Briefing Chat: Is DNA repair the secret to a long life? Whales and mole-rats offer tantalizing hints

0:00Hello and welcome to the Briefing Chat Show, the Friday show where we talk about a couple of stories that have been highlighted in the Nature Briefing. Well, actually, the Nature Briefing itself is on holiday this week, but we are still here, rest assured, listeners, we have stories for you. And joining me this week is Sharmini Bundel to tell me about hers. What have you got for us this time, Sharmini? So I've had to skip the briefing and go straight to nature.com where I found a cool news story

0:30about long COVID, which is interesting and mysterious and causing a lot of problems for a lot of people. People who have COVID-19, have an infection, get ill, and then certain symptoms carry on for months and months and months and can be really debilitating. And this study is looking at the link between long COVID and dormant viruses that live secretly inside us that you might have in your body right now, but not even know about it.

1:03Sounds ominous. Yeah, it's, well, it's usually not. I think that's the sort of point here is that, you know, usually they're dormant. So obviously, we've all had lots of infections with viruses in our life, particularly in childhood, you get loads and loads of infections. And if you are currently healthy, probably those infections have been defeated by your immune system. But sometimes some of these pathogens are never fully cleared. They're actually sort of lurking inside you,

1:34but kept in check by your healthy immune system. And that's partly also why in terms of certain conditions where your immune system is weakened, like an HIV infection, for example, it's often these dormant viruses resurfacing that cause a lot of other problems. So there was this idea, maybe is there some link here with COVID-19, with long COVID? Yeah, yeah. I guess if you have an infection, a bad one, like COVID, and then that weakens your immune system, then things could re-emerge. It makes sense.

2:05Yeah, that sort of raises a question for me, which I don't know the answer to, of whether that happens with other infections, in fact, and it's not something that we're aware of. But this particular study that was out in Nature this week, looked into the link between COVID-19 specifically, cases of people who were hospitalised in 2020 and 2021. And they've gone back and got a load of samples of blood and nasal swabs and lung fluids, and looked for these common viruses to see if they

2:37were in fact reactivated. And what they found is that nearly half of those people had a reactivation of common viruses in their body. And they then tracked those same people for a year afterwards, and found that the people who had had reactivated viruses later had increased bodily inflammation, elevated immune cell activity, and more cellular damage, which I don't think they specifically looked at long COVID diagnoses, which kind of long COVID is kind of hard to define at this point.

3:12But there definitely seemed to be a difference in the kind of long-term impact on your body, if you did have this reawakened virus. And that could potentially then lead to the fatigue and other symptoms that people with long COVID have reported. Is that the thinking? Well, so there is a lot that we don't know. This is just a link. This is just correlation. So, for example, they don't know exactly why these viruses are reawakening in the first place. One research quoted in the piece says it's probably that the COVID-19 is inducing the stress that then

3:48triggers the reactivations, and then the reactivations then further amplify the inflammation that's been caused by the COVID-19. So it's all kind of circular in that way. So they don't exactly know how that's working. And then they don't know whether the COVID-19 is causing the viruses to reawaken. And then the viruses are causing the long COVID symptoms. Or if the viruses reawakening are just another symptom of the immune system being exhausted, and all of the problems, it's just another problem being caused by the SARS-CoV-2 infection, and then that kind of illness. So yeah,

4:25cause and effect, not figured out yet. No. Well, what do they hope then they can use this study for? Could they give people antivirals or something when they get COVID to try and ward this off or something like that? Yeah, exactly. So apparently they've got a phase two clinical trial launched right now. And that's exactly the point, because they have looked at these reawakened viruses, various things, Epstein-Barr viruses, herpes virus, some viruses which are usually totally harmless that just in our body, but don't cause any symptoms. So seeing what they are. And then this particular

5:01trial is testing antivirals that are targeting herpes viruses. But the idea is that, and we don't know yet, but if these reactivating viruses are causing their own problems inherently, then maybe instead of treating COVID-19 by targeting SARS-CoV-2, maybe we should be treating COVID-19 with antivirals for other things. And maybe there is more to study more broadly about what all of these dormant viruses that are in a lot of our bodies are in fact doing, and how they in general interact

5:36with other illnesses that we have. Sounds like a classic case of some answers and many more questions, which, you know, is science, I guess. As usual, yeah. As usual. Promising, I think, and interesting. No, no, for sure. And hopefully they can figure out exactly what's going on there. So, you know, people can avoid some of the symptoms of long COVID and things like that. But my story this week is in a similar vein. There are some answers, and there are many more questions about how it all might work. Again, like you, I've been going into nature this week, and we've got a feature posing the question

6:10whether mending damaged DNA could prolong life. So what's the link here between damaged DNA and life? Because when you talk about damaged DNA, I'm thinking like, oh, is it a mutation? Am I getting cancer? Yeah. What do we mean by damaged DNA? Well, that is a very good point. And it means a lot of different things. So DNA damage can be changes to the base pairs of DNA. So the A's, C's, G's and T's, or it can actually be changes the chemical structure of them themselves. So it could be like an additional oxygen or something like that. So there are a few different things that DNA

6:44damage can mean. But what we do know about it is it is linked quite strongly with ageing. It seems to be behind many of the hallmarks of ageing. So as people get older, you get things like more inflammation, you get cell senescence. So the cells stop dividing, they end up in this sort of like fixed state where they're not dead, but not really alive in the same way they were before, mitochondrial dysfunction and things like that. And DNA damage seems to be behind a lot of that.

