Tales from an Italian crypt, and the science behind ‘dad bods’
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This is the Science Podcast for May 1st, 2025. I'm Sarah Crespi. First up on the show, we have contributing correspondent Andrew Curry. He talks with me about his visit to a 17th century crypt under an old hospital in Italy.

Researchers there are examining tooth plaque, bone lesions and mummified brains to learn more about the health, diet and drug habits of Milan's working poor. Next on the show, a mechanism for driving growth in fat stores with age or the source of the dad bod trope.

Producer Zakiya Watley talks with researcher Annabelle Wong about her work showing how middle-aged mice gain fat via dedicated progenitor cells that actually become more active as the animals age.

This week in science, contributing correspondent Andrew Curry wrote about a large series of crypts under an old hospital in Milan, just chock full of human remains that have been pretty much undisturbed since the 1600s. Now researchers are looking for clues about what people ate, the kind of drugs that they did, and how they died. Hi, Andrew. Welcome back to the Science Podcast. Hi. Thanks for having me on. This story is nuts. Like, I...

This is such a treasure trove of human bodies underground. How did you first come across this project?

So I was talking to somebody about detecting drugs in ancient bones. And he mentioned that somebody had recently published a study looking at opiate and cocaine residues in bones in Italy and some sort of religious or monastery context. And so I dove into this. Then last fall, I happened to be in Milan and I emailed the archaeologists, sort of invited myself to...

to go by and take a look. Yeah, I mean, it's an incredible site. The cool thing about the team is the research is sort of a collaboration between historians and archaeologists, but it's all centered through the

the forensic medicine department at the University of Milan, where they do a lot of modern like crime scene detection. So all these toxicology, like drug screening, et cetera, is modern methods then applied to this 400 year old population. What did it look like there? I mean, I said old hospital in Milan. Can you just create a picture for us?

It's pretty close to the center of Milan, and it's a beautiful campus almost that was built by the Duke of Milan in the late 1400s as the first public hospital in Europe. There had been religious hospitals before that, but this was the first one that was funded by the city for anyone. And today it's the main building of the University of Milan.

Yeah. And the photos, it just looks beautiful. It's stone, it's courtyards, it's arches. It's everything you would expect from a 1400s building in Italy. Yeah.

You cross that little quad and then go around a corner and down some stairs and you're under the chapel that they built for the hospital. And there's this underground level with archways and there were paintings and in the floor of that level, there's a bunch of manhole covers. And under the manhole covers are 14 chambers where for 50 years, anyone who died at the hospital was dropped through the manhole cover. They would tip a table and then the

the corpse would just slide on down into these repositories. Why? Why were they doing that this way? Not burying them or, I don't know, cremating them? So they had a space problem in Milan. This was pretty common at churches, was you would bury people and then every 20 or 30 years, you would dig up what was left, which was...

which was just the bones. And then you would stack the bones somewhere else. There's a church around the corner from this place that's literally decorated with human bones on the walls. That was the plan, but it didn't work out. It didn't work out because there's a river that runs right under this. And the water table is really high. And apparently the humidity was so high in these chambers that

And then they would periodically flood. It was so wet that the archaeologists compare it to like bog bodies. Okay. Where there was no oxygen, the bacteria were totally different. And there were so many. I mean, this was an average of about 10 people a day for 50 years. So they were stacked high and deep and they were subjected to these climatic conditions that said, what, you're not going to ever get bones out of here. You're going to get bog people out of here if you try to move these guys out? Apparently.

Apparently, after a while, the smell was so bad that like nuns in the church above would pass out. And so after 50 years, they said, OK, this clearly isn't working. We just have to seal it up and move on. They opened some of them in 1848 because there was a revolution and they had put people's bodies in. And then there was some bombing in World War II that damaged some of the crypts. But otherwise, it's been untouched.

And the preservation conditions mean you not only have over 2 million bones, but preserved brain tissue, skin, hair, all the things on the bones and the dead bodies that you can decode what their lives were like. And that is kind of a really important point

point in your story is, yes, it's a big group of people. They were all in the hospital. They all died. But it's like a subsection of the city of the people of Milan at the time. You just don't have a lot of information about. Exactly. So history, especially at this time, is usually about the rich, the elite, the nobles, the

The literate. Yeah, exactly. And this hospital was founded to keep the working poor of Milan working. It was founded for people who they would be working if not for their illness or their injury. So it's the lower class. We actually know very little about their lives, even though this is kind of the early modern period.

