The Hidden Reasons She Lived to 117.
In this YouTube interview, host Nick Norwitz talks with 26‑year‑old PhD student Eloy Santos Pujol, the first author of a Cell Reports Medicine study on a Catalonian supercentenarian referred to as “Maria” who died at 117 years and 168 days. The conversation covers how the project originated, Eloy’s personal motivation to study aging, and Maria’s personal traits (optimism, social ties, activity). The interview delves into the study’s key biological findings: Maria’s telomere length fell on the expected population line, suggesting telomeres may be a chronological rather than a health marker; her epigenetic age appeared 15‑20 years younger than her chronological age; her gut microbiome was enriched for Bifidobacterium; mitochondrial health was robust with high lactate and creatine; lipid profiling showed slightly elevated LDL but high HDL and low triglycerides, which the hosts argue should be interpreted in a holistic metabolic context. Genetic analysis revealed several homozygous variants linked to cognition, heart and immune function, plus three mitochondrial‑DNA variants and a Timeless gene variant previously associated with longevity in flies. Lifestyle factors included a Mediterranean‑style diet rich in olive oil, eggs, probiotic yogurt, modest alcohol, no smoking, and regular physical activity (walking, tennis, gardening) until late life. The discussion also touches on the broader implications for longevity research, the need to study family members, and the importance of moving beyond single‑marker thinking in clinical practice. The interview ends with Eloy’s contact information and a preview of future work on the family’s genetics and epigenetics.
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that probably has more longevity power than any dietary component.
I am a super young person studying a super old person.
She was older than me during World War II.
Maybe we have to change that paradigm.
That is a really astute point I didn't really think deeply about.
It's not about luck after all. Maybe it's more about habits.
Maybe we don't have to die at like a normal age, 120. Maybe we can engineer to live to 500, 1,000, or make Death optional. Dang, LDL cholesterol finally got her. All right everybody, we're back with another interview and this one is something special. But just to give it a little bit of framing, human longevity seems to feature more and more in headlines these days. I'm sure you've observed that too, and it makes sense. It's an area of immense public interest and sometimes the headlines are a little gimmicky and then other times they refer to studies that knock your socks off. So today I'm joined by, uh, Dr. to be Eloy Santos Pujol. I hope I pronounced that right. He's a PhD student in Catalonia, Spain, whose work focuses on the biology of aging. And he was the lead author, the first author on a widely circulated study published in Cell Reports Medicine. I have it printed out right here on a supercentenarian, a woman who passed last year at the age of 117 and 168 days. I was trying to wrap my 29-year-old head around that, and I realized She was older than me during World War II, which is kind of mind-blowing. And I'm thrilled to have Eloi with us here today to discuss his paper. And I also just wanna note a lot of the questions that I'm gonna bring up come from our Stay Curious community at staycuriousmetabolism.com, the newsletter. So thank you to everybody for putting in your questions. I passed a lot of 'em on to Eloi today and we can get his two cents. Eloi, thanks for joining me.
Thank you for inviting me.
So before we get into the nitty-gritty, I just wanna ask, so you're a PhD student. Having been a PhD student myself and having known many, I have to say this is a really immense project in scope and impact for, you know, a PhD project. How did this fall to you in the first place?
Well, we were already researching into longevity and human aging, and suddenly it came up to us that now the oldest, the world's oldest person oldest person in the world was then in Catalonia, right next to us. So it was like, okay, now it's a very good opportunity to continue our research in now the world's oldest living person. And yeah, that's how it came to us. It was a good opportunity for us to get hands-on on the most extreme longevity and also to have some clues on how the oldest people, the supercentenarians, these rare people can live and get to that exciting age.
Very exciting project. What did it feel like to take it on? Was there like a moment when they're like, hey, this is now your project?
Joale, it was like a responsibility for me because researching into the world of this person is something that not all people can do, you know, it was like for me, like too much. And yeah, I have enjoyed it a lot.
Well, your paper is absolutely phenomenal. Everybody should try to go read it. It's really well written. Before we get into Maria, I just want to ask a little bit more about your background. First, how old are you?
I'm 26. I am a super young person studying a super old person.
