- When the protecting ends of our chromosomes, called telomeres, wear down, our cells stop dividing and become senescent.
- This is one method the body uses to prevent cells with DNA damage from multiplying and dividing uncontrollably, which can lead to cancer.
- However, the gradual buildup of senescent cells contributes to aging-related disorders such as cardiovascular disease, diabetes, and dementia.
- A new study sheds light on how telomeres promote cellular senescence and age-related diseases.
Every time a cell divides, its chromosomes — the DNA bundles that code for genes — shorten a bit.
This is due to the fact that the cellular machinery for replicating DNA is incapable of copying the molecule all the way to the ends of each strand.
Telomeres preserve the ends of the chromosomes to prevent critical genetic information from being lost every time the cell divides.
These are expendable DNA strips that don’t contain any important information.
The telomeres, on the other hand, decay with each cell division until they can no longer preserve the chromosome.
A control mechanism kicks in at this moment, stopping the cell from dividing any further. The cell stays active and alive, but it undergoes senescence.
As people get older, their bodies develop senescent cells.
The disadvantage is that senescent cells increase inflammation, which experts believe is at the root of many aging disorders, such as cardiovascular disease, diabetes, and Alzheimer’s disease.
Researchers at the Université de Montréal in Montreal, Canada, have proposed a novel idea regarding how cells become senescent after observing cultures of human skin cells in their lab.
Their approach improves on the popular senescence idea, which states that cells cease proliferating when their telomeres get too short and stop functioning correctly.
Instead, the researchers argue that cells cease dividing only when chromosomal instability caused by telomere shortening causes irreversible genetic damage during cell division.
“What’s most surprising is that before really entering senescence, the cells divide one last time,” says senior author and cancer researcher Francis Rodier, Ph.D.
“In fact, telomere dysfunction causes such unstable cell division that it results in genetic abnormalities,” he says.
As a result, the researchers believe senescent cells’ genomes are defective.
Professor Rodier explains,
“Contrary to what was believed, senescent cells have an abnormal genome,”
The results of their research were published in the journal Nucleic Acids Research.
Aging skin cells
If a telomere becomes defective, a “DNA damage response” mechanism is activated, according to the established model of cell senescence.
As a result, a protein called p53 is activated, which stops cell division. The protein is recognized to have an important function in the prevention of cancerous tumor development.
According to the notion, a single damaged telomere should be enough to stop cell division.
However, various research groups have discovered that normal mammalian cells may have several damaged telomeres and still divide.
Prof. Rodier and his colleagues took a series of photographs of individual skin cells as they split and became senescent in order to learn more.
They discovered that defective telomeres initially just hindered cell division.
A cell only stopped dividing when its chromosomes began to clump together, which is generally prevented by functioning telomeres, resulting in irreversible damage.
Telomeres, like the main body of the chromosome, are made up of two strands of DNA.
The double strands of each chromosome unzip to generate two single strands of DNA when the cell divides. These combine with individual DNA building blocks (or nucleotides) to produce two copies of each chromosome, resulting in the formation of two new cells from each half of the dividing cell.
The two daughter chromosomes are known as sister chromatids.
A telomere that has been broken, on the other hand, has a sticky “loose end.” This is a single strand of DNA that can loop back on itself or cling to another damaged telomere, similar to the loose end of a roll of sticky tape.
A cell only became senescent after the damaged telomeres of two sister chromatids irreversibly united during cell division, according to the researchers.
Can we prevent senescence?
The findings might aid in the prevention of age-related diseases.
The scientists write in their report that:
“Paradoxically, our work reveals that senescence-associated tumor suppression from telomere shortening requires irreversible genome instability at the single-cell level, which suggests that interventions to repair telomeres in the pre-senescent state could prevent senescence and genome instability.”
Senescent cells may have a role in the low-level inflammation that underpins age-related illnesses, known as “inflammaging.”
Prof. Rodier told Medical News Today, “We believe that genomic instability plays a major role in initiating senescence-associated inflammation.”
“[I]t is possible that therapies aiming at protecting telomere ends before fusions occur would prevent genomic instability and senescence,” he stated “.
Cells with faulty telomeres that have yet to fuse, on the other hand, may have additional properties, such as altered gene expression, that contribute to inflammaging.
“If they do, then simple telomeric correction might not be enough to completely bring them back to normality,” Prof. Rodier noted.
The number of times a cell may divide is limited by telomere shortening.
This rule does not apply to sperm and egg cells. In these circumstances, an enzyme called telomerase rebuilds telomeres to guarantee that the following generation inherits a full, functional genome.
Cancer cells are an exception, as they can achieve “immortality” by activating the telomerase gene.
Prof. Lingner told MNT that telomerase is elevated in 90% of tumors and is responsible for cancer immortality.
According to him, a person’s telomere length is also linked to their risk of acquiring cancer.
Preventing telomere shortening, therefore, would virtually probably increase cancer growth.
Prof. Lingner said, “Thus, this strategy to counteract senescence-related disease would be extremely risky,”