{"version":"1.0.0","segments":[{"speaker":"Dominic Denk","startTime":1.52,"endTime":5.63,"body":"Of course, something you have to be careful as a physician, as a scientist, to say, yes,"},{"speaker":"Dominic Denk","startTime":5.63,"endTime":7.46,"body":"this might work, It might also not work."},{"speaker":"Dominic Denk","startTime":7.46,"endTime":10.02,"body":"But we have very strong data and the strong point."},{"speaker":"Dominic Denk","startTime":10.04,"endTime":14.39,"body":"These findings and the study is that this is already a supplement that has been approved"},{"speaker":"Dominic Denk","startTime":14.39,"endTime":15.83,"body":"and tested in human beings."},{"speaker":"Peter Bowes","startTime":21.86,"endTime":25.4,"body":"Hello again. Welcome to the Live Long and Master Aging podcast."},{"speaker":"Peter Bowes","startTime":25.4,"endTime":30.74,"body":"I'm Peter Bowes. This is where we explore the science and stories behind human longevity"},{"speaker":"Peter Bowes","startTime":30.77,"endTime":32.69,"body":". Today, very much the science."},{"speaker":"Peter Bowes","startTime":32.69,"endTime":37.91,"body":"We're going to delve deeper into the latest research around a natural compound called"},{"speaker":"Peter Bowes","startTime":37.91,"endTime":42.56,"body":"Urolithin A, which we've discussed at length on previous episodes."},{"speaker":"Peter Bowes","startTime":42.56,"endTime":47.54,"body":"And if you go to the index on our website, LLAMApodcast.com search for Urolithin."},{"speaker":"Peter Bowes","startTime":47.57,"endTime":52.85,"body":"A, you'll be able to catch up on our previous conversations about this metabolite, which"},{"speaker":"Peter Bowes","startTime":52.85,"endTime":55.1,"body":"is derived from our diet."},{"speaker":"Peter Bowes","startTime":55.1,"endTime":60.29,"body":"Certain foods like pomegranates, are particularly rich in the essential components."},{"speaker":"Peter Bowes","startTime":60.39,"endTime":66.06,"body":"They're called ellagitannins, which we need to produce Urolithin A which is hugely"},{"speaker":"Peter Bowes","startTime":66.06,"endTime":71.26,"body":"important for our mitochondrial health, the energy centers of our cells."},{"speaker":"Peter Bowes","startTime":71.28,"endTime":75.75,"body":"Well, today we're going to talk about some new research that suggests it could also be"},{"speaker":"Peter Bowes","startTime":75.75,"endTime":78.09,"body":"important in fighting cancer."},{"speaker":"Peter Bowes","startTime":78.12,"endTime":79.47,"body":"I'm joined by Dr."},{"speaker":"Peter Bowes","startTime":79.47,"endTime":85.05,"body":"Dominic Denk, a physician at Frankfurt University Hospital and one of the authors of a"},{"speaker":"Peter Bowes","startTime":85.05,"endTime":88.98,"body":"recent study carried out with the Frankfurt Cancer Institute."},{"speaker":"Peter Bowes","startTime":89.01,"endTime":93.39,"body":"Dominic Denk, welcome to the Live Long and Master Aging podcast."},{"speaker":"Dominic Denk","startTime":93.39,"endTime":94.53,"body":"Well, thank you very much, Peter."},{"speaker":"Peter Bowes","startTime":94.62,"endTime":99.78,"body":"The findings of this study are indeed very interesting and we're going to delve into them"},{"speaker":"Peter Bowes","startTime":99.78,"endTime":101.4,"body":"in some depth in a moment."},{"speaker":"Peter Bowes","startTime":101.4,"endTime":104.31,"body":"I thought it might be useful, just first of all, for you just to tell us a little bit"},{"speaker":"Peter Bowes","startTime":104.31,"endTime":109.38,"body":"about yourself, the work that you do in Frankfurt and your particular interests."},{"speaker":"Dominic Denk","startTime":109.38,"endTime":111.24,"body":"Well, I guess you summarize it brilliantly."},{"speaker":"Dominic Denk","startTime":111.24,"endTime":115.71,"body":"So I'm a physician at a hospital in Germany, large university hospital, and actually act"},{"speaker":"Dominic Denk","startTime":115.71,"endTime":121.05,"body":"as a clinician scientist, meaning I work in the hospital with patients at the bed every"},{"speaker":"Dominic Denk","startTime":121.05,"endTime":124.59,"body":"day treating internal medicine diseases, gastroenterology diseases."},{"speaker":"Dominic Denk","startTime":124.77,"endTime":129.63,"body":"But on the other hand, I also work in the lab at the bench trying to explore cancer and"},{"speaker":"Dominic Denk","startTime":129.63,"endTime":132.63,"body":"trying to find out what drives cancer and how to treat it."},{"speaker":"Dominic Denk","startTime":132.63,"endTime":137.4,"body":"So pretty much taking what I see in the hospital and then moving it into the bench and"},{"speaker":"Dominic Denk","startTime":137.4,"endTime":139.38,"body":"then back to the patient, hopefully at least."},{"speaker":"Peter Bowes","startTime":139.38,"endTime":144.75,"body":"And does that sort of dual purpose in terms of being a hands on physician and a researcher"},{"speaker":"Peter Bowes","startTime":144.75,"endTime":148.62,"body":"as well. Does that broaden your, I would say broaden your horizons, but perhaps broadens"},{"speaker":"Peter Bowes","startTime":148.62,"endTime":152.16,"body":"your perspective as well in terms of what the ultimate goals are?"},{"speaker":"Dominic Denk","startTime":152.16,"endTime":155.82,"body":"I do think so. I think it actually improves both both sides of the coin, actually."},{"speaker":"Dominic Denk","startTime":155.82,"endTime":161.76,"body":"So being a physician working in a lab, it means that I understand what drives disease and"},{"speaker":"Dominic Denk","startTime":161.76,"endTime":163.86,"body":"what patients need for their therapy."},{"speaker":"Dominic Denk","startTime":163.86,"endTime":166.56,"body":"I know which approaches are realistic, for example."},{"speaker":"Dominic Denk","startTime":166.71,"endTime":171.36,"body":"And on the other hand, I can also understand new developments from the lab if they"},{"speaker":"Dominic Denk","startTime":171.36,"endTime":173.31,"body":"actually make sense in the hospital as well."},{"speaker":"Dominic Denk","startTime":173.31,"endTime":177.81,"body":"And I understand the techniques that go into research and how long certain things take"},{"speaker":"Dominic Denk","startTime":177.81,"endTime":181.05,"body":"that we can't just treat cancer as it is that quickly."},{"speaker":"Dominic Denk","startTime":181.05,"endTime":182.52,"body":"Cancer is a very diverse disease."},{"speaker":"Dominic Denk","startTime":182.52,"endTime":184.2,"body":"Every type of cancer is different."},{"speaker":"Dominic Denk","startTime":184.2,"endTime":188.13,"body":"And even the same type of cancer in a different patient is widely different."},{"speaker":"Dominic Denk","startTime":188.13,"endTime":193.44,"body":"And it is so complex that it really makes sense to see both sides of the coin to, in an"},{"speaker":"Dominic Denk","startTime":193.44,"endTime":198.04,"body":"ideal case and hopefully in the future, have some individualized treatments for patients"},{"speaker":"Dominic Denk","startTime":198.04,"endTime":200.46,"body":"so we can treat everybody specifically to their needs."},{"speaker":"Peter Bowes","startTime":200.46,"endTime":204.72,"body":"And of course, one of the complexities is that not all cancers are equal."},{"speaker":"Peter Bowes","startTime":204.72,"endTime":210.12,"body":"The science behind how certain types of cancer evolve can in many cases be very"},{"speaker":"Peter Bowes","startTime":210.12,"endTime":210.71,"body":"different."},{"speaker":"Dominic Denk","startTime":210.72,"endTime":211.8,"body":"That is indeed the case."