Fountain of youth?

When an engineer would have to come up with a perfectly working human body, it would probably look quit different from ours. We came to be by trial and error. A new feature could be just right as it came, could be dismissed again, or be in need of some adaptation.

Human chromosomes (grey) capped by telomeres (white).

Human chromosomes (grey) capped by telomeres (white).

That is possibly how chromosomes ended up with telomeres, protective caps at their ends. These telomeres have two important, correcting functions. They make sure the essential information of the chromosome stays intact during cell division and they prevent fusions with neighbouring chromosomes. After studying telomeres started to gain momentum in the 1990s, it became clear they have unexpected complexity and are very significant to our health.

Cells are constantly being copied. This process starts with that one fused egg and sperm cell containing 46 chromosomes, 23 of father and 23 of mother, with the complete genome. Every chromosome in fact is a very long DNA molecule holding several hundreds of genes.

While copying this large package of information something can easily go wrong. Especially when you consider the fact that one copy follows another and another to finally end up with a complete human being. And this copying process of cells continues throughout your whole life.

Damage
Copies aren’t always as good as the original. To prevent damage due to the copying process, every DNA molecule is fitted with an irrelevant, extra part at the beginning and the end of the molecule, called telomere.

Compare the situation to a photocopier that can’t copy a complete page. The upper and lower edges of the paper are not completely clear anymore. To prevent important text to be left out, all the pages to be copied start and end with some nonsense lines. This way, the indispensable information will certainly be on your copy.

The copying process of cells continues throughout life. Every time a cell is copied a small part of telomere, an protective part, disappears. When all the telomere is gone the cell cannot copy anymore. This generally leads to the death of the cell. (© designua – Fotolia)

The copying process of cells continues throughout life. Every time a cell is copied a small part of telomere, a protective part, disappears. When all the telomere is gone the cell cannot copy anymore. This generally leads to the death of the cell. (© designua – Fotolia.com)

But every time you make a new copy of the copy, again a part of the nonsense lines at the top and the bottom of the page will disappear. You will end up with a copy that does not contain nonsense lines anymore, but only the relevant information. You cannot afford to lose this important information, so you have to stop copying.

This is what happens in cell division. With every new copy a small piece of telomere is left off. When all the telomere has gone, the cell cannot divide anymore. This almost always leads to the death of the cell. So, the shrinking telomere makes cells grow older.

It appears the length of the telomere determines the maximum life span of an organism. In humans, telomeres have such a length they can easily survive 75 to 90 years. Human cells can divide between forty and sixty times before they have run out of telomere. Cells of mice can be copied about fifteen times, but the cells of the Galapagos tortoise at least ninety times.

Environment
The length of the telomeres appears to vary a little between persons. If your parents had long telomeres, you will inherit long telomeres as well. But it certainly does not mean this fact guarantees that you will reach about the same age as your parents did, as was shown in a Swedish investigation.

Environmental factors have a big influence on telomere length. (© rusty elliott – Fotolia.com)

Environmental factors have a big influence on telomere length. (© rusty elliott – Fotolia.com)

Environmental factors have a far bigger influence on telomere length. When cells are damaged faster than usual and have to be replaced, more cell divisions take place in a shorter period and telomere runs out quicker. For example, stress or a large quantity of free radicals influences telomere length.

Telomere length is an interesting measure for how far the ageing process has affected your body. With this measure, researchers in the US have been able to establish that chronic stress makes you grow older faster.

They investigated two groups of mothers. One group had healthy children while the other group was taking care of chronically ill children what caused these women to be exposed to long-term stress. In the stressed mothers, the telomeres turned out to be considerably shorter than in the mothers with healthy children. Depending on the period they had already been taking care of their chronically ill child, they appeared between nine and seventeen years older as far as telomere length was concerned.

Repair
Telomeres don’t always only become shorter. A special protein, telomerase, is able to repair both ends of the DNA molecule and lengthens the telomere up to its original length. Telomerase is made by one of our genes and could give a cell eternal life.

A special protein called telomerase is able to lengthen telomeres again. The genes that make telomerase are shut off when an embryo is developing normally. Cancer cells are able to switch these genes back on again and can thus duplicate infinitely. (© designua – Fotolia)

A special protein called telomerase is able to lengthen telomeres again. The genes that make telomerase are shut off when an embryo is developing normally. Cancer cells are able to switch these genes back on again and can thus duplicate infinitely. (© designua – Fotolia.com)

Unfortunately, this gene is active for only a short period of time, mainly in egg cells and sperm cells. After all, they are the originals for all the copies that will follow. In an embryo that develops normally, the genes that make telomerase are switched off.

Even in adults, telomerase can still be found, namely in cells of the immune system. These have to keep on dividing themselves to effectively protect the body against intruders, like viruses, bacteria and parasites.

Cancer cells also make use of, or in fact abuse, telomerase. They are capable of switching on the gene that produces telomerase. Thanks to this ability they can duplicate infinitely.

One of the paths being followed in cancer research at the moment is aimed at this activation of the telomerase gene by cancer cells. The search is on for a method to counteract the production of telomerase triggered by cancer cells. If that would be possible, cancer cells would automatically die because they would run out of telomere due to their frequent cell division.

Immortal
After the discovery of telomeres and telomerase, naturally scientists thought they had found the fountain of youth. If we could activate telomerase genes and thus lengthen our telomeres time and again our cells would become immortal.

Many people dream of rejuvenation. (© giorgiomtb – Fotolia.com

Many people dream of rejuvenation. (© giorgiomtb – Fotolia.com)

In the laboratory, cells that had been genetically manipulated and that kept on producing telomerase, in fact were able to divide unlimited. Tests have also been done in genetically modified mice. From the moment the telomerase gene was switched on in the mice, they underwent a complete rejuvenation.

Most of those mice on the other hand fell ill with cancer and still died prematurely. Cancer cells use the telomerase gene as well, as explained earlier. Only mice that had been made cancer proof via another genetic intervention indeed lived longer.

The question is how far you could go intervening in genetic processes without upsetting the whole complicated and ingenious process. A telomerase therapy for humans still seems to be a long way off. For the time being, we will have to deal with our ageing cells and try to find ways to keep them healthy as long as possible.

Images

Fountain of youth? © Antonio Gravante – Fotolia.com
Dividing cells © richard finch – Fotolia.com

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