No, I, I actually, I, I think that's fascinating how, you know, our generation, so I'm 29, is interested in metabolic health and longevity. And I think it captures something about changing society. I think people say like, you know, death is part of life, but I think we're kind of getting to a place in science, medicine, a society where we're kind of just thinking in the back of our heads, maybe not articulating it, but maybe we don't have to die at like a normal age, 120. Maybe we can engineer to live to 500, 1,000, or make death optional. That's my two cents. I do want to ask, like, what got you interested in the biology of aging?
It's like an investment. I think that when we're young, we start thinking about economic investments, maybe, um, getting a house or getting a, a car to, to go to work. I think that it is the most important investment someone can do in their life, to start early, maybe in their 20s, 30s, to take care of their health. And if they can, and they have the lucky, the luck that they had to do some active research into it and help the world get healthier lives and longer lives if possible.
Well, I love your enthusiasm. And just to reiterate something that you were telling me before we started, the way you explained your interest in longevity, you were saying something to the effect of, and, and you can reiterate if I'm misquoting you, but we study all these things in silos, brain disease, Alzheimer's, cardiovascular disease, and they're all aging phenomenon. So you're like, why not just go to the root phenomenon? What can we uncover that is common to all these diseases? We're gonna get into it later, but I just wanted to tee that up for the audience because I thought like, that's how I think about metabolic health. You could call it longevity science or whatever, but it's the roots of the tree of disease. Which we so often overlook, you know, a siloed medical system. Actually, on that, before we progress, you know, I have experienced training in the medical system in the United States. How is it in Spain? Is it similarly siloed or do you feel like there's any more integration?
Well, yeah, and it has to do with what you were talking about. Um, all diseases have a single treatment. They are treated like everything has a drug. A different drug and a different research group researching into that disease. Okay, maybe we have to change that paradigm and maybe go to a future where we can research aging and then not only prevent those age-related diseases, but also treat them. We'll, we'll see where it's coming.
I, I agree. And there's one particular example that jumped up in the paper around cholesterol that I know we're gonna get into. But before we get to that, Maria, So Maria was the supercentenarian's name. What do you know about her? Did you ever have any interactions with her personally?
Yeah, sure. I visited her several times to get samples. She was super cute. This cute old woman that everybody would like to meet somewhere in life. And yeah, it was a pleasure to meet her. It was special how well she could reason what she was saying or how she could remember past events. How lucid her mind was, how sharp it was, and also how kind and generous she was to give us some samples to study her.
Yeah, that's really amazing. It didn't come through in the— I'm not sure you can articulate that in the paper, but it sounds like at the end of her life, she was still completely there, which at 117 is just like, is really incredible. I also heard that she requested to be studied. Somebody quoted her as like, please study me. Is that an accurate representation? Was it her request?
Well, I think that the first request came from us, and after that she was willing to collaborate fully with us and even told us that she wanted to be studied by us. I think that she knew that we could get a lot from her, but she was very humble and all the time she was saying, well, the only merit that I have is that I have lived like too, too long. Just that I haven't done anything special. She was very humble, but Yeah.
No, well, maybe we can get into more of her background later, but before we get into the biology, I find with all these stories of supercentenarians, they're all pretty diverse in their, like, you know, diet and lifestyle, but they tend to have maybe similar mental or cognitive traits. Were there like personality traits you alluded to a few, but that really stood out for you in interacting with Maria?
She was very positive and optimistic, and she was always surrounded by the ones that she loved. Friends, family, and even dogs. She loved dogs. And I think that this social part of longevity, which is very poorly studied, is something that also contributed to her longevity.
Yeah, I would tend to agree. It's, it's one of those things, maybe there'll be follow-up research. Ah, that's not her, she's passed. But like how concretely does something like social interaction, something that seems so abstract or like mindset impact biology. And, and just to kind of now go on my own little soapbox and tangent, like there are studies coming out. I can send you this one I just read. I think it was in Nature about like how psychological stress can like basically make your liver make sugar and change your metabolism. Like there are direct lines between the brain and the liver and other organs that like, it is hard biology. It's just also very hard to study. Because, you know, the mind is an emergent phenomenon of the brain. How do you operationalize all this? So that's a topic for another time, but you hit the nail on the head. I tend to agree there is something about mindset, attitude, social connection that probably has more longevity power than any dietary component. But with that, that's still an area of interest, so we'll dive into it. So I wanna get into the data. One striking result to me was her telomere length. Her telomeres were tiny. Tell us about that.
