Briefing Chat: What Brazilian centenarians could reveal about the science of ageing

0:03Hi listeners, Benjamin here. Welcome to the Nature Briefing podcast, the Friday show where we talk about a couple of stories we have read in the Nature Briefing podcast. is of course nature's daily roundup of the latest science stories we're actually recording this in the office today so you might hear a few folk walk past but one of the folk who hasn't walked past and is here to talk science with me is nick petrich how nick how you doing today i'm doing well ben i have indeed stopped to come and tell you about some interesting science that i think you'll agree shines a light on some new research well that has baited the hook i shall say but i've got a story that i'm going to talk about first and it's something that i read about in nature And it's about the preliminary findings from a study in Brazil investigating why some people live to a very big age, like over 100.

0:49So this is looking at things that I'm guessing allowed them to get to such a great age. Yeah, and it's something that we've covered on the show before, right? The science of aging is incredibly complex. But of course, it's of huge interest to a lot of researchers as well. Not just extending lifespan, but extending healthy lifespan as well. And this story in particular looks at the DNA Longevo study, which is Portuguese for long-lived DNA. And this study is still recruiting participants. But scientists have already sequenced the genomes of more than 160 centenarians, so folk over 100. And 20 participants are super centenarians.

1:31Those are people who've reached over 110 years old. Wow. Okay. So such incredible lifespans. And hopefully their genetics can tell us something about how they got there. And genetics is the important word as well. So, yeah, you're right. It's hope that understanding why folk like this can live so long is something that scientists are interested in investigating, you know, for clues about human longevity. And as I say, genetics is key. Because when you see a local news show and they've spoken to someone who's over 100 and you ask them about their lifestyle, they say, well, I smoke 20 cigarettes a day and I have a bottle of gin for breakfast, right?

2:03So we need to be a little bit careful taking them in isolation. And that appears to be relevant here as well. So early data showed that the super centenarians in this study did not have especially healthy diets or exercise ratios or access to high-end medicine for most of their lives. And this is why it's thought that the secret might be in their genomes. And so in a recent preliminary report, researchers hypothesized that it is their genetic diversity that could have a role in this resilience, because many of the participants have ancestries that are a mixture of European, African and Native American heritage.

2:41Oh, right. So by diversity, you mean like literal diversity, lots of different ancestors from lots of different places. Exactly right, which is in contrast to a lot of studies investigating the health of centenarians, which are focused on populations that are maybe more genetically homogeneous. genius so this study is hoping to maybe fill a gap by looking a bit broader in that sense and one of the scientists who's leading the project says you know quote we know that brazil has a highly mixed population and that may contribute to their longevity he says and another aspect that maybe sets this cohort of folk apart is that most of the participants have managed to stay relatively healthy despite having limited access to medical care many of them live in small villages apparently away from medical centers which suggest that this aging was driven by something other than having access to targeted therapies or early screening for disease and what speaks to that is the information about some of the participants which is absolutely wonderful i have to say and i'll give you some info on a couple of them one of them is a 106 year old woman who took up swimming at the age of 70 she won her first competition three decades later and longevity runs in her a family apparently she has two younger sisters over 100 and she has 110 year old aunt as well and this family lives in different parts of the country so it's not necessarily the fact they're in the same environment it suggests there's maybe something deeper and i'll give you one more as well this is a volunteer 107 year old man and he's thought to be the oldest person to hold a formal job in brazil he works in the supermarket organizing the shopping carts and the researchers said when they went to meet him at the supermarket they just walked past him because he was moving so quickly from one side to the other that's not what maybe they had in their head a view of what a centenarian would be like and so if this research is hoping that these volunteers would really help get a better understanding of why some people live so long yeah and you said this is a preliminary report do they have any sort of tentative findings that you know could give us an insight well what's happened so far is the researchers have been looking for genetic variants associated with extreme longevity, and they're comparing the participants' genomes to those from people in an existing biobank who died of natural causes at younger ages.

4:51Now, there's a slight kink to this, because ideally the comparison would be made with people born around the same time. But of course, that is very challenging when you're including people who are 106 years old, because there's not many of those. But there's a bunch of other things as well. The researchers are investigating the immunological profile of the participants, and they're measuring biomarkers as well. And one of the teams says, you know, there's not a lot of reference values for very old adults. So hopefully this will help generate these values and explain what normal looks like for this age group of folk who live a really, really long time.

