Effects of Telomeres and Telomerase on Cancer and Aging
The Importance of Telomeres and Telomerase
Intriguing evidence linking telomeres and telomerase to health is slowly accumulating. Telomeres are protective regions at the ends of chromosomes. The chromosomes are thread-like structures located in the nucleus of our cells. They contain genes and are vitally important in our lives. Telomeres become shorter during the process of cell division. Telomerase is an enzyme that prevents telomeres from shortening.
Some researchers think that controlling telomere length and the telomerase level in our bodies may have benefits. These benefits may include preventing cancer and extending our lifespan. Though neither of these advantages is definitely proven yet, the evidence that they are real is becoming stronger.
Structure of a Cell
What are Chromosomes?
A chromosome is made of a molecule of DNA (deoxyribonucleic acid) attached to a little 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 prevent the telomeres from decreasing in length. Most cell types make very little telomerase, however, while a few make far more.
When a chromosome replicates, it's temporarily joined to its copy by a structure called a centromere, as shown in the above diagram. The abbreviation CPD stands for cyclobutane pyrimidine dimer. Apoptosis means self destruction.
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 chromosome will be damaged and no longer function.
Telomeres and Cell Senescence
The Hayflick Limit
There's a limit to the number of times that a cell can divide. 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 every time 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 Discovery of Telomeres and Telomerase
Telomerase and Cancer
Cancer cells multiply rapidly, which results in shortened telomeres. However, telomerase is made in cancer cells, preventing the telomeres from becoming so short that the cells can no longer survive. If scientists could block the activity of telomerase they might be able to force the cancer cells to die.
Laboratory experiments in lab equipment have shown that tumor cells do die when they can no longer make telomerase. However, inside a human body, inhibiting telomerase might interfere with the action of other rapidly dividing cells. 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.
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 group of scientists genetically engineered mice so that they were unable to make the telomerase enzyme. As a result, the chromosomes of the mice shortened and the mice aged much faster than normal mice. 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 that are given telomerase. They point out that the genetically engineered mice didn’t age normally but were stimulated to grow old by artificial means. Another concern about using telomerase as a potential anti-aging drug in humans is that it might support the replication of cancer cells.
Other Factors That May Cause Aging
Other factors are believed to affect the aging process in humans in addition to telomere shortening. One of these factors may be oxidation, a process in which certain chemicals containing oxygen damage DNA, proteins and fats in the body. These effects are sometimes known as oxidative stress.
Another contributing factor to human aging may be the accumulation of advanced glycation end products (AGEs) in the body. These substances form from the reaction of sugar with proteins or fats. It's thought that they may contribute not only to aging but to certain diseases that appear in older people.
Lifestyle Changes May Lengthen Telomeres
Lifestyle and Telomere Length
While there are concerns about increasing telomere length artificially by the addition of telomerase, some very interesting research has shown that telomeres can be lengthened naturally, at least in one group of people.
A pilot study at the University of California San Francisco in 2013 examined the effect of lifestyle changes on prostate cancer patients. Patients who ate a healthy diet, exercised regularly, used techniques such as yoga or meditation to reduce stress and stopped smoking actually lengthened the telomeres in their cells. Patients who didn't change their lifestyle didn't lengthen their telomeres.
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.
When reading about telomere discoveries, it's very important to keep a popular saying of biologists in mind. "Correlation does not imply causation". Shortened telomeres have been repeatedly correlated with some diseases and conditions, but this doesn't necessarily mean that the shortened telomeres are the cause of the problems.
Telomere and telomerase discoveries are fascinating and offer the tantalizing possibility of improved health and longevity. However, there are many unanswered questions about telomeres and about the effects of changing telomere length or the telomerase level in our body. Lengthened telomeres are not yet considered to be the "fountain of youth", as some non-scientists claim. Human biology is very complex!
In the future, reducing telomere breakdown or increasing 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 this increased length has a number of benefits.
References and Further Reading - Latest Telomere Research
© 2011 Linda Crampton
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