November 29, 2010

By Brian Bujdos

Scientists have effectively reversed the aging process in some mice by working with a gene that activates the production of telomerase. Telomerase is an enzyme that makes small units of DNA that seal the tips of chromosomes. These seals are called telomeres, which the Wall Street Journal likened to the plastic caps at the ends of shoe laces, because they prevent chromosomes from fraying and the genes inside them from unraveling.

As people get older, their bodies do not produce as much telomerase, and this causes the tips of chromosomes (telomeres) to degenerate. This is one factor that causes people to age and generally become less healthy. Damaged telomeres cause cells to stop dividing, stem cells to become dormant, organs to atrophy and brain cells to die.

For instance, research shows that people with longer telomeres in their blood cells have an increased number of healthy years beyond the age of 60, according to Ronald A. DePinho, the lead author of the telomerase mice study. Conversely, people over the age of 60 who have the shortest telomeres display higher rates of diabetes, cardiovascular disease and Alzheimer’s.

Results of the important study appear this week in the peer-reviewed journal Nature. DePinho is a professor of genetics at Harvard Medical School and director of applied cancer science at the Boston-based Dana-Farber Cancer Institute. DePinho said the study produced results that were the equivalent of finding the famed fountain of youth – at least for the mice. He said future studies with mice should be undertaken, which could help provide more insight into the relevance of the study results for humans.

One concern that must be carefully researched is the possibility that the activation of telomerase (and more robust telomeres) could increase the chances of cancer. Although this was not the case for the mice in the study, cancer somehow activates the production of telomerase, which allows cancer cells to divide continuously.

It seems many cancer researchers are hard at work trying to discover how to deactivate the gene that causes the proliferation of telomerase – as this would decrease the proliferation of cancer cells in humans. Still, the study’s findings could indicate benefits to humans who have rare genetic disorders that are linked to telomeres, such as Werner’s syndrome, which causes humans to age prematurely. Even humans who age normally could benefit, but it is just too early to say for sure.

The researchers used genetically altered mice for their experiment. All of the mice had atrophied organs and testes, and small brains, among other challenges. The mice were the equivalent of 80-year-old humans, and the researchers said they were about to pass away.

After receiving the gene that activated telomerase, however, the treated mice showed surprising signs of rejuvenation after just one month. Their telomeres were longer and the telomerase levels increased. This aroused dormant brain stem cells, producing new neurons. The spleen, testes and brain grew in size. Key organs functioned better, and 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.

When it was all said and done, the treated mice went on to have a typical lifespan, but not longer than normal, non-genetically altered mice. Still, the mice were close to passing away, but showed amazing signs of rejuvenation that essentially made them younger and allowed them to live much longer.

The study authors stated that further, similar testing should be performed on normal mice that are not genetically altered. Research on telomerase/telomeres has taken off rather quickly, as three U.S. scientists won the Nobel Prize in medicine for unlocking some of the secrets about these bodily things in 2009.

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