We don't know what they were eating, but these remains are giving a great window into that. The first thing I want to touch on, this was such an amazing anecdote, was that the researchers were like, let's look at the soil down here. And it didn't look like any other soil they'd ever seen before. Yeah. So as I was saying earlier, there was this common practice where you would bury people and then dig them up after 20 or 30 years and take their skeletons. So let's talk about some of the techniques. The first one you mentioned was looking for drugs. Yeah.

in the tissue from there. So what they have here that they're really lucky with is they have both bone and brain tissue, for example, which some drugs don't preserve in bone. Or if you don't use them regularly, they don't preserve. At first, they just kind of wanted to see what this were because the archives of this hospital preserve, for example, everything that was in the pharmacy.

And so they knew that they were using opiates in the hospital. But what the pharmacy didn't have was cannabis and coca. So they did try that out and they were kind of shocked to find coca, cocaine, the chemical traces, because this is only a little more than a century after contact with the new world. That's where it came from?

Yeah. So somehow it already made its way over from the Americas to Europe and working class people were using it. Exactly. Because if it had been used as a medicine, it would be recorded in the archives. So people were using it for something else. And cannabis similarly was apparently not being used medicinally, but people were using it recreationally and they can find those traces.

That's so interesting. And the other thing they looked at regarding the Americas, this like recent contact, 100 years, was they were able to look at teeth, right? And look at what they were eating, which is another kind of like, oh, yeah, what were people who didn't have a lot of money eating in Milan 400 years ago? Some of the interesting conclusions were what they didn't find. Like they didn't find corn. Today, people in Milan love polenta. Mm-hmm.

Yeah, so good. They kind of have to assume that polenta only came in in the last 100 or 200 years because it isn't in these chambers. But they did find some potato and they always thought that potato, which is also a new world crop, was only introduced in the 1800s.

The historical record is that people were super suspicious of the potato for a while after contact with the neural. Some of the other stuff, there's wheat, there's grains, there's lentils, there's what you would expect poor people to be eating around this time. They also find basically grass and

And there's historical accounts of starving people turning to inedible plants, to these specific grasses. And, you know, women who have green mouths because they're so hungry, they're eating grass. And this is actual evidence in the plaque on their teeth.

That's amazing. What about the tomato? The other thing that maybe you'd associate with Italian cuisine that's not from there. No tomatoes, but tomatoes are tricky because they're soft, so they probably wouldn't preserve. But he's hoping that maybe tomato skin is often preserved during the digestive process. They have a lot of material to go through and maybe they'll find tomatoes in the future.

So what do we know about the identity of these people? Like you said, there were records about the drugs they were taking. There's also records of who was in the hospital, even dating that far back. Do we have a way of kind of lining up who these bones are and their identity?

So this is one of the coolest parts for me that, again, total surprise. And the reason it's so cool that the forensic medicine department is leading this work, Milan, around the same time as the hospital was founded, started recording every single death in the city.

and the cause of death and the name of the person who died. And the idea was to track health trends to stop plagues before they started or before they could really take off to make sure that they had the correct cause of death. They also had some of the first coroners in the world. There were people who worked at this particular hospital who dissected bodies.

And there's evidence of these dissections on the bones. And there are a few, I mean, none of these people had toe tags, so to speak. Right. But there are unusual deaths recorded in this. You know, somebody fell off his horse and he died nine days later with a broken leg that turned into an infection. So maybe if you find somebody the right age, the right sex with that injury, you could make a connection.

That's very forensic. This person had a fracture as a kid and here it is in the bone. And we thought, oh my goodness, that's amazing. There's also an incredible painting that's hanging in the archive above these chambers of the hospital courtyard at the time. And it's filled with characters. I mean, there's doctors, there's the archivist, there's patients coming in, and there's a man with dwarfism who's depicted sort of in the center foreground.

and they found a man with dwarfism in the chamber. You know, you can't be completely sure, but it's a pretty good connection. You said there are records of death, but is there kind of like themes that they're seeing in the bones or in the remains that are down there, like causes of death at this time in Milan? The bones preserve evidence of injuries. They preserve evidence of things like they found a lot of syphilis.

syphilis gets bad enough, it starts pitting your bone. They know from both the historical records and the skeletal remains that tuberculosis was a big problem. And there was a whole separate ward for the tuberculosis patients.