Well, in her case, I think that the telomere shortening, this extreme telomere shortening, was like a proxy of how old she actually was. It was like something that really revealed how old her cells were. Maybe it serves as not only to predict mortality or, or whatever are associated with susceptibility to diseases. Well, in her case, I think that it was just a very clear and accurate prediction of, uh, her, her close death. You know, I think that in this case, telomeres were not reflecting any health-associated trait, but just this chronological trait in herself.
Yeah, let me double-click on that and clarify, because I think I wrote a letter on it and then did a video coverage, and that was one of the most confusing things for people. So I'll show a graph on screen now, which is where Maria's telomere length— she's the orange dot— tracks with the general population. And what you can see is it's like right on line with the general population, exactly what you'd expect. So to your point, it's like telomeres, which, just to define them, they're these little caps of repetitive DNA on the end of your chromosomes to kind of protect, uh, genetic material. As cells replicate, you kind of lose the caps, so they protect the important genetic material. And as they're kind of like the aglet at the end of a shoelace, and as they shorten, the idea is like chromosomes tend to fray. You get, you know, it's thought to be a proxy for biological aging. And I really want to emphasize that. And my expectation would be that if Maria is aging slower than the average person, such that she can live out to 117 years, that her telomeres would be shortening at a lesser rate rather than having the telomeres just be like a clock of her actual chronological age. So by analogy, It's kind of like rings on a tree. The number of rings tells you how old the tree is. And in this case, that's kind of what happened for Maria. So my expectation wouldn't have been that she falls on a population distribution, that she— her telomeres are shortening at an average rate, just strung out to 117. But that's what happened. Now, the reason I'm really delving into this is because I don't know if you agree, but it suggested that telomeres aren't actually that important. As a marker of longevity and healthspan, whereas before I think we thought they were. What do you think?
Well, this is a study made in only one person. So to what extent can we conclude that? I don't know, maybe just in this person, uh, telomeres were not reflecting her younger biological age, but just the chronological one. And maybe that would be different in all the supercentenarians. But in her case, maybe her longevity, or at least this healthy-like phenotype, might not be coming from telomeres at all. Telomeres are only one of the hallmarks of aging. It's like there are different source of, uh, youth, uh, youthful traits. Maybe this was not the case for telomeres.
Yeah. To your point, a caveat, it's only an n 1. And there's other possibilities, like maybe at the very end of life, our telomeres shorten quite rapidly, but I did find it an interesting thing that I wanted to delve into a little bit. So you mentioned other marker or other hallmarks of aging. What stood out in Maria as maybe a very important hallmark of aging that contributed to her longevity?
In, in my opinion, it was microbiome and epigenetic age. And epigenetics are the chemical marks that are depositing onto the, the DNA that are controlling gene expression. In her case, these marks resemble those of younger people, even up to 15 or 20 years younger. It was like too much. And at the beginning we were like, okay, maybe we committed a mistake at analyzing these results, but no, it was actually like this. She had an epigenetic age much younger of what her ID card was revealing. And it was like, okay, well, it is possibly one of the pathways that were favoring her extreme old age and, and healthy quality of life. Also for the microbiome, we could see that there was a strong population of Bifidobacterium, which is quite beneficial and has already been seen to be linked with longevity. Lower levels of inflammation, and also this prevents the growth of, uh, damaging bacteria in the gut. So maybe, um, the contribution of these two hallmarks together with a good metabolism, another features that we have found in her might be contributing in a greater extent maybe to, to these extreme phenotype.
Yeah, I kind of threw you a hard ball there because with something like this, such a treasure trove of data, other things that stood out to me were her mitochondrial health. There was a line in the paper, you, you probably wrote it about her mitochondrial health was not only preserved but robust. And then her engaged lipid metabolism and other markers too. Like she had very high lactate and creatine levels. There's so much to delve into, but just to take a step back and think about what might have been some underlying factors contributing to all of this. So epigenetic age, mitochondrial health, good gut health. We'll get into diet in a minute, but do you think that there were other features of her life? That contributed to it beyond just luck and genetics?
