I am not a bio major but I have heard about Telomerese shortening in each cell division which leads aging and cellular death. I also read that Hayflick limit is about the number of divisions a cell can make before it dies.

So my question is, how is it possible for us to have constantly dividing cells such as in our hair or nails. They are also cells right? They constantly divide almost our entire life, so how come they do not die out of Hayflick limit?

Or is it like, when a cell divides for the first time, it loses one unit of Telomere but the second cell also have the same number of Telomeres as the first one? I mean if Hayflick limit is 50 for the first cell, is there like 49 and 49 for both cells after division? And when do they decide to divide, is the first cell waits its child to reach Hayflick limit before it divides again? Is this just too complicated to explain in layman terms or are we just not sure yet?

Please do not go hard on me if I have conceptual mistakes, I am just really curious about this.

  • IIRC, hair follicles/nail beds don't create hair by cell division, but instead by producing the keratin directly. – March Ho Nov 28 '15 at 9:28
  • And Adult Stem Cells replenish the tissue and have Telomerase turned on to extend the telomeres to overcome the 3' replication problem which causes telomeres to shorten. The net effect is that Adult Stem Cells do not lose telomere length. – AMR Nov 28 '15 at 16:40
up vote 2 down vote accepted

Let's do some math.

Also, let's ignore your examples, and use a clearer one - instead of fingernails, let's look at the cells that line the intestine. Intestinal epithelial cells are shed and replaced constantly and very rapidly, roughly every 5 days. So that means about 50-70 cell generations per year.

Each time the cell replicates, it loses a little bit off the end of its telomeres. How much does it lose?

We know that for lymphocytes, adults lose roughly 30 base pairs of telomeres per year. Lymphocytes don't replicate as fast as the colonic mucosa, though. The estimate for these rapidly-dividing cells is about 44 bp/year. We can say 50 for a round number.

That doesn't tell us much unless we know what we're starting and stopping with. Humans start life with about 10,000 bp of telomeres. At least in cultured cells, once telomeres reach 1000-2000 bp, cells become senescent and stop, or greatly reduce, their growth rate.

So we start at around 10,000, we can lose up to 9000, and we lose around 50 per year. That means that the intestinal epithelium, which have about the most rapidly-dividing cells in the body, are good for about 180 years of life, assuming that the loss remains constant.

(I don't know if loss does remain constant in these cells, but in lymphocytes, the loss of telomeres accelerates in elderly people, from about 30 to about 60 bp/year in people over 60. However, it's likely that reflects increased lymphocyte turnover in older people, not something intrinsic to the age per se.)

So bottom line, we're good for it.

More generally, keep in mind that the popular media have seized on telomeres as a simple answer for everything related to aging. Obviously, that's not reality. Telomeres certainly reflect aging; in some cases, perhaps many cases, they may be one influence on aging; but in most cases, telomere shortening is probably only a minor aging factor, and many other causes are more important.

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    Is there a clean explanation for why telomere length decreases roughly linearly with time (or with number of cell divisions) rather than exponentially? Or is this mostly an empirical observation? – Jess Riedel Nov 28 '15 at 15:09
  • The end-replication problem means that there is a loss of a constant number of telomere bases, not a fraction of the length. Hence, linear loss – iayork Nov 28 '15 at 16:17
  • I'm sorry, but your answer is wrong. The cells that are lost are replaced by adult intestinal stem cells nature.com/nrm/journal/v15/n1/fig_tab/nrm3721_F1.html Adult stem cells keep telomerase active so that telomeres are extended with each replication. – AMR Nov 28 '15 at 16:25
  • I admire your confidence in not even reading the references I helpfully linked for you before your attempted correction. While embryonic stem cells have active telomerase, adult stem cells (which is what we're talking about here) do not have enough to maintain telomerase length. – iayork Nov 28 '15 at 16:52

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