The Hayflick limit is the limit of cell replication due to the shortening of telomeres with each division. The Hayflick limit is a concept in biogerontology that a culture of human cells divides in vitro only 48-50 times on average. The Hayflick limit, or Hayflick phenomenon, is the number of times a normal, differentiated population of somatic cells will divide before cell division stops.
The American anatomist Leonard Hayflick showed that a normal population of human embryonic cells will divide 40 to 60 times in cell culture before entering senescence. Shortening of telomeres in humans ultimately makes cell division impossible, and this aging of the cell population seems to be related to the general physical aging of the human body. It is true that our telomeres get shorter as we age, but only for certain cells and only for a certain amount of time.
Hayflick and Moorhead identified a specific type of cellular senescence that occurs after extensive proliferation resulting from telomere loss due to a marked reduction in endogenous telomerase activity. Interestingly, when the mutated RAS gene was introduced into normal cells, they did not divide as rapidly as expected when entering cancer cells, but stopped senescence. The mouse cells produced enough telomerase, an enzyme that replaces degenerated telomeres with new ones.
However, cancer cells tend to retain their aging response and use it in response to genotoxic stress. Such cells are hypersensitive to stress if the amount of growth factor ligand is otherwise limited. The result of each shortening was that these cells were more likely to age.
When we looked more closely at the structure and dynamics of telomeres, it became clear that the simple idea that each division cuts off some DNA and eventually causes the cell to stop dividing is false. A curious young biologist noticed that cells growing in culture reproduce by dividing. American anatomists Leonard Hayflick and Paul Moorehead mixed the same number of normal male human fibroblasts multiple times (doubling the cells in population 40) with female fibroblasts that divided only a few times ( The cells of the 10th population doubled). Cultures that do not contain telomerase-active pluripotent stem cells will be populated with telomerase-inactive cells, which will undergo 50 + – 10 mitotic events until cellular senescence as described in the findings of American anatomist Leonard Hayflick.
Hayflick then set out to show that the cessation of the cells’ normal ability to replicate he observed was not the result of viral infection, poor culture conditions, or some unknown factor. American anatomist Leonard Hayflick says his findings about the limited ability of normal cells to replicate could be important for understanding human aging at the cellular level. Leonard Hayflick proposed that the limited ability of cells to replicate is associated with cellular senescence and thus in humans.
His work focused on arguing that age is inherent in cells of every kind and that they follow the Hayflick limit, thus establishing a programmed age at which an organism will die. In this article, Leonard Hayflick concluded that a cell can complete mitosis, or cell duplication and division, only forty to sixty times before undergoing apoptosis and subsequent death. The Hayflick Limit states that a normal human cell can only replicate and divide forty to sixty times before it can no longer divide and rupture through programmed cell death or apoptosis.
Cellular senescence, a phenomenon also referred to as the “Hayflick limit”, is defined as a process that limits the proliferation of normal human cells in culture. For 60 years, it was dogma that the possible death of normal human cells in culture was not due to some intrinsic property, but to ignorance of the proper conditions for growing them. Some, such as Harry Rubin of UC Berkeley in Berkeley, California, argued in the 1990s that Hayflick’s restriction only affects damaged cells.
For example, careful study shows that the Hayflick limit is determined by the number of cell divisions, not the duration of the culture. The Hayflick Limit has helped scientists study the effects of cellular aging on human development from embryonic development to death, including the discovery of the effect of shortening repetitive DNA sequences called telomeres at the ends of chromosomes. Nobel Laureate biologists Elizabeth Blackburn and Carol Greed have shown how a cell can count the number of times it divides, approaching the Hayflick limit.
Each time a cell divides, structures called telomeres get shorter, this loss is the basis of what Leonard Hayflick described not as a clock (a process independent of time measurement), but as a counting device, a “replimeter”. After many divisions, telomeres are depleted and the cell begins apoptosis.
They can still die, and a group of cells immortalized by the cell division of an immortalized cell has no limit to the number of cell divisions that can occur between the cells that make up such a group of immortalized cells. Telomere shortening can be seen as a clock mechanism that determines the limited replicative potential of normal cells, set by the Hayflick limit, which tumor cells must exceed. In the early 1960s, Leonard Hayflick discovered that healthy cells can only divide a limited number of times. The limited replicative capacity of human fibroblasts observed in cell culture has been reported to far exceed the number of replicative events that non-stem cells undergo in vivo during the normal postnatal life.