The 2009 Nobel Prize in Physiology or Medicine was awarded to three scientists who solved a major problem in biology: how the chromosomes can be copied in a complete way during cell division and how they are protected against degradation. The Nobel Laureates have shown that the solution is to be found in the ends of the chromosomes – the telomeres – and in an enzyme that forms them – telomerase.
The ability to maintain and elongate telomeres is believed to endow stem cells with the ability to endlessly replicate themselves. Researchers studying aging believe that this same ability could slow or halt natural aging, at least in human cells.
Now researchers in George Daley's, lab at Children's Hospital Boston have reported successfully reactivating the cellular enzyme telomerase, which maintains the telomeres, in patients with dyskeratosis congenita. In this rare genetic disorder, genetic mutations cause telomerase to be defective, leaving the chromosomes without protection from damage and unable to compensate for the natural shortening of telomeres that occurs when a cell divides.
As a result, a patient's cells "age" more quickly, leading to bone-marrow failure (an inability to make enough blood cells), degradation of multiple tissues, premature aging-like symptoms and a much-shortened lifespan.
The findings suggest the possibility of developing drugs to help patients with dyskeratosis congenita maintain their telomeres, prolonging their lives. But the study also has broad implications for stem-cell research, as well as research on aging and even cancer. In the cancer field, telomerase is thought to contribute to the "immortalization" and uncontrolled growth of cells that marks human cancer, and has become a target in attempts to treat cancer.
"This paper illustrates how reprogramming a patient's skin cells into stem cells can teach us surprising lessons about human disease," said Daley, who is also associate director of the Stem Cell Program at Children's.