Posted on 2nd November 2021
What are telomeres, and what do they do? Telomeres are structures found at the ends of chromosomes that are made up of DNA sequences and proteins. They protect the ending of a chromosome.
Telomeres are short nucleotide sequences that protect the genetic material at the ends of linear chromosomes. Furthermore, telomeres in vertebrates feature the hexameric sequence TTAGGG. They are essential for cell division in practically all species, from the simplest to the most advanced. Telomeres get progressively shorter with each cell replication until they’re so short that your cells can’t divide any longer. Tissues age when cells stop dividing. Telomeres, on the other hand, can be regenerated by an enzyme called telomerase to allow cell division to resume.
The double-stranded DNA is unraveled during DNA replication, and DNA polymerase synthesizes new strands. Only the leading strand can be duplicated repeatedly because DNA polymerase operates in a unidirectional way (from 5′ to 3′). DNA replication is interrupted in the case of the lagging strand. Short RNA primers bind to the lagging strand DNA in humans, and the DNA is produced in small segments of 100-200 nucleotides known as Okazaki fragments.
These Okazaki fragments are attached together when the RNA primers are withdrawn and replaced by DNA. It is hard to link an RNA primer to the end of the lagging strand, implying that a little portion of DNA is lost each time the cell divides. This ‘end replication problem’ has massive repercussions for the cell because it means that the DNA sequence cannot be reproduced correctly, resulting in the loss of genetic material.
In order to prevent this, telomeres are repeated hundreds to thousands of times at the end of the chromosomes. Each time a cell divides, a little part of telomeric sequences is lost due to the end replication problem, preserving genetic material. Telomeres become severely short at some time. Cell senescence, in which the cell is unable to divide, or apoptotic cell death results from this depletion. The Hayflick limit, or the number of times a cell can divide before approaching senescence, is based on telomeres.
What Happens to Telomeres as We Age?
Each time a cell divides, the ends of the telomeres of each chromosome lose 25-200 nucleotides.
Through cell division, two primary factors contribute to telomere shortening:
End replication problem: During DNA replication, there is an issue known as the “end replication problem”: Each cell division results in the loss of roughly 20 base pairs.
Oxidative Stress: A loss of 50-100 base pairs every cell division is due to oxidative stress. Lifestyle factors such as food, smoking, and stress are thought to influence the level of oxidative stress in the body. The chromosome reaches a ‘critical length’ when the telomere becomes too short, and it can no longer be duplicated.
How Is Telomere Length Maintained?
In our somatic cells, telomerase activity is only found in trace amounts. Because these cells do not use telomerase regularly, they age and lose their ability to operate normally.
An aging body is the product of aging cells.
Germline cells (egg and sperm) and stem cells have high quantities of telomerase. Telomere length is maintained in these cells following DNA replication, and the cells do not age.
Cancer cells have large quantities of telomerase as well. This allows cancer cells to live forever and continue to replicate. Cancer cells’ telomeres would shorten until they reached a ‘critical length’ if telomerase activity was turned off. This would stop cancer cells from dividing out of control and becoming tumors.
Telomerase activity also keeps cells reproducing and prevents them from aging.
On a biological level, telomere shortening is implicated in every element of the aging process. The length of our telomeres represents our biological age rather than our chronological age.
There is a clear link between short telomeres and cellular aging, according to numerous scientific research.
Accelerated Telomere Shortening May Increase the Pace of Aging
In humans, telomere length appears to be decreasing at a rate of 24.8–27.7 base pairs per year. A telomere length that is shorter than the average telomere length for a given age group has been linked to an increased risk of age-related disorders and/or a shorter lifespan. Donor age, epigenetic make-up, genetic, and social, environmental, and economic status, body weight, exercise, and smoking are all factors that influence telomere length. The rate of telomere erosion does not appear to be influenced by gender. Senescence and/or apoptosis occur when telomere length falls below a crucial threshold.
Many age-related health concerns, such as coronary heart disease, diabetes, increased cancer risk, heart failure, and osteoporosis, are linked to accelerated telomere shortening. Individuals with leukocyte telomeres that are three times shorter than the average telomere length are three times more likely to develop myocardial infarction. When telomere length is measured in elders, it is discovered that those with shorter telomeres have a substantially greater death rate than those with longer telomeres. Telomere shortening that is excessive or rapid can have a variety of consequences for one’s health and lifetime.
