organismal consequences of wide-spread endogenous DNA damage signalling activation in vivo1. Telomere loss and uncapping provokes progressive tissue atrophy, stem cell depletion, organ system failure and impaired tissue injury responses1. Here, we sought to determine whether entrenched multi-system degeneration in adult mice with severe telomere dysfunction can be halted or possibly reversed by reactivation of endogenous telomerase activity. To this end, we engineered a knock-in allele encoding a 4-hydroxytamoxifen (4-OHT)-inducible telomerase reverse transcriptase-oestrogen receptor (TERT-ER) under transcriptional control of the endogenous TERT promoter. Homozygous TERT-ER mice have short dysfunctional telomeres and sustain increased DNA damage signalling and classical degenerative phenotypes upon successive generational matings and advancing age. Telomerase reactivation in such late generation TERT-ER mice extends telomeres, reduces DNA damage signalling and associated cellular checkpoint responses, allows resumption of proliferation in quiescent cultures, and eliminates degenerative phenotypes across multiple organs including testes, spleens and intestines. Notably, somatic telomerase reactivation reversed neurodegeneration with restoration of proliferating Sox2+ neural progenitors, Dcx+ newborn neurons, and Olig2+ oligodendrocyte populations. Consistent with the integral role of subventricular zone neural progenitors in generation and maintenance of olfactory bulb interneurons2, this wave of telomerase-dependent neurogenesis resulted in alleviation of hyposmia and recovery of innate olfactory avoidance responses. Accumulating evidence implicating telomere damage as a driver of age-associated organ decline and disease risk1, 3 and the marked reversal of systemic degenerative phenotypes in adult mice observed here support the development of regenerative strategies designed to restore telomere integrity.

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About E.M.Smith

A technical managerial sort interested in things from Stonehenge to computer science. My present "hot buttons' are the mythology of Climate Change and ancient metrology; but things change...
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4 Responses to Aging Mice Rejuvinated

  1. j ferguson says:

    E.M.
    The potential for offspring of a 75 year old is very worrisome.

  2. Gary P. Smith says:

    Great! There goes Social Security down the drain.

    Didn’t Heinlein or Asimov write a novel about this?

    Can you spell “Soylent Green”. ;-)))

  3. E.M.Smith says:

    One is left to wonder how long it will take for an underground market in TERT to develop… The ‘summer of love” generation is used to buying ‘stuff’ from the ‘informal’ markets, and that was in the 1960s, so if they were 20 ish then, they are about 65 now…

    As someone with an 86 year old mother-in-law who is in serious need of such things as better ability to stand, walk, dress, think, and feed herself: I can see a great deal of advantage to even low dose therapies.

    Oh, and the reduction in costs on Medicare / Medicaid ought to cover the added costs to longevity. As it stands now “granny” is running about $5000 a month for nursing care and an added hospital run a month or so (figure a grand or two…) to the big hospital. That’s far more than the SSI check.

  4. Terrence says:

    I have seen some clinical studies regarding elderly folks who took up relatively light resistant weight training, three times a week for several months.

    I think Dr Doug McGuff (Body by science dot net) quoted some of these studies.

    As I recall, one study only had people who used walkers or wheelchairs. The result was that ALL the participants give up their walkers or wheelchairs; they ALL regained ALL their mobility.

    The other studies had similar results, with most participants regaining their mobility.

    I think these results show that regular resistant training returns and/or maintains mobility in the elderly (use it or loss it). I think this is far preferable to having old folks take even more drugs.

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