Nataliia Bohdanova

In1961, Leonard Hayflick, a professor of anatomy at the University of California, San Francisco, observed that human fibroblast cultures stop dividing after approximately 50 cycles. Even after various interventions, such as freezing the cells or altering their cultivation conditions, the cells “remembered” the number of previous divisions and continued dividing only up to the remaining limit before reaching the 50-division threshold. This phenomenon, known as the Hayflick Limit, formed the basis of the hypothesis that the human lifespan is genetically programmed.

Toexplain Leonard Hayflick’s experimental findings, theoretical biologist and expert in the biology of aging Alexey Olovnikov proposed the theory of marginotomy. This theory describes cellular aging and the limitation of cell divisions as a result of incomplete replication of DNA sequences at the ends of linear chromosomes — the telomeric regions. According to the theory, bacteria do not “age” due to the circular structure of their DNA, while in stem and cancer cells, telomeres are protected by constant elongation during each division. This elongation is facilitated by a specific enzyme, originally called tandem DNA polymerase (now known as telomerase). Eleven years later, scientists at the University of California, Berkeley, successfully isolated telomerase from cells, confirming the hypothesis.

The Hayflick Limit: Theories and Observations

Several theories explain the nature of the so-called Hayflick Limit.

Leonard Hayflick, together with Paul Moorhead, conducted experiments that revealed normal cells have a limited capacity for division, unlike cancer cells, which are considered immortal:

1. Normal human fetal fibroblasts in culture can divide only a limited number of times.
2. Cells that have undergone cryogenic treatment retain a “memory” of how many times they divided before freezing.

The main theory suggests that the Hayflick Limit is associated with the accumulation of random genetic damage during each replication cycle. Various factors, both external and internal, influence the process of cell division, including radiation, chemical substances, and metabolic byproducts. All these factors interfere with the precise copying of DNA in daughter cells.

Although cells possess DNA repair mechanisms that address many transcription errors, it is impossible to eliminate all of them. Over time, with repeated cell divisions, these damages accumulate, leading to disruptions in protein synthesis and cell function. As a result, diseases associated with aging, such as cardiovascular conditions and tumors, begin to develop.

Telomeres and the Hayflick Limit

Another theory links the Hayflick Limit to telomeres — non-coding repetitive DNA sequences located at the ends of chromosomes. The primary function of telomeres is to protect genetic information. Telomerase, a specialized enzyme, lengthens telomeres, allowing DNA polymerase to synthesize complete copies of chromosomes, including their terminal regions.

During cell division, the DNA strands unwind, and copies are created for the next generation of cells. However, with each division cycle, telomeres gradually shorten; the daughter cells inherit slightly shorter telomeres than the parent cell. This process is referred to as terminal under-replication. Once telomeres reach a critical minimum length, further cell division becomes impossible, leading to cell death. Thus, terminal under-replication is a key factor in aging, and telomere length is considered an indicator of an organism’s biological age.

Anexample of this phenomenon is Dolly the sheep, cloned from the somatic cell of an adult animal. Her telomeres were as short as those of the donor adult organism, rather than resembling those of a newborn lamb. This was one of the reasons for her relatively short lifespan.

It is worth noting that there are three types of cells to which the Hayflick Limit does not apply: germ cells, cancer cells, and certain types of stem cells. Cancer cells produce the enzyme telomerase, which restores telomeres at the ends of chromosomal DNA, enabling their unlimited division and uncontrolled growth.

Telomerase and Nobel Recognition

The ability of telomeres to lengthen through a specific enzyme was first predicted by Alexey Olovnikov, who proposed that telomerase acts as a template. Years later, this was demonstrated by American scientists, for which Elizabeth Helen Blackburn, Carol Greider, and Jack Szostak were awarded the Nobel Prize in Medicine in 2009 with the citation: “for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase.”

Experiment with Telomerase: Elizabeth Parrish

InSeptember 2015, 44-year-old Elizabeth Parrish, the CEO of the pharmaceutical company BioViva, became the first person in the world to attempt genetic modification to delay aging. She used a special virus to activate the enzyme telomerase in her body. There is a hypothesis that this method can extend youth, and Elizabeth hopes to prove it through her own experience.

Stages and Results of the Experiment

The experiment was conducted in two stages:

1. Addressing muscle dystrophy and sarcopenia: By the age of 80, humans lose up to half of their muscle tissue. In this experiment, scientists used myostatin to combat this process.
2. Slowing cellular aging: This process is directly linked to the length of telomeres, which naturally shorten with age.

The results were remarkable. From 2013 to 2015, telomere length increased by 20% and continued to grow. In 2015, the telomeres measured 6.71 kb, but by 2018, their length had reached 8.12 kb, corresponding to the biological age of approximately 30 years. Thus, the 48-year-old woman effectively reversed her biological age by 15 years. Furthermore, research on Elizabeth’s body confirmed that her muscles were also in excellent condition.