And they're looking for things that they find in the historical records like leprosy or the plague or other things like that that don't necessarily show up in bone, but might show up in bacteria. And the problem is it's such a soup of all kinds of DNA down there. Yeah, you don't want to do environmental DNA in there. There's just so much that it would be hard to pick anything specific out. It would be pretty hard to find a

a comparison of people who were not in the crypt, but maybe buried in a cemetery, right? You're not going to get all this detailed evidence of what their lives were like. This group, I mean, they're looking at Milan cemeteries from the Roman era to the modern day. And this is just their largest single data set, which is really cool because it's one specific population. It's a specific 50 years. And it's stratified. There's like decades of people.

Yeah, but they can compare it somewhat to the 1400s or to the Roman era. It seems like people were actually healthier in the 1400s, that this is not a great time for Milan. You described so much material. People...

In these crypts, years and years of bodies. How far are the researchers in analyzing all of this stuff? It's a fraction. I think there are 14 of these chambers and they've worked through half of one. The lead researcher said his grandkids could be working on this if they wanted to. So how far into this space did you go? Were you in there where the bones are located?

They let me look down through the manhole cover, but you need both protective gear and then special training to be down there because you're walking on human remains and they have to be really careful. But in the story, they have some fantastic pictures of what it looks like down there.

And they want to open this to the public. And they have some really cool exhibits down in that space above the manhole covers, including some of the original bones. And they've done facial reconstructions of some of the people using forensic techniques. So, yeah, if you're in Milan, hopefully this is something that you can go see in the future. How related to modern day Milan are the people that were interred in these crypts?

very related. The DNA results so far suggest that up until kind of the 14-1500s, there was a lot of turnover. Italy was super diverse. The Roman period had people from all over. And then the Middle Ages really homogenizes Italy. And the people in this crypt look very much like modern day human

What are some of the big questions that this research group is trying to answer with this? They're really interested in a comparative look at the health stuff. And then it's this really interesting period in medical history and European history that often gets ignored because it's in the Italian context. It's, you know, it's only 400 years ago. And so people are much more interested in the Romans and this really old stuff. You know, there are churches that are older than the cemetery in Milan, but it's

It's this critical period. Leonardo da Vinci worked at this hospital, probably watching them dissect corpses. They're introducing the concept of specialized wards for different diseases. The river that ran under the hospital, the hospital was placed over that river to get rid of waste and keep it hygienic.

So there are a lot of innovations that then spread elsewhere and understanding what people, the patients were all about helps you understand that period in medical history too. Is there anything that we didn't get to touch on that you wanted to talk about? I think I was just really impressed at how interdisciplinary it is. I mean, with the forensic folks, the soil specialists, the toxicologists, the archaeologists, and then the archivist and the historian on the project who the archivist was super, I'm

I met him too when I invited myself to the site. But he said, you know, I know the names of all these people and all these paintings because they gave money to the hospital. And now I'm learning about the nameless patients and who they were. It was really moving. Andrew, thank you so much for talking with me. You're welcome. Thanks for having me. Andrew Curry is a contributing correspondent for News from Science. You can find a link to the story we discussed at science.org slash podcast.

Stay tuned for a conversation with producer Zakiya Watley and researcher Annabelle Wong about how the body builds up fat in middle age. When we talk about gaining weight in middle age, we typically think about slower metabolism or changes in lifestyle. But what if there's something happening inside your fat tissue itself, something that's much more active than we thought?

In this segment, I'm speaking with Dr. Annabelle Wong, whose new study explores how fat expands during middle age and what kinds of cells are driving that process. She and her team discovered a previously unknown population of progenitor cells that only shows up in visceral fat, and that's the kind that surrounds your organs.

And not only does it only show up in visceral fat, but it only shows up during middle age. These cells aren't just storing energy. They're multiplying and making entirely new fat cells. This is a fascinating shift in how we think about fat biology, and it raises some new questions about how that tissue behaves as we age. Thanks for joining us today, Dr. Wong. Thank you so much for having me here. I'm excited about it. Me too. So let's start with the foundation.

Not all body fat is the same. So can you explain the difference between the different types of body fat? In this study, we'll focus on visceral fat, which is the intra-abdominal fat. So it refers to the fat that surrounds internal organs like the pancreas, liver, intestines. And this is quite different from the subcutaneous fat. Okay, so subcutaneous fat is just underneath our skin and the visceral fat is what's around our organs.

But why is visceral fat more closely tied to the metabolic health problems that we often hear about when we think about gaining weight? The visceral fat is just because they're very close to your internal organ, they're going to secrete a lot of inflammatory side effects that really have a profound impact on your organ health, like how your pancreas acts, how your liver functions, or how your intestines.

in testing works. So visceral fat are more being focused on because of their flexibility and their function and their proximity to the internal organs. Now, your paper is zeroing in on a specific period, middle age, and that's when that visceral fat around our organs starts to increase.

