Telomeres And Ageing

By Dr Harold Gunatillake - Health Writer

Let's first understand what DNA means. Friedrich Miescher in 1869 isolated DNA from fish sperm and the pus of open wounds. Since it came from nuclei,(every cell has a central office that controls all activities within the cell called the nucleus), Meischer named this new chemical, nuclein. Subsequently the name was changed to nucleic acid and lastly to deoxyribonucleic acid (DNA).

Each DNA is composed of units called nucleotide. Each nucleotide consists of a 5-carbon sugar (deoxyribose), a nitrogen containing base attached to the sugar, and a phosphate group. There are four different types of nucleotides found in DNA, differing only in the nitrogenous base. The four nucleotides are given one letter abbreviations as shorthand for the four bases.

The shape of each DNA strand is composed of a double helix twisted on it; imagine it as a twisted ladder. Each nucleotide base contain adenine (A), guanine (G), cytosine (C), and thymine (T)

Now a chromosome is a long strand of DNA (shown in diagram). At the end of a chromosome is a telomere, which acts like a bookend.

Telomeres keep chromosomes protected and prevent them from fusing into rings or binding with other DNA. If cells divided without telomeres, they would lose the ends of the chromosome. The genetic material within each cell nucleus takes the form of chromosomes. A chromosome is composed of DNA and contains all the hereditary information of a cell. In other words the Genes are packaged in bundles called chromosomes Each time a cell in our body divides as in normal growth, the DNA within each chromosome unwraps and the information is copied. When the cell has copied and finished the dividing, the DNA comes back together. This process is called 'Replication'. The telomere loses a little bit of length each time the cell divides.

When a cell divides and copies DNA, the strands of DNA get snipped to enable the copying process. The places that are snipped are the telomeres. Since the telomeres do not contain any important information, more important parts of the DNA are protected. The telomeres get shorter each time a cell divides, like a pencil eraser gets shorter each time it's used.

When the telomere becomes too short, essential parts of the DNA can be damaged in the replication process. Scientists have noticed that cells stop replicating when telomeres are shorter. In humans, a cell replicates about 50 times before the telomeres become too short. This limit is called the Hay flick limit (after the scientist who discovered it). Researchers can use the length of a cell's telomeres to determine the cell's age and how many more times is will replicate. This is important in anti-ageing research. When a cell stops replicating, it enters into a period of decline known as "cell senescence," which is the cellular equivalent of ageing. However, another reason telomeres are important is cancer.

Jack Szostak, Nobel Prize winner 2009, said in an interview recently that he had already won the Lasker Prize, for identifying the nature and biochemistry of telomeres, the tips at the ends of chromosomes. He said, "Understanding them may be the key to unlocking the mysteries of cancer and cell ageing" He further said, "Before I began working on telomeres, I'd been studying DNA recombination. What do cells do when they see a broken piece of DNA? Cells don't like such breaks. They'll do pretty much anything they can to fix things up. If a chromosome is broken, the cells will repair the break using an intact chromosome. That process is called recombination. And that's what I was looking at".

Cancer cells helping to solve the ageing process
Every system in our body is balanced, in the sense that the cells do replicate and die. If the cells stop dying as in cancer cells where replicating occurs rapidly and the balance is disrupted, the cancer cells start replicating and growing and spreading locally and to distant sites. Studies have found that cancer cells create an enzyme called telomerase, which prevents telomere shortening.

Every cell in your body has the genetic code to make telomerase, but only certain cells need to produce this enzyme. White blood cells and sperm cells, for example, need to have telomere shortening switched off in order to make more than 50 copies of them through your lifetime. In advanced cancer, the cancer cells also seem to be producing telomerase, which allows them to continue to replicate without dying. The Nobel Prize winner Szostak further said, "That It became clear that the loss of DNA from telomeres might have something to do with ageing.
Subsequently, it's turned out that in almost all cancers, telomerase is turned on so those cells grow indefinitely. Of course, it's very nice that work we did so long ago turned out to be important! But the truth is my work has gone off in several different directions".

When Szostak was asked how far he has gotten in ageing research, he said, "Maybe I can say we are halfway there."

He further said, "We think that a primitive cell has to have two parts. First, it has to have a cell membrane that can be a boundary between itself and the rest of the earth. And then there has to be some genetic material, which has to perform some function that's useful for the cell and get replicated to be inherited. The part we've come to understand reasonably well is the membrane part.

The genetic material is the harder problem; the chemistry is just more complicated. The puzzle has been understanding how a molecule like RNA can get replicated before there were enzymes and all this fancy biological stuff, protein machinery, that we have now in our cells".

Some reference from Longevity-March 29, 2007
Ref: Interview with ClaudaDreifus- The New York Times

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