Telomere research has its origins in the question of chromosome end protection, a very fundamental issue originally studied in yeast, maize and several protozoan organisms. In fact, the conservation of mechanisms and structures means that this work has opened the door to a number of questions of medical importance. This is often the case. Let me remind you that RNA interference was discovered from work on the color of petunia petals (the search for a deep purple), and retrotransposition from studies on the variegation of corn kernel colors within the same ear. None of this work, so rich in medical applications, would have been funded by an anti-cancer plan or a program to combat Alzheimer's disease. In these times, alas not new, when politicians of all stripes seem incapable of understanding the need to preserve and develop fundamental research, there are certain obvious facts that need to be borne in mind. Once we have been definitively left behind by our neighbors, it will be too late to whine about our loss of competitiveness. We can console ourselves with a visit to the amusement parks.
Telomeres are defined as the ends of linear chromosomes. They consist of repeated sequences protected by specific proteins. In sapiens, the telomeric sequence TTAGGG is repeated over several thousand bases (10 kb in umbilical cord blood, i.e. over 1500 repetitions of the basic sequence). Protein complexes constitute the shelterin (shelter or shelter) and their role is to prevent telomeres from being recognized as broken DNA and to prevent fusions between DNA fragments (preservation of genome integrity).
Numerous studies have confirmed the role of telomeres in cellular aging. In fact, the replication machinery cannot go all the way to the end of the chromosome, let alone beyond it, and reproduce itself, so to speak, underneath it. As a result, the end of the DNA cannot be copied, and the telomere diminishes in size with each division. Hence the idea that telomere size constitutes a molecular clock, and that after a certain number of divisions, cells enter senescence. There is, however, a compensatory mechanism based on telomerase, an enzyme which, as its name suggests, lengthens telomeres.
In fact, Armanios and Blackburn(Nature Reviews Genetics, 13: 693-xxx, 2012) point out that beyond the initial studies alluded to above, it was in the 1990s that telomeres were considered in the context of pathologies, particularly cancer, since telomerase activity is increased in most cancers, making this enzyme an important pharmacological target in oncology. This is easy to understand, given that tumor cells can multiply indefinitely, whereas normally each division shortens the number of divisions, and the cells should enter senescence and apoptosis fairly quickly (after around 24 divisions). The same problem applies to stem cells, including neural stem cells, on which I'll dwell at the end of the lecture. Are they depleted or protected by high telomerase activity? This is important because, as you'll recall, exercise increases neural stem cell proliferation (DIA V.2) by acting on the amplification compartment, since one of the properties of stem cells is that they divide very slowly. But I wouldn't go so far as to say that exercising is bad for your health, especially after I've already suggested that running causes holes in muscle membranes and that thinking breaks DNA. The only thing left to do would be to advise you to smoke cigars, and that would be the icing on the cake (DIA V.3).
In the early 2000s, the genetic basis of a disease called dyskeratosis congenita 1 (DKC1) was discovered with the identification of a gene encoding a protein called dyskerin, which was soon shown to be a subunit of telomerase. This pioneering work was followed by numerous other studies and, in recent years, the number of diseases explained by a telomere problem has increased enormously, leading to them all being grouped together under the term "telomere syndromes". These syndromes are primarily associated with age, and are marked by premature aging, since telomere shortening is an "acquired" part of aging.