Telomeres are protein complexes with RNA that protect the end segments of linear DNA chromosomes, consisting of a repeating sequence of nucleotides. In humans and other vertebrates, the repeating unit has the formula TTAGGG (letters representing nucleic bases).
In 1971, Russian scientist Alexei Matveevich Olovnikov first suggested that with each cell division, these end segments of chromosomes shorten, leading to “replicative aging” of the cell. In other words, the length of telomeric segments determines the “age” of the cell – the shorter the telomeric “tail,” the “older” it is. This assumption was experimentally confirmed by English scientist Howard Cooke 15 years later. However, nervous and muscle cells in the adult organism do not divide, and their telomeric segments do not shorten, yet they still “age” and die. Therefore, the question of how a cell’s “age” is related to the length of telomeres remains open to this day. One thing is certain – telomeres serve as a kind of counter for cell divisions: the shorter they are, the more divisions have occurred since the birth of the predecessor cell.
The enzyme telomerase “works” in cancer cells, sperm, and egg cells. Its existence was also predicted by A.M. Olovnikov in the early 1970s. The enzyme was discovered in 1985 in ciliates and later in yeast, plants, and animals, including human ovarian and cancer cells.
Telomerase is an “extender” enzyme, its function is to build up the end segments of linear DNA molecules by “sewing” repetitive nucleotide sequences – telomeres – to them. Cells in which telomerase functions (germ cells, cancer cells) are immortal. In ordinary (somatic) cells, which make up the majority of the organism, telomerase “does not work,” so telomeres shorten with each cell division, eventually leading to cell death. In 1997, American scientists from the University of Colorado obtained the telomerase gene. Then, in 1998, researchers from the Southwestern Medical Center at Texas University in Dallas integrated the telomerase gene into human skin, retinal, and vascular epithelial cells, where the enzyme does not normally “work.” In such genetically modified cells, telomerase was “functional” – it attached nucleotide sequences to the ends of DNA, so the length of telomeres did not change from division to division. This method allowed scientists to increase the lifespan of ordinary human cells by one and a half times. It is not excluded that this method will help find the key to extending life. The length of telomeres, a marker of cellular aging, decreases with age, and this is associated with age-related diseases. Environmental factors, including dietary and lifestyle factors, influence the rate of telomere shortening, which can be reversed with telomerase. It is believed that the activation of telomerase by natural molecules is an anti-aging modulator that may play a role in the treatment of aging-related diseases. Some studies have shown that short telomere length is associated with age-related diseases, including cardiovascular diseases, stroke, cancer, arthritis, osteoporosis, cataracts, type 2 diabetes, hypertension, mental illnesses, chronic obstructive pulmonary disease (COPD), and dementia. The shortening of telomeres can be influenced by environmental factors such as physical activity, body mass index (BMI), hormone replacement therapy, smoking, chronic inflammation, oxidative stress, dietary antioxidants, and vitamins. For example, DNA damage caused by various environmental factors triggers a DNA damage response at telomeres, protecting them from instability and shortening. It is suggested that telomere length is a biomarker of somatic cell aging, whereas the rate of short telomere growth is associated with the lifespan of mammals. Indeed, when telomere length shortens below a threshold, cell growth is limited, and cells undergo cellular aging or apoptosis.