},{"speaker":"Dominic Denk","startTime":211.8,"endTime":216.81,"body":"And then the big complexity comes from the fact that cancer is not just only the cancer"},{"speaker":"Dominic Denk","startTime":216.81,"endTime":220.89,"body":"cell, right? So back in the day, many decades ago, we figured out, okay, we have our"},{"speaker":"Dominic Denk","startTime":220.89,"endTime":226.02,"body":"cells in the body, they change, they undergo mutagenesis, meaning the genes change."},{"speaker":"Dominic Denk","startTime":226.02,"endTime":229.35,"body":"And that means that the cell then becomes malignant and we have cancer."},{"speaker":"Dominic Denk","startTime":229.35,"endTime":233.73,"body":"And if we just nuke these cells, we treat them with chemotherapy, for example, we'll keep"},{"speaker":"Dominic Denk","startTime":233.73,"endTime":235.8,"body":"this growth in check and cancer is cured."},{"speaker":"Dominic Denk","startTime":235.8,"endTime":241.59,"body":"But what we see now these days is that cancer is actually quite a generous disease and we"},{"speaker":"Dominic Denk","startTime":241.59,"endTime":244.77,"body":"have many cells inside the cancer, not just the cancer cell."},{"speaker":"Dominic Denk","startTime":244.77,"endTime":249.24,"body":"We have immune cells, we have fibroblasts or stromal cells, and they all actually"},{"speaker":"Dominic Denk","startTime":249.24,"endTime":252.45,"body":"interact with the cancer cells and they can drive disease progression."},{"speaker":"Dominic Denk","startTime":252.45,"endTime":257.31,"body":"So to really understand what's going on, even if two patients have the same type of"},{"speaker":"Dominic Denk","startTime":257.31,"endTime":260.73,"body":"cancer, you really have to deconstruct that cancer itself."},{"speaker":"Dominic Denk","startTime":260.73,"endTime":265.38,"body":"Which cells are inside that cancer and how do they interact to then actually target it"},{"speaker":"Dominic Denk","startTime":265.38,"endTime":268.92,"body":"specifically? So not going for the cancer cell alone because that will not be enough,"},{"speaker":"Dominic Denk","startTime":268.92,"endTime":270.27,"body":"unfortunately."},{"speaker":"Peter Bowes","startTime":270.27,"endTime":272.53,"body":"So we're going to talk about Urolithin A."},{"speaker":"Peter Bowes","startTime":272.53,"endTime":276.84,"body":"Perhaps we could go back to basics to start with and you could explain to us, as we have"},{"speaker":"Peter Bowes","startTime":276.84,"endTime":280.2,"body":"discussed this on the podcast quite a few times before, but I think it is worth"},{"speaker":"Peter Bowes","startTime":280.2,"endTime":282.39,"body":"explaining again what Urolithin A is."},{"speaker":"Peter Bowes","startTime":282.39,"endTime":286.8,"body":"I mentioned it's a metabolite, but what is it and why do we need it?"},{"speaker":"Dominic Denk","startTime":286.8,"endTime":288.99,"body":"So it's actually quite an interesting compound."},{"speaker":"Dominic Denk","startTime":288.99,"endTime":295.35,"body":"So there's certain fruits, pomegranates, berries or nuts, for example, that are very rich"},{"speaker":"Dominic Denk","startTime":295.38,"endTime":297.6,"body":"in natural compounds called ellagitannins."},{"speaker":"Dominic Denk","startTime":297.75,"endTime":299.52,"body":"And the thing is."},{"speaker":"Dominic Denk","startTime":299.63,"endTime":303.53,"body":"Those are actually metabolized inside the gut by the local gut material into something"},{"speaker":"Dominic Denk","startTime":303.53,"endTime":307.92,"body":"called urolithin A. And urolithin A is something that has been shown to induce mitophagy."},{"speaker":"Dominic Denk","startTime":307.94,"endTime":311.69,"body":"So now you have to kind of go back and explain mitophagy and understand that"},{"speaker":"Dominic Denk","startTime":311.78,"endTime":316.25,"body":"mitochondria, as we all know from school, I guess, are the powerhouses of the cell."},{"speaker":"Dominic Denk","startTime":316.34,"endTime":320.89,"body":"So Mitophagy is a program that leads to degradation of mitochondria to to renew them."},{"speaker":"Dominic Denk","startTime":320.9,"endTime":324.68,"body":"So if you have aged mitochondria, they get replenished and get made better."},{"speaker":"Dominic Denk","startTime":324.83,"endTime":326.63,"body":"So that's what evolution does."},{"speaker":"Dominic Denk","startTime":326.66,"endTime":331.25,"body":"And the main issue usually is that you need an appropriate gut microbiome, meaning not"},{"speaker":"Dominic Denk","startTime":331.25,"endTime":333.02,"body":"everybody can produce urolithin A."},{"speaker":"Dominic Denk","startTime":333.2,"endTime":338.15,"body":"Otherwise I could just recommend you eat tons of pomegranates, but only just about a"},{"speaker":"Dominic Denk","startTime":338.15,"endTime":343.01,"body":"third of all age people actually can produce urolithin A and as we age and now we come"},{"speaker":"Dominic Denk","startTime":343.01,"endTime":347.93,"body":"back into aging, actually that proportion of material gets lower and lower."},{"speaker":"Dominic Denk","startTime":347.93,"endTime":351.98,"body":"So we have to find a way to actually get Urolithin A into our body as it has many"},{"speaker":"Dominic Denk","startTime":351.98,"endTime":355.7,"body":"diverse, important effects on us, on aging and on cancer importantly."},{"speaker":"Dominic Denk","startTime":355.88,"endTime":361.29,"body":"So taking urolithin A directly, it seems to be a very nice approach to kind of circumvent"},{"speaker":"Dominic Denk","startTime":361.29,"endTime":363.81,"body":"this issue of taking it up."},{"speaker":"Dominic Denk","startTime":363.81,"endTime":368.19,"body":"And there's this group in Switzerland, which I guess you discussed in previous podcasts"},{"speaker":"Dominic Denk","startTime":368.19,"endTime":371.85,"body":"by Professor Auwerx that actually deconstructed the pomegranate."},{"speaker":"Dominic Denk","startTime":371.88,"endTime":375.57,"body":"Having seen that there are certain diseases that are associated with better outcome."},{"speaker":"Dominic Denk","startTime":375.69,"endTime":379.56,"body":"People consume pomegranate and just looking at this fruit, they looked at all the"},{"speaker":"Dominic Denk","startTime":379.56,"endTime":384.0,"body":"molecules inside it and then they actually found out that Urolithin A is one of those"},{"speaker":"Dominic Denk","startTime":384.0,"endTime":387.93,"body":"compounds. Actually the one compound inside the fruit that drives all this?"},{"speaker":"Dominic Denk","startTime":387.93,"endTime":392.76,"body":"And this is how they started to isolate that compound, to synthesize it themselves."},{"speaker":"Dominic Denk","startTime":392.76,"endTime":396.18,"body":"And this is what really started all this biomedical research on this compound and"},{"speaker":"Dominic Denk","startTime":396.18,"endTime":399.48,"body":"ultimately drove us to study euphony in cancer."},{"speaker":"Peter Bowes","startTime":399.48,"endTime":405.06,"body":"And so we are able to varying extents, to produce urolithin A ourselves."},{"speaker":"Peter Bowes","startTime":405.06,"endTime":408.71,"body":"And that ability oftentimes deteriorates as we get older."},{"speaker":"Peter Bowes","startTime":408.72,"endTime":412.41,"body":"There's no way of knowing, is there, unless we have a very specific test."},{"speaker":"Peter Bowes","startTime":412.41,"endTime":416.16,"body":"There's really no way of knowing where we stand individually."