Sediba's backbone, and antibacterial bacteria

Bones that confirm how Australopithecines walked, and microbes that can fight off skin infections...
02 February 2022
Presented by Chris Smith
Production by James Tytko, Chris Smith.

SEDIBA-VERTEBRAE.jpg

Australopithecus sediba, lumbar vertebrae

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This month, the bones missing from Australopithecus sediba's backbone are uncovered, but what do they reveal about this ancient hominid's posture? Also, why a link to the nervous system is crucial for salamander limb regeneration, the bacteria that can treat bacterial infections, the social stomach in ant colonies, and even old worms can combat the ageing process...

In this episode

Australopithecus sediba, lumbar vertebrae

00:43 - Missing Sediba vertebrae fill in gaps in hominid posture

Discovery of the lumbar spine from Australopithecus sediba confirms upright posture...

Missing Sediba vertebrae fill in gaps in hominid posture
Scott Williams, New York University

In the late "noughties", Chris Smith was fortunate enough to be in South Africa at a cave site called Malapa, which turned out to harbour some of the most important fossils of our early ancestors. Almost complete skeletons, much of them in full articulation - and even the hands - are preserved from several australopithecines. They almost certainly fell - 2 million years ago - into what would have been a mud-filled hole. That mud turned to stone and has preserved a near pristine snapshot of these early hominids. But there were some bits missing: because miners had got there first, with dynamite, a century ago. Luckily, the missing material wasn’t blown far away and analysis of the surrounding terrain has turned up some crucial pieces, including the parts that Scott Williams was extremely keen to get his hands on…

Scott - My research has largely focused on the evolution of bipedalism, how we walk on two legs. And so we're looking for fossils that have a mix of traits indicating they climb trees and a mix of traits indicating that they walked on the ground, like we do. And species like Australopithecus, that we're working on, are really demonstrating a mosaic mixture of these features.

Chris - How old are they?

Scott - They're quite variable in their age. The oldest ones push to 4 million years, and some of the younger ones, like Australopithecus sediba, date to just under 2 million years.

Chris - And that's the one we're talking about here. Isn't it? Because that was discovered about 15... 14... Years ago now?

Scott - That's correct, yeah, 2008.

Chris - So tell us a bit about what you're actually doing, then. Tell us about the project.

Scott - So my role in the project, has been really to work on the spinal remains of Australopithecus sediba. I was writing my dissertation when these fossils were initially published, and Lee was kind enough to invite me on the team to work on the vertebrae, the backbones.

Chris - This is Lee Berger, whose son Matthew - actually we should give proper acknowledgement, shouldn't we - I think he was about 12 at the time when he actually found what was a very important piece of our evolutionary history?

Scott - So I've been working on the vertebrae for over a decade now and you know, we were missing really important parts of the lower back, and those fossils are what we published on recently in eLife. They were recovered a few years ago and we were able to visualize them, using some 3d methods, and then describe and publish them.

Chris - Now, if the original fossils came out of this hole in the ground in 2008, why has it taken such a long time since to get your hands on these key bits that you wanted?

Scott - So the initial fossils that were recovered, some of them were outside of the pit at Malapa, which is an old cave that has since weathered away quite a bit. And it is really just an open pit. The initial fossils that Matthew discovered there were outside that pit and that's because miners were dynamiting the site over a hundred years ago. Lee then excavated the site itself, once they found out where those fossils came from, and that produced a juvenile male and an adult female that were published. Now, it's taken a long time because there are lots of blocks, other blocks of this thick material called breccia, which contains the fossils plus other minerals that have sort of encased them. And those blocks are all around Malapa, they've been pulled out of the pit. They've been taken from areas that were blasted. In this case, the fossils that I worked on, they had actually been blasted by the miners out of the pit and then used to make sort of a little mining trackway where they could roll carts and things like that. That was taken apart in 2016. And when that was done, blocks were removed and those blocks went to the lab and in the lab, they were slowly, very slowly excavated apart until fossils were discovered. And those fossils are what this new paper is based on. And they happened to interestingly fit perfectly with the fossils we had previously from the adult female individual.