5:24Well, a super interesting story, and I'm sure we'll be doing more stories like that and maybe following up on this study in the future. But for now, I think we can move on to my story this week. And this one is looking a little bit more down a microscope. This is about proteins that can be sort of remote-controlled using magnets. Some really key words there for me, Nick. You know, I've covered magnets on the podcast in the past, but a magnetically-controlled protein seems very exciting. I mean, it's still very early stages, yeah. And like your study, this is quite preliminary. But yeah, eventually, this could open the door to proteins that you could control or antibodies that you could switch on and switch off to bind to things more strongly by using magners.

6:07So this is a story that I was reading in Nature, and it's based on a Nature paper, along with some preprints on the same topic. And essentially, you're probably familiar with green fluorescent protein, GFP. This is a workhorse of the lab. And as it turns out, about two years ago, some researchers discovered that it's sensitive to magnetic fields. so they showed that it dimmed by about one percent when exposed to a weak magnet which is not a great amount but now in these studies that are covered in this article they've created new proteins based on this are more sensitive to magnets and that's such an interesting finding off the bat right because gfp i mean any molecular biologist listening to this show now we go oh yeah of course right the protein that we use to see stuff in many cases and and this tiny difference when it's magnetized Yeah, yeah, yeah.

6:56So what's happened here is they've basically taken GFP and created different versions of it, newer versions that are more sensitive to magnetic fields. So in this new paper that came out in Nature, they've created a protein called MagLov. And this dims by about 50 % when exposed to a magnetic field. So a lot stronger effect. And as you mentioned there, GFP is a workhorse of cellular biology. If you look down a microscope, it's great to see things and it's great to label specific things. So having something that you can turn on and off is great. And in this study, they actually showed that they could identify bacteria that had this Maglov protein in them through a silicon block.

7:38So they could find like specific bacteria and they could switch this effect on and off. And this is done from a distance, right? With a magnet? Yeah, exactly. It's done from a distance with a magnet. And that opens up the possibility, if these proteins are sensitive to magnetic fields, could you make other proteins like them that are also sensitive to magnetic fields that could do different things other than dimming or glowing more brightly? And so there has been some work on an antibody, which is called a mag body, and its binding strength can be controlled by a magnet. So you could get a antibody, which are things that bind to proteins on the surface of cells.

8:14You could get it to bind more or less strongly by using magnetic fields. And magnets, of course, you know, are fairly commonplace in medical settings. For example, I think of MRI, which uses incredibly strong magnets, but maybe weaker magnets could be used to guide proteins to where they need to be. Yeah, they think there's a lot of different things that this proof of principle could be used for. There's some researchers who were interviewed for this article who weren't involved in this work, and one of them said that they think this idea has a lot of great potential. And what they've been doing as well, the researchers behind this, is they've been doing something called directed evolution.

8:49And this is where you basically start off with a protein or a gene or something like that, and then you have a desired outcome and you basically mutate it you do a bunch of mutations and then you look at which one of the resultant proteins or genes come closest to your desired outcome and then you repeat the process to sort of like guide evolution he says in inverted quotes towards your particular goal so they've done this for this to try and create proteins that have stronger effects and you could do this for other things as well so you said then this is kind of a proof of principle early steps in this pathway then what happens next this as i said was done in bacteria it won't surprise you to learn that it was done in ecoli ecoli again a workhorse of the lab so the next steps would be to try and do it in animals and there has been a preprint that has shown that this works in c elegans again another workhorse of the lab all the workhorses of the lab are coming together and so while there's been some preliminary things you could use this to monitor different cellular processes as you said this is magnets it can be done from a distance so you could like monitor things as they go along and it can penetrate tissues as well magnets so you could do a lot more with this but obviously a lot more work to be done well illuminating stuff nick thank you very much as always listeners we will put links to both of those stories in the show notes and a link on where you can sign up for the nature briefing where you can get even more stories like this delivered directly to your inbox but for the time being i've been benjamin thompson nick petrich how thank you so much for being here thank you for having me