Harnessing nature for better human health | Davide D’Amico

What does it mean to grow old?  Put another way, what are the hallmarks of aging?  They are questions that have long since intrigued biologists and longevity researchers, with a wide range of theories about what drives the aging process.  We understand the impact of weaker muscles, frailty, cognitive challenges and greying hair, but it is the underlying factors - molecular and cellular mechanisms - that researchers are striving to understand.  Dr. Davide D’Amico, Research and Development Group Leader with the Swiss cellular nutrition brand, Timeline Nutrition, is studying how compounds derived from plants can be used to reverse muscle decline and boost mitochondrial health. 

In this conversation we cover:

- The 'hallmarks of aging,' which refers to the key features of human aging, such as genomic instability and mitochondrial dysfunction.

- How the understanding of aging is not simply a chronological process, but also includes the concept of biological aging and the potential for reversing or slowing down this process.

- The potential benefits of supplementing with Urolithin A, a compound found in certain foods that can improve mitochondrial health and reduce inflammation.

- The importance of muscle strength and physical health in promoting longevity and preventing age-related diseases.

- How the ability to convert the precursor molecules found in plants into beneficial compounds like Urolithin A can vary among individuals and is influenced by the diversity and composition of their gut microbiome.

- The potential benefits of Urolithin A for the immune system, cartilage health, and overall mobility and quality of life in older adults.

- The importance of personalized approaches to health and longevity, with a focus on maintaining quality of life rather than simply extending lifespan.

- The overall goal of preventing age-related diseases, supporting optimal health, and promoting a compressed morbidity, where the period of decline in health near the end of life is relatively short.

- The need for education and awareness about lifestyle interventions for healthy aging, involving doctors, researchers, politicians, and educators.

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Transcript

Davide D'Amico: 0:00

How do we want to live? Do we want to live longer? But then in a suboptimal health status? Or is it enough to live more or less the lifespan that we have nowadays? Maybe a bit longer or a bit shorter, but focus more on the quality.

Peter Bowes: 0:16

Davide D'Amico, welcome to the Live Long and Master Aging Podcast.

Davide D'Amico: 0:20

Thank you very much.

Peter Bowes: 0:21

We often hear about the hallmarks of aging, and I think in terms of general discussions about longevity these days, that phrase is becoming better known. But I'm just curious from your perspective, what do you understand by it?

Davide D'Amico: 0:37

Yeah. So the phrase hallmarks of aging became famous exactly ten years ago. It was 2013. There was this now landmark publication called Hallmarks of Aging. Back that day, the authors, which are leading scientists in the field, they listed nine features that are key features of human aging, and they include hallmarks like genomic instability, which means an ensemble of mutation and alteration that you have in your genomic material or energetic dysfunction like mitochondrial dysfunction, which means the fact that your energy producer, the mitochondria, are declining in function with age. What is interesting is that now in 2023, after exactly ten years, almost the same authors published in the same exact journal, a cell journal, a revisited version of The Hallmarks of aging. And they call it an expanding universe. And the reason of this name is that, well, ten years of research is quite a lot. And we expanded our knowledge on what is happening during aging. And this new version is including now three new hallmarks on top of the nine that were described in 2013.

Peter Bowes: 2:00

Is aging purely a chronological process? I get from your answer that it isn't, and that we need to incorporate the concept of biological aging and the idea of possibly being able to reverse that process or at least appear physically to be younger than our age in terms of the average condition of a human being at a certain age. That word aging or age is quite flexible in terms of our definition and understanding of it.

Davide D'Amico: 2:33

Yeah, you're right. There is a chronological age that you have on your document and then there is a biological age, and this depends on many factors. And first of all, we need to understand what is driving aging. And once we understand it, we can theoretically measure it and then tell if your body is getting older very quickly or if you're having a healthy lifestyle. And so your biological age is slowing down.

