Hayflick limit
The Hayflick limit is the number of times a normal cell population will divide before it stops, presumably because the telomeres reach a critical length.[1]
Overview
The Hayflick limit was discovered by Leonard Hayflick in 1961, at the Wistar Institute (Philadelphia), when Hayflick demonstrated that a population of normal human fetal cells in a cell culture divide between 40 and 60 times. It then enters a senescence phase (refuting the contention by Alexis Carrel that normal cells are immortal). Each mitosis shortens the telomeres on the DNA of the cell. Only abnormal cells with predominant cancer cell properties are immortal. These cells produce the enzyme telomerase that keeps the telomeres from shortening. This telomere lengthening mechanism is believed to have evolved primarily to protect the body from creating a potentially cancerous cell.Telomere shortening together with telomerase activation is one of the most prevalent aberrations in pre-cancerous lesions. Cite error: A <ref> tag is missing the closing </ref> (see the help page). as well as appearing to reduce the telomere shortening rate.[2]
Mechanism of the telomere shortening
As telomere ends of each chromosome shorten on each of the two arms on each side of each chromatid, appears that the RNA primer factor leave gaps 70-200bp, which do not actually play any role in the DNA end-replication problem (Hayflick limit), as the deletions are actually done via this novel t-loop deletion factor, leaving 50-300bp 3’ overhangs on both sides of each chromatid, after each DNA replication, as after each DNA replication there are t-loops forming (Stoyanov, 2009). The t-loop deletion factor explains also the different ratios of telomere blunt ends and how telomere blunt ends result in overhangs on both sides of each chromatid. Thus it is the t-loop deletion factor mechanism, which is responsible for the DNA end replication problem (Hayflick limit). Thus anti aging strategies need to focus on the 5' t-loop deletion factor 50-300bp telomere shortening, instead of the 3’ RNA primer factor (Stoyanov, 2009). Comparing the current known telomere deletion factors show us why the Hayflick limit is so important:
- 50-300bp deletions via the t-loop deletion factor (Stoyanov, 2009) has also effect on every cell division.
- 70-200bp gaps via the RNA primer factor, resulting always in 50% blunt ends (in vitro) (Harley et al, 1990) has no effect on telomere deletions.
- Up to 500bp deletions via the T-loop sized deletions (Wang et al, 2004) has no effect on every cell division, but only in abnormal cases, e.g. cancer.
- About 2000bp deletions on average, via the telomere rapid deletions (TRD) can shorten single telomere by several Kb in a single generation (A. thaliana) (Watson & Shippen, 2007) has no effect on every cell division, but only in abnormal cases, e.g. cancer.
See also
References
Stoyanov V (2009) T-loop deletion factor showing speeding aging of Homo telomere diversity and evolution, Journal of Anti Aging, 1(1), 5-19. [1]
Harley C, Futcher A & Greider C (1990) Telomeres shorten during ageing of human fibroblasts, Nature, 345, 458–460.
Wang R, Smogorzewska A & Lange T (2004) Homologous Recombination Generates T-Loop-Sized Deletions at Human Telomeres, Cell, 119, 355–368.
Watson J & Shippen D (2007) Telomere Rapid Deletion Regulates Telomere Length in Arabidopsis thaliana, Molecular and Cellular Biology, 27(5), 1706-1715.
- ^ Hayflick L. (1965). "The limited in vitro lifetime of human diploid cell strains". Exp. Cell Res. 37 (3): 614–636. doi:10.1016/0014-4827(65)90211-9. PMID 14315085.
- ^ Shao L (2004). "L-carnosine reduces telomere damage and shortening rate in cultured normal fibroblasts". Biochem Biophys Res Commun. 324 (2): 931–936. doi:10.1016/j.bbrc.2004.09.136. PMID 15474517.
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