Chris - They're basically bits that were blown out of the hole where she had been laying and they ended up part of that path. I've walked on that path! I didn't realise, when I first went there 14, 15 years ago, that I was walking probably on your work; it sounds terrible, doesn't it? That, basically, people were dynamiting some of the most precious things that we have in terms of documenting our evolutionary past!

Scott - Exactly. Yep. But we wouldn't probably wouldn't have discovered the sites initially if they hadn't been dynamited. A bit of a mixed bag!

Chris - Well, that's true. That's true. So you've now got this amazing, I mean, it's the gift that keeps giving, Malapa, isn't it? Not only have you got these fossils, but you've now got the bits that were missing. So why is the backbone, though, so important from your perspective?

Scott - If we're talking about the evolution of bipedalism, we're basically envisioning an animal that is something that is evolving from more of a tree-living animal, that probably had different posture than us and perhaps carried itself more like a living chimpanzee, that is going to give rise to a bi-ped, something like us, something that walks on two legs. And when you're doing that, obviously one of the main targets is the lower limb; the feet, thighs, the pelvis; but another really important area is the lower back. And that's because we humans have what's called lumbar lordosis. Our lower backs have a curvature to them that allows us to sort of balance our upper bodies over our pelvis and lower limb. The lumbar vertebrae have clear adaptations to upright posture and bipedalism, so that's what we're looking for in these fossils. And we had basically a couple of vertebrae of the very low back that sit right above the pelvis. These new fossils basically fill in the rest of the lower back all the way up to the top of the lower back. And they demonstrate that not only are there these adaptations to bipedalism, but there are some other features we didn't quite expect that indicate that this animal was also spending a lot of time climbing in trees.

Chris - So you really have got something that's a hybrid. It would have walked upright, as we had speculated, but it was also well adapted to doing other things like tree dwelling as well?

Scott - Exactly, yeah. I mean, this is something that we kind of, we knew about, right? We knew that members of this genus Australopithecus, going back to Lucy and even before that, we knew that they had this sort of mosaic morphologies. They were pretty clearly bipeds like us, but their upper limb bones, largely their arms and hands, had features suggesting they could climb trees. And what's really interesting about these new fossils is that it sort of bridges the gap. If we think anatomically it's sort of a missing link in the sense that the lower back connects the upper body to the lower body. And it demonstrates this mosaic set of features, clear evidence for bipedalism, but also strong evidence for climbing around in trees and spending lots of time in trees.

Chris - Have you got more specimens where this came from? Because you know, talking to Lee Berger and, other researchers, there's an enormous amount of material still there or still to be processed. So have you got more individuals? Are we going to get more clarity from this or, have we now eventually got to the end of that road that had been dynamited?

Scott - No, I think there'll be a lot more to come. You know, I mean one major piece that's been missing is the head of the adult female; the skull, we don't have it. We have the head of the juvenile male, which is really amazing and interesting, but it would be really nice to have an adult skull to compare with other adult Australopiths, and other species. So that's yet undiscovered, but could be there somewhere. We definitely have other materials still. I mean, I'm aware of some vertebrae that have been recovered recently that I haven't had a chance to study yet. There's more material from Malapa for sure. You know, there's still many, many blocks that are in the lab waiting to be excavated.

Limb regeneration in a salamander

08:45 - Axolotl limb regeneration needs nerves

Regenerating salamander limbs require growth instructions from the central nervous system...

Axolotl limb regeneration needs nerves
Catherine McCusker, Massachusetts University

Some animals can regrow amputated body parts, and axolotls are among them. If they lose a limb, for instance, they can generate a fully functioning new one. Scientists are obviously very interested in how this process plays out, because it might give us clues to why this doesn’t happen naturally in humans, and how we could make it happen. But one of the key questions is what controls the process? How does the replacement body part “know” how big it should become? One key part of this, appears to be an intact connection to the nervous system. Speaking with Chris Smith and from the University of Massachusetts, Catherine McCusker…

Catherine - We work with a really amazing model organism known as a Mexican axolotyl. And this animal is capable of regenerating a variety of different complex structures, one of them being their limbs. Lots of people have been studying limb regeneration, all different aspects of limb regeneration, particularly at the really early stages. But nobody had really looked at the later stages of regeneration and the different steps that happen to make a fully functional limb.

