Ever heard of your telomeres? If you haven’t, prepare to learn, because they’re right at the centre of the modern day search for a not-so-mythical way to stay young forever.
In short, you have 46 chromosomes in 23 pairs and every time that your cells need to replicate, each of those 46 bundled DNA strands needs to be duplicated. Unfortunately for you, the DNA replication system is somewhat ‘faulty’ and will cut off 3 to 5 DNA base pairs every time.
Now, 3 to 5 pairs may not seem like much out of your total of 3 billion pairs. But if your cells are replicating every couple of days (some last months or years, check out this site for many cell replication times by tissue type), then you have more of a problem.
Say that your white blood cells replicate twice a week. 52 weeks in a year. 104 replications per year. Losing 3-5 base pairs per chromosome. In one year, that’s over 19,000 base pairs on average sliced off the ends. With an average lifespan of 82.5 years, that’s nearly 1.6 million base pairs, approximately 0.05% of the genome or equivalent to the entire code for a gene (20,500 genes are coded for in your DNA). *
And if you lost an entire gene, obviously, bad things would start to happen. But you don’t have to even lose the whole thing. If you lose the first section of the gene, that bit won’t code for the correct amino acid, so the cell won’t be able to make any of the correct protein. So all of a sudden, your cell can’t make a protein, even after very little change to its DNA, and that cell will probably die, or be extremely unhealthy. Across your whole body, we view this breakdown of cells and tissues over time as ageing.
And where do telomeres come in?
Now, some of you will have started to wonder why your entire body isn’t completely broken by now. After all, if losing just part of a gene prevents a protein from being made, shouldn’t you have seen more effects by now?
Thankfully, our cells have an elegantly designed system built in to prevent complete dysfunction. The trick is that at the end of each chromosome is a whole section of completely random nonsensical repetition of DNA pairs. These don’t serve any function in terms of making protein or performing cell signalling, simply because their function is as sacrificial barriers to protect the rest of the DNA.
When the cell replicates, 3 to 5 base pairs are still sliced off the end, but all of those base pairs come from this section of otherwise useless sections of DNA. These section of DNA are called telomeres and they form protective caps over the ends of the chromosomes and get shorter every time the cells divide, sacrificing their base pairs to protect the important DNA that’s involved in protein creation and signalling.
In the end, the telomeres do end up gradually shortening, up to the point where they are entirely consumed by ongoing DNA replication. And then we end up back at the first scenario where your cells stop producing proteins, start dying, and you get old as things stop working inside your body.
All well and good, but what do we do about it?
This is where it starts getting very interesting and ties into the modern day search for a “fountain of youth”. Scientists are excited because they’ve found a major player in the process of ageing, so now they want to use their knowledge to help extend lifespan.
This story starts about 40 years ago when the newly-discovered role and function of telomeres started to raise some interesting questions. What about unicellular organisms? They can replicate a lot faster than human cells, even every 20 minutes (for certain bacteria) and they have less DNA to start with. And they don’t tend to suddenly die out or age in their population.
Some further research lead to the discovery of telomerase, an enzyme that goes around and adds to the end of chromosomes. So then, when the cell divides, the telomeric DNA is shortened, but then added to again!
And if that happened in every single DNA replication, the cells, tissues and, by extension, whole organism could live on indefinitely.
Unfortunately, as with all things, there are down sides and problems inherent with trying to maximise or enhance telomerase activity as an anti-ageing treatment. Most notably amongst these is increased risk of cancer (if a cell replicates indefinitely, the chance of its DNA mutating at some point to create tumorous growth becomes far higher). There’s also more research into different ways we could employ telomerase to prevent ageing, or inactivate it as a method of fighting cancer, but we’ll cover that in more detail next week!
*Note that these numbers a rough estimate and will differ significantly for different people and cell/tissue types.