},{"speaker":"Peter Bowes","startTime":416.16,"endTime":421.17,"body":"There isn't a simple test and it isn't a regular blood test that your local doctor would"},{"speaker":"Peter Bowes","startTime":421.17,"endTime":421.71,"body":"likely give."},{"speaker":"Dominic Denk","startTime":421.71,"endTime":426.63,"body":"You know, there's no simple test companies that actually commercially sell urolithin A"},{"speaker":"Dominic Denk","startTime":427.32,"endTime":431.91,"body":"they have such tests where you can, for example, drink pomegranate juice and then send"},{"speaker":"Dominic Denk","startTime":431.91,"endTime":436.89,"body":"them your dry blood before and after to see if we actually did produce urolithin."},{"speaker":"Dominic Denk","startTime":436.89,"endTime":442.35,"body":"A But there's no test by your local doctor that can actually assess this adequately, and"},{"speaker":"Dominic Denk","startTime":442.35,"endTime":448.32,"body":"we're not entirely sure how to really look at the gut microbiome in a very feasible"},{"speaker":"Dominic Denk","startTime":448.32,"endTime":452.22,"body":"manner to actually see if you and me, if we actually have the adequate gut microbiome,"},{"speaker":"Dominic Denk","startTime":452.22,"endTime":455.22,"body":"just also knowing that it's very complicated, very expensive."},{"speaker":"Dominic Denk","startTime":455.22,"endTime":456.84,"body":"So it's not that simple."},{"speaker":"Dominic Denk","startTime":456.84,"endTime":462.78,"body":"But you can probably assume that if you are over 40 or 50, there's less than half of a"},{"speaker":"Dominic Denk","startTime":462.78,"endTime":464.37,"body":"chance that you can actually produce it."},{"speaker":"Dominic Denk","startTime":464.37,"endTime":470.07,"body":"And even then you would need to use tons of urolithin A containing fruits or pomegranates"},{"speaker":"Dominic Denk","startTime":470.07,"endTime":474.06,"body":"like multiple liters of juice per day to actually get the same amount."},{"speaker":"Dominic Denk","startTime":474.06,"endTime":474.87,"body":"So it's not that easy."},{"speaker":"Peter Bowes","startTime":474.87,"endTime":477.66,"body":"And you mentioned pomegranates several times."},{"speaker":"Peter Bowes","startTime":477.66,"endTime":481.98,"body":"Indeed, I mentioned pomegranates in the introduction and pomegranates are very closely"},{"speaker":"Peter Bowes","startTime":481.98,"endTime":483.51,"body":"associated with UROLITHIN."},{"speaker":"Peter Bowes","startTime":483.51,"endTime":487.38,"body":"A I think we should probably also stress that they're not the only foods."},{"speaker":"Peter Bowes","startTime":487.38,"endTime":493.02,"body":"There are other fruits, indeed foods that are not fruits that can help us produce"},{"speaker":"Peter Bowes","startTime":493.05,"endTime":498.33,"body":"urolithin. A And people might be watching or listening to this saying, well, I actually"},{"speaker":"Peter Bowes","startTime":498.33,"endTime":499.86,"body":"never eat pomegranates."},{"speaker":"Peter Bowes","startTime":499.86,"endTime":504.87,"body":"That doesn't necessarily mean that they are unable to produce urolithin A as they need"},{"speaker":"Peter Bowes","startTime":504.87,"endTime":505.11,"body":"it."},{"speaker":"Dominic Denk","startTime":505.15,"endTime":507.96,"body":"That is correct. Of course. I mean, it's also in other fruits and raspberries."},{"speaker":"Dominic Denk","startTime":507.96,"endTime":509.13,"body":"It's the nuts, for example."},{"speaker":"Dominic Denk","startTime":509.13,"endTime":515.64,"body":"So if you are having a somewhat balanced, so to say, healthy diet, you will produce"},{"speaker":"Dominic Denk","startTime":515.64,"endTime":520.56,"body":"probably Urolithin A just not in the amounts you would really need to get these"},{"speaker":"Dominic Denk","startTime":520.56,"endTime":524.07,"body":"beneficial effects that we have seen in our study that people have seen for muscle"},{"speaker":"Dominic Denk","startTime":524.07,"endTime":528.03,"body":"studies, for example. But yes, if you have a balanced diet, you have plenty of other"},{"speaker":"Dominic Denk","startTime":528.03,"endTime":531.98,"body":"sources of urolithin A, pomegranate is very rich in urethane a and this is why they're,"},{"speaker":"Dominic Denk","startTime":531.99,"endTime":535.74,"body":"so to speak, the poster child of of urolithin A because this is where you get the most"},{"speaker":"Dominic Denk","startTime":535.74,"endTime":536.97,"body":"from."},{"speaker":"Peter Bowes","startTime":536.97,"endTime":540.69,"body":"So let's talk about the study and I'll let you explain the basis for the study."},{"speaker":"Peter Bowes","startTime":540.69,"endTime":548.01,"body":"But essentially the finding is that urolithin A could indeed help us improve the function"},{"speaker":"Peter Bowes","startTime":548.01,"endTime":552.54,"body":"of immune cells and there could be implications there for fighting cancer."},{"speaker":"Dominic Denk","startTime":552.54,"endTime":557.25,"body":"Exactly. So to kind of get into this, you have to look a little bit broader spectrum."},{"speaker":"Dominic Denk","startTime":557.25,"endTime":560.67,"body":"What drives cancer and how the body actually treats cancer."},{"speaker":"Dominic Denk","startTime":561.12,"endTime":565.86,"body":"So usually we have an immune system that's actually built to recognize malignant cells,"},{"speaker":"Dominic Denk","startTime":565.86,"endTime":570.78,"body":"right? And the way this is usually done is that each and every cell presents so-called"},{"speaker":"Dominic Denk","startTime":570.78,"endTime":575.49,"body":"antigens. So pretty much a little sign, this is me, this is what's inside of me."},{"speaker":"Dominic Denk","startTime":575.61,"endTime":578.64,"body":"I'm a healthy cell or even if I'm an infected cell."},{"speaker":"Dominic Denk","startTime":578.64,"endTime":584.22,"body":"So, for example, this is the normal pathway an infected cell could show to the outside."},{"speaker":"Dominic Denk","startTime":584.22,"endTime":586.11,"body":"Look, I'm infected by a virus."},{"speaker":"Dominic Denk","startTime":586.41,"endTime":589.11,"body":"The antigen gets recognized by an immune cell."},{"speaker":"Dominic Denk","startTime":589.11,"endTime":592.11,"body":"And this is then the signal for the immune cell to kill that cell."},{"speaker":"Dominic Denk","startTime":592.11,"endTime":595.74,"body":"And this is how we usually limit infections in cancer, for example."},{"speaker":"Dominic Denk","startTime":596.04,"endTime":599.49,"body":"So that's the one thing you need an antigen that needs to be recognized by the."},{"speaker":"Dominic Denk","startTime":599.6,"endTime":604.16,"body":"And so and we're wondering about the question how we can improve this interaction,"},{"speaker":"Dominic Denk","startTime":604.16,"endTime":608.72,"body":"because in many cancers, antigens are down regulated by the tumor."},{"speaker":"Dominic Denk","startTime":608.75,"endTime":612.5,"body":"The immune cells get exhausted, which is pretty much just a fancy way of saying they get"},{"speaker":"Dominic Denk","startTime":612.5,"endTime":613.82,"body":"tired, they don't function as well."},{"speaker":"Dominic Denk","startTime":613.85,"endTime":615.44,"body":"We wanted to kind of improve this."},{"speaker":"Dominic Denk","startTime":615.62,"endTime":621.11,"body":"So basically the work in the lab that I work in, they've seen recently that you can"},{"speaker":"Dominic Denk","startTime":621.11,"endTime":622.88,"body":"improve antigen presentation."},{"speaker":"Dominic Denk","startTime":622.88,"endTime":627.86,"body":"So this little signature here, I'm infected, I'm a cancer cell by inducing mitophagy."