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Is There a Magic Key to Longevity?

Is There a Magic Key to Longevity?

Tuesday, October 1, 2024 AntiAging Biotechnology

In our current era of unprecedented scientific, medical, and technological advancements, research on aging and the quest to prolong human life have captured widespread attention. As the average age of the world’s population continues to increase, there's a keen interest in understanding the biological, psychological, and social aspects involved in the human body’s aging process.

In this interview with Supertrends, Victor Björk, molecular biologist, business development professional and founder of Victor Björk Geroconsultancy, talks about the aging process and human longevity. He discusses the latest research findings, challenges facing the development of anti-aging drugs, the importance of bridging the gap between research and clinical applications, the social implications of our quest to extend human life and more.

Interview Transcript

Supertrends: Welcome to Supertrends interviews. Today our guest is Victor Björk, a molecular biologist with many years of experience in different biotech companies. And today we will be talking about aging, anti-aging, and longevity-related topics. Hello Victor.

Victor Björk: Thank you. I'm very pleased to be here.

Supertrends: Maybe we could start with something more general first. Could you explain what aging actually is from a biological point of view? What are the processes involved in the aging?

VB: Yes, absolutely. Aging is a very complex process that involves many different parts of the body. It is not a genetic problem by itself. It's a lack of repair. So, in the broadest sense, you could compare aging to the aging of non-living things like a car that gets rustier with time. But there is no gene in that car that makes it rusty. It just falls apart because it's not able to repair itself. Our bodies are able to repair themselves, but only partially. At some point, the damage that accumulates exceeds what the body is able to repair, and then you end up with degraded function and all the age-related diseases like osteoporosis, cancer, dementia, heart disease, and many other conditions.

Supertrends: I understand. Therefore, I guess there is no such process that we could call a magic key to longevity. So a single biological process that, with the right approach, would guarantee us longevity and stop aging.

VB: Indeed, which makes it more complex because if aging was caused by a gene, you could just turn off that gene and make people not age. But we are dealing with a very complex “disease process” in that regard.

Supertrends: And what about the processes which are commonly associated with aging, like, for example, the shortening of telomeres or mitochondrial dysfunction? What do you think? How important are they?

VB: So there's a consensus, you could call it, in the scientific community that there are several different hallmarks of aging: the processes that are particularly relevant, that we have identified, and there is currently existing evidence for that they matter in aging. So while we have not mapped everything related to aging and we don't know everything about the human body, we can at least draw a very rough roadmap that if you could fix this, you would be able to at least get some level of life extension and health improvement.For example, telomeres shorten with time in cells. But it is a very complex issue, because it's not like we get shorter and shorter telomeres, which would end up damaging our DNA eventually in our cells. But it is also a response to damage from other factors. And the different types of aging damage accumulate at very similar rates. So it's often hard to understand which are the most important ones.Then the question is, from an aging research point of view, which damage is relevant. And that you can see by simply trying to repair that particular type of damage in a mouse. Then you see, does the mouse get healthier from this? Does the mouse get healthier with longer telomeres, for example? The answer is yes, they do, but only to a certain degree. By only targeting telomeres, as an example, you can get about a 10 to 15 percent life extension, some health improvement, and some decrease in frailty and cancer risk. But they don't live forever.You can do many other interventions in mice, like clearing damaged cells, so-called senescent cells. When people and mice get older, they accumulate damaged cells. Those cells are toxic for the body. If you reduce that number, the mice get healthier and live longer. So you can extend life a bit, but they certainly don't live forever because the different hallmarks tend to overlap. So you have to fix multiple things at once if you want to actually achieve something dramatic.

Supertrends: So if I understood correctly, we already know many different processes that are involved in the larger process of aging. However, we cannot just focus on one, pick one, and hope that we can significantly prolong our lifespan but we have to look at the bigger picture?

VB: Indeed. And that's partially where the research is going. For example, being able to look at combinatory studies. If you target multiple things in the same mouse, how much healthier can you make that mouse and how much longer can you make it live? Some research is now pushing in that direction, which makes it a very, very exciting field.

Supertrends: Talking about research, can you recall the last time when you came across a piece of research and you thought, “Oh, wow, this is something huge!” Can you recall such a situation from when you were looking at the recent discoveries in the longevity field?

VB: I can say multiple things. I want to point out that the different techniques that we have to probe the human body and be able to understand aging might not be developed specifically for aging research. But they are super important to accelerate the field. For example, artificial intelligence. There's so much research that can be done much, much quicker as a result of that compared to what we had previously. But if we are going to look at purely biological things, I think it's only about 10 or 12 years ago that we discovered that we could extend lifespan by clearing senescent cells, as an example. So that's an example of a field within aging that we did not understand. And suddenly it emerged, and you got a biotech industry out of it and you got awareness about it. That can be said for other areas as well. But I do think that much of the more exciting things are things that are not necessarily developed for impacting aging but that are harnessed by the researchers in the process.

Supertrends: You mentioned artificial intelligence. It looks like these days artificial intelligence is present in basically every field of research. How does it look in longevity? Do you have any examples where artificial intelligence has helped discover something new in the longevity field?