Chris - If you take one of these axolotls and you remove a limb, does it grow a new limb and start with a really small one and make it big, or does it just grow a complete blob of tissue, which then moulds from something about the right size into something resembling a limb?

Catherine - Essentially the regenerating limb goes through multiple steps. So the first step is that it forms a blastema and a blastema is actually really similar to a structure that forms in the developing embryo when the embryo is making a limb. And then that blastema goes through the process of making a limb. But, initially, the limb is very small in size proportionally to the rest of the animal. And then that small limb - that we have called the tiny limb - grows very rapidly compared to the rest of the animal until it reaches the appropriate size. And then it slows down.

Chris - So how does it know how big the animal that's attached to it is?

Catherine - That's really kind of the heart of the question that we were trying to answer figuring out, what that source is that controls the growth of regenerating limb. And, essentially, what we discovered was that signals that are coming from the limb nerves are regulating this growth.

Chris - Oh, right! So the nerves talk to the developing tissue and, in some way, promote it to get the right size? So how do the nerves know what messages to send to the tissue? I mean, do we understand how this works?

Catherine - No, we don't. And that's really the future of what we are trying to answer in the lab, how the nerve knows the limb has been amputated and how it knows to control the growth. And when it knows to stop the growth. These are all really important questions that we need to answer. And that's what we're trying to do right now.

Chris - How did you find that the nerve had this role in the first place?

Catherine - It was kind of a serendipitous accident. When I was a postdoc, I had been doing a histological analysis on limbs that had regenerated a long time ago. And one thing that I noticed was that the limbs seemed to have a lot more innervation than a normal, unamputated limb. And so I kind of filed that in the back of my brain saying, "I think that this might be important some day, but I don't know what it will be important for." And so, when we actually started getting into studying this process of growth regulation and sizing, and during these later stages of regeneration, I remembered those studies that I had done and said, "maybe we should look at the nerves!" And then the more we actually dove into the previous literature on neural signaling and any kind of correlation with size, we said, "wait a minute, I think there might be really something here."

Chris - Do you know whether the nerves are the be-all and end-all, or is there another link in the chain you've yet to discover: do the nerves talk directly to the tissue and that makes the effect; or do the nerves talk to something else and that changes the chemical milieu, which then affects the growth?

Catherine - The studies that we have indicated that the nerve is talking with that regenerating tissue. And we don't know if there's an intermediate there, or if it's directly talking with that tissue. I think, once we start to get at the heart of the molecular mechanism of what signals are coming from the nerve, then we can start to get at kind of those downstream signals. But one thing that we do know is that the nerve must be receiving signals from something upstream. And the reason why we know that is because we developed a new kind of test - or assay - to see whether nerves alone, when they're separated from the central nervous system, can still regulate growth. And actually we were really surprised to find that they don't regulate growth all on their own. They have to be connected to the central nervous system.

Chris - Are they motor nerves, or are they sensory nerves, or both; because, obviously, the pathway that they follow is quite different for those two different classes of neuron?

Catherine - Absolutely. Yeah. So, we are not a hundred percent sure yet. The assay that we developed focused on sensory neurons. So we know that the sensory neurons are not capable of regulating size on their own. So it absolutely is possible that the motor neurons actually do have this information, that regulates scaling and size. We have to test that in the future.

Chris - So how are you going to pursue this? Because, obviously, finding those factors is going to be absolutely critical because, not just for informing this study, but the whole kind of understanding of how tissue regeneration might or might not play out in other animals, how are you gonna try to get underneath what the nerves are doing?

