Ageing reversed in mice: Study

By Dr. Ananya Mandal, MDNov 29 2010

A scientific team at Harvard-affiliated medical centers genetically manipulated mice to age faster. Then they used gene therapy to lengthen telomeres. Telomeres are compounds found at the ends of strands of DNA that are related to age. This lengthening of telomeres reversed age-related problems such as decreased brain function and infertility.

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 said, “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… We were so struck by the findings that we rushed to get the study published.”

At ends of each of human chromosomes are protective caps called telomeres. Enzymes called telomerases protect the telomeres and reduce DNA damage thought to contribute to tissue ageing. But with age, the cells produce less telomerase; telomeres are cut shorter and eventually fail to protect DNA from damage. The team boosted this telomerase enzyme in the mice. DePinho said the mice that were equivalent to ages 80 to 90 in human years returned to the equivalent of middle age. He said, “This [research] indicates there’s a point of return for these tissues… The fact that you can bring a tissue to the brink and then bring it back this dramatically is remarkable.”

Earlier studies have shown that shortening telomeres are not just linked to ageing but also age-related diseases such as heart disease and Alzheimer’s disease. In the experimental ageing mice the brains were 75% of the normal brain as seen in Alzheimer’s disease. After the gene therapy the brain’s regained their normal size.

DePinho however warns that ageing is complex and telomeres are only one part of the story. But this is one step in learning more about not only the slowing of ageing, but also the reversal. He said, “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.” Authors write, “Generally, the shortening of telomeres in normal tissues shows a steady decline, except in the case of cancer, where they are maintained.” DePinho warned that it is too early to speculate if similar results are possible in humans and the implications this study had on cancer research.