Are telomeres the key to living forever?

From Alexander the Great’s quest for the fountain of youth to Qin Shi Huang’s search for the legendary elixir of life, immortality has been sought after since the dawn of humanity. In the 1930s, Barbara Mcclintock and Hermann Muller discovered the telomere, a barrier that exists on the ends of chromosomes that could stop aging.

A telomere protects the ends of chromosomes from being cut off or joining onto the ends of other chromosomes, which could lead to problems for a human cell such as the misfolding of proteins that could be catastrophic to cell function. Telomere dysfunction has also been linked to signs of aging like mitochondrial dysfunction, genomic instability, senescence, and stem cell exhaustion. 

When cells divide, telomeres become shorter and eventually deplenish. In cells that divide rapidly, an enzyme called telomerase replenishes these short telomeres so that they can continue to protect the chromosomes. It is possible for these telomeres to continuously be replenished in all cells if telomerase is also present in all cells. However, telomerase activity is not present in most human cells. 

A study conducted by scientists at the Stanford University School of Medicine in 2015 attempted to remedy this by using modified mRNA containing the coding sequence for TERT – the active component of telomerase – to extend telomeres in normal human cells. Furthermore, an advantage of this newly developed technique was that it was temporary, allowing for research to be done on extending human telomeres without any possible side effects of permanently inducing the production of telomerase. However, are telomeres really the fountain of youth that they appear to be?

While telomerase is essential to human cell function and extends the number of times a cell can replicate, they also cause these cells to accumulate far more mutations than any normal cell would in its lifespan by preventing apoptosis. This prevention of apoptosis is also a key function in preventing the formation of cancer, which is caused by mutations in human cells.

Furthermore, a study published in the New England Journal of Medicine in 2023 found that longer telomeres caused by a mutation in the POT1 gene was associated with a range of benign and malignant tumors, further suggesting that longer telomeres may not be entirely positive.

While the study’s results may seem concerning, its reliability is limited by its small sample size that only included 17 people with the POT1 mutation.

While recent research into telomerase has yielded unfortunate results, it is important to note that more research has to be done into telomerase and lengthening telomeres to rule them out as tools to extend our lifespans.

Sources: The New England Journal of Medicine, National Centre for Biotechnology Information, Mia Rochelle Lowden, Stanford Medicine