Peter Bowes: 3:06

And as a scientist, what's your view of the phrase that's often used in the longevity space or the industry of longevity, and that is simply age reversal or reversing aging reversal to me suggests going backwards. Is that physically possible?

Davide D'Amico: 3:24

Well, this is a very dynamic field, right? It's not a field where we have clear answer yet. What is still ongoing is to develop actually a universally accepted way to measure aging. There are still a lot of different technologies and players. So reversing aging is still it's very fascinating, might be true in the future. We still need more science for this.

Peter Bowes: 3:54

But at least you've hinted at this. The idea, the concept of having a lower biological vehicle age that isn't equivalent to our chronological age is in large part potentially linked to our muscle strength, our physical strength, our mitochondrial health, which is of course directly related to our muscle strength. And that is your specialty in terms of at least what you're doing with this company and the interventions that could help us improve mitochondrial health. So maybe let's just go back to basics and for regular listeners to this podcast, we've discussed mitochondrial health many times. We understand that we have mitochondria in every single cell of our body apart from red blood cells and that they are important for, for the energy that we have and the energy that we need to get through every day. But there is much we can do to improve the health of those mitochondria. Where do we start?

Davide D'Amico: 4:51

Well, you're totally right. Mitochondria are important and mitochondria start aging like we do at the macroscopic scale, and the more they age, the less functional they become. And I would say it's not only about energy, it's not only this, the reason why mitochondria are important. Definitely. When mitochondria, when our cells age, the mitochondria become less functional. And simply speaking, our cells cannot produce enough energy to function properly. But at the same time, when you have faulty mitochondria that accumulate in your cell with aging or diseases, well, they start signaling. They are not isolating the cell. They talk to the the other cellular compartment and when they are not functioning well, they are triggering stress signals to the rest of the cells, to the tissue and then to the body. So inflammation, for instance, which is, we know, not healthy when uncontrolled. Well, now there is growing evidence that this can derive from dysfunctional mitochondria. So it's important to keep your mitochondria healthy, to get enough energy, but also to prevent these detrimental side effects like inflammaging. So this excessive inflammation that you have with aging.

Peter Bowes: 6:11

Just to put a maybe even a skeptical question related to that, what seems like a natural process, at least to many people, that mitochondria in terms of health and functionality will deteriorate as we grow older, as we grow older, clearly chronologically, that that is just part of aging. And for some people, tinkering with nature isn't always what they want to do. So I'm just wondering what the justification is for trying to alter that situation, to tinker with the health, to change the health of those mitochondria.

Davide D'Amico: 6:49

That's a good point. We should not play with nature too much. At the same time, we should harness the potential of nature as much as possible and the goal is really to support health. It's not necessarily about living forever or becoming superhuman, it's just to be as healthy as possible for the longest timeframe and leaving less years with chronic disease, being able to, I don't know, play with your grand children for longer, being able to climb stairs. So it's as simple as as this. Living a healthy lifespan, not necessarily a longer lifespan.

Peter Bowes: 7:33

And what's interesting to me is how we can embrace again, this comes to the work that you do embrace the qualities and the components of plants to enhance human health span, the number of years that we enjoy optimum health. And that's largely what you're doing here with the development of Urolithin A science, and I think this is still in its infancy in terms of developing this understanding and applying it to human health. Would that be a fair statement that there is a tremendous amount that we can learn and therefore utilize from the plants around us?

Davide D'Amico: 8:09

Absolutely true. You made the example of the fruits and the fruits that we we studied originally and from which we identified new natural actives. Well, the story behind is that there are many of these natural derived food that have some health benefits. But then what we discovered with preclinical and then clinical research is that many of the healthy molecules are actually not directly present in the food that we eat, but the food that we eat contains some precursor molecule and that these precursor are metabolized by our body and in particular by the bacteria in our gut. The gut microbiome. And all of these byproducts of the precursor are actually the molecules that are exerting a beneficial effect. The one that are absorbed by our body goes in our cells and then improve our health. What is also interesting, going back to the concept of harnessing nature is that not everyone is able to do all these conversions. So some of these conversion can be done only if you have the right gut microbiome to do the conversion.

