German zoologist Friedrich Leopold August Weismann in 1889 in his work “Essays on Heredity and Relatedness of Biological Problems” for the first time tried to explain the problem of aging from a scientific point of view.
А. Weismann considered aging to be the result of evolution: “…non-aging organisms are not only not useful, but also harmful, since they take the place of young ones”, which is why, in his opinion, evolution leads living organisms to aging.
The idea of aging as a result of evolution was debunked by English biologist Sir Peter Brian Medawar in 1951 in a report to the Royal Society of London entitled An Unresolved Problem in Biology. He noted that animals in nature rarely live to old age, so the course of evolution has no effect on the aging process.
In 1960, Medawar, together with the Australian virologist Sir Frank Macfarlane Burnet, received the Nobel Prize in Physiology or Medicine “for the discovery of artificial immune tolerance”, but they could not explain anything specific about the causes of aging. The deciphering of DNA structure in 1953 did little to clarify either, only posing even more questions to scientists with many unknowns.
British biologist Francis Crick, American biologist James Dewey Watson and British-New Zealand scientist Maurice Hugh Frederick Wilkins were credited with deciphering the structure of DNA in 1962.
In those years, scientists were inclined to believe that the human cell was capable of proliferation in the body and could reproduce indefinitely in culture. If this were true, it would mean that people age and die not according to the program of cellular degradation, but due to extracellular processes occurring at a higher physiological level (Kvitko A.V., Koneva I.I. et al., 2000).
Only forty years later scientists began to approach more or less general views on the theory of aging. In 1961, the American scientist Leonard Hayflick, professor of anatomy at the University of California in San Francisco, discovered that even in ideal conditions the cell is capable of dividing only a limited number of times, and that as this limit is reached, the signs of aging appear. Hayflick L., Moorhead PS, 1961).
The division limit is established for cells of almost all multicellular organisms. The greatest number of divisions depends on the type of cell and on the organism. It was found that for most human cells this limit is 52 divisions. It was also found that as the age of the donor increases, the number of divisions decreases significantly.
That is, in the body of any living being there is something like a “biological clock”, a division counter that sets a limit on the total number of cells (Hayflick L., 1998). This limit is called the Hayflick limit.
How does this “counter” work? In 1971, the Soviet scientist Alexey Olovnikov, based on data on the principles of DNA synthesis in cells, proposed the theory of marginotomy (the theory of marginotomy), explaining the mechanism of such a “counter”. According to Olovnikov, during matrix synthesis of polynucleotides DNA polymerase is unable to fully reproduce the linear matrix; the replica comes out always shorter than its initial part. Thus, with each cell division the DNA is shortened, which limits the proliferative potential of the cells and seems to be the “counter” of the number of cell divisions (Olovnikov AM, 1971).
In the late 1980s, a series of discoveries by scientists Elizabeth H. Blackburn, Jack W. Szostak, and Carol W. Greider confirmed Olovnikov’s hypothesis. It was these three scientists who were awarded the Nobel Prize in Physiology or Medicine in 2009. They managed to figure out the mechanism by which chromosomes are copied completely during cell division, that is, somehow the chromosomes are protected from degradation.
The solution was found at the ends of the chromosomes: the telomere (from the Greek Telos – end and meros – part, a name suggested by Herman Joseph Meller in 1932) and the enzyme that forms the telomere, telomerase. The long spirals of DNA molecules carrying gene information are packed into chromosomes that have telomeres, protective caps, at their ends.
It has been found that the shorter the telomere, the older the cell, and vice versa, if telomerase activity is high, the same telomere length is constantly maintained – the cell does not age, but there is a danger of cancer cells developing, also striving for immortality. Certain hereditary diseases are characterized by the presence of defective telomerase, which leads to rapid aging of the cell. The mysterious telomere of a chromosome contains a genome, the carrier of which is a DNA molecule.