VB: Well, generally, it definitely speeds up drug discovery a lot. It makes it much, much more convenient to screen and find a target that actually works for a particular biomedical problem. But the issue is that we should not yet rely on it too much because cell biology is extremely complex, and you can see artificial intelligence making lots of predictions that appear mathematically correct, but that’s not what actually occurs in reality. So you have to constantly revise models to keep up with what is actually reality.

Supertrends: What about regenerative medicine? Could you elaborate a bit on that in the context of longevity research and anti-aging?

VB: Yes, definitely. I do think that the field of endogenous regeneration, triggering this natural repair system and the ability to replace lost cells that are damaged by aging, is going to become bigger. You can sometimes induce that by removing a particular form of aging damage. For example, when it comes to senescent cells, if you remove senescent cells in a particular area, you can get proliferation of healthy cells that were prevented from being there due to the presence of these senescent cells. You get like a partial natural repair. That is natural. But I definitely think that some part of aging is going to be targeted by drugs that trigger the body to regenerate certain tissues like dormant stem cells, the stem cells that could be triggered to function but are dormant.

Supertrends: What about other technologies, besides AI and techniques in regenerative medicine, that you think could have a big impact on longevity and anti-aging research?

VB: Gene therapy is very important and is a very hard thing to do. The benefit is that if you have a gene therapy, it often becomes much easier than having to develop a drug that the patient has to take continuously. So, from that angle, I do think that it's going to be very interesting, but gene therapy is currently more efficient against very specific identified conditions, like hypercholesterolemia. People with this condition have dangerously high cholesterol determined genetically and get heart problems early in life. But for the people for whom it is not really clear that they have a specific issue, who are going to live to 80 or 90 years old, like most people, it's going to be difficult or it could take a longer time to justify a gene therapy for a particular form of aging damage. But you could imagine gene therapy for many purposes, like naturally increasing the ability of the body to remove senescent cells or break down a particular form of waste product that we accumulate with time, potentially.

Supertrends: You have mentioned hypertension as something that is determined, partially at least, by our genetics. Are there any other genetic traits or genetic variants that determine how fast we age or how long we can live?

VB: Yes, definitely. There are some. There's not that much data on it in humans. There's some genetics that are associated with longevity, but there is not a lot known. And not having any of the genetic variants associated with longevity doesn't necessarily mean that you cannot live a long time. I would say for people who are over 110 years old, the supercentenarians, people who are extremely long-lived, we have still not identified any particular gene that they have in common. So to a large degree, longevity is also a matter of the absence of problems rather than having something that enhances you. If you look at it that way, you're initially normal because you're just a normal person. You don't have any specific health issues. So you end up living a very long time, but you don't have anything that you can target and induce, the same thing, in another person.

Supertrends: So, CRISPR-Cas9 gene editing that seemed to have potential in the treatment of many different diseases and fixing many problems is not really a solution in the case of aging, right?

VB: No, but it might potentially be used to some degree in a specific, particular thing, in a specific, particular aging-related process. But it alone, it is never going to do it.

Supertrends: We've touched a little bit on the subject of genetics in aging already, but what about environmental factors and lifestyle? So, if you have to compare genetics, environmental factors, and lifestyle, what in your opinion is the most important? Can we even determine this?

VB: Well, if you include drugs in the environment, you have medications like rapamycin and metformin that do extend life. Metformin isn't very efficient at extending life by itself. There was a lot of talk about it a few years ago. But it's synergistic with another drug, rapamycin, which is used for organ transplants in humans. They extend lifespan by roughly 15 percent in mice, so it's quite a robust effect. Some people self-experiment with this drug, but it's not approved for an aging condition, so that's very interesting.When it comes to basic lifestyle, there's a lot of data showing that not being extremely obese, exercising, not smoking, and so on are strongly associated with living a long life. You decrease your risk of death before 80 and increase your chance of living to 90. But when it comes to extremely old people, that breaks down because many who have lived to 110 have smoked and been overweight. It's as if they're protected somehow against this. But for the average person, yes, it makes sense to follow established lifestyle recommendations. If you look at certain places in the world like Okinawa in southern Japan and Sardinia in the Mediterranean, where people live longer, it should be noted that when these people move away from those islands and to the US, for example, their lifespan is identical to those in the US. So, living healthier with more exercise and locally produced food helps, but the effect isn't massive; it's about five years longer. So yes, it's better, but it's not a miracle.

Supertrends: You have mentioned these two drugs that, at least in mice, seem to prolong lifespan. Could you elaborate more on them, like what processes they target?