It's not about luck, uh, after all, maybe it's more about habits because that's what is mostly influencing both epigenetic age and microbiome, especially for epigenetic age. It might be contributing the way you sleep, whether you are doing exercise, whether you are socializing actually, or also for the microbiome. Everybody knows it's tightly connected to the way we are eating. In her case, she was keeping a Mediterranean diet rich in fiber her yogurt and supplemented with her, uh, protein. Maybe it was all this combination of habits together with those special variants that we found in her genome, which would have driven her to, to this special longevity and good quality of life throughout her life.
I wanna delve into that and, and forgive me in advance for some yes or no questions. There are a lot of things that my audience wanted me to follow up on, but first on her diet. So I looked at her meal plan. Thank you for providing that. It's like rich in eggs, egg protein, olive oil, probiotic yogurt. My first question is, do you know why she followed this particular pattern?
Well, it, it's the same meal plan that it's given to all people living in that residence for the elderly. Maybe diet was something very common in that place for everybody. It's, it's true that it was special for her, the fact of eating so many yogurts. She, she loved it. And of course the, the people in the residence couldn't say no to her at, at her age. So they gave her all the yogurts she asked. And after all, maybe it could have contributed actually to this enormous population of Bifidobacterium. We don't know. We'll have to validate it with larger cohorts and see whether this healthy population might be actually contributing that much to longevity.
How about anything about her activity? So we mentioned her social connection. Was she an active person? Did she like exercise?
When she was young, she could do exercise. She went walking with friends, also socializing while doing exercise. This is something very, very interesting to think about. And also she played tennis, she played with the dogs, she kept a garden. Well, she was active. She was active and she kept being active until the end, until she could. There was a point where she couldn't move too much and she had to stop doing exercise. But at the end, she still had very good sleeping patterns and diet that might also help make up for that absence of exercise during her last years of life.
That's really impressive. How about, um, was she on any supplements or medications?
Well, just supplementation in egg, uh, with a protein, uh, to make up for sarcopenia, which is very common in old people. Uh, this loss of muscle during time. And that's all. Um, when she had some fever or, or some infection by bacteria, well, I suppose she got all the drugs necessary for that, but not chronic drugs. You know, this kind of drugs that you are consuming every day.
Wow. And did she have any like medical comorbidities, any history of heart disease or anything?
Well, diverticulum disease, some vertigo, the hair loss, diseases that appear with age. Yeah. I, I would actually be surprised if she wouldn't have all these problems, at least one of them. Yeah. At the, at the end of her life.
So it doesn't sound like any like proper diseases, just general declines in organ systems, which yeah, you have a little bit of hearing loss. But otherwise she sounded pretty dang healthy. Any alcohol intake or smoking history?
Very small quantities of alcohol in very special occasions and no tobacco, no smoking at all.
Well, and I wanted to get on some to something I found particularly interesting. So in the supplement you mentioned her LDL cholesterol and her LDL particle count. Both of these were actually above the recommended range. Now they weren't astronomical. I guess I'll ask a, a provocative question first. Why were these put in the supplement and not the main text?
Well, the, the LDL cholesterol is in the main figures. It's in the, the figure 2 where there's a cycle summarizing all the, all the parameters concerning.
So it was like marked with red as, as quote unquote high.
Exactly. That's a good summary of her cardiovascular disease measured by those different parameters. And the LDL cholesterol, yeah, you are right. It, it was a little bit increased in comparison to the general population. It wasn't that much. I think that the threshold was at 100 and she had 120-something. Yeah. It wasn't that high, but all the other parameters also contributing to that cycle, summarizing the cardiovascular disease, were okay. Specifically, esterified cholesterol, free cholesterol, HDL particles, which is the good cholesterol, which was quite increased in comparison to the rest of the population. I think that we have to take into account all those parameters in order to have a whole picture, a full picture of what her cardiovascular disease risk was, well, this is true. LDL cholesterol might be important for some diseases and health conditions, but taking all into account all the parameters related with that, I don't think it was that high and that it was contributing that much to the overall disease risk or, uh, all-cause mortality risk.