},{"speaker":"Dominic Denk","startTime":627.86,"endTime":631.4,"body":"So by induction of mitochondrial replenishment."},{"speaker":"Dominic Denk","startTime":631.76,"endTime":637.13,"body":"The thing is, in that study they used a mouse model genetically ablated some genes, which"},{"speaker":"Dominic Denk","startTime":637.13,"endTime":639.11,"body":"is something you cannot do in human beings, right?"},{"speaker":"Dominic Denk","startTime":639.11,"endTime":640.52,"body":"If you're in the hospital."},{"speaker":"Dominic Denk","startTime":640.52,"endTime":644.06,"body":"And here comes once again the idea how can this improve our daily care?"},{"speaker":"Dominic Denk","startTime":644.36,"endTime":648.87,"body":"You need to find some sort of dietary supplement or medication that does just this that"},{"speaker":"Dominic Denk","startTime":648.87,"endTime":652.19,"body":"the patient can take so you can help with the cancer treatment."},{"speaker":"Dominic Denk","startTime":652.22,"endTime":657.95,"body":"So quite innocently, actually, we just wanted to induce this antigen presentation by"},{"speaker":"Dominic Denk","startTime":657.95,"endTime":662.46,"body":"inducing mitophagy and we looked on the web, looked at the recent literature, as you do"},{"speaker":"Dominic Denk","startTime":662.46,"endTime":667.65,"body":"as a scientist. And we found this this compound urolithin A that has been studied in"},{"speaker":"Dominic Denk","startTime":667.65,"endTime":669.18,"body":"muscle models, actually."},{"speaker":"Dominic Denk","startTime":669.18,"endTime":674.7,"body":"And this group in Switzerland, they have seen that it's an inductor of mitophagy and it"},{"speaker":"Dominic Denk","startTime":674.7,"endTime":678.96,"body":"improves muscle strength and endurance in worms and rodents."},{"speaker":"Dominic Denk","startTime":678.96,"endTime":683.7,"body":"So we figured, wait a minute, if this is something that's already tested in animal"},{"speaker":"Dominic Denk","startTime":683.7,"endTime":688.26,"body":"models, it's safe to consume in humans and it does what we want to see."},{"speaker":"Dominic Denk","startTime":688.29,"endTime":693.0,"body":"Why don't we try this in our cancer models just to once again see antigen presentations"},{"speaker":"Dominic Denk","startTime":693.0,"endTime":698.46,"body":"upregulated. So we did this and we tested this on mouse models of cancer."},{"speaker":"Dominic Denk","startTime":698.67,"endTime":703.74,"body":"And quite surprisingly, we saw that the tumors were not even surprisingly at this point,"},{"speaker":"Dominic Denk","startTime":703.74,"endTime":707.79,"body":"but we saw that the tumors were smaller in the mice that had very aggressive tumor forms,"},{"speaker":"Dominic Denk","startTime":707.79,"endTime":709.53,"body":"and they were actually treated quite nicely."},{"speaker":"Dominic Denk","startTime":709.89,"endTime":713.79,"body":"And when we then looked more into the detail, into the tumor microenvironment, so seeing"},{"speaker":"Dominic Denk","startTime":713.79,"endTime":719.1,"body":"which cells are actually inside the tumor, we could see that were actually more T cells."},{"speaker":"Dominic Denk","startTime":719.1,"endTime":723.06,"body":"So immune cells that are there to fight the cancer inside the tumor."},{"speaker":"Dominic Denk","startTime":723.27,"endTime":727.8,"body":"And we figured this cannot be the effect of antigen presentation alone."},{"speaker":"Dominic Denk","startTime":727.8,"endTime":733.1,"body":"It must be also that, yes, there's more signal that there is cancer, but the immune cells"},{"speaker":"Dominic Denk","startTime":733.11,"endTime":736.44,"body":"recognize this. They must also function better one way or another."},{"speaker":"Dominic Denk","startTime":736.56,"endTime":740.7,"body":"And this is what really kicks this off, because then we went into studying the immune"},{"speaker":"Dominic Denk","startTime":740.7,"endTime":742.2,"body":"cells more into detail."},{"speaker":"Dominic Denk","startTime":742.23,"endTime":743.76,"body":"We exposed them to urolithin A."},{"speaker":"Dominic Denk","startTime":744.09,"endTime":749.91,"body":"And long story short, we found out that urolithin A yes, it acts on the cancer cells, but"},{"speaker":"Dominic Denk","startTime":750.06,"endTime":754.53,"body":"more specifically actually acts on the immune cells and it rejuvenates immune cells in a"},{"speaker":"Dominic Denk","startTime":754.53,"endTime":759.93,"body":"way they become more potent, they last longer, and they constantly replenish the immune"},{"speaker":"Dominic Denk","startTime":759.93,"endTime":763.77,"body":"system so that we always have fresh pools inside the tumor, which is one of the main"},{"speaker":"Dominic Denk","startTime":763.77,"endTime":768.24,"body":"issues in cancer. Because T cells enter the tumor, they become tired, they don't function"},{"speaker":"Dominic Denk","startTime":768.24,"endTime":770.55,"body":"as well. And this were many therapies fail."},{"speaker":"Dominic Denk","startTime":770.55,"endTime":775.68,"body":"So we think it's a very interesting and novel approach to not necessarily treat the"},{"speaker":"Dominic Denk","startTime":775.68,"endTime":780.45,"body":"cancerous cell, but treat the immune system, which then in turns treats the cancer, which"},{"speaker":"Dominic Denk","startTime":780.45,"endTime":782.61,"body":"is actually what our body is built to do."},{"speaker":"Peter Bowes","startTime":783.69,"endTime":786.6,"body":"You're listening to the Live Long and Master Aging podcast."},{"speaker":"Peter Bowes","startTime":786.6,"endTime":787.86,"body":"Our guest is Dr."},{"speaker":"Peter Bowes","startTime":787.86,"endTime":791.25,"body":"Dominic Denk from Frankfurt University Hospital."},{"speaker":"Peter Bowes","startTime":791.25,"endTime":793.47,"body":"We are talking about Urolithin."},{"speaker":"Peter Bowes","startTime":793.47,"endTime":800.16,"body":"A And really, Dominic, this is quite exciting the way you've just laid out the study and"},{"speaker":"Peter Bowes","startTime":800.16,"endTime":801.18,"body":"the findings."},{"speaker":"Peter Bowes","startTime":801.18,"endTime":804.87,"body":"Where do you go next with these really promising findings?"},{"speaker":"Dominic Denk","startTime":804.87,"endTime":808.86,"body":"Well, of course the first answer would be, 'well off to the clinic, you go, let's treat"},{"speaker":"Dominic Denk","startTime":808.86,"endTime":813.18,"body":"some cancer patients.' There's two limitations of this or one major limitation."},{"speaker":"Dominic Denk","startTime":813.21,"endTime":816.51,"body":"Of course, the studies we performed their mouse studies."},{"speaker":"Dominic Denk","startTime":816.54,"endTime":821.94,"body":"We also used human T cells to show the switch, to show that these T cells actually become"},{"speaker":"Dominic Denk","startTime":821.94,"endTime":826.17,"body":"more or they change their phenotype, at least we don't know if they're more potent yet."},{"speaker":"Dominic Denk","startTime":826.26,"endTime":830.07,"body":"And as I said, we want to use this in the clinically feasible manner."},{"speaker":"Dominic Denk","startTime":830.07,"endTime":834.51,"body":"So ideally you take a pill, you take these supplements that are already approved and"},{"speaker":"Dominic Denk","startTime":834.51,"endTime":837.6,"body":"already deemed safe and then treat patients with this."},{"speaker":"Dominic Denk","startTime":837.96,"endTime":844.65,"body":"And to really fairly approach this, I think, and to really to be able to tell patients,"},{"speaker":"Dominic Denk","startTime":844.65,"endTime":846.57,"body":"hey, this is what might help you."