Peter Bowes: 9:22

I want to delve into that a little bit deeper with you. What I haven't asked you so far is from a personal perspective, what brought you to this area of research? Could you give me just a little potted history of what you've previously been doing, your academic interests and what brought you here?

Davide D'Amico: 9:41

My academic journey. So my academic journey started with a PhD in metabolism and cancer. So slightly different topic. And it was in Italy and after the PhD I decided to cross the Alps and come to Switzerland, where I joined a very cutting edge group that was working on metabolism and well, I wanted to focus more on metabolism rather than on diseases. On basic mechanisms of aging and. Well, the at that time, the group was working on muscle aging, which is, of course, critical. We all know how our muscle quickly, quickly age. Yeah. So the reason I think we're two one was to study something that was applied that was close to what is happening in my everyday life. And well, as an example, we are here in Switzerland and, well, I spent quite a lot of time enjoying the beautiful outdoor activities here and it's good to be self aware of what is happening also in your body when you do exercise, when you outdoor in a healthy, then you feel healthy when you do exercise. So I wanted also to know more what was happening in my cell and why. There are some interventions, some things that are better for our health and how can we stay healthy for longer.

Peter Bowes: 11:09

Which comes right back to mitochondria being important for muscle health. And I think that's what you're talking about, being physically able to climb the mountains to go on the hikes, to do whatever you enjoy doing in your spare time. So this issue of us being made different, our microbiome is different. We have different abilities to utilize or to produce urolithin A Which is this all important, well, you can explain, metabolite that is clearly linked to the components, the compounds that we get from plants. To what extent are we all different and and what is the reason for us being different.

Davide D'Amico: 11:46

The extent is well for you brought up the specific example of urolithin A and just to do a step before the foodstuff where we find or the main foodstuff where we find the precursor of this molecule are pomegrannites, red berries, nuts, very healthy food. And in this food we have very large molecules, polyphenols called ellagitannins. And as I was mentioning before, they can be metabolized by our gut microbiome. And one of the the main product of this conversion is called urolithin A. Now we and independent groups did some studies. They took a number of individuals. And for instance, in our study, we gave pomegranate juice and out of 100 people we saw that only between 30 to 40% of the subjects were able to convert precursor into urolithin A. And the reason why 70% of subjects cannot do it resides on their bacteria in the gut. We did some studies and we saw that it's critical to have a very diverse and varying gut microbiome. This is driving the change, the exact mechanism, the exact bacteria. These are still under investigation.

Peter Bowes: 13:08

That's fascinating. And it's important to add and as you just indicated, further studies are needed. Further human studies are still needed to understand the reasons behind what you're saying. And I guess those studies could take some time. The very nature of clinical trials and getting the the infrastructure and the people that are going to carry out the research, but to take part in the studies, That is a long time process, isn't it?

Davide D'Amico: 13:35

Yeah, and it's not a very obvious question, especially on this. I can tell you I did try myself if I'm a converter or not and I'm not, I can take six glass of pomegranate juice and I won't be able to produce any urolithin A even if I think to have a relatively healthy lifestyle. So it's not just about being healthy that makes you able to do this conversion. There is still more that we we don't know.

Peter Bowes: 14:04

Which is really interesting. So I also took that test and I'm the opposite of you. I appear to be a good converter and I got a good thumbs up from the test.

Davide D'Amico: 14:16

Lucky You!

Peter Bowes: 14:16

But what's interesting to me is I wonder, so this is part of the research. This is what we're trying to find out. Do you have any thoughts on that? You and I probably come, clearly do come from very different backgrounds. Where did you grow up?

Davide D'Amico: 14:28

I grew up in Switzerland.

Peter Bowes: 14:30

In Switzerland,

Davide D'Amico: 14:30

Yes.