I 100% agree. And the, there's a few things that you said, particularly the whole picture that I just wanna emphasize, and I, I'll disclose the reason I asked this question of you. Is because in my experience, both as a, a scientist and a medical trainee, that marker, the LDL cholesterol takes up so much airtime. It gets like keyhole focused on and generally in a very black and white manner. So when you get like your lab report back, there's a threshold. In this case you mentioned it's 100, and if you're above that, you're in the red and then the biomarker gets treated, but not in the full context. So I totally agree with the way you framed it up. It's like, look, she has great overall metabolic health. You used the term engaged with metabolism. There's markers of that, her high HDL cholesterol and high HDL particle count, very low triglycerides and very low triglyceride-rich particles, VLDL. So the fact that her LDL was elevated in this context, in this context, I don't think has much bearing on her cardiovascular health or her longevity. So I very much agree with the way you framed it and the fact that those markers were deemphasized. The reason I'm bringing it up is not to give you a hard time, but to juxtapose it to at least my experience with how conventional medicine is practiced, where it's like you have the marker that you know how to treat, in this case LDL with say statin drugs. If it's out of range, you just hit it with the drug and it's not taken into the, you know, fuller context of other metabolic markers in the patient. That's why I wanted to bring this up. I don't disagree with it being, you know, that number being de-emphasized to an extent, but you know, I thought it was, it was relevant. Anything to add on that before I ask you your next set of questions?
Actually, I don't think it was the main reason she died.
I don't think so. Actually, I think I dropped a video yesterday. I think the top comment, which was said in jest, I'll pull up the screenshot here. Somebody says, ah, 117, that dang LDL cholesterol finally got her as just like a joke to be like, dirt goats. Anyway, I found that funny. That had me laughing a lot. So moving on though, her genetics. So you mentioned a ton of gene variants. What stood out to you in her genetics?
It stood out to me some genetic variants that were found in homozygosis, which are present in both alleles, the one coming from the father and the one coming from the mother, which are the ones that may be contributing stronger, stronger to, to, to her phenotype. Some variants related with cognitive function, also heart function and immune function, and especially those variants in the mitochondria, which are only inherited from the mother. So they might be contributing somehow to, to that robust mitochondrial function that you were mentioning earlier. Were they?
So just for people's background, your mitochondria, quote unquote, the powerhouse of the cell, they have their own genetic material, their own DNA. Um, I forget how many genes there are in that, but they also have contribution of nuclear DNA. So the main kind of host genome, were her particular mitochondrial variants predominantly from the mitochondrial DNA or the nuclear DNA?
There were 3 from the mitochondrial DNA and a couple, or, or 3, I don't remember now, that were codified in the nuclear DNA. So it was a combination of both.
Okay, cool. Yeah, that's super interesting. I also actually now tangenting a little bit more, one area of active research. I was interviewing Professor Michael Snyder and he's consulting for a company called Mitrix. I have no affiliation, but is mitochondrial transplantation. So ex vivo generating mitochondria en masse and then transfusing it into people. So yes, this is n 1, but my mind is now worrying because when we're talking about longevity science, you can't edit a human's nuclear DNA, but you can transfuse them with mitochondria with their own DNA, youthful DNA, and mitochondria actually circulate around in the body in small extracellular vesicles and free mitochondria. That's a whole nother topic, but provides a lot of hope for actual medical interventions that could expand longevity and healthspan, in my opinion. So exciting stuff. And a couple markers people were asking about, did she have an LP per chance in her lipid profile anywhere?
The lipoprotein profile was the, the Lp, you mean?
There's a, there's something called the lipoprotein little a. I didn't note that marker. I didn't know if it was anywhere. My assumption was it was not, but I got that question and I looked and I couldn't find that marker. I don't know if it's something that we were able to measure or there any bio samples. It's another marker of cardiovascular risk. They're kind of like LDL particles, but they have this little tail that makes them more clotty. I can send more information if it's not something you're familiar with, but it was just an area of interest for those interested in her cardio metabolic health.
Sure.
I agree.