},{"speaker":"Dominic Denk","startTime":846.78,"endTime":849.99,"body":"You want to see if the same stuff happens when you take these compounds."},{"speaker":"Dominic Denk","startTime":849.99,"endTime":854.73,"body":"So what we want to do is we want to take urolithin A, these already approved supplements"},{"speaker":"Dominic Denk","startTime":854.73,"endTime":860.52,"body":"and take healthy volunteers, aged adults, between 45 and 70, for example, and have them"},{"speaker":"Dominic Denk","startTime":860.52,"endTime":864.87,"body":"take these compounds for just a month and to see if we see the same T cell switch,"},{"speaker":"Dominic Denk","startTime":864.9,"endTime":868.71,"body":"because you can assess this in the lab, you can just see what are the transcriptomic"},{"speaker":"Dominic Denk","startTime":868.71,"endTime":872.04,"body":"programs of these cells, what receptors do they express?"},{"speaker":"Dominic Denk","startTime":872.04,"endTime":876.69,"body":"And then we actually know if this is the same thing we see in our mouse models and we saw"},{"speaker":"Dominic Denk","startTime":876.69,"endTime":880.35,"body":"in the lab before, we know, hey, something is going on and something is happening here."},{"speaker":"Dominic Denk","startTime":880.35,"endTime":884.16,"body":"And then the next step, I think then it's really fair to go to cancer patients and then"},{"speaker":"Dominic Denk","startTime":884.16,"endTime":888.45,"body":"really maybe even have some promise of that, hey, this is what might be working."},{"speaker":"Dominic Denk","startTime":888.45,"endTime":890.22,"body":"So we're getting closer and closer."},{"speaker":"Dominic Denk","startTime":890.22,"endTime":893.88,"body":"We're starting off this this first clinical trial that is outlaid actually this week."},{"speaker":"Dominic Denk","startTime":893.88,"endTime":897.78,"body":"And I think within the next 1 or 2 years we can hopefully, if the results are positive,"},{"speaker":"Dominic Denk","startTime":897.81,"endTime":902.41,"body":"go into actual disease application, try to treat patients with this."},{"speaker":"Peter Bowes","startTime":902.56,"endTime":906.46,"body":"Which really just prompts what was going to be my next question, that I'm very conscious"},{"speaker":"Peter Bowes","startTime":906.46,"endTime":908.86,"body":"often doing interviews like this that I don't want to give."},{"speaker":"Peter Bowes","startTime":908.89,"endTime":914.38,"body":"We don't want to give people false hope that there is something that is immediately"},{"speaker":"Peter Bowes","startTime":914.38,"endTime":919.54,"body":"around the corner that is going to help them with a condition that there is more research"},{"speaker":"Peter Bowes","startTime":919.54,"endTime":921.82,"body":"to be done, there are more clinical trials to be done."},{"speaker":"Peter Bowes","startTime":921.82,"endTime":925.96,"body":"But you outline the possible timeline there."},{"speaker":"Peter Bowes","startTime":925.96,"endTime":928.87,"body":"And to me it sounds as if we're on the brink."},{"speaker":"Peter Bowes","startTime":928.9,"endTime":934.31,"body":"We're getting quite close to some findings that could be of real practical use to people."},{"speaker":"Dominic Denk","startTime":934.33,"endTime":938.8,"body":"Indeed, of course, it's something you have to be careful as a physician, as a scientist,"},{"speaker":"Dominic Denk","startTime":938.8,"endTime":940.33,"body":"to say, yes, this might work."},{"speaker":"Dominic Denk","startTime":940.33,"endTime":942.43,"body":"It might also not work to the same extent."},{"speaker":"Dominic Denk","startTime":942.43,"endTime":943.78,"body":"But we have very strong data."},{"speaker":"Dominic Denk","startTime":943.78,"endTime":949.81,"body":"And the strong point of this of these findings in the study is that this is already a"},{"speaker":"Dominic Denk","startTime":949.81,"endTime":952.78,"body":"supplement that has been approved and tested in human beings."},{"speaker":"Dominic Denk","startTime":952.81,"endTime":956.68,"body":"The thing how it usually works when you when you treat cancer in the lab and you find"},{"speaker":"Dominic Denk","startTime":956.68,"endTime":960.41,"body":"something new, it's usually it's a new medication, right?"},{"speaker":"Dominic Denk","startTime":960.41,"endTime":961.43,"body":"It's a new approach."},{"speaker":"Dominic Denk","startTime":961.43,"endTime":964.01,"body":"So this usually has to be validated in further studies."},{"speaker":"Dominic Denk","startTime":964.01,"endTime":969.05,"body":"You have to show it's not toxic to diverse animal models, and then you have to go to"},{"speaker":"Dominic Denk","startTime":969.08,"endTime":973.07,"body":"multiple stages of trials to see phase one, phase two, phase three."},{"speaker":"Dominic Denk","startTime":973.07,"endTime":974.81,"body":"So the compound is not toxic."},{"speaker":"Dominic Denk","startTime":974.84,"endTime":977.18,"body":"It actually doesn't harm the patient."},{"speaker":"Dominic Denk","startTime":977.18,"endTime":981.83,"body":"And only then at the very stage, which usually takes 7 to 10 years, you can go towards"},{"speaker":"Dominic Denk","startTime":981.83,"endTime":986.51,"body":"the final step, the exciting step to see in a double blinded manner, does this actually"},{"speaker":"Dominic Denk","startTime":986.51,"endTime":991.34,"body":"work? But now that we skip all these steps and we know it's it's relatively safe or it is"},{"speaker":"Dominic Denk","startTime":991.34,"endTime":996.32,"body":"safe to consume at this point in the doses we're trying to test, the only we could"},{"speaker":"Dominic Denk","startTime":996.32,"endTime":999.8,"body":"actually start right now, but the only thing we're doing now is this fairness approach of"},{"speaker":"Dominic Denk","startTime":999.8,"endTime":1001.75,"body":"actually knowing that something might be happening."},{"speaker":"Dominic Denk","startTime":1001.75,"endTime":1003.7,"body":"So I think we are close."},{"speaker":"Dominic Denk","startTime":1003.7,"endTime":1007.24,"body":"That, of course, doesn't mean we're going to cure all cancers immediately."},{"speaker":"Dominic Denk","startTime":1007.24,"endTime":1012.88,"body":"Of course not. But I think for certain subsets of people with a dysfunctional immune"},{"speaker":"Dominic Denk","startTime":1012.88,"endTime":1018.25,"body":"system, with an aging immune system that get or receive certain types of therapies that"},{"speaker":"Dominic Denk","startTime":1018.79,"endTime":1021.79,"body":"are built on the immune system, we could probably help here."},{"speaker":"Dominic Denk","startTime":1021.79,"endTime":1024.46,"body":"And it's as easy as just adding it to the therapy."},{"speaker":"Dominic Denk","startTime":1024.49,"endTime":1028.0,"body":"That's, of course, the idea and the hope that we would have."},{"speaker":"Peter Bowes","startTime":1028.15,"endTime":1031.99,"body":"Now you've just used the word cure, which obviously is what a lot of people would be"},{"speaker":"Peter Bowes","startTime":1031.99,"endTime":1037.69,"body":"looking for. But is there also potentially a preventative element to this as well with"},{"speaker":"Peter Bowes","startTime":1037.69,"endTime":1039.19,"body":"these new therapies?"},{"speaker":"Peter Bowes","startTime":1039.19,"endTime":1042.22,"body":"And we're not talking about eating lots and lots of fruits and pomegranates."