August 17, 2007

Hayflick limit, Telomere and Aging

DNA double helixWe keep our pens capped so that the pen tips don't get damaged and the ink doesn't dry. Similarly, the DNA in the chromosomal ends are 'capped' by protective molecules, called the telomeres. Telomeres consist of about 1000 repeats of 'TTAGGG" sequence, where T stands for Thymine, A for Adenine and G for Guanine. All these are nitrogen containing molecules (nitrogenous bases).

During replication, the double helical DNA molecule is first unwound by an enzyme called helicase, it is then split by another enzyme, gyrase (=type 2 topoisomerase: it does it by un-twisting the DNA helix in the opposite direction, by introducing negative supercoils, and then makes a nick in one DNA strand, so that it can be copied), and only after all this can DNA polymerase copy the DNA template.

But after each replication, some of this telomere, the so called 'non functional strand' of DNA, is lost. This occurs, since DNA polymerase can not copy one end of the DNA (the 5' end). Thus it has been seen that after about 50 cell divisions, the cell dies (Hayflick limit). When the telomeres are shortened up to a certain limit, the cell sends a signal to p53 protein (known as the guardian of the genome), and the cell then stops dividing and goes into 'replicative senescence'. Stem cells, germ cells and cancerous cells can bypass this limit by the help of telomerase, an enzyme capable of replenishing lost telomeres. Telomerase is actually a reverse transcriptase (normally DNA generates RNA and this process is called transcription. When RNA generates DNA it is thus reverse transcription. In AIDS, another reverse transcriptase wrecks havoc). Telomerase (hTERT= human telomerase reverse transcriptase) and a RNA template (template=dice, just like webpage templates) is enough for telomere reconstruction. However, the idea of restoring telomerase for cellular 'immortality' is not assuring enough as immortality in cells other than stem cells or germ cells means malignancy.

Some substances like alpha hydroxy acids (AHA) glycolic acids, when applied on the skin (face) promotes cell division, thus prompting the growth of new cells, the facial skin gets a cosmetic lift; but due to enhanced cell division, after a certain stage, cells approach the Hayflick limit, and the skin gets aged and wrinkled.

Thus telomerase manipulation should be cautiously weighted against its accompanying risks.

Related article: Aging: From a General and Evolutionary Perspective
Aging, Mitochondria and Free Radicals
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