Not always and not everywhere the life cycle of a cell is predetermined by telomeres. There is a mechanism that makes a cell virtually immortal, and its name is telomerase.

The existence of telomerase was predicted back in 1974 as a way to explain the absence of aging in some cell types – both healthy (stem cells) and pathologically altered (e.g., cancer cells). The existence of this enzyme was predicted by 45-year-old Soviet scientist Mikhail Olovnikov, who called it tandem-DNA polymerase. Seven years later, in 1981, American Elizabeth Blackburn confirmed Olovnikov’s theory by isolating the enzyme.

Together with her graduate student Carol Greider, Blackburn isolated and purified the enzyme, showing that in addition to proteins, it also contains RNA. By the mid-1980s, a series of experiments showed that organisms with mutations in telomerase RNA have accelerated telomere shortening and that the cells of these organisms develop very slowly and eventually stop growing. Elizabeth Blackburn confirmed this phenomenon in tetrachymen (freshwater infusoria), Carol Greider in human cells and another American scientist, Jack Szostak, in yeast culture. These three scientists have one more thing in common: in 2009 they were awarded the Nobel Prize “for the discovery of how telomeres and the telomerase enzyme protect chromosomes”.

These discoveries turned the corner on the genetics of aging. Many scientists vied with one another to declare that telomerase was the key to eternal youth, not just for a single cell, but for the body as a whole. However, further events showed that it is not that simple – and one single key will not open all the doors. But more about that later.

Diseases related to telomeres and telomerase
Dysfunction of telomerase and telomeres leads to many pathological conditions and diseases. Most of them were described long before the discovery of the “immortality enzyme”, in the first half of the 20th century. For example, in congenital dyskeratosis, due to gene mutations and related TERT and TERC defects, patients’ telomeres are very short. This leads to a disruption of the normal division cycle in most cells and increased genomic instability.

Perhaps the most well-known disease associated with telomere defects is infantile progeria, or Hutchinson-Gilford syndrome. In this disease, there is a mutation in the LMNA gene, which is responsible for the synthesis of laminin, a protein that is part of the envelope of the cell nucleus. The defective form of laminin, called progerin, disrupts many genetic processes, including severely shortening telomeres.

Some diseases involve telomere dysfunction, which only further undermines an already weak body. Such is Huntington’s chorea, an autosomal dominant genetic disease. It is not caused by telomeres, but by a gene encoding a protein called huntingtin, which has a function that scientists do not yet know. However, among other things, the development of Huntington’s chorea entails a shortening of telomere length. A study conducted by Mexican scientists showed that patients with manifesting symptoms had telomeres about one and a half times shorter than in healthy individuals or in patients at an early stage.

As telomere length decreases, the cell can either die normally or degenerate into cancer. / ©researchgate.net
As telomere length shortens, a cell can either die normally or degenerate into cancer. / ©researchgate.net
Chantingtin accumulation in the mitochondria likely causes more reactive oxygen species to be produced there, leading to oxidative stress and telomere damage. At the same time, the mutant protein blocks the enzymes that are responsible for DNA repair, so the defective telomeres remain shortened.

And, of course, when talking about telomeres, we cannot ignore cancer. In this case the problem is no longer too short, but excessively long telomeres. An important fact: most often tumor structures arise exactly in the constantly renewing tissues, where telomerase activity is high even in the normal state.

This fact suggests that the normal state of our body and the way it ages is a natural “golden mean”, a way to keep the balance between aging too fast and becoming a mass of constantly proliferating cells. The study of telomerase in the context of cancer inevitably leads to the conclusion that long telomere length as such does not lead to either eternal or at least prolonged youth.

An excellent confirmation of this is in mice. Normally, telomere length in these rodents is noticeably longer than in humans: sometimes four to five times longer. In some lines of laboratory mice, the length of telomeric sequences can even reach 150,000 pairs of nucleotide bases (in humans this figure usually does not exceed 15,000 pairs). This is largely why laboratory mice are a popular model object for studying the mechanisms of tumor formation and treatment.