Under the Microscope:The instructions that control day-to-day activities in your body's cells are encoded in DNA, the genetic material, and this DNA is packaged into structures called chromosomes. When the cell divides to form two daughter cells, exact copies of the chromosomes are passed on to each daughter, writes Prof William Reville
Because the genetic material is so critically important, the cell has several mechanisms to protect DNA and to repair it if it suffers damage. One such protective mechanism is the telomere, a compound structure located at the end of a chromosome. Telomeres are associated with ageing and may also affect risk of contracting cancer.
Each of our body cells contains 23 pairs of chromosomes, one set coming from each parent. Each chromosome is a single, long DNA molecule, mostly tightly bunched up and complexed with proteins. The genetic information in DNA is encoded in the sequence of its building-block nucleotides. There are four different kinds of nucleotide, denoted by the letter symbols ATGC. The DNA molecule is made of two nucleotide strings wrapped around each other in a double helix. The nucleotide sequence on one string is complementary to the sequence on the other, because A on one string always pairs with T on the other, and G always pairs with C. If you know the nucleotide sequence of one string, you automatically know the sequence of the other. The information coded in DNA determines the kinds of proteins made by the cell, which in turn determines the activity of the cell.
The telomeres are special stretches of DNA on the ends of each chromosome, made of repeating sequences of TTAGGG on one strand paired with AATCCC on the other strand. The telomeres do not contain protein coding information. They function like the plastic tips at the ends of shoelaces. If the tips were not there the laces would fray and pretty soon become useless. The same thing would happen to the chromosome if the telomeres weren't there, and in addition, frayed ends of different chromosomes would stick together, which would scramble the genetic information, causing cancer, other diseases or death.
Each time the cell divides the telomere gets shorter, because the DNA-copying machinery is unable to copy the very ends of the DNA molecule. Eventually when telomeres get too short, the cell is unable to divide and becomes inactive or dies. If chromosomes didn't have telomeres, the main parts, containing the genetic information essential for life, would shorten every time the cell divided and chaos would ensue. Telomeres are 8,000 nucleotides long at birth in human blood cells but later shorten to 3,000 nucleotides, and decline as low as 1,500 in elderly people. Normally cells can divide 50-70 times before the telomeres get so short the cell becomes inactive, or dies, or contracts genetic damage that may cause cancer.
Cells of many tissues such as skin, blood, bone and so on must divide actively in order to renew the tissue. In some tissues such as muscle, where cells do not divide continually, telomeres don't shorten with age.
Telomere shortening is counteracted by an enzyme called telomerase that adds nucleotides to the ends of telomeres, preventing them from shortening too much in young cells. But there is insufficient telomerase to keep this up as the cells repeatedly divide and the telomeres gradually shorten. There is one exception to this situation - sperm and egg cells. Telomerase activity remains adequate here to maintain telomere length. If this weren't the case we would have gone extinct long ago.
Cells become cancerous when the mechanisms that regulate cell division go awry, allowing the cells to proliferate out of control. This rapid cell division would quickly shorten the telomeres to such an extent as to prevent further cell division, but cancer cells are able to super-activate telomerase, thereby preventing the telomeres from getting too short. One approach to fighting cancer therefore is to block telomerase activity in these cells, thereby prompting the malignant cells to die. However it is not that simple - blocking telomerase increases risk of fertility impairment, healing of wounds and blood cell production.
Research by Richard Cawthon at the University of Utah has shown that in older people shorter telomeres are associated with shorter lives. People older than 60 with shorter telomeres were three time more likely to die from heart disease and eight times more likely to die from infectious disease. However, it is not clear whether shorter telomeres contribute to ageing, or simply signal ageing. If the former is the case, the possibility arises of extending lifespan by preserving or restoring telomere length with telomerase. It has been proposed that up to 30 years could be added to average human lifespan by stopping telomere shortening. Of course, in turn, this might increase cancer risk.
However, telomeres alone do not dictate life span. For example, humans have much shorter telomeres than mice, who only live a few years. Other factors that contribute to ageing are oxidative stress and glycation. Oxidative stress is damage to our DNA, proteins and other chemicals by oxidants naturally generated because we must breathe oxygen. Glycation is the binding of glucose, which we need to generate energy, to DNA and protein, leaving them useless at performing their normal jobs. This problem gets worse as we get older. And various other risk factors increase as we get older.
Cawthon estimates that if all ageing processes could be eliminated and oxidative stress damage could be repaired, people could live to 1,000 years. Most deaths would then be from accidents, suicide, murder and some infectious diseases.
William Reville is associate professor of biochemistry and public awareness of science officer at UCC - understandingscience.ucc.ie