But fat feels like such a known and accepted tissue to me. What got you interested there? When I was a postdoc, I constantly see, especially male mice at one year old, which is considered mid-age, they actually just look like obese. They're just considered to be healthy adults. They just gain a lot of fat.

So I wonder what happened to them, right? It's really like the literature said, adult stem cells actually have reduced proliferation and differentiation. I just can't stop thinking about like why they are really increasing that much of their fat. Okay, so you wanted to figure out how they were getting fat during that specific time.

What do we know about how fat tissue typically changes? There are two ways we can increase our fat tissue. Firstly, a fat tissue is full of fat cells, right? Those fat cells are already very huge and very flexible in size.

The first response when the fat tissue expands is always from hypertrophy, which is just increase of the size of the cell. Their lipid droplets and along with their cell membranes can increase two or three folds. So that, of course, will increase the overall mass of the tissue. Another way for fat tissue to increase is through adipogenesis, making new fat cells from fat-presenting cells.

So this will give the tissue an unlimited potential right to expand. Okay, so there's two ways to expand fat tissue, either by making adipocyte cells bigger or by generating new adipocytes, aka adipogenesis.

Now, you mentioned using lineage tracing. Can you walk us through what that is and why it's so powerful in the context of what you're studying? So the lineage tracing technique is basically describing mouse models that we can do in vivo tracking of a certain cell type to see the

Did they turn into other cell types? Do they really transform? Do they undergo final differentiation or they're all gone? There's no trace of them. With linear chasing, we found that in the young, healthy adult, we don't really see a double genesis. So there's really low level of making you a double set in all the adverse tissue, actually. We actually use two linear chasing systems. One is positive linear chasing, one is negative.

For the negative lineage tracing, you labeled mature adipocytes in young mice. You let them grow to middle age, and then you looked to see if the visceral fat cells had labels or not. If it was labeled, then the mature adipocytes got bigger. But if there was no labeling, then this meant the new adipocytes in adipogenesis

were responsible for that fat expansion. And also we use the positive labeling system, which will label all the APCs, the progenitor cells. And then we can see by histology, if they stay like a progenitor cell or they have to freshen into fat cell because their morphology is quite different. So from the two Danish systems, we found actually in male mice with stroke fat at one year old

almost like 80% of the fat cells are actually generated from 9 months old to 12 months old. So it's really early meat aging. So somehow the meat aging period is already changing many tissues

to respond and may contribute to the later development of chronic metabolic disorders. Yeah, I think that the mini-chasing is really the start of everything in this paper because we saw massive with the progenesis that's a lot during this mid-age period. Okay, that's really interesting to only see that change during that period. So you investigated the role of the adipose progenitor cells or APCs, and those are the precursors to the fat cells. But those APCs, they're not one single type.

This is a heterogeneous group with cells of different types and subtypes, and your team identified a previously uncharacterized subpopulation that you see popping up only in middle-aged visceral fat, and that's the CPAs, or committed pre-adipocytes that are age-specific.

Tell me how you found this population of cells. We did a single cell sequencing of the APCs from the visceral fat of male mice. Kind of to our surprise, we found that there is a very unique comedic pre-adipocyte population only existing in the mid-age visceral fat. So if you compare with young, you don't really see, you only see a few cells compared to like thousands of thousands of cells in the age population. Because they have markers of

comedic pre-adipocyte, so we named them as comedic pre-adipocyte age-specific. Wow, so you're seeing the subset of cells that only shows up in the visceral fat of your middle-aged mice. Well, there's a tiny bit in the young mice, but there's 20 times more in the middle-aged mouse population. So they're age-specific, mid-age to be exact, and they are progenitor cells that are committed to becoming adipocytes. They have those markers, so the name reflects that.

But then you have the tricky business of determining or proving that these cells are the ones that are causing the middle age increase in visceral fat. So then we did a lot of APC transplantation just to validate actually those APCs

autonomously gain a very high adipogenic capacity. And then we set out to do the single cell sequencing experiment to sequence the APCs and to identify which molecular switch or maybe if we can find a new population there. This is fascinating because first of all, you say there's no change to the diet and you're seeing this rapid change in composition where those APCs are stimulating adipogenesis out of nowhere, it seems like. And

And such a huge percentage of that weight gain is due to this.