7:14And in animals that live a long time, and also maybe in humans that live a long time, having enhanced DNA damage repair is associated with a longer life. As in just naturally, certain people and species might have a better DNA repair system? Yes, exactly. So I know that one of your favourite species, the naked mole rats, are quite long lived, and they have an excellent DNA damage repair system as one example. Another example is the bowhead whale. So bowhead whales are these huge whales that live for more than 200

7:48years, and they do so rarely getting cancer. So not only do they live a long time, they also don't get some of the things that we get as we get older. So researchers have been investigating these animals, and they're starting to give hints of things that we could maybe do to promote DNA repair and perhaps stave off ageing. So in the example of the bowhead whales, this was a story we actually covered on the podcast last year, they found a protein called cold inducible RNA binding protein. And this seemed to be

8:22associated with really enhanced double strand break repair. So double strand break is a really damaging form of DNA damage. When they were looking at the whales, they're like, why don't they get cancer? But it looked like it wasn't so much about them having some of the genes that people often associate with less cancer. It was actually more about this DNA damage repair that was so important to them not getting cancer and also the longer lives. Because this even worked when they took this protein, this cold inducible RNA binding protein, and put it in human cells and in flies.

8:54Oh, wow. So certain species have these mechanisms that we don't have. And then I guess the question is, can we borrow them and stick them in our own cells somehow? That is the tantalising, tantalising hope. However, as is often the case, things are complicated. So this is not a new thing. Researchers have been trying to enhance human DNA damage repair for a long time. But there are many different systems. So there's about six main systems of DNA damage repair.

9:26And they all interact with each other. And sometimes they overlap. And sometimes one needs one thing and the other needs another. So they're very complicated. They're very intertwined. And when researchers have boosted one, they've seen very limited effects. And sometimes they've even made things worse. So it's not as easy as just being like, okay, let's just boost these and away we go. So it's a very complicated procedure. But as I say, some of these animal studies are starting to give hints of, you know,

9:58certain things that we might be able to do. But this is still at the stage of figuring out how it's working in these different species and maybe trying some things in cells in a dish. Well, no, we're actually getting to human trial stages, which is quite interesting. So the same team that did the work on the bowhead whales had also looked at rodents. And they looked at the differences between rodents. So beavers, for example, live 10 to 12 years, whereas mice live maybe a couple. And they found the overexpression of a certain enzyme called CERT-6 was linked to the

10:32extended lifespan in the different species. And this also seems to be true in human centenarians. So people who live more than 100 years, it seems that they may actually carry a superior variant of this CERT-6. And there's more. There is also a compound called fucoidin, which naturally occurs in brown seaweed and activates this CERT-6 protein. And this could be a potential therapeutic. And so now there is a study where they're giving fucoidins to men aged 50 to 80 to see how this sort of plays

11:07out. But obviously, more work to be done. Why is this study only in men? I want to live forever. Live a long time.

11:17I'm not sure why it's only men. Maybe because men live less long than women in general. So maybe it's easier to link it to it. I'm not sure. And something that we have discussed before is extended lifespan, like just living longer versus a sort of healthy lifespan, living healthier. But this seems to be sort of talking about both of those things, because you're talking about reduced incidence of cancer, reduced sort of incidence of the things that cause you to sort of damage and age. I think that is the hope. It's not always the case, though. And it doesn't always necessarily

11:51mean that getting rid of DNA damage stops cancer occurring. Like there is some evidence for that, but it's not entirely clear that one necessarily leads to the other. Perhaps in the bowhead whales, of course it does. But, you know, things may be more complicated in people. So yeah, that is certainly the hope. But also, I think researchers in this article were a little bit cautious as well, because there's been a lot of hype around some of these things. You know, I mentioned like frucoidin. There's other molecules that people are interested in as well, because they've been

12:22associated with DNA repair, such as nicotinamide, adenine dinucleotide, which is involved in metabolism, and of course, DNA repair. And there's a lot of hype around supplements that try to raise this molecule's levels, but there's not a lot of evidence they actually work. So I think my reading of this feature was that researchers saying there was definitely possibilities there, and there may be things we can do, but we do need more research and, you know, human trials and things to really figure out what's going on. There are promising hints from other animals and things, but we need to do

12:56more research to really figure it out. Wow. Well, so another sort of human trials yet to come story, but we do like our basic mechanistic science here at Nature, figuring out some of the underlying things about how it all works. So that's fascinating. And I think we'll put links to both of those Nature news articles so you can read those stories yourself in our show notes. We'll also put a link to the Nature Briefing, Nature's daily email newsletter for the latest science news. That will be back in action next week so you can join in after their summer break and get more science articles like

13:31these ones direct to your inbox. And if you're on social media and want to hear more about what we're doing or want to reach out to us, you can find us on various social media sites with the handle at naturepodcast, or you can just email us directly, very old-fashioned, but we are podcast at nature.com. I'm Shamni Bundel. And I'm Nick Petrich-Hell. Thanks for listening.