Telomeres: what they are, characteristics and how they are linked to ageing

Let's see what telomeres are and how they relate to health and aging

Time passes for everyone, and that is an undeniable reality. It is impossible to conceive of life without death.For all organic matter degrades, loses form and transforms. Without going any further, the most adequate definition we can think of to define life from a biological point of view is the following: the intermediate state between birth and death.

Time passes in an inalienable way, yes, but you will be surprised to know that it does not do so equally for everyone. Chronological (chronometric) age indicates the movement of the hands of the clock, but this physical magnitude has nothing to do with what happens inside our bodies. The phases of a biological process do not have the same quality or nature as those of a physical process as merely successive.

In the physiological study of living beings, the phases of a process are determined by the dynamics of the "intrinsic process" and not by the impositions of a physical element, such as a clock. Thus, a 40-year-old alcoholic may have the liver of an 80-year-old, for example, while an octogenarian athlete may have the lower body musculature of a 60-year-old sedentary person. Time passes, yes, but biological age may be different from what the calendar indicates..

Many of the parameters that modify the biological age of living tissues are completely linked to the individual's lifestyle, but there are other complex and fascinating concepts that explain, in part, why the cellular aging process is unique and interchangeable. We explain the secret of life and death with a term that is as exciting as it is useful: learn all about telomeres..

How are chromosomes organized and where are the telomeres?

Let's start from the beginning, like life itself. We human beings present, in each of our cells, DNA enclosed in a nucleus. Through a series of processes that do not concern us here, the DNA information is transported from the nucleus to the ribosomes in the cell cytoplasm, so that they can synthesize proteins. Protein synthesis is the basis of the metabolism of living organisms, so it could be said that DNA contains all the information necessary for life to exist..

In humans, DNA condenses into chromatin, forming chromosomes. Each non-sexual cell in our body (in general) has 23 pairs of chromosomes (46 total), of which 23 come from the female gamete (n) and 23 from the male gamete (n), which together form a zygote (2n). The parts of a chromosome are as follows:

• Film and matrix: each chromosome is bounded by a membrane enclosing a jelly-like substance.
• Chromonemes: filamentous structure that makes up each of the sister chromatids (one chromatid being each half of the "X" shaped chromosome).
• Chromomeres: succession of granules that accompany the chromoneme along its length.
• Centromere: place where the two sister chromatids meet. For the sake of clarity, it is the center of the "X".
• Telomeres: the terminal parts of the chromosome, its "tips".

We have left out some specific sections in order not to get lost in technicalities, but we have already come across the term that concerns us here for the first time. It is time to explore it in depth.

What are telomeres?

Based on what we have seen so far, the telomere is almost self-defining: it is the tip of the chromosome. Telomeres are highly repetitive regions of non-coding DNA (they have no information necessary for protein synthesis), whose function is to give stability to chromosomes in eukaryotic cells throughout their lifetime. Based on the existence of these structures, we can partially explain two phenomena that take the breath away from every human being: aging and cancer. Let's see how.

1. During DNA replication, telomeres do not replicate in their entirety.

Somatic cells divide by mitosis and, for this to be possible, the DNA of the primordial cell that will give rise to the offspring lineage must be duplicated. With each replication process, and due to certain characteristics of the enzymes that make it possible, the telomeres are shortened..

Telomere length in humans decreases at a rate of 24.8-27.7 base pairs per year. With time and cell division, the telomeres of the chromosomes of the descendant cells become so short that the cell can no longer divide and thus, with the death of the last cellular entities, tissue death occurs. To make a "walking around the house" parallelism, it is as if we remove a little water every time we pass it from one glass to another. At first it may not be noticed, but after repeating the process X times, the transfer can no longer be done, because there is no water left to transfer.

For this reason, telomeres are said to be an excellent marker of biological age.Based on their length, scientists can estimate how much longer a cell group, and thus the entire organism, has left to live. Telomeric shortening is part of the normal aging process, but certain agents associated with a specific lifestyle can promote chromosomal DNA damage and thus faster telomere shortening.

2. The importance of telomerase

We have explained the mechanism of aging, but things get even more interesting if we know that, incredible as it may seem, the body itself has the solution for immortality at a theoretical level, at least in the first stages of life.

Telomerase is an enzyme responsible for maintaining the length of telomeres by adding repeated genetic sequences to the telomeres.. This biological process has a "trick": the activity is present in germline cells and certain hematopoietic cells, but mature somatic cells inhibit its functionality after birth. Thus, it is the organism itself that encodes its programmed degradation.

3. Telomeres and cancer

Current studies suggest that humans could reverse the process of cellular senescence by artificially increasing telomerase activity in the somatic cells that form the tissues of our body. Unfortunately, this could have a double effect: in experimental settings, if telomerase activity is stimulated and certain tumor suppressor genes are inactivated, cellular immortalization takes place that promotes cellular immortalization that significantly promotes the appearance of a tumor..

We go further along this line of thought, as 75-80% of cancers arising from somatic cells have telomerase activity. This does not necessarily mean that telomerase causes cancer, but everything seems to indicate that high levels of this enzyme are a clear indication of the possible malignancy of a tumor. If a cell is immortal, it can replicate indefinitely: we are explaining almost word for word the formation of cancer.

Based on this premise, various anti-telomerase treatments are being developed at the experimental level. In cell cultures, the results are promising to say the least: in some Cancer cell lines, inhibition of telomerase activity leads to spontaneous death of the lineage after about 25 divisions.The telomeres are shortened and cannot be replenished in any way.

Summary

After being exposed to data like this, it is impossible not to feel hopeful. Cancer is one of the most important and tragic health problems today, because behind every death and every number there is a story of struggle, sadness and hope. A neoplastic tumor is not just a cluster of cells growing out of control: it is fear, a battle of science versus physiology, acceptance or denial and, in the worst cases, the early loss of a life.

The mechanisms of cellular senescence help us understand tissue aging and the process that leads to death, but the ultimate goal is not to find immortality. The real challenge, today, is to save all those lives hanging by a thread because of a group of rebellious cells that mutated to turn against us. that mutated to turn against their host.

Bibliographic references:

• Arvelo, F., & Morales, A. (2004). Telomere, telomerase and cancer. Acta Científica Venezolana, 55, 288-303.
• Couto, A. B. (2008). Telomerase: source of youth for the cell. Medisur: Revista Electrónica de las Ciencias Médicas en Cienfuegos, 6(2), 68-71.
• Influence on telomeres lifestyle and longevity, genotypy. Retrieved March 4 at https://genotipia.com/estilo-vida-telomeros-longevidad/.
• Membrive Moyano, J. (2017). Telomerase enzyme as a therapeutic target.
• Moyzis, R. K. (1991). The human telomere. Research and Science, (181), 24-32.
• Salamanca-Gomez, F. (1997). Telomerase. Immortalizing without maligning. Gac Med Mex, 8, 385.
• Telomere, NIH. Retrieved March 4 at https://www.genome.gov/es/genetics-glossary/Telomero.
• Vargas, E., & Espinoza, R. (2013). Time and biological age. Arbor, 189(760), 022.