Catherine - We're essentially taking two approaches. The first approach is really using a list of candidates that we found in the literature that we know are regulated by the nerves and maybe have been already correlated with growth at earlier stages of regeneration. But we also want to use some NextGen sequencing to really characterise both the expression patterns that are happening in the nerve, as well as the regenerating tissue and better understand the changes in the molecular signatures that are present in those tissues during different stages of growth.

Cat sticking out its tongue

15:38 - Antibacterial bacteria

How friendly feline bacteria can be used to fight off antibiotic-resistant bad bacteria...

Antibacterial bacteria
Alan O'Neil, University of California San Diego

Some have dubbed it the "antibiotic apocalypse"; others have said the looming crisis of antimicrobial resistance is a bigger global threat than terrorism. This is prompting researchers to think outside the box, or even the pill packet, about other ways to treat certain kinds of infections. And one way is to fight fire with fire and use so-called "friendly microbes" as antibiotic factories that can applied to wounds where they defeat the overgrowing bad guys. Speaking with Chris Smith, Alan O'Neil is at the University of California, San Diego...

Alan - One of the main problems in medicine at the moment is the emergence of antimicrobial resistance in pathogens such as Staph aureus. And one of the issues is most pharma and biotech industries have ceased discovery of antimicrobial compounds due to the emergence of antibiotic resistance. And so one of the things that we try to do in our lab is try to identify new antimicrobials that could be therapeutically used. And also we try to identify the organisms themselves that produce these antimicrobials and use the antimicrobial isolates as a bacterial therapy approach. So, as opposed to just isolating and purifying the compounds for therapeutic applications, we actually seek to use these microbes themselves, which are commensal, healthy microbes, and then transplant them. For example, onto patients who have skin infections with these drug resistant bacteria.

Chris - Why would it be better to use the microbes themselves rather than a tube of cream, or pop a pill?

Alan - The issue with a lot of antimicrobials is that they have poor pharmacological properties. Some antimicrobials can be hydrophobic, poor solubility, poor penetration into the skin. So it's very hard to produce these antimicrobials and have them effective in the clinic. But instead, if we apply the bacteria that naturally produce these antimicrobials, we think that this would be a much better approach given that the bacteria should be able to colonise the skin, be stable over a period of time, and essentially have a longer period to outcompete the pathogen.

Chris - Indeed, it's a bit like taking the pharmaceutical company factory to the wound, isn't it? Because they're just going to churn out the stuff and make it at the site where it's needed. But how do you get rid of the microbes when their job is done? Are we not potentially at risk of solving one problem and creating another one?

Alan - So the approach that we take is really to look at the commensal microbes. These are the healthy microbes. They don't have any pathogenic activity. We make sure that these microbes are sensitive to common antibiotics. The other benefit is that these microbes tend to produce bacteriocins, these antimicrobial peptides, which tend to have much more selective activity against the pathogen. So, due to that activity where it's not a broad spectrum where you're targeting the entire microbiome and killing everything on the skin, it's much more selective and specific. So in that case, we tend to think of these microbes being much more beneficial and having a much more holistic approach that you can reestablish a healthy commensal microbiome after applying these bacteria.

Chris - How have you actually approached this then?

Alan - We have different animal models that we use. So mice infected with Staph pseudintermedius and after applying the pathogen onto the skin of mice, we normally see a lot of redness scaling erythema. And after we apply the Staph felis, this antimicrobial isolate, we see that the redness goes down, the colonisation rates of the pseudintermedius strain also goes down and we see a therapeutic benefit here. We've also used other commensal Staph microbes, such as Staph hominis, and we've already done small phase one clinical trials in humans where we've applied the Staph hominis onto skin of human atopic dermatitis patients. And we've seen good clinical benefit after applying these bacteria onto skin.

Chris - Do the microbes you're applying actually kill off or drive out the infecting organism, or do they achieve their effect by modulating the skin's repair capacity or changing the way the immune system is working in that patch of skin? Or is it combination of these factors?

Alan - We think it's probably a combination of these factors. For sure, the important component of this approach would be the antimicrobials that these bacteria secrete into their environment would definitely have a very strong effect in limiting the growth and the survival of the pathogens. But we also know these antimicrobials also can exhibit anti-inflammatory activity too.

Chris - Given how common skin infections are and other problems where you get overgrowth of the wrong sorts of microbes, how far away are we from doing what you are doing and actually giving people basically a microbiome reset and treating their infection that way.

Alan - I think we're making really good progress on this and it will still take some time, but we are in phase two clinical trial at the moment in our lab with one of the antimicrobial strains. So we think this is a very powerful approach for certain infections. It would have difficulty, for example, in systemic infections, where of course you have an infection in the blood, but definitely for soft tissue infections we think that this could be a powerful approach.

Chris - Is it one size fits all, as in if I've got some skin inflammation or infection, and so have you, we would both slap on the same bug and treat it, or are you going to have to do horses for courses here and sort of tailor-make particular combinations of therapies for specific infections or specific people?

Alan - I think for specific infections, different microbes needing to be applied. But we know for certain skin diseases, for example, patients that suffer with atopic dermatitis, we know that they have a predisposition to Staph aureus colonisation and Staff aureus drives this disease. So it may be a case where we screen the patient first to identify which pathogen that they are actually colonised by. And once we identify that, that may dictate what type of antimicrobial isolate that we then apply. But we know that there are skin pathogens that very common in a lot of skin diseases. So we think that it won't be too diverse in terms of the antimicrobial isolates available.

Carpenter ant trophallaxis (social exchange of gut contents)

22:58 - Ant social stomachs

Some ants have an adapted stomach to permit social exchange of food...

Ant social stomachs
Adria Le Boeuf, University of Freiborg

How many stomachs do ants have? Anatomically, the answer's one. But the real answer is - for some species at least - two, because, by passing stomach contents among themselves, the colony has a shared "stomach" that enables them to distribute resources among all the members. But it's even cleverer than that, because alongside the calories that go into that community larder are a whole host of signals that can help to control how ant society operates, as Adria Le Boeuf explains to Chris Smith...

Adria - All insects, including all ants, have three sections of their stomach. The first section, in some ants, has been commandeered into a social stomach. So it's basically this special sack that they use to hold food that they can then share with their nest mates, something that they can use to hold the nice things that they find outside foraging that they can then regurgitate and share. So we're talking about vomit here.

Chris - Nice. So is, the aim that they'll hang onto this and decide what carries on down the digestive tract and what gets shared. Can they actually exert control over what's in that first stomach?

Adria - We think so, they also add a lot of interesting things that they make themselves into this fluid. So it's not just food that they're sharing around. They're adding a whole bunch of other things in there, either products of their own metabolism or potentially manipulative things, helpful things. This is really exciting because it kind of allows a globalised metabolism over the scale of the colony. Well, this was the idea and that's what we wanted to test.

Chris - How?

Adria - One very convenient thing is that we can, you know, gently squeeze the ants in just the right way, and we can get them to regurgitate and share the contents of this social stomach. So we set about taking different ants within the colony, which we know how different roles: ants that care for the young, and ants that go out to forage. We thought we might see differences between colonies that have kind of different priorities. A young colony is just starting out and they need to rapidly grow. And a mature colony, they need to disperse: new queens, new males to start new colonies. And we thought maybe they would also be sending around different molecules over this social circulatory system.

Chris - And is that what happened?

Adria - What we found we are looking mostly at proteins is that yes, indeed. There are differences between different individuals, the nurses and foragers, and we saw differences, big differences between the young colonies and the mature colonies. The mature colonies seem to be passing around consolidated resources, big storage proteins. So it's as if they are very wealthy and they can consolidate their and process their resources and pass them around over the social circulatory system. While the young colonies, they were sharing simple processing of sugars and in the nurses and foragers these different ants within a colony, we saw that nurses tended to have some sort of anti-aging proteins in their, socially exchanged fluid. And that was cool because it presented two possibilities for why that might be. So nurses tend to be the younger ones, and they're also closer to the queen. And so it is possible that either they make more of these anti-aging proteins themselves, or maybe they're feeding them to the queen, or maybe other individuals in the colony produce them and give them to the nurses or give them to the queen. So, there's a lot more work left to be done.

