Epithalon file, Professor Ronald DePinho

dossier-depinho-epitalon-agag-telomere2Professor DePinho became famous thanks to its scientific study that showed, the first to be published in Nature, the transformation of mice under the action of telomerase. Old mices are reverted young after activating the production of telomerase in their cells.

It was highly publicized because it showed that the body and the organs of the mice regained their original shape, as in a young individual.

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# Extracts from Wall Street Journal :
“Aging Ills Reversed in Mice”

Previous experiments with calorie restriction and other methods have shown that aspects of aging can be slowed. This appears to be the first time that some age-related problems in animals have actually been reversed.

“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 experiment focused on telomerase, an enzyme that makes small units of DNA that seal the tips of chromosomes. These DNA units, known as telomeres, act like the plastic caps at the ends of a shoelace, preventing the chromosomes from fraying and the genes inside them from unraveling. In 2009, three U.S. scientists won the Nobel Prize in medicine for illuminating the mysteries of telomerase.

As people age, low levels of telomerase are linked to the erosion of telomeres. Dr. DePinho and his colleagues wanted to see if by reactivating telomerase in mice they could halt—or possibly reverse—the shortening of telomeres, and thus turn back the clock on some aspects of aging.

One 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.
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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.

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.

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# Extracts from The Harvard Gazette :

Researchers led by Ronald A. DePinho (above), a Harvard Medical School professor of genetics, say their work shows for the first time a dramatic reversal of many aspects of age-related degeneration in mice, a milestone in aging science achieved by engineering mice with a controllable telomerase gene.

With ageing in humans, low levels of telomerase are associated with progressive erosion of telomeres, which can then contribute to tissue degeneration and functional decline in the elderly. By creating mice with a telomerase switch, the researchers were able to generate prematurely aged mice. The switch has allowed scientists to determine whether the reactivation of telomerase in the animals would restore telomeres and mitigate the signs and symptoms of aging.

The work showed a dramatic reversal of many aspects of aging, including reversal of brain disease and infertility.

Telomere loss created a cascade of signals that cause the cessation of cell division or self-destruction, stem cells are retiring, the organes atrophy, and brain cells die.

Here for example the story on ABC channel, talking about the mice rejuvenated by Dr. Pihno, but as you can see they had less than 25,000 visitors, proving that the general public is kept uninformed, and believes that aging is a mandatory thing …

 

# ABC News, reverse aging in mice:
Click here to view on Youtube

renverse-aging-ABCStudy Suggests Scientists Reversed Age-Related Diseases in Mice

Scientists have turned back the clock in mice they engineered to age faster than normal, an advance they suggest is the first time aging in mice has been reversed.

Researchers at Harvard-affiliated medical centers genetically manipulated mice to age faster, and then used gene therapy to lengthen telomeres — compounds found at the ends of strands of DNA — which reversed age-related problems such as decreased brain function and infertility.

“We at best expected it to be a slowing of the process or perhaps an arresting of the process. We did not anticipate that it would be so dramatic a reversal in all of the problems that the animal was experiencing,” said Dr. Ronald DiPinho, professor of medicine and genetics at Dana-Farber Cancer Institute and Harvard Medical School, and co-author of the paper published Sunday in the journal Nature. “We were so struck by the findings that we rushed to get the study published.”

A human cell holds 23 pairs of chromosomes, each containing protective caps at each end called telomeres. Enzymes called telomerases protect the telomeres and reduce DNA damage thought to contribute to tissue aging. But as we age, our cells produce less telomerase; telomeres are cut shorter and eventually fail to protect DNA from damage.

Researchers boosted telomerase in the mice cells — which hold 20 pairs of chromosomes — to prevent telomeres from getting shorter. They found restoring the enzyme not only stopped aging but revived failing organs and even restored dark fur to mice who had turned grey. DePinho said the mice that were equivalent to ages 80 to 90 in human years returned to the equivalent of middle age.

“This research indicates there’s a point of return for these tissues,” said DePinho. “The fact that you can bring a tissue to the brink and then bring it back this dramatically is remarkable.”

Previous studies suggest that even in humans, shorter telomeres may be associated with age-related diseases such as heart disease and Alzheimer’s disease.

In fact, the brains of the age-modified mice were 75 percent of the size of a normal brain, much as happens in a patient with Alzheimer’s disease. But when researchers reactivated the telomerase, the brains returned to a normal size, according to the study.

The aging process is complex and telomeres are just one element that contributes to its course. But DePinho said this is one step in learning more about not only the slowing of aging, but also the reversal.

“Telomere dynamics in mice has taught us the role of telomeres in [diseases like] cancer and helped us better understand how to take advantage of these situations,” said DePinho.

 

# Video about this amazing experiment: