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Limit to divisions of a normal human cell

The Hayflick limit, or Hayflick phenomenon, is the number of times a normal somatic, differentiated human cell population will divide before cell division stops. However, this limit does not apply to stem cells. The concept of the Hayflick limit was advanced by American anatomist Leonard Hayflick in 1961,

Macfarlane Burnet coined the name "Hayflick limit" in his book Intrinsic Mutagenesis: A Genetic Approach to Ageing, published in 1974. However, other scientists have been unable to replicate Carrel's results,

Also, it has been theorized that the cells Carrel used were young enough to contain pluripotent stem cells, which, if supplied with a supporting telomerase activation nutrient, would have been capable of staving off replicative senescence, or even possibly reversing it. Cultures not containing telomerase active pluripotent stem cells would have been populated with telomerase inactive cells, which would have been subject to the 50 ± 10 mitosis event limit until cellular senescence occurs as described in Hayflick's findings. Hayflick next set out to prove that the cessation of normal cell replicative capacity that he observed was not the result of viral contamination, poor culture conditions or some unknown artifact. Hayflick teamed with Paul Moorhead for the definitive experiment to eliminate these as causative factors. As a skilled cytogeneticist, Moorhead was able to distinguish between male and female cells in culture. The experiment proceeded as follows: Hayflick mixed equal numbers of normal human male fibroblasts that had divided many times (cells at the 40th population doubling) with female fibroblasts that had divided fewer times (cells at the 15th population doubling). Unmixed cell populations were kept as controls. After 20 doublings of the mixed culture, only female cells remained. Cell division ceased in the unmixed control cultures at the anticipated times; when the male control culture stopped dividing, only female cells remained in the mixed culture. This suggested that technical errors or contaminating viruses were unlikely explanations as to why cell division ceased in the older cells, and proved that unless the virus or artifact could distinguish between male and female cells (which it could not) then the cessation of normal cell replication was governed by an internal counting mechanism. This occurs due to the uneven nature of DNA replication, where leading and lagging strands are not replicated symmetrically. The telomeric region of DNA does not code for any protein; it is simply a repeated code on the end region of linear eukaryotic chromosomes. After many divisions, the telomeres reach a critical length and the cell becomes senescent. It is at this point that a cell has reached its Hayflick limit. Hayflick was the first to report that only cancer cells are immortal. This could not have been demonstrated until he had demonstrated that normal cells are mortal. A proposed treatment for cancer is the usage of telomerase inhibitors that would prevent the restoration of the telomere, allowing the cell to die like other body cells.

Hayflick suggested that his results in which normal cells have a limited replicative capacity may have significance for understanding human aging at the cellular level. In addition, it has been suggested that no inverse correlation exists between the replicative capacity of normal human cell strains and the age of the human donor from which the cells were derived, as previously argued. It is now clear that at least some of these variable results are attributable to the mosaicism of cell replication numbers at different body sites where cells were taken. Comparisons of different species indicate that cellular replicative capacity may correlate primarily with species body mass, but more likely to species lifespan. Thus, the limited capacity of cells to replicate in culture may be directly relevant to organismal aging.