Peter Bowes: 14:31

Okay. So we're both from Europe. We've got clearly different cultural backgrounds, but that's not going to make any difference, presumably to. Well, perhaps it will, because we probably grew up on different diets. And I'm just wondering, could that play a role in this?

Davide D'Amico: 14:46

It could. We did studies in different regions, some in the US, some are in Europe, and we don't see dramatic changes in these percentages. So. To be honest, I don't know if it's genetic or environmental, if it's a mix of the two. It's still to be discovered.

Peter Bowes: 15:08

Watch this space will hopefully talk about it.

Davide D'Amico: 15:11

That's research, right?

Peter Bowes: 15:12

Yeah, exactly. So let's talk about other we've talked about Urolithin A and the importance based on our discussion just now of supplementation to greater or lesser extents for individuals, some of the other potential benefits. Now, clearly muscle strength. It's obvious why that is important. But the immune system is also coming into play here, potentially benefiting from urolithin A supplementation. Can you explain the background to that? And again, I understand that there's many more studies to be done, but what are you beginning to learn?

Davide D'Amico: 15:49

Well, the things we are learning, this comes from research from different research groups actually is that the same molecule that is acting on improving mitochondrial health has also an anti-inflammatory activity. So when we use experimental models where inflammation is a bit higher than normal and we administer this compound, the inflammation levels are always going down. And we saw this recently in two independent clinical studies. We enrolled healthy subjects. In both cases, no disease, but in both cases the population was, let's say, not the fittest and the healthiest. And we could see a basal level of inflammation that was a bit beyond, let's say, the optimal health. And after four months of supplementation with urolithin A in both study population, we saw a consistent decrease in inflammation and well, the biomarker that we used is called CRP, which is the short for C-reactive protein. And this is really one of the most established and accepted markers that indicates inflammation in our body.

Peter Bowes: 17:06

So this is interesting. And I guess the the common factor over all of the potential benefits through supplementation with Urolithin A is the aging process and the potential conditions, diseases that we're likely to encounter, whether that is frailty through deteriorating muscle strength, whether it is some of the killer diseases potentially of old age and some of those diseases that could potentially kill us, that there is an umbrella issue, it is slowing or potentially preventing some of those diseases of old age. Is that a fair way to summarize it?

Davide D'Amico: 17:47

Yes. Well, for to claim specifically a preventive effect, well, we would need much longer studies. What we can say is that the same markers that we see changing like improved mitochondrial function and reduced inflammation, they have been clearly associated with the risk of diseases. So we are improving certain feature or hallmarks, let's say, of health, that we know can increase the chance or have been seen by others to be correlated to health and disease.

Peter Bowes: 18:21

And I think in terms of going back to muscle strength, the preventative element there is is quite obvious to see that if you're improving muscle strength, you reduce the chances of falling in old age. Falling can often be the, to use the phrase, the beginning of the end for older people that a fall can result in a sedentary lifestyle that can reduce in other ailments, that can lead to diseases that can ultimately kill a person. And I mean, it's a familiar story that someone has a fall in their could be 60s, 70s, 80s and there's a very direct relationship there with with how long they are going to live. And I often talk about healthspan being the number of years that we enjoy optimum health. And to me, at least, optimum health means being able to move around and physically do what we could do when we are 20 or 30 years younger. So again, I'm looking into longevity and the aging process. Is that your understanding of the long term benefits of this?

Davide D'Amico: 19:24

That's my wish. Clearly, I completely agree that healthspan should be the goal and preventing the detrimental effects of aging and enjoying our life as much as possible until the last years, without debilitating diseases or risk of falling and being hospitalized, as you were mentioning. And the data that we are generating are going in this direction, we are improving muscle function, which is the one of the clinical parameter that is more closely associated with risk of mortality and disease. And then we are also expanding to other areas which are linked to healthy aging. Muscle is important. We recently published a study in experimental models where we looked at joint. This is another organ that is of course key for mobility together with with muscle. And we see that when we are working with model of arthritis, of osteoarthritis, well, the molecule is working also on joint on cartilage, not only on the muscle. So we might have also in a clinical setting, this requires, of course, specific studies, but this suggests the combined effect of Urolithin A on multiple tissues that are linked to healthy mobility, the muscle, the cartilage, maybe the immune system. And all this combined effect through mitochondrial inflammation sums up and is really the strength of this molecule, which is targeting several hallmarks of aging at the same time to to support our health.