It might be super interesting, but to be honest, I, I'm not familiar with this. I'm, I'm not so focused on metabolism like you. I'm not that expert. I, I'm more expert in genetics, epigenetics, and, and yeah, I'm not that familiar with that protein, but I will have a look at it. Sure.
And did she get an insulin level at any point?
No, we couldn't, uh, measure that, but we know that she didn't have any diabetes going on, uh, especially type 2 diabetes. We asked the, the clinician, she didn't have any disease related with diabetes, hypertension, and all the stuff that you are often checked in, in the clinic. In her case, apparently everything was okay. And there were some metabolic variants that could reflect the absence of, of, of high levels of, of glucose in the blood. For example, the GLYK-A and GLYK-B, apart from being markers of inflammation, they are markers of high sugar in the bloodstream. In her case, those glycoproteins were very low and we can see that she wouldn't have, uh, a, a lot of quantity of, of sugar in her bloodstream. I'm sure.
I agree. I think based on all the mountain of data that were provided, won't get into it, she doesn't have high insulin hyperinsulinemia or insulin resistance. Yeah, I think it's a fair conclusion. Kind of getting towards the end, is there anything people you feel are misunderstanding about Maria's case or this paper that you want to clarify?
Well, actually, maybe people is thinking that yogurt's maybe the major contributing factor in longevity. I could see ads reporting the brand of the yogurt that she was eating. This, this major presence of yogurt in her life. Well, maybe it's not the case. Maybe it was just like a help that she had to have a good microbiome. But the microbiome was not the only thing that had youthful traits in her. It was also the epigenetics closely related to our habits, and also that genetic, uh, those genetic variants that we could see related with cognitive function, heart disease, and metabolism, also with immune system. We saw also a variant called Timeless, which has already been described to be contributing to longevity in Drosophila. I mean, there were a plethora of things going on in this person to help her live to the 117 years of age. There's something that nobody is, is talking about, it's the death cause. Uh, we don't know, uh, when, when someone that old is dying, nobody asks, uh, whether she died well for some reason in particular. Everybody takes for granted that she died from being old. But what does it mean? What does dying from being old actually mean? I think that this is something that scientists will have to explore in the future if we had some clues about what she— what drove her to succumbing to death, maybe we would be having some clues to do some interesting research in the future. We will see. I think that this is something very, very interesting to talk about, the real death causes of people dying super old.
That is a really astute point that I have to admit I didn't really think deeply about. And I think now thinking about it, we have just internalized this idea that you can die of old age, but it's a vacuous hand-wavy thing.
Yeah. What does it mean? Yeah.
What took her? That's a, that's a really great point. That's fascinating. I don't know. Well, you're the guy who's gonna figure out the answer. So you, what's next for this line of research? So you're, early on in your career, you're 26 doing your PhD. Do you have a new project that's chasing this up or areas of research?
Yeah.
Now, are they interested in—
now we have to look at the daughters and her grandsons. I think it, it would be interesting to look at her family, how the genetics variants were inherited in her genealogic tree and see whether it also had, um, a role in their epigenetic age, telomere attrition, all the stuff. I think that now it's time for us to look at her family.
How many kids does she have? And grandkids and great-grandkids and maybe even great-great-grandkids. I don't know. Her family tree must be crazy.
She had two daughters and a son. Uh, the daughters are still alive and we'll study them for sure. And regarding, uh, grandsons and grand-grandsons, I don't know how many, but she has a lot.
That's really incredible. All right. Is there anything I should have asked you, Eloi, something about Maria, the paper, anything that you want to share?
Well, I think we talked about everything more or less, so, and it was very interesting.
I really appreciate your time. Is there anywhere you want to direct people to other than the paper, which I'll post below, you know, your socials or research pages?
Yeah, they can follow me on Twitter @eloissantospujol, also Instagram @ivael. And well, stay tuned because our research won't stop here and we'll continue looking at the family and and also doing different studies to help understand longevity and human aging.
Amazing. All right. This is definitely a guy to follow. Gonna be a leader in the longevity field for the next 100 years until somebody studies you and you pass at 126. Anyway, thanks for joining me and yeah, I'm sure everybody appreciated this conversation.
Thank you, Nick.