Chris - Do these stomachs lie downstream in terms of signaling of somewhere else in the ant, or is the stomach the origin of, the signal? So, in other words, if the ant, does the ant get a pheromone, that then changes its behavior in a range of ways. And that impacts also what it does to the stomach contents, or is actually the stomach reacting to what's going into it and, doing something to it.

Adria - We have indications from work that we haven't yet published that other aspects of the, ants physiology control, what they put into the social stomach. We're also doing some work to see if they can perceive what they have there. Is there a message that comes in through the social stomach that they can then perceive? And we don't know. I mean, thinking a little bit about democracy and when is it worthwhile to be able to sort of have polls? It might not be worthwhile to be able to read the ballots that you're receiving.

Chris - The thing that's niggling me, that's, when you used the "V" word earlier, and said " vomit", it's something that we are programmed from an early age to be repelled by because of infection control implications. Is this used slash abused in the way in which infections are controlled or spread, or, other threats are detected and responded to in colonies?

Adria - That's a fantastic question. Yes. Ants are very susceptible to epidemics or illnesses because they live in close quarters like humans and things can spread like wildfire. There have been different results seen in different species about whether ants do more of this fluid exchange when they're sick, or less, there are some species that definitely do more of it. And when we look at the proteins in the social fluid, we do see a number of things that are related to immunity. So I think it's quite likely that at least in the species we're working with is that when they're sick, they produce more of certain things that they can then pass to their nest mates that can protect their nest mates from illness.

Chris - And have you tried manipulating it as in it's one thing, obviously, to do an observational study where you pick up an ant, you establish where it's pecking order is in the queue and, then see what's in its stomach. But if you add something to the stomach, can you change either the behaviour of that or the recipients?

Adria - Yeah. So one of the cool things that we've seen, this social stomach contains all sorts of things, more than proteins. There's small RNAs, there's hormones, there's lots of cool stuff, and we've done some work on the major hormones that we find there; they seem to be targeting the larvae. So when an ant colony is passing around a lot of this hormone called juvenile hormone, it makes the larvae develop into bigger adults and helps them develop faster. And more of them get reared to adulthood. It's kind of like a parallel to breast milk or seminal fluid, where there are all these different kinds of messages that end up in here along with the important cargo. And we've seen from studies in humans and model organisms that there are many things that can shift these kinds of, socially exchanged materials. What we're seeing in the ants is your social role, your behavioural role within the colony. Also the age of the whole colony you're with inside and all these things can impact what is being shared, which is very exciting because it means there's so much to discover in how these different components are manipulating receivers, are communicating important information, and understanding how groups really work together collectively.

C. elegans roundworm

30:28 - Intervention doubles worm lifespan, even given in old age

Flipping a genetic switch, even at old age, can rejuvenate elderly worms...

Intervention doubles worm lifespan, even given in old age
Collin Ewald, ETH Zurich

As Benjamin Franklin is often quoted as saying, "nothing certain except death and taxes." But before the death bit usually comes ageing first, and that's something of a scientific mystery: why does it happen, how does it happen and can we do anything to slow down the process? Our knowledge of how we age is growing, but most of the studies that have looked into this topic have tweaked aspects of biochemistry in younger individuals and shown they live a bit longer. But, when it comes to humans, what about if we've lived fast and loose most of our lives and might now be coming to the healthy living party a bit late in the day? Can interventions at that stage still bear fruit and reverse the arrow of time? That's what Collin Ewald, at ETH Zurich, wanted to know. As he explained to Chris Smith, would worms in which an ageing-linked gene is deactivated later in life still benefit?