Peter Bowes: 21:02

And of course, there are other ways, perhaps in combination to enhance our muscle strength- strength training, I mean, it could be going for a hike, it could be lifting weights in a gym. And also our nutrition strategies, combined supplementation, nutrition, strength training and possibly even a fasting regime which has been shown to and not at this moment to delve too much into that science, but to promote autophagy. Mitophagy the natural process of improving our mitochondrial health. There's a combination of strategies here that could help us in this respect in terms of muscular strength.

Davide D'Amico: 21:42

Well, exercise is clearly the first choice. I would select if you're asking me how to improve your muscle health, this is clear. There is plenty of literature on the on the topic, on the different exercise regimen. And I like a lot. For instance, all the recommendations that are coming from the American Heart Association, where you can really find how much exercise and what kind of exercise one should have, or at least a minimum to maintain a healthy lifestyle. So we need to find this right balance of making our our heart pump and do some endurance training and combine it with resistance, which is supporting also muscle strength.

Peter Bowes: 22:24

And of course, the beauty of exercise, physical training, strength training, resistance training is it's open to everyone. It's relatively easy to do even if you don't have a gym membership, you can take a hike. It's great to do here. You can climb a mountain, you can climb up a hillside. That in itself you can take long, regular walks. That in itself is hugely valuable.

Davide D'Amico: 22:47

Absolutely. There are some conditions or situations where you cannot do exercise, but otherwise this should be our base to to keep us healthy.

Peter Bowes: 22:58

So what's next? Where are you in terms of your bigger picture issues, in terms of research, maybe more even from a personal perspective, what is your vision of the future as it applies to your area of research?

Davide D'Amico: 23:15

Sure. This goes back to a topic we discussed earlier, which is measuring our health. I think this is the really the frontier of the topic. We heard a lot about personal and personalized medicine in the last year, which is the best drug that I should take if I have a certain disease. But now we are moving into personalized nutrition and personalized health, and it's still in an embryonic phase. But we are gathering more and more information with artificial intelligence and large data set that are really and will be able to tell us at one point, you know, this is your health status, this is your biological age or mitochondrial age or immune age, and this is what is best for you to do how much exercise, what to eat, which supplement to take. So the vision and I think the hope is to develop a way to measure our health and a way to improve our health. And the ultimate goal is to prevent diseases, is to support our health and avoid getting into the diseased zone where we we have to revert the disease.

Peter Bowes: 24:28

And looking to the future, do you have a vision of what is possible in terms of human longevity? I often hear 110, 120 years old and there is some evidence that if we embraced the science that we understand now and very often that can just come down to moderation in everything, whether it be red wine/alcohol or indeed extreme exercise or general nutrition, optimize sleep, all of those. Is good. Basic things that we understand often are what our grandparents told us, that sometimes it isn't deep science that we need to acknowledge here. But what's your vision of the future in terms of potential? A, Healthspan and B lifespan?

Davide D'Amico: 25:15

Lifespan? As you said, there are many theories and I'm not sure we have a final answer. The question is how long can a human being live? It's at least in my opinion, not even the right question to answer. It's the right question is how do we want to live? Do we want to live longer? But then in a suboptimal health status? Or is it enough to live more or less the lifespan that we have nowadays? Maybe a bit longer or a bit shorter, but focus more on the quality. And to me, this is really the at least my personal vision is to focus on quality rather than on quantity of our life.

