Telomere Multi Activator

Telomere Multi Activator

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TELOMERASE NOBEL PRIZE More than 35 years ago, telomerase activity was discovered by Elizabeth H. Blackburn and Carol W. Greider. Today, this enzyme is a promising approach to curing some age-related diseases as well as cancer, but it took time for telomerase to be in the spotlight. The existence of an enzyme, a DNA polymerase, that could elongate the ends of chromosomes or telomeres was predicted in 1984 on the basis of telomere maintenance and net telomere elongation in both ciliates and yeast1. Some fifty years before that discovery, the work of Hermann Müller and Barbara McClintock had showed the occurrence of a special structure at chromosome ends — which Müller termed the telomere — that was essential to prevent chromosomes from fusing to each other2,3. The subsequent elucidation of the structure of the DNA molecule and the understanding of the DNA replication mechanisms posed the question on how to maintain the ends of chromosomes throughout cellular and organismal generations. James D. Watson and Alexey M. Olovnikov had envisioned that the ends of linear DNA molecules, such as chromosomes, would shorten every time a cell divides, owing to the incomplete replication of the ends by the conventional polymerases, a problem termed the end replication problem. Thus, to allow for species maintenance, an enzyme must exist that would compensate for the ever-shorter telomeres associated to cell division. Such an enzyme was predicted by Elizabeth H. Blackburn and Jack W. Szostak to elongate the 3´ ends of telomeric repeats to compensate for telomere loss associated to cell division, so that in this manner the ends of chromosomes would not wear away after a few cell divisions, generating chromosomal instability. To find such an enzyme was of potential great importance, as its telomere elongating activity or the lack thereof could explain the limited life span of normal cells, also known as the Hayflick limit4 as well as organismal aging and longevity. Such an activity
could also explain the immortal nature of cancer cells and their ability to divide indefinitely. While working at Joe Gall´s group, Blackburn had sanger-sequenced the first chromosome end from the ciliate Tetrahymena and found a gene-less repeated sequence heterogeneous in length5. Possibly, the fact that the ends of chromosomes did not harbour any gene that could explain their function decreased the enthusiasm of the scientific community but not that of Blackburn, who was convinced that such repeated DNA must somehow hold the key to aging and longevity of life. The Nobel Prize in Physiology or Medicine 2009 Elizabeth H. Blackburn, Carol W. Greider and Jack W. Szostak “how chromosomes are protected by telomeres and the enzyme telomerase“ This year’s Nobel Prize in Physiology or Medicine is awarded to three scientists who have solved a major problem in biology: how the chromosomes can be copied in a complete way during cell divisions 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 long, thread-like DNA molecules that carry our genes are packed into chromosomes, the telomeres being the caps on their ends. Elizabeth Blackburn and Jack Szostak discovered that a unique DNA sequence in the telomeres protects the chromosomes from degradation. Carol Greider and Elizabeth Blackburn identified telomerase, the enzyme that makes telomere DNA. These discoveries explained how the ends of the chromosomes are protected by the telomeres and that they are built by telomerase. If the telomeres are shortened, cells age. Conversely, if telomerase activity is high, telomere length is maintained, and cellular senescence is delayed. This is the case in cancer cells, which can be considered to have eternal life. Certain inheri diseases, in contrast, are characterized by a defective telomerase, resulting in damaged
cells. The award of the Nobel Prize recognizes the discovery of a fundamental mechanism in the cell, a discovery that has stimulated the development of new therapeutic strategies

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