},{"speaker":"Peter Bowes","startTime":1042.22,"endTime":1047.23,"body":"We're talking about supplementation, as you've described that supplementation already"},{"speaker":"Peter Bowes","startTime":1047.23,"endTime":1052.63,"body":"exists. But is there a preventative measure, in other words, supplementation for healthy"},{"speaker":"Peter Bowes","startTime":1052.63,"endTime":1056.23,"body":"people with an eye on what could occur in the future?"},{"speaker":"Dominic Denk","startTime":1057.19,"endTime":1061.72,"body":"So, of course, once again, cautious answer."},{"speaker":"Dominic Denk","startTime":1062.47,"endTime":1064.24,"body":"Likely. Possibly."},{"speaker":"Dominic Denk","startTime":1064.24,"endTime":1069.22,"body":"So what we have seen in mouse models, we actually did kind of this that you outlined."},{"speaker":"Dominic Denk","startTime":1069.25,"endTime":1074.86,"body":"We we had mice that we fed this urolithin A rich diet for over a week."},{"speaker":"Dominic Denk","startTime":1074.86,"endTime":1077.2,"body":"And then we started the tumor induction."},{"speaker":"Dominic Denk","startTime":1077.2,"endTime":1080.95,"body":"And so as a preventive measure, indeed, and we could actually see that the tumors then,"},{"speaker":"Dominic Denk","startTime":1080.95,"endTime":1083.95,"body":"although every mouse develops a tumor, it's a very aggressive model."},{"speaker":"Dominic Denk","startTime":1083.95,"endTime":1087.79,"body":"The tumor is smaller and gets onset much later."},{"speaker":"Dominic Denk","startTime":1087.88,"endTime":1093.79,"body":"And knowing that cancer often arises on a background of a dysfunctional immune system."},{"speaker":"Dominic Denk","startTime":1093.79,"endTime":1097.27,"body":"So the immune system doesn't recognize the first cancerous cells."},{"speaker":"Dominic Denk","startTime":1097.45,"endTime":1103.24,"body":"The idea that you can probably rejuvenate the immune system or help it function better"},{"speaker":"Dominic Denk","startTime":1103.27,"endTime":1106.75,"body":"might lead to the conclusion that this actually would be something you could take"},{"speaker":"Dominic Denk","startTime":1106.75,"endTime":1109.96,"body":"preventatively. That's the concept behind it."},{"speaker":"Dominic Denk","startTime":1109.96,"endTime":1111.06,"body":"It could work."},{"speaker":"Dominic Denk","startTime":1111.07,"endTime":1115.99,"body":"We don't have, of course, enough data if such interventions on the immune system on a"},{"speaker":"Dominic Denk","startTime":1115.99,"endTime":1120.64,"body":"long term scale. Now I'm speaking 20, 30 years and hundreds of thousands of people"},{"speaker":"Dominic Denk","startTime":1120.64,"endTime":1121.93,"body":"actually has an effect."},{"speaker":"Dominic Denk","startTime":1121.93,"endTime":1127.15,"body":"But the idea of it and the main idea and concept we have of the immune system and cancer"},{"speaker":"Dominic Denk","startTime":1127.15,"endTime":1130.99,"body":"would lead us to the conclusion that this could be something that might be working."},{"speaker":"Dominic Denk","startTime":1130.99,"endTime":1136.09,"body":"But for how long you would have to take this, I do not know and I wouldn't recommend this"},{"speaker":"Dominic Denk","startTime":1136.09,"endTime":1137.44,"body":"yet to to go that far."},{"speaker":"Dominic Denk","startTime":1137.44,"endTime":1138.13,"body":"Of course."},{"speaker":"Peter Bowes","startTime":1138.37,"endTime":1141.22,"body":"I just want to delve into and again, we've talked about this before."},{"speaker":"Peter Bowes","startTime":1141.22,"endTime":1147.49,"body":"You've mentioned mitophagy several times, autophagy, mitophagy referring to mitochondria,"},{"speaker":"Peter Bowes","startTime":1147.49,"endTime":1153.01,"body":"which really is right at the heart of, of everything you're talking about, that essential"},{"speaker":"Peter Bowes","startTime":1153.01,"endTime":1158.41,"body":"process of renewal or kicking out of cells that don't work properly and replacing them"},{"speaker":"Peter Bowes","startTime":1158.41,"endTime":1161.11,"body":"with cells that are new and vital."},{"speaker":"Peter Bowes","startTime":1161.11,"endTime":1165.19,"body":"I was wondering if you could just encapsulate the importance of that, that basic"},{"speaker":"Peter Bowes","startTime":1165.19,"endTime":1166.6,"body":"biological principle."},{"speaker":"Dominic Denk","startTime":1166.9,"endTime":1170.32,"body":"Yes. So what you need to know and I guess you dropped into this before in your previous"},{"speaker":"Dominic Denk","startTime":1170.74,"endTime":1174.52,"body":"podcast that every cell consists of mitochondria, right?"},{"speaker":"Dominic Denk","startTime":1174.55,"endTime":1179.89,"body":"They're tiny guys, tiny organelles that are inside every single cell, and they drive the"},{"speaker":"Dominic Denk","startTime":1179.89,"endTime":1181.33,"body":"metabolism of the cell."},{"speaker":"Dominic Denk","startTime":1181.33,"endTime":1185.65,"body":"They drive what the cell consumes, how it works functionally, which nutrients it"},{"speaker":"Dominic Denk","startTime":1185.65,"endTime":1192.22,"body":"consumes, and ultimately the Transcriptomic program and what we have seen and also people"},{"speaker":"Dominic Denk","startTime":1192.22,"endTime":1198.58,"body":"in aging disease and cancer disease have seen that mitochondria are quite important to"},{"speaker":"Dominic Denk","startTime":1199.18,"endTime":1200.41,"body":"healthy medical functions."},{"speaker":"Dominic Denk","startTime":1200.41,"endTime":1206.72,"body":"Quite important to treat disease and to prevent disease, because if mitochondria don't"},{"speaker":"Dominic Denk","startTime":1206.72,"endTime":1208.46,"body":"function as well, they accumulate."},{"speaker":"Dominic Denk","startTime":1208.49,"endTime":1212.99,"body":"They have this tendency to accumulate and then the cell usually goes into programs that"},{"speaker":"Dominic Denk","startTime":1212.99,"endTime":1216.8,"body":"rendered less functional, render it to the point where it doesn't fulfill its function"},{"speaker":"Dominic Denk","startTime":1216.8,"endTime":1220.31,"body":"for the immune system. For example, the cell ages faster."},{"speaker":"Dominic Denk","startTime":1220.34,"endTime":1224.99,"body":"It means the cell, even if it recognizes the cancer cell, it will not fight it because"},{"speaker":"Dominic Denk","startTime":1224.99,"endTime":1227.39,"body":"there's just not the playground there."},{"speaker":"Dominic Denk","startTime":1227.42,"endTime":1233.12,"body":"The base work there because the metabolic features of the cell to really upregulate these"},{"speaker":"Dominic Denk","startTime":1233.12,"endTime":1234.77,"body":"programs, it means are not there."},{"speaker":"Dominic Denk","startTime":1234.77,"endTime":1240.23,"body":"So really keeping mitochondria fresh means keeping all cellular functions fresh."},{"speaker":"Dominic Denk","startTime":1240.23,"endTime":1244.58,"body":"And the issue with aging, of course, is then that usually these mitochondria they"},{"speaker":"Dominic Denk","startTime":1244.58,"endTime":1245.27,"body":"accumulate."},{"speaker":"Peter Bowes","startTime":1245.48,"endTime":1247.85,"body":"And Dominic, a broader question."},{"speaker":"Peter Bowes","startTime":1248.15,"endTime":1254.66,"body":"As we look at longevity, there are many tools in the box, if you like, that we can use in"},{"speaker":"Peter Bowes","startTime":1254.66,"endTime":1260.75,"body":"terms of interventions to pursue a longer lifespan or a longer health span, as I prefer"},{"speaker":"Peter Bowes","startTime":1260.75,"endTime":1261.83,"body":"to talk about it."