Peter Bowes: 25:57

Which is a beautiful definition of healthspan. And I often hear this phrase compressed morbidity where the period of time from moving from healthspan at its maximum to dying is relatively short, and that we live well physically, mentally, socially to a great age. And then clearly we're going to die at some point and something kills us quite quickly. Do you think and that doesn't apply for most people at the moment. I mean, sadly, most people in this world die after quite a long, protracted period of decline in health. Do you think we're moving closer to a time when most of us could enjoy a compressed morbidity?

Davide D'Amico: 26:40

There is more awareness. We are still not there. If you look at the lifespan curves and probably healthspan data, we are surprisingly reverting the curves. Even if we know more about our body, we have more awareness, more strategies to improve our health. We still need more education, way more education to explain people that we need to embrace these strategies, which is exercise healthy diet, healthy nutrition supplements early during our life. To get into what you were saying, compressed morbidity. Nowadays, the habits of the vast majority of the population is actually not healthy and we see that we are in certain countries starting to to die earlier than the curve of increased lifespan is flattening down.

Peter Bowes: 27:39

Yes. And that actually goes against what most people think. You often hear the phrase we're living longer when in reality we're not, which really in 2023 is quite disturbing that, as you say, there's some evidence in the Western world, in the United States, for example, that people are dying at a younger age. So I guess that communication issue that you refer to, that getting people to really understand about these potential interventions is quite a mountain to climb. And I'm wondering if who should feel the the pressure to do something about that? Is it doctors more effectively communicating the message? Is it researchers like yourself? Is it politicians playing a role in terms of global health? Or perhaps more truthfully, is it a combination of all of those?

Davide D'Amico: 28:28

It is definitely a combination. I hope there will be more education from well, from school where we have proper education on healthy nutrition and on health class, on health and healthspan perhaps because that's where everything starts. We start developing bad habits and we can revert them and we should revert them already at during our early education and then the rest should come from a combination of communication of different actors.

Peter Bowes: 29:06

So just in closing, you've you've already told me that from a personal perspective, you enjoy outdoor activity, you enjoy hiking. I'm curious, based on the knowledge that you have in this area, what is your lifestyle? What is your daily routine? What's your morning routine as it applies to your own longevity, which I guess you must think about quite a lot in terms of the years to come. I suppose what I'm asking is, do you do you practice what you talk about and what the research tells you?

Davide D'Amico: 29:36

I do. I try my best. Not always easy, but sleeping. I try to maintain a good sleep regimen with at least seven eight hours of sleep, which is scientifically proven to be good, at least for most of the people. There are some lucky ones who can sleep less. I have a healthy eating and exercise. Well, I. Have. I'm happy I'm lucky to to like outdoors. So that's not a big problem for me to go out and run and climb in the Swiss outdoors.

Peter Bowes: 30:11

You've got a healthy eating regime. Just focusing in on that. What does that involve?

Davide D'Amico: 30:16

Well, I have a good breakfast. First of all, I have a good Swiss cereals, Swiss muesli, as we call it here, which is actually a very balanced breakfast of carbs with fruit and a lot of fibers, which is actually what we should all eat during our most of our meals. I have Italian origins, so I clearly tend to prefer a mediterranean-like diet where there is a lot of fruits and vegetables, preferably seasonal, a lot of olive oil, which is great for your health, for your heart health. Yeah. Generally speaking, it's light meal and rich in micronutrients, fibers, good proteins and good fat.

Peter Bowes: 31:03

And a meat eater, plant based diets, vegetarian vegan, pescatarian?

Davide D'Amico: 31:07

I am a I'm eating a bit of everything. Mediterranean diet is a good example of, you know, a very varying diet where you should not miss anything, but you should be careful with certain food, certain meat. So I eat meat, not a lot, but I do eat.

Peter Bowes: 31:23

This has been really interesting. Your work is fascinating. I'm going to continue to follow it. Really good to talk to you. Thanks so much.

Davide D'Amico: 31:29

Thank you very much.