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Hayflick limit

From Molecular Biology Wiki

Leonard Hayflick in 1965 discovered the Hayflick limit during research at the Wistar Institute in Philadelphia, which was an observation that cells dividing in cell culture divided about 50 times before dying. As cells approach this limit, they show more signs of old age [1], [2].


Contents

The Hayflick Limit - A Limit of Cell Division

The limit to the number of times a cell divides has been observed in all human cell types that have been fully differentiated, as well as in other organisms. The Hayflick limit varies amongst different cell types, their physiological age, and more so from organism to organism.

The human limit is around 52. Fetal cells can divide 50 +/-10 times. The Hayflick limit has been linked to the shortening of telomeres, a region of DNA at the end of chromosomes. However, it has been shown that the telomere length (TL) decrease is a correlate of cell proliferation that cannot alone account for the Hayflick limit, which primarily depends on parameters of cell population kinetics. It has been demonstrated that free radical damage influences the Hayflick limit not through TL but rather by affecting the ratio of the rates of events that commit cells to mitoses or to proliferation arrest [3].

The Hayflick Limit, Cell Division and Aging

Interestingly, most cells from patients that are afflicted with "accelerated aging" syndromes such as Werners syndrome and Progeria have fewer cell divisions and shorter telomereres than normal individuals who are of the same chronological age. However, it has been shown that expression of increased telomerase in some Hutchinson-Gilford progeria (HGP) patients was not sufficient to confers resistance to 'telomerisation', suggesting that there are pathways separate from the telomerase enzyme that can also affect aging [4].


Also, the number of times cells can divide decreases with age. This has given rise to the hypothesis that there is a limit of cell division and that increases towards the limit of cell division corresponds with aging.

It has been thought that if the shortening of telomeres can be slowed or prevented, life expectancy can be extended. Much research is happening in this area. The only known way of circumventing the Hayflick limit is with the enzyme telomerase, which regenerates telomeres during DNA replication.

Cell Types, Cell Lines and the Hayflick Limit

Stem cells, by definition, have not yet been fully differentiated, and therefore many of these cells may continue to regenerate new cells for the entire lifespan of the organism, without limit, thus constituting a notable exception to the Hayflick limit in humans and other organisms. While the manifestations of the constant regenerative effects of stem cells is most easily seen in tissues which must constantly produce replacements for existing cells, such as skin and blood cells, stem cells of one form or another are found in every tissue of the human body, even if only as dormant stem cells known as "spore-like cells" [5].


Cancer Cells and the Hayflick Limit

Cancer cells constitute the other main exception to the limits on cell division. It is believed that the Hayflick limit exists principally to help prevent cancer. If a cell becomes cancerous and the Hayflick limit is approaching, the cell will only be able to divide a certain number of times. Once it reaches this limiting number of divisions, the formed tumour will no longer be able to reproduce and the cells will die off. Cancers become problems after having reactivated telomerase-encoding genes. Cells that have found a way around the limit are referred to as "immortal". Such immortal cells may still die, but the group of immortalized cells produced from cell division of an immortal cell has no limit as to how many times cell division might take place among the cells that constitute such a group of immortalized cells.

It is believed by some that some or all cancers start off as stem cells that become genetically damaged over their long lives [6]. This would mean they already aren't limited by the Hayflick limit and can easily metastasize into the pool of cells in their final cell type destination.

See also

Reference

  1. Hayflick L. The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 1965;37:614-36. PMID 14315085
  2. Shay JW, Wright WE. Hayflick, his limit, and cellular ageing. Nat Rev Mol Cell Biol. 2000 Oct;1(1):72-6.
  3. Golubev A, Khrustalev S, Butov A. An in silico investigation into the causes of telomere length heterogeneity and its implications for the Hayflick limit. J Theor Biol. 2003 Nov 21;225(2):153-70.
  4. Wallis CV, Sheerin AN, Green MH, Jones CJ, Kipling D, Faragher RG. Fibroblast clones from patients with Hutchinson-Gilford progeria can senesce despite the presence of telomerase. Exp Gerontol. 2004 Apr;39(4):461-7.
  5. Vacanti, M. P., A. Roy, J. Cortiella, L. Bonassar, and C. A. Vacanti. 2001. Identification and initial characterization of spore-like cells in adult mammals. J Cell Biochem 80:455-60.
  6. Scientific American, "Stem Cells: The Real Culprits in Cancer?, July 2006
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