Telomeres and Telomerase: Possible Roles in Aging and Cancer
What Are Telomeres and Telomerase?
Telomeres are protective regions at the ends of chromosomes. The chromosomes are thread-like structures located in the nucleus of our cells. They contain our DNA and its genes and are vitally important in our lives. Telomeres become shorter whenever chromosomes undergo replication in preparation for cell division. When the chromosomes are very short, a cell dies. Telomerase is an enzyme that prevents the telomeres from shortening.
Some researchers think that controlling telomere length and the telomerase level in our bodies may have benefits. These benefits might include extending our lifespan and reducing the chance of cancer development. Neither of these effects has been proven by scientists. The discoveries about telomeres are intriguing, however.
What Are Chromosomes?
A chromosome is made of a molecule of DNA (deoxyribonucleic acid) attached to protein. The DNA molecule contains the genetic code that gives us many of our characteristics. Telomeres act as caps that protect the ends of a chromosome from damage and stop the ends of different chromosomes from joining together.
Just before a cell divides, the chromosomes are replicated so that a copy of each chromosome can go into each daughter cell. Telomeres shorten every time chromosomes are copied.
Cells do have a way to fight telomere shortening. Telomerase helps to prevent the telomeres from decreasing in length. Most cell types make very little telomerase, however, while a few make far more.
DNA, the Genetic Code, and Protein Synthesis
A DNA molecule is the main component of a chromosome. The molecule is made of two strands joined together and twisted into a spiral shape. This is why it's often referred to as a double helix. If the helix is unwound, the molecule looks like a ladder, as shown below. Alternating sugar and phosphate molecules form the sides of the ladder. Bonded chemicals known as nitrogenous bases form the rungs.
The genetic code is composed of a sequence of nitrogenous bases. These bases are adenine (A), thymine (T), cytosine (C), and guanine (G). Just as the letters of the alphabet can be arranged in specific sequences to produce different words, the nitrogenous bases in a DNA molecule are arranged in specific sequences to code for different amino acids. Amino acids join to make protein.
When the cell “reads” the code in the DNA, amino acids specified by the code are brought into position and joined together in the correct sequence to make proteins. Only one strand of the molecule is read when proteins are being made.
If we know the order of bases on one strand of a DNA molecule we also know the order on the other strand, since bases bond in a specific combination. Adenine on one strand joins to thymine on the other, while cytosine on one strand joins to guanine on the other strand, as shown in the diagram above.
The Nature of Telomeres
A segment of deoxyribonucleic acid that codes for a particular protein is called a gene. A single DNA molecule contains multiple genes. Some of the base sequences in the molecule don’t code for proteins, however, and are referred to as non-coding DNA. Telomeres consist of non-coding DNA.
In the telomere region of a chromosome, the bases are repeating sequences of TTAGGG on one DNA strand in the chromosome and AATCCC on the other strand. Generally, a person’s telomeres are longest at birth and gradually decrease in length as the person ages.
Telomeres are needed to prevent the coding portion of the DNA from shortening. They are often likened to the plastic covers on the tips of shoelaces that prevent the laces from fraying. Without their plastic tips, it's hard to thread the laces through the holes created for them. The ends of the laces will fray and the laces will soon become nonfunctional. Similarly, if the telomeres at the end of chromosomes are destroyed, the chromosomes will be damaged and no longer function.
Researchers have discovered that a protein complex named shelterin apparently protects the bases in the telomeres of chromosomes. The relationships between shelterin, the bases of a telomere, and telomerase are still being investigated.
The Hayflick Limit
There's a limit to the number of times that a cell can divide, at least under normal conditions. This limit seems to be about 60 divisions. It's known as the Hayflick limit after the researcher who discovered it. The limit depends on the length of the telomeres, which shorten just before the cell divides. When its telomeres are very short, the cell no longer divides. Instead, it ages or senesces and eventually dies.
The enzyme known as telomerase is present in a very small amount in most of the body’s cells. Telomerase lengthens telomeres by adding bases to the end of chromosomes. Egg and sperm cells have a relatively high level of telomerase activity. The idea of adding telomerase to cells that lack it in order to keep telomeres long and cells active has occurred to some researchers.
The Nobel Prize in Physiology or Medicine 2009 was awarded jointly to Elizabeth H. Blackburn, Carol W. Greider and Jack W. Szostak "for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase".— Nobel Prize website
When reading about telomere discoveries, it's very important to keep a popular saying of biologists in mind. "Correlation doesn't imply causation." Shortened telomeres have been repeatedly correlated with some diseases and conditions. This doesn't necessarily mean that shortened telomeres are the cause of the problems or that lengthening telomeres can solve the problems.
Telomerase and Aging
There is a great deal of debate and uncertainty about the factors that cause human aging. Scientists have observed that older people have shorter telomeres, but they aren't sure how big a role this plays in the aging process.
In 2010, a team led by a Harvard Medical School scientist performed an interesting experiment in mice. The experiment involved genetically engineered mice that were unable to make the telomerase enzyme. The chromosomes of the mice shortened during the experiment and the mice aged much faster than normal ones. Their spleen, testes, and brain shrunk. In addition, the mice developed disorders that in humans are more common in older people, such as osteoporosis, diabetes, and nerve degeneration.
