Dan's Papers - August 10, 2007 - Would You Want To Live Forever?

As the summer comes to an end, the dream of enjoying the Hamptons forever is one that lingers on every East Ender's mind. And though immortality might seem like the stuff of fairy tales, scientists are closer to uncovering the secrets of stopping aging and perhaps, death, at a remarkable pace.

Dr. Titia de Lange, the Leon Hess Professor at New York City's Rockefeller University, has been one of the most innovative minds in the age-old quest to uncover the secrets of immortality and aging. Dr. de Lange's research involves unraveling the mysteries behind the telomere, a DNA structure found on the ends of chromosomes responsible for the protection, stabilization and replication of that chromosome, which dictates the senescence, or aging, and death of every cell in the human body. Every time our cells divide, they lose telomeres. After fifty divisions, there aren't enough telomeres at the ends of the chromosomes to protect the chromosome ends and the cell activates the self-destruction process. However, cancer cells have the power to regenerate their telomeres - thus bypassing the body's usual process of telomere loss and cell death. If healthy human cells could be changed in order to allow them to regenerate telomeres as cancer cells do, then they too could divide forever and be made immortal.

Dr. de Lange first became interested in telomeres in 1980, while studying blood parasites as part of her graduate studies. Following the biological path of these parasites led her to the end of the chromosome and it is there that she first encountered telomeres. Now, more than twenty years later, she can say with conviction that human cells "can be immortalized if their telomere loss is reversed."

On Dr. de Lange's laboratory website, she details two different ways of preventing cell death. The first method simply removes the cell's capability to induce senescence by blocking the pathways by which the compounds that make senescence occur reach the cell. Though this method can keep a cell from dying, it will not protect chromosomes from becoming injured or dangerously binding together, because blocking pathways does not regenerate telomeres and telomeres are essential in protecting chromosomes. However, there is another way to prevent cell death. Telomerase, the compound capable of immortalizing human cells by regenerating telomeres, has been identified. A specialized DNA replication complex, telomerase can restore telomeres, thus allowing the cells to divide indefinitely. Cancer cells employ telomerase to divide indefinitely, as do the germline cells (cells giving rise to oocytes and sperm) and some stem cells. Normal human tissues cells, in general, lack telomerase. But if healthy tissue cells could be given the use of telomerase, they could replicate their telometric DNA patterns over and over again. Their telomeres would never shorten and they would never die.

However, Dr. de Lange warns that, "Preventing cell death would have disastrous consequences. We need cell death for normal development. Moreover, cell death is a major mechanism by which mammals limit the formation of cancer. If we interfered with the cell death pathway, we'd see tumors occurring rapidly." Infected cells divide more rapidly than normal cells and those that have activated telomerase can escape the body's natural tumor-killing system, which can only function if enough telomeres are lost to signal to the cell that it must die. By activating telomerase in all of our cells, healthy cells would be indistinguishable to the body from harmful cells, which would spell disaster for our health, if not our longevity.

Currently, Dr. de Lange's laboratory is investigating a protein complex called shelterin. Shelterin is the compound that binds telomeres together and gives the body the signal that a chromosome's ends are functioning. Dr. de Lange counts the discovery of shelterin as her most exciting discovery and over the next ten years, Dr. de Lange hopes to discover "how shelterin really works. How does a protein complex at the end of a piece of DNA tell cells that this DNA is different from a broken end?"

The more Dr. de Lange discovers about the function of each piece in the telometric puzzle, the closer we will all become to spending more years enjoying all the Hamptons have to offer. Perhaps no one will ever discover how to keep us swimming in the ocean and playing summertime sports indefinitely, but scientists like Dr. de Lange are very close to finding ways to add more years to our lives and make the years we do have healthier, happier and more vibrant.