},{"speaker":"Peter Bowes","startTime":1261.83,"endTime":1267.39,"body":"And we can be talking about exercise, we can be talking dietary interventions, sleep,"},{"speaker":"Peter Bowes","startTime":1267.39,"endTime":1271.68,"body":"mental health, they all in terms of the whole body, they all play a role."},{"speaker":"Peter Bowes","startTime":1271.68,"endTime":1275.91,"body":"And then of course, there is supplementation and that's what you're talking about here."},{"speaker":"Peter Bowes","startTime":1275.91,"endTime":1280.59,"body":"And we're learning a lot more about the kind of supplements that are really effective in"},{"speaker":"Peter Bowes","startTime":1280.59,"endTime":1286.89,"body":"pursuing a long healthspan I'm just curious, maybe just looking to the future where you"},{"speaker":"Peter Bowes","startTime":1286.89,"endTime":1294.45,"body":"stand on supplementation, to what extent is it going to play a major role in how we live"},{"speaker":"Peter Bowes","startTime":1294.45,"endTime":1297.78,"body":"and how we pursue a longer lifespan?"},{"speaker":"Dominic Denk","startTime":1297.78,"endTime":1304.23,"body":"So I think at the current state right now, 2023, we don't have yet enough data to to"},{"speaker":"Dominic Denk","startTime":1304.23,"endTime":1308.67,"body":"postulate. Now, speaking as a cancer scientist to take supplements to prevent cancer, of"},{"speaker":"Dominic Denk","startTime":1308.67,"endTime":1312.33,"body":"course. But I think there will be a time and we're actually actively studying this these"},{"speaker":"Dominic Denk","startTime":1312.33,"endTime":1316.95,"body":"days where we can actually say, yes, there are certain supplements that are safe that we"},{"speaker":"Dominic Denk","startTime":1316.95,"endTime":1318.87,"body":"can take that actually have an effect."},{"speaker":"Dominic Denk","startTime":1319.2,"endTime":1323.82,"body":"You were you were speaking of basic measures such as lots of sleep, exercise."},{"speaker":"Dominic Denk","startTime":1323.84,"endTime":1326.06,"body":"Those are actually proven to work."},{"speaker":"Dominic Denk","startTime":1326.06,"endTime":1330.32,"body":"We know those are things they reduce inflammasome activity."},{"speaker":"Dominic Denk","startTime":1330.32,"endTime":1334.13,"body":"So inflammatory signaling inside the body, which is one of the main drivers that actually"},{"speaker":"Dominic Denk","startTime":1334.13,"endTime":1337.73,"body":"drives immune dysfunction and drives mutagenesis and cancer cells."},{"speaker":"Dominic Denk","startTime":1337.73,"endTime":1341.6,"body":"So it drives cancer cells to become more malignant and it drives the immune system to be"},{"speaker":"Dominic Denk","startTime":1341.6,"endTime":1348.05,"body":"dysfunctional. So reducing stress, getting healthy amounts of sleep and exercise are very"},{"speaker":"Dominic Denk","startTime":1348.05,"endTime":1354.71,"body":"important. Then nutrition, of course, such things as reducing whole body fat composition."},{"speaker":"Dominic Denk","startTime":1354.71,"endTime":1355.94,"body":"Those are all things you can do."},{"speaker":"Dominic Denk","startTime":1355.97,"endTime":1360.98,"body":"Yes. Speaking as a immunologist and cancer scientist, now, I guess you're thinking of"},{"speaker":"Dominic Denk","startTime":1360.98,"endTime":1365.93,"body":"some supplements that are actually studied in anti-aging, metformin, rapamycin, those"},{"speaker":"Dominic Denk","startTime":1365.93,"endTime":1370.91,"body":"kind of things. There's actually very similar pathways that regulate immune function that"},{"speaker":"Dominic Denk","startTime":1370.91,"endTime":1374.9,"body":"are also affected by these kind of let's call them drugs or supplements."},{"speaker":"Dominic Denk","startTime":1374.9,"endTime":1380.63,"body":"So T cell stemness - so the, the functional properties of an immune cell attacks cancer"},{"speaker":"Dominic Denk","startTime":1381.17,"endTime":1385.11,"body":"are most likely, judging by the current literature affected positively affected by"},{"speaker":"Dominic Denk","startTime":1385.11,"endTime":1387.36,"body":"metformin but rapamycin as well."},{"speaker":"Dominic Denk","startTime":1387.36,"endTime":1389.28,"body":"Those are actually the same, the same pathways."},{"speaker":"Dominic Denk","startTime":1389.4,"endTime":1394.17,"body":"They all converge at the same level, but we just don't know how long you have to take"},{"speaker":"Dominic Denk","startTime":1394.17,"endTime":1398.28,"body":"them in which doses you have to take them and when is the right time point?"},{"speaker":"Dominic Denk","startTime":1398.28,"endTime":1401.67,"body":"Because once again, cancer is a very diverse disease, right?"},{"speaker":"Dominic Denk","startTime":1401.67,"endTime":1406.38,"body":"So even if we know and I think the the data is quite convincing at this point that these"},{"speaker":"Dominic Denk","startTime":1406.38,"endTime":1408.36,"body":"things work for anti-aging."},{"speaker":"Dominic Denk","startTime":1408.36,"endTime":1410.97,"body":"They work at reducing inflammation, inflammation activity."},{"speaker":"Dominic Denk","startTime":1410.97,"endTime":1413.19,"body":"They work at helping the immune system."},{"speaker":"Dominic Denk","startTime":1413.19,"endTime":1417.69,"body":"We're not entirely sure how they act on other components of the tumor per se, because"},{"speaker":"Dominic Denk","startTime":1417.69,"endTime":1421.29,"body":"sometimes you might even need inflammation to activate the immune system."},{"speaker":"Dominic Denk","startTime":1421.29,"endTime":1423.84,"body":"So long story short, I think it is coming."},{"speaker":"Dominic Denk","startTime":1423.84,"endTime":1427.88,"body":"I think science is making great advances and one of these things are currently staying"},{"speaker":"Dominic Denk","startTime":1427.89,"endTime":1432.72,"body":"already available right now will be one of the keys that we can probably supplement, not"},{"speaker":"Dominic Denk","startTime":1432.72,"endTime":1435.48,"body":"just with a therapeutic intervention, but also preventative."},{"speaker":"Peter Bowes","startTime":1435.96,"endTime":1437.85,"body":"And again, this is a broader question."},{"speaker":"Peter Bowes","startTime":1437.85,"endTime":1443.79,"body":"Is there, do you think, enough support from the the scientific and broader community for"},{"speaker":"Peter Bowes","startTime":1443.79,"endTime":1445.95,"body":"this kind of research?"},{"speaker":"Peter Bowes","startTime":1445.95,"endTime":1451.95,"body":"We've heard recently a lot of high profile politicians talking about pursuing a cure for"},{"speaker":"Peter Bowes","startTime":1451.95,"endTime":1453.66,"body":"cancer, which is great."},{"speaker":"Peter Bowes","startTime":1453.66,"endTime":1457.98,"body":"I mean, if that were to happen, obviously fantastic, but it's often very simplistic"},{"speaker":"Peter Bowes","startTime":1457.98,"endTime":1463.17,"body":"language. And you've spelled out very well for me and for us that this thing, this sort"},{"speaker":"Peter Bowes","startTime":1463.17,"endTime":1464.49,"body":"of thing doesn't happen overnight."},{"speaker":"Peter Bowes","startTime":1464.49,"endTime":1466.62,"body":"And there are trial after trial after trial."},{"speaker":"Peter Bowes","startTime":1466.62,"endTime":1472.86,"body":"And the last thing we can or should do is create any kind of false hope that we're"},{"speaker":"Peter Bowes","startTime":1472.86,"endTime":1474.54,"body":"talking about decades."