A protective structure known as a telomere is located at the ends of our chromosomes. By preventing DNA damage or chromosome fusion, these molecules protect our chromosomes.
DNA repeats form telomeres, which are linked by a protein called shelterin. It is often helpful to imagine them as aglets on a shoelace, which prevent the ends from fraying.
We all experience a shortening of our telomeres as we age. A shortening process can be accelerated in some individuals, or some cases, the length is abnormally short.
What do telomeres do?
There are three main functions of telomeres:
- They organize the 46 chromosomes in our nucleus. Our cells are controlled by the nucleus (control center).
- These caps protect our chromosome ends, similar to the plastic tips on shoelaces. Chromosomes may stick to each other if telomeres are not present.
- The chromosomes are properly replicated when a cell divides: Does DNA replication take place? During replication, there is an average shortening of 25-200 bases (A, C, G, or T).
Only the telomere is lost, not the DNA, due to the telomere protection at the ends.
Telomeres protect DNA during cell division (usually 50 to 70 times per cell). It would eventually lead to the loss of entire genes.
What happens to telomeres during cell division?
Each chromosome of an original cell must be duplicated when it divides so that each new cell has a copy of its genetic information. However, only one part of each chromosome cannot be copied, and that is the end. Consequently, when a chromosome is replicated, the telomeres of the chromosomes become shorter.
Thus, telomeres play a significant role in ensuring genetic information encoded on the chromosomes is protected and not lost during the replication process by acting as a buffer.
The short telomeres in the cells act as signals to warn the dividing cells to stop dividing or die to protect the genetic information.
How is telomere length maintained?
- Chromosome ends are capped by TTAGGG telomere sequences added by telomerase.
- Somatic cells only contain deficient levels of telomerase. As a result of not using telomerase regularly, these cells age and lose their ability to function normally.
- An aging body results from aging cells.
- There is a high level of telomerase in the germline: stem cells and reproductive cells (eggs and sperm). The telomere length of these cells remains the same after DNA replication, which means the cells do not show signs of aging.
- Cancer also contains high levels of telomerase. In this way, cancer cells can remain immortal and replicate indefinitely. Cancer cells whose telomeres are turned off would have their telomere lengths shortened until they reach ‘critical length.’ It would prevent tumors from forming uncontrollably if cancer cells did not multiply uncontrollably.
- In addition to preventing aging, telomerase keeps the cells multiplying.
Use of telomeres in medicine
- Cancer and aging could be combated with research on telomeres and telomerase.
- Telomeres are not known to have any medical significance.
- In lab cultures of human cells, cells whose telomeres do not maintain their length after division stop dividing when telomerase is inactivated.
- When the cells reach senescence, they become inactive. The cells can divide again after telomerase is reactivated.
- Telomerase may also be able to extend the life of human cells so they could be mass-produced for transplantation. A range of conditions can be treated with these cells, including severe burns and diabetes.
What happens when something goes wrong?
Some individuals struggle with this process. Telomeres may be short because they are inherently short. The process of telomere shortening may be accelerated. All of these factors may be contributing to the problem. There may be a problem with the telomerase enzyme or a defect in the telomere protective structure preventing a healthy telomere length from being maintained.
Those with Telomere Biology Disorders (TBDs) have problems extending, replicating, or maintaining telomeres.
Telomere-damaged cells can affect any organ in the body, which explains the wide variety of symptoms associated with TBDs. As an example, pulmonary fibrosis primarily affects the lungs. The most common symptom of congenital dyskeratosis is bone marrow failure, but there is a wide range of other symptoms that can occur due to the condition.
It has been observed in recent years that genetic mutations result in shorter telomeres and longer TBDs; however, in many of these cases, we do not yet understand the root cause of the TBD. A telomere length test can play a critical role in diagnosing and treating these cases, in particular.
Telomerase counteracts telomere shortening.
Telomeres are extended by an enzyme called telomerase. Telomerase protects telomeres from becoming too worn down in young cells. The cells’ telomeres become shorter as they repeatedly divide, so they age.
During the generational transfer, sperm and eggs remain active, transmitting telomerase from one generation to another. A reproductive cell without telomerase would soon become extinct if it did not maintain the length of its telomeres.
Telomeres and cancer
The telomeres of cancerous cells become very short as they divide more frequently. Cells can die if their telomeres shorten too much. Sometimes, the telomerase enzyme helps these cells avoid dying by preventing the telomeres from becoming shorter.
Cancers of the skull, neck, bone, prostate, bladder, and lung have shortened telomeres.
There is a possibility that telomerase can be measured in order to detect cancers. It may be possible to fight cancer by stopping telomerase if scientists learn to stop it. Cells grown in the laboratory were inhibited from expressing telomerase, resulting in the death of cancer cells. The risk is there, however. By blocking telomerase, fertility could be impaired; wound healing could be slowed, as well as the production of immune system cells and blood cells.
Telomeres and aging
According to a study by geneticist Richard Cawthon and colleagues, shorter telomeres correlate with shorter lives. Death from heart disease was three times higher among those with shorter telomeres over 60, and infectious diseases were eight times higher among those with shorter telomeres.
The shortening of telomeres has been linked to aging, but no one knows whether shorter telomeres contribute to aging or indicate it.
Is telomerase capable of preventing normal cells from aging if it makes cancer cells immortal? Is it possible to extend lifespan with telomerase by preserving and restoring telomere length? Do you think that would increase our chances of getting cancer if that were the case?
Scientists aren’t sure yet. Human cells can divide beyond their standard limit with telomerase but will not become cancerous if the cells are kept from dividing.
It would be possible to create mass-produced human cells that can be transplanted if we used telomerase to “immortalize” human cells. This would include insulin-producing cells for treating diabetes, muscle cells that can treat muscular dystrophy, cartilage cells that can treat certain types of arthritis, and skin cells that can heal severe wounds and burns. It would also be easier to test new drugs and gene therapies if an unlimited supply of normal human cells were available in the laboratory.
Telomeres and other diseases
A disease called dyskeratosis congenita causes telomeres to shorten much faster than they should. Death and premature aging are common problems for these people. Besides infection, leukemia, other blood cancers, gastrointestinal disorders, cirrhosis of the liver, and pulmonary fibrosis, a deadly lung stiffening, they are at risk for life-threatening infections, leukemia, and other blood cancers. As a result of their age, they are also more likely to experience gray hair, balding, poor wound healing, spots on their skin, intestinal disorders, weakening of their bones, and learning disabilities. Accordingly, it seems reasonable to conclude that telomeres probably play a role in all those conditions since they all involve tissues with a high rate of cell division. It has also been discovered that shortened telomeres may be associated with certain diseases, including Alzheimer’s disease, artery hardening, high blood pressure, and type 2 diabetes.
References:
https://www.yourgenome.org/facts/what-is-a-telomere/
https://www.jax.org/news-and-insights/minute-to-understanding/what-are-telomeres
https://learn.genetics.utah.edu/content/basics/telomeres
https://repeatdx.com/what-are-telomeres/
