Telomeres are the ends of chromosomes, which have an essential role in protecting their integrity in the process of cellular replication. One common analogy is that they are like the plastic caps at the end of shoe laces which keep the laces from unraveling. Telomeres are formed by tandem repeats of a DNA sequence, which is highly conserved (TTAGGG in vertebrates) and associated proteins (the so-called telomere-binding proteins or “shelterins”). The function of telomeres is to protect chromosome ends from chromosome fusions and degradation, therefore, ensuring the proper functionality and viability of cells. Why are telomeres important?
Cells stop duplicating when telomeres become too short. Therefore telomere length is considered to be an excellent biomarker of tissue renewal capacity and, consequently, of organismal aging. Telomeres progressively shorten with increasing age as a consequence of cumulative cycles of cell division that are required for tissue repair and regeneration. This occurs both in differentiated cells as well as in the stem cell compartments, and this shortening has been demonstrated to impair the ability of stem cells to regenerate tissues when needed. There is strong evidence from genetically modified mouse models demonstrating that accumulation of critically short telomeres is sufficient to cause organismal aging. lntervention that decrease the rate of telomere shortening with age, such as forced expression of the telomere-synthetizing enzyme telomerase, is also sufficient to delay aging and increase longevity. Thus, therapeutic strategies based on telomerase activation are envisioned as potentially important for intervening in age-related problems. Telomeres and telomerase are also relevant for cancer biology. More than 85% of all types of tumors activate telomerase during their formation in order to achieve immortality. Telomerase is, therefore, considered necessary to sustain cancer growth. Therapies aimed at inhibiting telomerase activity are currently tested in clinical trials of various types of human tumors.
