### The Inherent Difficulty in Telomere Length Measurement

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**Fri Mar 27, 2015 1:29 am****During a discussion of our Telomere Length study (http://www.vitamincfoundation.org/forum/viewtopic.php?f=24&t=11815&p=39189#p39189) with Dr. William (Bill) Andrews, author of Curing Aging and CEO of Sierra Sciences, over the phone, he made comments about TE length testing in general that were were disappointing to me. The gist was that if you take 10 blood measurements of the same person you are likely to get 10 different telomere length results, although in his opinion, Life Length, with their "shortest telomere" analysis is the superior LE length test. Anyway, I emailed him wondering if it was an intractable problem, just based on numbers alone, and the small sample size of the blood used for the measurement. His wonderful email response (below) is illuminating to say the least!**

Dr. Andrews has kindly allowed me to post his email back to me.

Dr. Andrews has kindly allowed me to post his email back to me.

Bill Andrews wrote:A human is made up of 10^14 cells. That’s 100 Trillion. And, that equates to 5X10^15 – 10^16 telomeres depending on the phase of the cell cycle that the cell is in.

However, human blood only contains 5x10^10 (50 Billion) cells; not counting the red blood cells that don’t contain chromosomes.

When you collect 5 mls of blood for a telomere length test, that contains about 40 million cells. With that many cells any statistical test would show you that any population of 40 blood million cells will be indistinguishable from any other 40 million blood cells from the same person at any given time. So, even if telomere shortening wasn’t uniform, the different tests should still give the same results.

So, that is not one of the issues with telomere length measurement.

Here is one of the main problems. Let’s pretend that human cells have only two chromosomes and each chromosome only has one telomere (to make the math simple). When the chromosomes replicate each will make a new chromosome with a shorter telomere. When the cell divides each chromosome pair goes into the daughter cells randomly.

Let’s start over. Let’s say that the chromosomes are called A and B. Lets also say that new chromosomes are shorter by one unit. So, in the beginning each cell has A and B. When the DNA replicates the new chromosomes are one unit shorter indicated by A-1 and B-1. So, after the DNA replicates there are 4 chromosomes (i.e. 2 pairs). They are A, A-1, B, and B-1. When the cells divide the pairs will be separated into the new daughter cells randomly. That is, some daughter cells will have A-1 and B-1, some will have A-1 and B, some will have A and B-1, and some will be identical to the parent cell with A and B. So, you have four types of cells now. If we now take that one step further and let these chromosomes replicate and the cells divide we will now have the following cells:

1 X (A-2 and B-2)

2 X (A-2 and B-1)

1 X (A-2 and B)

2 X (A-1 and B-2)

4 X (A-1 and B-1)

2 X (A-1 and B)

1 X (A and B-2)

2 X (A and B-1)

1 X (A and B)

Now, take this out 50 cell divisions and remember that there are 23 chromosomes each with 2 telomeres. This becomes a really big mess with 51 different lengths of telomeres and 51^2 = 2601 different types of cells (based only on telomere length differences). So, if you measure the telomeres in 40 million cells from a 50 year old (assuming 1 cell division per year) that is the population that you will see. The distribution would be so broad that all you can do is measure the average or the percent that are below a critical size.

Another main problem is that the ability to measure the average or the percent that are below a critical size is so inaccurate using today’s methods that the reproducibility of measuring telomeres is decreased even more. The exception appears to be Life Length (http://www.lifelength.com) who appears to be able to measure the percent of telomeres that are short fairly accurately.

And, one other problem is that every day we are exposed to new environmental insults that stimulate some white blood cells to divide and others to not divide. This creates even more havoc and as a result people can often find that their telomere lengths have changed drastically, up or down, in just a few days.

So those are the main issues with measuring telomere lengths. But, if we could find a drug that would lengthen all the telomeres it would be no trouble at all to see them increase even in the background of all this havoc. Unfortunately, nothing exists that is potent enough to lengthen all the telomeres. At best, we can only decrease the rate of shortening or lengthen just the shortest telomeres. That is all TAM-818 does. We believe that it does lengthen the shortest telomeres (which could account for the age reversal effects that are being observed) but the average telomere length still shortens (albeit at a slower rate).