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James Hilton’s fantasy of a Shangrila — the land of eternal youth in his novel The Lost Horizon — may not be pure fiction after all. Recent studies indicate that a single enzyme telomerase may well be that elusive elixir of youth. The role of this enzyme in preventing the inevitable disintegration that comes with old age was discovered by researchers at Harvard Medical School, the US. It has now been shown that telomerase increases the life span of cells, and thereby retards the ageing process, by repairing telomeres — the strands of DNA that tie up the ends of chromosomes and ensure their proper replication.
At the same time, it has been found that telomerase is also responsible for increasing the life span of cancer cells, causing them to multiply abnormally. So if researchers can find a way to regulate telomerase in cells (switch it on in normal human cells to delay ageing and switch it off in cancer cells), they will be able to fulfil two of the dearest wishes of humankind — prolonged, if not eternal, youth and a cure for cancer.
Telomerase is an enzyme that is normally active only in cells that give rise to sperm or egg cells and in some stem cells. The function of telomerase, a ribonucleoprotein, is to enhance the longevity of these cells by synthesising telomere sequences onto the end of chromosomes.
Telomeres consist of specialised repeated sequences of DNA that serve to maintain the structural integrity, positioning and accuracy of replication of the chromosomes that carry the genes, which are the blueprint for all life functions. Analysis has shown that in the absence of telomerase, human telomeres lose about 50-200 nucleotides from their DNA every time a cell divides. At this rate, after a finite number of cell divisions (mitosis) the telomeres would be completely gone and the cell would die (senescence). Also, well before the death of a cell, the rate of mitosis declines.
These observations indicated a direct link between telomere length and the number and rate of cell divisions. It has now been clearly established that the progressive shortening of our telomeres, due to the inactivity of the enzyme telomerase, is indeed the cellular clock that determines the ageing of our cells.
But can telomerase activity be initiated in other human cells as well? And will the lengthening of the telomeres actually prolong the life of these cells? Research by groups from the South Western Medical Center and Geron Corporation, the US, has proved just that. By introducing the telomerase reverse transcriptase (hTRT) gene, they induced telomerase activity into three different kinds of human cells and in all the three cell lines, the telomerase knit new DNA onto the ends of chromosomes, artificially elongating the telomeres. And all three cell lines lived much longer than usual.
More recently, tests have revealed that when mice, whose skin, brain, gut and other organs resembling those of an 80-year-old human, were given a drug that triggered the activity of telomerase in their cells, the mice almost completely rejuvenated within a period of two months. It is now speculated that similar drugs could be developed that would work on humans too.
On the flip side, it has been established that it is the activity of telomerase in cancer cells that makes them immortal, giving them the ability to multiply abnormally that leads to rapid growth and spread of cancerous tumours. So can telomerase activity in cancer cells be switched off? Medical scientists are presently engaged in finding that out. One of the most promising treatments for cancer being tried out in the UK — on about 1,000 men and women with pancreatic cancer, one of the deadliest forms of the disease — is a vaccine called Telo-Vac. This vaccine encourages the body’s immune system to destroy telomerase activity of cancer cells and prevent their proliferation. This study has already yielded results that hold great hope for the future.
Although much more research is required to determine the full implications of telomerase activity in different human cells, this enzyme seems to hold the key to attaining two long-held dreams of man.