Shorter telomeres can cause genomic instability by facilitating interchromosomal fusion, which can lead to telomere stabilization and cancer formation. In most cancer cells, telomerase activity is consistently higher, although telomere length is continuously decreased when compared to equivalent control cells.
We discovered that cancer cell lines and primary cancer cells purified by laser capture microdissection have shorter telomeres. In immortal/cancer cells, however, blockage of telomere maintenance mechanisms and continuous telomere shortening causes senescence and/or apoptosis. Shorter telomeres have been linked to an increased risk of cancer in several studies. Bladder, renal cell, lung, gastrointestinal, head, and neck cancers appear to be more common in people who have shorter telomeres. Certain people may be born with shorter telomeres or suffer from a genetic condition that causes shorter telomeres. Premature aging and premature coronary heart disease are more likely in these individuals.
Use of Telomeres in Medicine
Telomeres and the role of telomerase are being studied in the hopes of learning more about how to slow down the aging process and fight cancer.
The medicinal significance of telomeres is debatable.
Because the length of telomeres is not maintained after cell division, normal human cells cultivated in the lab have been found to stop dividing when telomerase is inactivated. The cells then enter a dormant state known as senescence. On the other hand, the cells can continue to divide after telomerase is reactivated.
It may be possible to mass create cells for transplantation if telomerase can let human cells live forever. These cells may then aid in the treatment of a variety of ailments, including severe burns and diabetes.
Is It Possible to Lengthen Your Telomeres?
Because of the link between telomere shortening and disease, some people are looking for strategies to prolong their telomeres. Is this, however, even possible?
Telomere lengthening research is still in its early stages. However, so far, the outcomes are promising. While it’s uncertain whether you can prolong your telomeres, there are probable ways to slow down the process.
A short pilot study from 2013 looked at the telomere length of 10 men with low-risk prostate cancer. They were asked to adopt the following lifestyle changes:
- consuming a nutritious diet
- daily exercise
- stress management through yoga and support groups
The 10 men with low-risk prostate cancer who made the lifestyle changes had longer telomeres five years later than the 25 who didn’t. Again, this was a small study with just guys participating.
This modest study, on the other hand, lays the groundwork for more recent studies into the effects of food, exercise, and stress management on telomere length.
Why Do Telomeres Get Shorter?
Each time a chromosome duplicates, your DNA strands get a little shorter. Telomeres aid in the prevention of gene loss throughout this process. However, your telomeres can shrink when your chromosomes duplicate.
This is where the enzyme telomerase comes in. It is found in some cells and aids in the prevention of excessive wear and tear. Your telomeres can shrink as a result of this. Telomerase does this by attaching telomere sequences to your chromosomal ends.
Since telomerase is absent from the majority of your body’s cell types. It suggests that the majority of your telomeres are shortening with time.
Telomeric DNA repairs oxidative damage less well than other parts of the chromosome, and oxidative stress speeds up telomere degradation while antioxidants slow it down. Oxidative stress shortens telomeres and telomere-driven replicative senescence is essentially a stress response. This could have developed to stop cells from growing if they were at high danger of mutation.
Telomeres and Cancer
Telomeres and telomerase are two possible targets for developing novel cancer treatments.
Cancer cells have active telomerase, which allows them to become immortal and divide uncontrollably. This is a disease in which cells divide rapidly and without control. These cells would become dormant, stop dividing, and finally die if telomerase activity was not present.
Drugs that block telomerase activity or destroy telomerase-producing cells have the potential to halt and kill cancer cells. This could have an impact on cells that rely on telomerase activity, such as sperm, platelets, eggs, and immune cells.
Disrupting telomerase in various cell types could have an impact on fertility, wound healing, and infection resistance. Telomerase activity in somatic cells, on the other hand, is quite low. The anti-telomerase medication would consequently have little effect on these cells.
Telomere biology is extremely essential in human cancer, and scientists are working hard to figure out how to best apply what they’ve learned to improve cancer treatments.