},{"speaker":"Peter Bowes","startTime":1474.54,"endTime":1479.85,"body":"And with so many different diverse kinds of cancer, there is a tremendous amount of work"},{"speaker":"Peter Bowes","startTime":1479.85,"endTime":1480.96,"body":"still to be done."},{"speaker":"Dominic Denk","startTime":1481.59,"endTime":1486.27,"body":"That is true. So once again, as you mentioned briefly before as well, cure is a very"},{"speaker":"Dominic Denk","startTime":1486.27,"endTime":1487.56,"body":"dangerous word."},{"speaker":"Dominic Denk","startTime":1488.55,"endTime":1493.02,"body":"Cure implicates that the entire disease is gone forever, which is often not what happens"},{"speaker":"Dominic Denk","startTime":1493.02,"endTime":1494.49,"body":"when we treat cancer."},{"speaker":"Dominic Denk","startTime":1494.49,"endTime":1500.01,"body":"Importantly, metastatic disease we achieve to get stable disease, stable conditions,"},{"speaker":"Dominic Denk","startTime":1500.01,"endTime":1502.56,"body":"meaning you might have a lump in your liver in your brain."},{"speaker":"Dominic Denk","startTime":1502.65,"endTime":1504.66,"body":"But you don't feel it. It doesn't get bigger."},{"speaker":"Dominic Denk","startTime":1504.69,"endTime":1506.57,"body":"It's. It's all good."},{"speaker":"Dominic Denk","startTime":1506.58,"endTime":1510.36,"body":"And that's what you're mostly scared when you hear of cancer, of metastasis, of course."},{"speaker":"Dominic Denk","startTime":1510.36,"endTime":1515.55,"body":"So we don't necessarily look for cure, but we want to keep stable disease and now going"},{"speaker":"Dominic Denk","startTime":1515.58,"endTime":1520.32,"body":"towards preventing cancer, I think it's even more so important than treating it because"},{"speaker":"Dominic Denk","startTime":1520.32,"endTime":1522.06,"body":"there this is what."},{"speaker":"Dominic Denk","startTime":1523.02,"endTime":1526.89,"body":"Having having cancer in the first place is what drives all the issues of having to find a"},{"speaker":"Dominic Denk","startTime":1526.89,"endTime":1533.43,"body":"cure. So if we can identify basic measures, but also medications that might help us"},{"speaker":"Dominic Denk","startTime":1533.43,"endTime":1537.84,"body":"decrease the cancer risk, we avoid running into many other issues that we have in the"},{"speaker":"Dominic Denk","startTime":1537.84,"endTime":1541.86,"body":"first place. And one of these things, for example, can just be having a somewhat healthy"},{"speaker":"Dominic Denk","startTime":1541.86,"endTime":1546.6,"body":"immune system that detects cancer in the early stages that will not avoid all cancers."},{"speaker":"Dominic Denk","startTime":1546.6,"endTime":1551.01,"body":"Of course, we just know that most people in their life will have a cancer diagnosis."},{"speaker":"Dominic Denk","startTime":1551.01,"endTime":1555.06,"body":"About one third of all people throughout their lifetime can be any kind of cancer."},{"speaker":"Dominic Denk","startTime":1555.18,"endTime":1558.54,"body":"But it is something that I'm very confident we can reduce."},{"speaker":"Dominic Denk","startTime":1558.54,"endTime":1563.22,"body":"And with things like early screening or even just preventing the onset by itself, those"},{"speaker":"Dominic Denk","startTime":1563.22,"endTime":1564.63,"body":"are very important measures."},{"speaker":"Peter Bowes","startTime":1564.78,"endTime":1567.24,"body":"I think it is hugely important research."},{"speaker":"Peter Bowes","startTime":1567.24,"endTime":1571.98,"body":"I just wanted to ask you in closing more generally, I'm always interested in talking to"},{"speaker":"Peter Bowes","startTime":1571.98,"endTime":1577.74,"body":"people like yourself in terms of your own personal ambitions and goals, in terms of"},{"speaker":"Peter Bowes","startTime":1577.74,"endTime":1580.05,"body":"longevity and perhaps your lifestyle."},{"speaker":"Peter Bowes","startTime":1580.05,"endTime":1584.71,"body":"What do you do on a daily basis knowing what you know in terms of digging deep into the"},{"speaker":"Peter Bowes","startTime":1584.71,"endTime":1589.51,"body":"science? But what do you do on a daily basis to nurture your own healthspan."},{"speaker":"Dominic Denk","startTime":1590.05,"endTime":1591.97,"body":"Well, I would do everything wrong."},{"speaker":"Dominic Denk","startTime":1591.97,"endTime":1596.17,"body":"In that case, actually - being a physician means long working hours."},{"speaker":"Dominic Denk","startTime":1596.17,"endTime":1601.06,"body":"It means lack of sleep and doing this dual lifestyle of being a clinician and a"},{"speaker":"Dominic Denk","startTime":1601.06,"endTime":1603.97,"body":"scientist. You don't actually do the right things."},{"speaker":"Dominic Denk","startTime":1603.97,"endTime":1608.35,"body":"But what I try to achieve and that's what I actually prioritize as much as I can, is"},{"speaker":"Dominic Denk","startTime":1608.35,"endTime":1611.56,"body":"getting healthy amounts of sleep and exercising regularly."},{"speaker":"Dominic Denk","startTime":1611.56,"endTime":1616.54,"body":"Just knowing that we've increased age 30 plus your your muscle function decreases, your"},{"speaker":"Dominic Denk","startTime":1616.54,"endTime":1617.92,"body":"immune function decreases."},{"speaker":"Dominic Denk","startTime":1617.92,"endTime":1622.87,"body":"So getting healthy amounts of sleep, exercising and watching your diet in a way that you"},{"speaker":"Dominic Denk","startTime":1622.9,"endTime":1628.27,"body":"keep high amounts of protein, low amounts of carbohydrates and fat, those are the main"},{"speaker":"Dominic Denk","startTime":1628.27,"endTime":1629.32,"body":"basic things you can do."},{"speaker":"Dominic Denk","startTime":1629.32,"endTime":1634.42,"body":"I don't take any supplements myself at this point, just knowing that the science might"},{"speaker":"Dominic Denk","startTime":1634.42,"endTime":1638.41,"body":"not be yet, But I'm keeping very close eye on that and actually working on this myself."},{"speaker":"Dominic Denk","startTime":1638.41,"endTime":1642.55,"body":"So as soon as we have convincing data, I think that's something we could postulate."},{"speaker":"Peter Bowes","startTime":1642.79,"endTime":1645.1,"body":"Well, Dominic I think you're doing fascinating work."},{"speaker":"Peter Bowes","startTime":1645.1,"endTime":1648.37,"body":"I intend to follow it with a huge amount of interest."},{"speaker":"Peter Bowes","startTime":1648.4,"endTime":1649.72,"body":"Thank you very much indeed."},{"speaker":"Dominic Denk","startTime":1650.05,"endTime":1651.49,"body":"Well, thank you. Thank you for having me."},{"speaker":"Peter Bowes","startTime":1652.0,"endTime":1655.93,"body":"And if you'd like to dig a little deeper into the study that we've just been talking"},{"speaker":"Peter Bowes","startTime":1655.93,"endTime":1660.4,"body":"about, there's a link to it in the show notes for this episode, along with a full"},{"speaker":"Peter Bowes","startTime":1660.4,"endTime":1662.32,"body":"transcript of this conversation."},{"speaker":"Peter Bowes","startTime":1662.32,"endTime":1666.37,"body":"You'll find them at our website, which is LLAMApodcast.com."},{"speaker":"Peter Bowes","startTime":1666.37,"endTime":1669.46,"body":"That's LLAMAPodcast.com."},{"speaker":"Peter Bowes","startTime":1669.49,"endTime":1673.48,"body":"The Live Long and Master Aging podcast is a Healthspan Media production."},{"speaker":"Peter Bowes","startTime":1673.48,"endTime":1675.82,"body":"We'll be back soon with another episode."},{"speaker":"Peter Bowes","startTime":1675.91,"endTime":1677.14,"body":"Thank you so much for listening."}]}