By Nicole Garneau, PhD
How does a blood test tell you how long you might live?
It's all in the DNA- but not the sequence of the DNA- in the
replication of the DNA.
Background: When cells want to divide and make daughter
cells, they need to first make copies of their DNA (shown as
smiley faces in the cells above) so that both the original
cell and the daughter call both have the same DNA (instructions)
for making the cell work properly. Many organisms, like humans,
have double stranded DNA in the form of the double helix (like a
twisted ladder). The sides of the ladder are the complimentary
strands of DNA twisted together.
To copy the DNA, the DNA ladder is unzipped to access
sequence of nucleotides (A, T, G, and C) the letters that make up
the DNA alphabet. The order of these nucleotides, just like in a
book, spells out exactly how to make different things the cell
needs to live. When the order gets messed up, or parts of the
sequence are deleted, the cell has problems making the things it
needs and can die depending on how big or important the change is.
So when the cell copies its DNA, it has to do it very
carefully.
This is no problem for one strand of the DNA, called the
leading strand. It get read in a specific way by using a dock
(small piece of RNA, kind of like DNA) that matches the beginning
in order to start making a copy, almost like putting your finger at
the beginning of the sentence and reading left to right in the
English language (5' to 3' in the DNA language). The other strand
though, called the lagging strand is the compliment of the leading
strand, and so it is also read left to right, but the order of the
letters is backwards. So the cell has to read by jumping forward in
short stints to read the order correctly. It would be like having a
book be written in reverse (down would be written "nwod"), and you
put your finger a few words into the first chapter (covering a word
or two) and then read in reverse move forward a few words, make a
copy and then have to move your finger to the next few backwards
words, continuing on until the end of the chapter and then
connecting all the fragments by filling in the words that your
finger had covered initially.
But there's a problem, the very last section of the
chapter you read you have to put your finger down knowing that
whatever your finger covers on this last bit, you won't be able to
fill in because there is nothing after it (this is the last Okazaki
fragment). Scientists know this to be the "End
Replication Problem" because towards the end of the lagging strand
there's not enough room to place your finger and still read the
last words to copy them.
The blood test just released in the UK doesn't look at the
part of the DNA that contains the instructions for your cells; it
looks at the end part of the DNA, called telomeres. Telomeres are
how the cell solves the "End Replication Problem" by giving a
little bit of extra sequence at the end to fill in gap in
instructions. So the ends of the DNA, which do not give
instructions to the cell, do undergo shortening over time in order
to prevent the instructions in the center part of the DNA from
being subject to that shortening. But all good things must come to
an end, and eventually the telomeres are exhausted, cycles of
copying leaving them diminished, and leaving the DNA open to
progressive shortening in the instructions section.
As mentioned above, any time you have significant changes
or deletions in the DNA, it can affect survival. The "Hayflick
Limit" is the theory that when the telomeres run out, the cell
dies. Although a hypothesis, there is mounting evidence that this
might be true. The scientists behind the UK blood test are cashing
in on this hypothesis by correlating the length of a person's
telomeres to how much longer their cells and therefore they will
live. These questions remain: what is the science behind this
correlation, how accurate is the prediction, and what are the
repercussions of this knowledge to the person seeking it and to
others if it were to get in the wrong hands?
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