And in your work, you showed that CPAs really rely on the signaling pathway to become fat cells. I'd like you to talk a little bit more about that pathway and tell us what it typically does and why it's important here in this context. The CPA populations, when we identify them, we can actually find a few markers, right? And one of the markers is a LEAF-R, so it's a leukemia inhibitor factor receptor. Yes. So this is a gene well studied in immunology and some cancer studies.

It's known for cell proliferation and cell survival, but its role in APCs is not really studied because it's not really expressed in a young APC. The downstream of leaf R is actually JAK-STAT pathway. We find an inhibitor of leaf R and also inhibitor of the STAT3 pathway. If we do that, actually, both in vivo and in vitro, we find the CPSK

cannot undergo that high level of adipogenesis again. And very interesting is that if we just take the young APCs out and we apply the same inhibitors, it actually doesn't matter for them. So this indicates that the LEAF-R STAT3 pathway is unique for this age-enriched DPA population to actually undergo very active adipogenesis at this stage. I thought that was a really elegant way to demonstrate that too.

So I want to switch gears a little bit into thinking about that mouse to human gap, because there are some things that mouse models are great for understanding. And although 12 months is not middle age for me, thank goodness, I do think some of those things pair with what we know about human health and how our bodies change over time. So you found CPA-like cells in human visceral fat.

But I think right now there's still some unknowns. So what do we know about these cells in humans so far? And what do you think remains to be answered? That's a very, very important question. I think there's much more to be done after this.

So the question I got being asked most is actually, is this lipogenesis a good or bad thing for metabolic health? People would generally believe it's a bad thing because you don't want fat expansion anyway, right? We don't have evidence yet, but I think it might be a good thing for humans. We need to figure out if humans like that, because humans have a

Fat expansion is not linearized with age, right? When you reach the advanced age, you already have a lean phenotype. So is that the APC exhaustion? So that will lead to another run of failure of a fat tissue to function and then cause dysfunction of other metabolic active tissues like liver, muscles are actually very important, right? There's no evidence. So we're developing more mouse models and we're also trying to work with clinicians to see

If this adipogenesis is a good thing or a bad thing for metabolic health. This provides so many new insights because so much of the conversation around fat gain and aging has focused on slowing metabolism or losing willpower to exercise or eat healthy. But I feel like your study reframes this and you show that the fat tissue itself has its own changes in a very active way.

Now, you mentioned working with clinicians, but how do you hope this changes how scientists and clinicians think about fat gain in middle age?

I don't want people to think double genesis making you fat cells is definitely a bad thing, right? You need a certain amount of healthy fat cells to help you to store energy, to respond to fasting-related lipolysis, to respond to when you have a melt, you can update glucose in your bloodstream, right? So I was even thinking if in the future evidence shows that this mid-age-related double genesis is a good thing, or maybe CPA is not that evil, it might be.

helping her body metabolism. So then we can actually transplant the CpA back to extremely aged individuals who are lean but metabolically unhealthy, or even like cancer carcassia patients. So yeah, we think we can actually utilize this new population in many new ways.

I love that. So I think my final question for you is, what are you most excited to explore next? Whether that's a CPA mechanism, translational work or something entirely new. Like what's next on your plate with all of this information? Yeah, I think this is the thing I didn't talk about because the study we are reporting is really interesting.

age, location, and sex specific. Because we didn't really see a double genesis or even increasing fat tissue in the females. But then we look into the females, for males at least, if they increase fat mass at mid-age, it's dependent on their reproduction history. Oh. Yeah. So we think females is equally important, but it's more complicated. So we have another project we are doing, a really comprehensive project

comparisons with reproduction history, lactation or not. And then at mid-age, do they have the CPA population or even they have a totally different type of population. We don't have any conclusion yet or even having reproduction history is good or bad to metabolic health. And it's very complicated if you read the reviews. But I think there is a lot of things unknown on the female side and which we're equally or even more excited about. That is definitely exciting. So I

All the work you did before was in male mice, and now the ladies or the female mice are having their chance. That was Dr. Annabelle Wong, and her study is published in Science, and you'll find a link to it in our show notes. Thank you so much, Dr. Wong, for your time. Thank you so much for having me today. Thank you so much.

And that concludes this edition of the Science Podcast. If you have any comments or suggestions, write to us at sciencepodcast at aas.org. To find us on podcast apps, search for Science Magazine or listen on our website, science.org slash podcast.

This show was edited by me, Sarah Crespi, and Kevin McLean, with special thanks to Zakia for all her work on fat cells and aging. We had production help from Podigy. Our music is by Jeffrey Cook and Wenkui Wen. On behalf of Science and its publisher, AAAS, thanks for joining us.