Point of view of biomedicine: would telomeres bring immortality to humans?

Los Angeles, California, United States - 01-19-2023 (PR Distribution™) -

The way a little part at the end of the human chromosome can influence our understanding of the life cycle.

At the ends of each of our chromosomes there are little areas called telomeres. Opposed to the rest of a chromosome, telomeres do not encode any information. Being present in the majority of organisms, in vertebrates it is a TTAGGG sequence and in plants it is TTTAGGG.

In the process of cell division, all the DNA is replicated — the coding part with the information and telomeres at the ends. However, there is a part which is not replicated. Certain peculiarities of the DNA polymerase (an enzyme taking part in DNA replication) influence the process, making the strand of each chromosome shorter after every division. New shorter strands are known as under-replicated.

Obviously, with the loss of a part of a strand upon every division, we would lose a part of information. This is where telomeres stand guard: under-replication only happens to the telomere region, thus the DNA code itself is not damaged. Telomeres have certain limits, though: in the majority of cells telomeres can survive about 50 divisions. This limit was discovered by the anatomist Leonard Hayflick and thus is named after him ‒‒ the Hayflick limit. After those 50 divisions are done, telomeres become too short to support their function, which leads to apoptosis (programmed cell death).

Experiments on humans

Holding human experiments are by far more complicated than stem studies or even animal tests. Also, the results with humans differ profoundly. 

One of the well-known human experiments with telomeres is a study by Elizabeth Parrish. Being the first (and, probably, the only) client of BioViva company, she states that she was injected with viruses charged with telomerase-producing and follistatin genes. The aim was to prove that telomeres should rejuvenate the cells making telomeres longer and the follistatin should block myostatin (a protein inhibiting the growth of muscle).

In 2016 the first paper on this experiment was published. The reaction was varied. Media presented this paper as a new medical breakthrough, while Parrish’s colleagues-scientists were much less enthusiastic. Parrish stated that she looked 20 years younger than her real age based on the average speed of telomere loss. According to her, the telomerase from injections made her telomeres longer by the same amount that would be lost over 20 years. However, the conclusion that it made her body 20 years younger was rather bogus.

Later scientists ran some checks on her studies and found out that the way of telomere measurement was not reliable enough to be accepted.

Parrish did not stop with the publication of her first results. In order to support her findings, she compared MRI scans of her thighs from before the injections and two years after. She claims that decreased muscle fats prove the effect of follistatin. Again, the scientific community debunked her findings: the MRI pictures do not clearly show any significant difference and could be explained by only different positions of the body during both scans. Also, scanners used “before” and “after” might have been different, hence the difference in the pictures.

Currently, there is one more similar experiment on the way: Libella Gene Therapeutics, a new startup, aims to hold similar research. In 2019 they planned to start a clinical trial on the transduction of active telomerase in order to retard aging and treat Alzheimer's disease and critical limb ischemia therapy. However, the company is still recruiting volunteers, so there is no more information about the advancement of their project so far.

Do telomeres hold any future for us? 

The medical industry is already working on drugs affecting telomerase. Their main application is to help cure cancer. Scientists are now trying to prove that by fighting telomerase activity in cancer cells we can make the cancer development slower or even stop it altogether.

The most complicated part of the task is to create a drug that is going to target only telomerase in cancer cells, not in healthy cells of our body, as, obviously, its suppression in other cells (e.g., reproductive cells) would be dangerous.

In this research, scientists employ artificial intelligence and machine learning technologies. They help search for a good drug substance. One of the applications of IT is to interpret big amounts of data from a genome-wide screening — for one of the experiments scientists needed to hold a genome-wide functional screening of cancer cell telomerase genes. They were trying to point out promoter mutations leading to increased enzyme activity. Once they identify the mutations, we could try to suppress the enzyme activity with a specific therapy.

Since almost any research now includes big data analysis, it is virtually impossible to go without a supercomputer for analysis. Using the computer makes finding or designing a necessary drug faster and easier. If we are ever able to find a drug that can suppress telomerase in cancer cells only, leaving out other functional cells, it is not going to be done without a computer.

At this point, it is already clear that the length of telomere and the activity of telomerase are not the only factors to be taken into account for fighting aging and age-related conditions. Even though they are important factors, the extent of their influence is limited. 

About the author 

Rustam Gilfanov, investor, benefactor, and a partner of the LongeVC fund.

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