Telomeres & Aging
Every living organism larger than a cell, has (once) been a cell or is comprised of cells. Thus, it is super important for us humans to understand these fundamental building blocks.
The whole biology is a counterpoint between two themes: astonishing variety in individual particulars; astonishing constancy in fundamental mechanisms.
In this article, we are not going to talk about the entire cell — just the telomeres and their relation to aging.
And inside, there’s a nucleus along with other organelles (which are not labeled).
The DNA that is organized within the cell is in the form of linear chromosomes. So instead of those tangled threads you see in that nucleus, they are actually more like two McDonald fries together in an x shape.
That above is a more realistic model of how chromosomes will look (humans will have 23 of them in each nucleus). See those bright spots at each chromosome worm’s end?
Those are telomeres and they are a form of protection for the chromosome.
The End replication problem
When Chromosomes replicate, due to the DNA replication process, the replication process will not fully complete. What?
This is due to a situation with RNA primers; In leading strand replication, one RNA primer can replicate a long stretch of DNA, but in lagging strand replication there is a need of a RNA primer after a gap of 100–400 nucleotides. So, there’d be no more primers to further replication until the end of the lagging strand.
What does that mean?
Essentially:
The preprocessing takes place: helicase does the separation, topoisomerase makes sure that dna strands don’t supercoil up, and the single strand binding (SSB) protein makes sure the strands don’t snap pack together.
When the replication process begins for the leading strand, the RNA primer is made and the DNA polymerase III will start attaching nucleotides to the primer. ATGC, matching to the bases of template leading strand.
This goes smoothly, as more dna is “coming out” in the same direction the polymerase can continue attaching, one RNA primer does the job for replicating the leading strand.
This is not so legit for the lagging strand. The leading strand template is from 3' to 5' (left to right), so the lagging template will be from 5' to 3' (left to right). The problem is here:
DNA Polymerase only attaches nucleotides in the 5' to 3' direction
So, our body decided to attach nucleotides in the opposite direction compared to the leading strand. The RNA primer would then be created periodically, leaving a gap on the left for DNA Polymerase III to fill.
Unfortunately, this is a problem.
When more template strand dna comes out from the right, a gap is created between the existing RNA primer and more template DNA (indicated by x). So, more RNA primers will come in to fill in the gap and allow Polymerase III to fill in the region x.
This is bad because the number of RNA primers for replication isn’t infinite. Periodically, as stated before, there needs to be a RNA primer per 100–400 nucleotides. So, we will arrive at the limit for the lagging strand and there will be a gap of template DNA that isn’t replicated.
This is bad. If there were no telomeres on the ends of the chromosome, then every time the DNA replicates, there’s almost guaranteed DNA genetic damages. Thank your own 30 trillion telomeres right now.
Telomeres
Instead of DNA taking the damage, telomeres takes the hit. You ask, but wait, if telomeres are hit each time, won’t that be bad?
By now you have probably heard of the analogy that telomeres are the shoelace tips on the chromosomes. Thats essentially the nutshell of telomeres.
Technically, telomeres are also DNA, so they are part of the chromosome, but they are comprised of different DNA.
Telomeres contain “tandem repeats” of a nucleotide sequence, which is essentially useless in the situation of DNA
For humans, that repeated sequence is TTAGGG. Exactly how many of repeats? You’d have to know the age. Here’s a resource
As replications happen, telomeres are slowly trimmed away, leaving the chromosome to be damaged by the replication process.
Thats the end replication problem.
Our Limit
Because of the end replication problem, there’s a durability limit for chromosomes, and a limit for replication.
This is graph is sad, especially if I were a chromosome.
Due to the telomeres’ importance to protecting the chromosome, when the telomeres are short to a certain length the cell enters a state of Replicative senescence.
Meaning that the cell is still functioning but will stop dividing and just chilling in our body.
However, there are anomaly cells that break through the limit.
Once the cell reached the point where the shelterin complex (internal structure) of telomeres have collapsed. They will do one of two things.
The first option is to die, from severe chromosome damage. Or, they can activate telomerase.
Telomerase is the enzyme responsible for maintenance of the length of telomeres by addition of guanine-rich repetitive sequences
However, in this situation, the chromosome may have been damaged and accumulated changes so that when a restored telomere is present and the cell starts dividing, cancers may occur (tumors).
Aging
As we age, our cells divide more and more, avg telomere lengths are then reduced and more replicative senescent cells are present. As A LOT of cells die in our body per day, there’s gradually less and less to fill those spots as we age.
But, right now a lot of scientists are tackling the problem of how to safely use telomerase to help increase healthy cell division duration, and avoid the probability for cancers to occur. (Activating Telomerase)
Some cool longevity intro
- Laura Deming’s Longevity FAQ
- News, Longev research — LifeSpan.io
- Guide to longevity — Reddit Post
Thanks for reading :) 👋
Would love to chat with you about longev or anything integrity of the world, throw me an email or just directly schedule a time to chat!
