What can we learn from immortal animals?

28 November 2017

Interview with

Aziz Aboobaker, University of Oxford

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Some animals are what is known as biologically immortal - they don't ever appear to age and die. Can we learn from studying them? Georgia Mills spoke to Aziz Aboobaker from the University of Oxford...

Aziz - If you go down to your local river - make sure it’s not too deep - and you pick up some rocks and stones at the bottom and turn them over. If the water there is quite clean you’ll see little, normally dark brown or black curled-up things and, as the light hits them, they’ll start to crawl around and the chances are those will be flatworms also called planarians.

They’ve been of interest to scientists for well over 100 years because you can take these worms and chop them up into little pieces, and each little pieces will regenerate a whole new worm.

Georgia - Oh wow. So if I took one of these flatworms, chop it up into eight, I’d have eight flatworms?

Aziz - You’d have eight flatworms. Each one would be smaller than the original one but it would regenerate all the missing organs so the brain, the gut, the nervous system, the skin would all regenerate and form a whole new worm. So any piece you cut, any bits that were missing from that piece are remade in that tissue, and that’s done by stem cells. These animals are chock full of really amazing stem cells and it’s these same stem cells that we think are responsible for allowing them to avoid the ageing process. 

Georgia - Why do we think they don’t age?

Aziz - The kind of experiment you’d like to do is sit there forever with them and make sure they don’t age and are still there. Unfortunately, we would obviously age and we would die before you could prove it, but there’s actually a very strong evolutionary argument as to why we think they’re immortal. And the reason for that is some species of these worms are entirely asexual and they only reproduce by splitting in half, so that means they actually split somewhere down the middle and the two halve regenerate the missing bits. Because that’s how they reproduce, that means that the cells in there, the somatic cells, must be immortal.

Most animals, like us, reproduce secually so we use germ cells - sperm and egg, and so the species continues through this process of sexual reproduction. But these animals have done away with that, they just have adult animals that split in half, so for the species to persist, they therefore must be immortal. We’re looking at things that people theorise or know cause ageing in other animals and seeing how the stem cells in these animals have adjusted to cope with that.

We’re starting to find really exciting examples of how they’ve done it. Some of them are just quite simple innovations that mean a particular problem is dealt with. Other’s look like they’re going to be much more complicated and take a lot more time to try and understand.

Georgia - Oh, right. Can you give me a couple of examples?

Aziz - A simple example - we think about humans, as we get older the risk that we’ll get cancer increases. In a planarian that’s highly regenerative, here’s an animal that’s full of stem cells, but it can regenerate. So one stem cell gets transformed and divides out of control and that’s really bad, obviously, for the animal because a cell dividing out of control is going to make a clone of cells that grow and cause damage somewhere. But in these animals that are highly regenerative that damage get’s quickly recognised, and the other stem cells, which are normal, will respond and repair the damage. In that sense, for example, these animals avoid the effects of age to do with cancer or transform stem cells that have gone rogue by being able to repair the damage very efficiently which, obviously, we and other mammals tend not to be able to do.

Another example I can give you is an example of telomerase. Telomerase is an enzyme that is involved in lengthening the ends of our chromosomes, so because of the mechanism cells used to replicate their DNA. Every round of cell division, it turns out, the ends of chromosomes get a little bit shorter, and shorter, and shorter. That causes a problem eventually such that after many divisions, unless you do something, the ends of chromosomes get so short that the cell has to stop dividing otherwise it becomes unsafe. You start to get instability and you can cause mutations. This enzyme, telomerase, is actually responsible for adding back the ends of chromosomes - adding these repeat units called telomeres - to the ends of chromosomes to undo this effect that happens during cell division.

This problem is called the end replication problem, the stem cells and planarians must have found a way to deal with it. So a very simple hypothesis would be that they were able just to switch on telomeres, this enzyme, whenever they need it. Of course, that’s turned out to be what they do, so when they regenerate and when the stem cells proliferate, they are able to just switch on telomeres and add repeats back to make up for the fact there’s been lots of cell division.

So you might ask the question: well, why don’t our cells do that? Well, it comes back again to cancer actually. It turns out that the end replication problem in mammals and humans is used as a way to stop cancers forming. So if you imagine a stem cell goes rogue and out of control, it’s going to get shorter and shorter chromosome ends. If it’s cycling out of control, and the chromosomes get to critical length, that’s a way of shutting down proliferation, so it’s a protection mechanism against cancer. In that scenario, you don’t want telomeres switching back on because you want to keep the stem cells that are rogue shut down.

But as I mentioned earlier, of course, planarians have a way to deal with that another way, the ability to regenerate to deal with that. So they don’t have to worry about that, they can just switch telomeres back on when they need it...

Comments

"Telomeres is an enzyme that is involved in lengthening the ends of our chromosomes..."
Telomerase not Telomeres

Thank you for picking that up: I think it had been mis-typed. It's now correct.

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