The scientists then gave the mice a chemical which turned on telomerase production in their bodies. The chemical reversed the aging effects and caused degenerating organs to become active once more. Even the brain enlarged. The cognitive abilities of the mice also improved.
Although the results of the mouse experiment are very impressive, some scientists are uncertain that similar results will be found in humans who are given telomerase. Experimental results in mice often apply to humans, but this isn't always the case. Another concern is that the genetically engineered mice in the experiment didn’t age normally but were stimulated to grow old by artificial means. In addition, some scientists are worried that increasing the telomerase level may increase the risk of cancer. The possible link between cancer and the telomerase level in cells is described below.
Telomerase and Cancer
Cancer cells multiply rapidly, which would normally result in shortened telomeres. Cancer cells make telomerase, however, preventing the telomeres from becoming so short that the cells can no longer survive. If scientists could block the formation or the activity of the telomerase they might be able to force the cancer cells to die.
Experiments in lab equipment have shown that tumor cells die when they can no longer make telomerase. If we are ever able to inhibit telomerase production in the human body, however, a new problem may develop. Inhibiting the production of the enzyme might interfere with the action of other rapidly dividing cells in addition to cancer ones. These include the bone marrow cells that make the blood cells, the cells that heal wounds or fight infections, and the cells that line the gut. Despite the fact that these cells divide frequently, they generally aren't cancerous. Frequent division is a normal part of their life and is helpful for us.
There may be another factor linking telomeres to cancer. Scientists from the Wistar Institute have discovered that specific genetic mutations cause protein alterations in the shelterin complex protecting the telomeres. These alterations have been observed in some types of human cancer. This doesn't necessarily mean that the mutations cause cancer, however. There may be another factor responsible for the observed link between the altered protein and the disease.
Telomeres in Progeria Cells
Progeria is a disorder in which children age rapidly and often die in their early teens. In 2017, researchers from the Houston Medical Research Institute reported a discovery that might one day be helpful for children affected by the disease.
The researchers observed that the telomeres were abnormally short in people with progeria. When the scientists placed cells from progeria patients in lab containers, they were able to stimulate telomerase production in the cells. The cells lacked the enzyme before they were stimulated. The lead researcher said that the effects were "dramatic." As a result of the telomerase production, the function of the cells improved and they lived for longer. It would be wonderful if the procedure was both helpful and safe in the body of children with progeria.
Lifestyle and Telomere Length
While there are concerns about increasing telomere length artificially by the addition of telomerase, some interesting research suggests that telomeres may be lengthened naturally, at least in one group of people.
A small study at the University of California in San Francisco examined the effect of lifestyle changes on thirty-five men. All of the men had localized, early-stage prostate cancer. The ten patients who ate a healthy diet, exercised regularly, used techniques such as yoga or meditation to reduce stress, and stopped smoking lengthened the telomeres in their cells by about ten percent. The twenty-five patients who "were not asked to make major lifestyle changes" experienced shortening of their telomeres by about three percent during the five years of the experiment.
More research with larger numbers of people needs to be performed. We need to discover whether the research applies to other people besides prostate cancer patients. We also need to find out whether the lengthened telomeres are linked to better health.
Smoking and Telomere Length
Our knowledge about telomeres is still incomplete. In 2019, researchers at Newcastle University made a somewhat puzzling announcement after studying the results of medical surveys. As in investigations by other scientists, they found that smokers have shorter telomeres than non-smokers. They couldn't find evidence that the telomeres of smokers shorten faster over time compared to those of nonsmokers, however.
The scientists suggest that the desire to smoke and the presence of shorter telomeres than normal might both be triggered by a third factor in life, which may be physical or emotional stress. They haven't proved this idea yet. The discovery does show that we have some way to go before we completely understand changes in telomere length, however.
Telomere and telomerase discoveries are fascinating. There are many unanswered questions about them and about the effects of changing telomere length or the telomerase level in our body, however. Telomeres are not yet considered to be a potential "fountain of youth", as some non-scientists claim.
New and interesting discoveries continue to be reported. The discoveries are sometimes problematic, however. Some show an association between telomeres or telomerase and a particular effect but don't prove that the chromosome caps or the enzyme are causing the effect. In cases where experiments appear to show definite benefits from telomere length or telomerase control, uncertainty exists due to the experimental conditions or to the fact that the results may not be the same inside the human body.
In the future, controlling telomere length may be one of several techniques used to improve our lives. For now, though, it seems like a good idea to improve our lifestyle (if this is necessary) in order to experience the many proven health benefits of this action. Perhaps scientists will eventually demonstrate that improving our lifestyle also increases our telomere length and that controlling this length or the amount of telomerase in our cells has a number of benefits.
- Telomeres in relation to aging and cancer from the University of Utah
- Information about the Hayflick limit from The Conversation
- Elizabeth Blackburn discusses telomere length in an interview with The Guardian newspaper
- A description of an experiment exploring telomerase and aging in mice from the Nature journal
- The role of a telomere capping complex in cancer from the Wistar Institute
- Telomere length and progeria from the Medical Xpress news site
- Lifestyle and telomere length in patients with prostate cancer from the University of California
- Relationship between telomeres and smoking from Newcastle University
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© 2011 Linda Crampton