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I had the following understanding (now after reading a popular science article seeming wrong understanding):

DNA in (regular) cells (in human and some other organisms) are protected by telomers. Telomeres are shortened at each division. When telomeres reach zero size, nucleotides of the ends of DNA become "stripped" so that the DNA shortens a little. The shortened DNA does is not fully functional. This leads to aging of the organism.

But in a popular science article I've read that telomeres however shortened seem not to reach zero length. So the DNA nucleotides at the ends of DNA are never stripped. However shortening telomeres leads to the cell to become not divisible or even death of the cell.

So two related questions:

  1. Are coding/regulatory nucleotides (not just telomeres) at the ends of the DNA ever stripped as a result of aging?

  2. If they are not stripped and so the DNA itself is not damaged, how shortening telomeres may lead to aging? That is how aging can be caused by just shortening telomeres which however do not reach zero length?

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    $\begingroup$ There seems to be a slight confusion. Telomeres are made of nucleotides. Telomeres are not adds up at the end of the chromosome, they are the end of the chromosomes. Telomeres are repetitive sequences. For example the repetition of the sequence TTAGGG is commonly found in telomeres in vertebrates. $\endgroup$ – Remi.b Jan 13 '16 at 18:52
  • $\begingroup$ I suppose you might want to rephrase your question to ask whether the chromosomes are sometimes shortened enough so that coding sequences or regulatory sequences get stripped. $\endgroup$ – Remi.b Jan 13 '16 at 19:03
  • $\begingroup$ Also, could you post the article you read? $\endgroup$ – March Ho Jan 14 '16 at 20:39
  • $\begingroup$ @MarchHo med.stanford.edu/news/all-news/2015/01/… $\endgroup$ – porton Jan 14 '16 at 20:41
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The Stanford article that you read is correct, in the sense that telomeres do not need to be completely removed by cell division before deleterious effects occur and cells start undergoing senescence.

This Nature article describes an experiment in which the minimum length of telomeres (beyond which chromosomal fusion occurs) was determined:

The critical telomere length was 12.8 repeats (of six base pairs) long, they found — any shorter and the chromosomes began to fuse together at their ends (R. Capper et al. Genes Dev. doi:10.1101/gad.439107; 2007). Baird suggests that without sufficiently long telomere caps, the cell may perceive the chromosome ends as broken strands of DNA and attempt to piece them together.

Therefore, we can conclude that while it is not impossible for non-telomeric nucleotides to be stripped from chromosomal ends, this generally does not happen, since cellular defense mechanisms such as non-homologous end joining (NHEJ) and microhomology-mediated end joining (MMEJ) would activate before that point, and start joining chromosomal ends together. This would then lead to issues during mitosis, which would likely halt further cell divisions.

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  • $\begingroup$ Are you sure that the research was replicated? From what I am familiar with, human telomeres usually require somewhere between 2kb-4kb of TTAGGG repeats to prevent senescence. I thought it had to do with the ability for the telomere to loop over on itself and form a T-Loop with strand invasion into the D-loop. I thought that that chromosomal architecture is what imposes the limit, and you can get much shorter than that as still form the T-loop. $\endgroup$ – AMR Jan 14 '16 at 21:59

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