Nothign to do with furrys... buts its what a furry is studying and this could one day be BIG news!


Telomeres and Telomerase
There is one thing in biology that no matter how many times I read it, I get excited and want to know more. It is called Telomeres. We all have them on the endings of our chromosomes. They are non-coding strands of DNA found at the linier ends of all your chromosomes. But, these simple strands allow the cell to continue dividing until they are gone. The most interesting fact about them is that that they are tied up in the theory of why organisms age. I believe that further and deeper study of and telomerase and telomeres could lead to amazing and huge preventions in human aging. Telomeres have a very specific build and function for the chromosomes for the cell. While they have the ability to make cells and the ability to divide for and extended amount of time the enzyme called telomerase is able to make the cells divide infinitely.
Telomeres are the linier ends of chromosomes. They are a repeated sequence of bases in the form 5’ TTAGGG 3’, in humans this can be repeated up to two thousand times. These end caps are very important to the life of the cell, stability, protection of the DNA, and provides a means for counting cell divisions . Telomeres protect the ends of the chromosomes and allows the cell to determine between broken DNA and chromosome ends. If the DNA was broke the cell would have a few choices. First, the Homologous Recombination process. The process is error free, but it requires homologues bases to be near by. This happens by nucleotide sequences’ being traded by two similar or identical strands of DNA. The cells second choice is non-homologous end joining. This is a highly error prone choice, but it can save the chromosome from degradation. This uses short homologues DNA sequences, micro-homologies, to guide the repairs. Mistakes in repair can lead to translocations and telomere fusions. Telomeres prevent chromosomes from fusing in the non-homologous end joining process. During cell division the DNA is replicated by enzymes. During replication the enzymes copy the DNA, but as it copies its unable to copy the strands all the way to the end so little by little the telomeres shrink with each division. Up to fifty to two hundred bases pairs with each division. Once the telomeres shrink down enough the cell will stop dividing in an effort to not lose curtail parts of the DNA. When this happens its said that the cell reaches its Hayflick limit. These cell can live on in the body but normally will never divide again.
The reason that the Telomeres shrink is due to the way chromosomes are replicated. Replication starts at the origins of replication, where the DNA polymerase can start replicating the DNA uninterrupted till it reaches another replication bubble; a splitting of the DNA so that replication can happen. Replication that goes along the 3’-> 5’ strand moves until stopped. On the 5’ ->3’ strand however has to be discontinuous because it has to start and stop the replication, leaving fragments of DNA unconnected called Okazaki fragments. Later, an enzyme called DNA ligase comes threw and connects the Okazaki fragments together. This process will continue till close to the end of the chromosome. As the replication fork get close to the end of the DNA there will no longer be enough of the strand to continue making Okazaki Fragments. So the 5’ strand of the daughter strand cannot be completed. Therefore, each subsequent daughter strand will be shorter and shorter till the cell will no longer divide.
With each division the Telomeres are shrinking this will impose a finite life span on cells. When cells are taken from a new born and put in culture they will divide about 100 times. During the cells “aging” the rate of mitosis declines to less than one every two weeks. When the cells of and older person are cultured the cells would manage only a couple of dozen mitoses before they stopped dividing and died out. This phenomenon is called replicate senescence. Though the theory is still very controversial, many biologist believe that senescent decline, or biological changes that take place in organisms as they age, is caused by increasing number of cells reaching there hayflick limits. If large amounts of the body cell are unable to divide then functions of defense, maintenance,
and repair would start to become hard for the body and the remaining cells to pick up the slack of the work the old cells are no longer able to provide. Hence, why degrading telomeres and hayflick numbers can account for the loss of efficiency and causes for again in the mature animals. This theory only works is if telomere length contributes to aging only and if replicate senescence contributes to aging. If both these facts are shown to be true then telomerase will prevent aging and the possibility to restore youthfulness.
If there was no way to stop the slow down of the process of replicated senescence, then cells that have linier chromosomes would be doomed to a short life span. This is because the cells in their reproductive tissues would meet their hayflick limit. Fortunately, we have a enzyme called Telomerase. Telomerase is part protein and part RNA. It has the ability to lengthen the telomeres beyond that of past parent cells, slow or even halt erosion of the telomeres all together. The genes that make telomerase are in every replicating cell in the body. But, its only turned on in very few of them. Genes that have active telomerase genes are found in early fetal development. Beyond that its only found in anti-body producing cells. Cells that remake the lining in the gut, and the cells that produce sperm. The way it works is that Telomerase adds Telomere repeat sequences to the 3’ end of the DNA strands. By doing this the NDA polymers are able to complete the synthesis of the incomplete ends of the opposite strand.
The big concern about turning all the telomerase back on in the cells is that 85-90% of cancer cells have also regained the use of telomerase. Cancer cells produce high amounts of telomerase, thus extending their telomeres making them able to divide for much longer or an infinite amount of times. On the other hand knowing this information can also allow us to create new weapons to fight the disease, such as telomerase inhibitors, by preventing the expression or the action of the gene. However, all actions have a reaction. If the telomerase activity, no mater how brief, is essential we could mess up the sequence of life. And if lack of telomerase hastens to replicate senescence, it may also hasten the aging of tissues that are vital for our health. The likely trade off is not worth the cost.
All the risks and advantages considered, I believe that further and deeper study of telomerase could lead to amazing preventions in human aging. It seems as though there has not been enough research done on this topic to determine what it can do in a clinical setting.





Bibliography

Campisi. “Telomeres” Campisi Diagrams. 2000 Berkeley University 07 Oct. 2009
http://mcb.berkeley.edu/courses/mcb.....telomeres.html

Kimball. “Telomeres” 25 November 2008. 07 Oct. 2009.
http://users.rcn.com/jkimball.ma.ul.....Telomeres.html

“Telomeres” Oct. 08 2009. http://www.telomere.net/