Collin - If you think about aging, you want to do interventions that work very late in life. So you think about when you are 60, 65 and age-dependent diseases start to hit, you want to do an intervention that could either postpone or prevent those diseases. Most interventions that have been tested in animal models are done usually when you are pretty young, maybe midlife, but not when you are really, really getting really old. So what we were wondering is, is it possible to extend the lifespan of an organism close to death, or when most of the population already died?

Chris - So if you're a member of the Rolling Stones, and you've got a well-lived-in body, it's not too late for you would be where you're going with this!

Collin - I think this is the natural hope everybody has, to rejuvenate at old age, but there's no evidence that this is even possible in any organism.

Chris - And of course, it's also frustrated by the fact that how long it takes to study aging in an long-lived species. So can we look at something that short lived and ask some of these questions there to try and get answers sooner?

Collin - This approach we took. So we chose this little roundworm called C.elegans. It's a great model organism for ageing research because it lives for three weeks. Just a single mutation in a single gene was able to double the C.elegans lifespan. So we thought, "this is a great system," so we could really measure those effects and quantify this.

Chris - What was the intervention that you did with the C.elegans?

Collin - So one of the best studied interventions, besides caloric restriction, is reducing insulin IGF-1 receptor. In C.elegans, the insulin-like growth factor one receptor is called daf-2, which stands for dauer abnormal formation and usually drives the animal in a dauer-like stage where they can endure for a long time. So we thought like, you know, daf-2 two would be the right place to start. One way to do this is to use RNA interference, which people have done. And you also able to double the lifespan with RNAi. But the promise with RNAi, it works great when the animal's younger, but then the RNAi efficacy just declines and doesn't work. So nobody knows whether interfering with IGF-1 receptor would work post reproduction, or even later in life.

Chris - I see what you're saying. So we know that animals that have changes in this particular gene do live longer. But what we don't know is whether intervening and manipulating that gene starting later in life would have the same benefit as if you target it at a younger age?

Collin - That's correct.

Chris - Is there a way around that?

Collin - When we were looking for ways around it, we stumbled across a system that has been used in plants and then optimized C.elegans. It's called the auxin-degron system. So auxin is a plant hormone that binds a sequence of a protein called degron. And then, wherever the sequence is attached to, that protein is then marked for degradation by the proteasome within half an hour.

Chris - In other words, you've got a switch on switch off system for whatever you want, whenever you want, in the worm's life cycle. I'm gonna guess then that you've, you've got a population of worms that have got this wired into them and you leave it inactive until they're old, and then you turn it on. So you can rob them of that particular gene. And you can then ask, "what happens to the ageing of those worms when our intervention comes, when they're already elderly?"

Collin - That is correct. So that was the original idea.

Chris - Okay. And what happened then when you did that, do the animals live longer once you switch this on when they're old?

Collin - So we aged out C.elegans until day 21 of adulthood. And that's a time point when about 75% of the population has died. So you only have 25% of the population still remaining. So if you don't treat any of those animals, then they die within four days. However, when we applied to half of that population auxin, that was sufficient to increase the lifespan. And it was not only sufficient to increase the lifespan by a couple more days, it was sufficient to increase the lifespan up to 26 days.

Chris - That's double! That's twice as much, isn't it. That's like me living to 200!

Collin - That's correct. And that was extremely surprising and fascinating at the same time, because, as you said, we were able, even at this very old age, to get the same effect as even the animals would be young.

Chris - The thing is that, in medicine, we dwell less on lifespan and we focus more on "health span", reasoning that actually there's no point in living forever if you're not able to make the most of it. Now, are these worms just going on forever and failing to die, but they're pretty clapped out, or are they healthy and doubling their lifespan?

Collin - I personally went into the lab to repeat that experiment because it seems so exciting. So when I was doing it and applying the auxin and see how the non-treated generation just deceased, right, I mean, at that age, the animals are just like couch materials, they just lay there basically! So when I did the intervention, what I noticed that the ones that got the auxin, right, they were still moving around. So to me, this suggests the health-span is also increased, but we need to quantify this.

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