VB: Rapamycin targets a pathway called mTOR, which controls growth in the body and gets overregulated as you age. So, rapamycin dampens it down to a more moderate level, reducing cancer risks and potentially many other diseases as well. However, it's not yet tested for anti-aging in humans. Those who take rapamycin for organ transplants use it at extremely high doses, and it's generally well tolerated. However, these individuals aren't studied for longevity, often having other serious life-shortening diseases due to the transplants. In theory, based on biochemistry, rapamycin could extend life as shown in mice. It would reduce the risk of cancer and improve the immune system, despite being an immune suppressant. It might actually enhance the immune system, because aging can lead to overactivation in the wrong way. So, dampening it down a bit could help focus on fighting disease.So, I do think that people who would take it would likely be better off, but I'm cautious about speculating too much because we only have data from mice.

Supertrends: Of course, of course, understood. What about precision medicine? How does this relatively new trend impact the approach to longevity and anti-aging?

VB: I do think that this is very important and a very exciting area: precision medicine or personalized medicine, both terms are being used. The more data we have about an individual, the easier it becomes to intervene in disease processes, detect diseases early, and target them before they become clinically evident. Building up banks of human data is crucial, because understanding human biology is not as simple as assuming humans are big mice. We need to truly understand all the genomic, transcriptomic, proteomic, and the entire omics data of an individual. This is paramount to identifying which targets make the most sense for drug development. I would also add drug repurposing as a quicker path to the market. When you have already approved drugs that are also shown to work on aging, you can more rapidly get them to patients because drug development is super expensive and takes forever.

Supertrends: What about epigenetics? Are there any epigenetic changes that tend to accumulate during our lifespan and are proven to be involved in aging?

VB: Yes, there's definitely an epigenetic change with age. There are multiple ways of measuring it and correlating it with disease. So you can definitely measure it. Some companies sell consumer-based products where you can measure your own DNA methylation. Then we're able to track across large populations how it correlates with disease. You can get a benchmark for how healthy you are versus others of the same age in that regard. We should interpret all this epigenetic data with caution, but we can say that a certain epigenetic profile is strongly associated with being 80 years old and another with being a healthy 20-year-old. So, it's possible to measure. But for exact predictions, we still need more data. While it's good to test yourself, interpret the results with caution. It might not lead to anything more actionable than eating healthy and exercising, despite having the data.

Supertrends: We've discussed precision medicine and AI involvement in research, but are there any other trends you think will be important or are already important in the context of longevity and anti-aging research?

VB: Well, there's so much in general that is being learned about molecular biology. Setting up exact predictions of what will be translated into humans is very challenging. I view it a bit like fishing in a lake: you may stand there for hours with no fish, and then suddenly a swarm appears, and you catch a huge amount of fish at the same time. Very often, that's what happens in research. There's a lot of basic laboratory work ongoing, refining different techniques, and then suddenly many actionable findings emerge simultaneously, which can become medicines for patients. So, from that perspective, I'm very optimistic because we have much better tools now.

Supertrends: Yes, we observe a lot of progress in research. There are many different new techniques and technologies currently being developed, and our knowledge is expanding. If you were to guess for people born today, how long do you think they could live on average?

VB: It's difficult to put a number exactly to that. I do expect people to benefit. I don't think our generations are going to age in the same manner as previous generations. However, implementing these advancements in humans and informing people about them is crucial. There are many more issues than just the data in the lab. Something might seem like a breakthrough, but getting drugs out on the market, ensuring compliance, and informing the public about options all add complexity. Additionally, obtaining safety data is vital. So, there's much more to it than simply showing we can triple the lifespan of a mouse. It's a tricky process, especially when implementing it in older people. If you target people that are in their 80s and 90s now, can they reach 130? That's something we need to find out.

Supertrends: Is the re any technology, innovation, or trend that you personally think requires more attention, and people should focus on it right now because it has big potential for anti-aging?

VB: I think building a good database, being able to landscape the whole area and putting pieces together. It is a very large thing to identify those specific gaps and specific challenges. Because, if I'm going to give a very general answer to that, it's the failure of translation and the expense and cost to test the things in humans. And, also, the fact that the aging processes themselves are much harder to target from a clinical trial standpoint, because aging is also not a disease in itself: It's not considered a disease in itself. But whether you consider it a disease or not, you still have to have some target of fundamental aging damage and not just the end-stage disease, because when you try to influence things when people are very ill at the end of their lives, it's often very late. But when you try to target something in a younger person to prevent them from getting ill, then that's often seen as, “Why would you do this? The person is healthy. You shouldn't touch anything.” So that's a very tricky area.

Supertrends: It's a very interesting point. So basically, it's difficult to test anti-aging drugs in clinical trials in young people?

VB: Yes, so, under the legal framework and everything. To give a concrete example, we know that when you get older, you get more senescent cells, damaged cells that are hanging around in the organs, and they contribute to aging. If you have them in your blood vessels, you get atherosclerosis, heart disease, and strokes. You get osteoporosis if you have them in your bones. So, they are strongly linked to a fundamental aging damage, and they are linked to so many age-related diseases that people get when they're older. But having them, in itself, is not considered a disease. So, people go after the clinical outcome: “Oh, you have brittle bones,” that is what they go after. They don't go after how you have too many senescent cells in your bones. And a person who doesn't have very brittle bones but has a lot of senescent cells is still considered healthy, because if you didn't break your bones, you're healthy. From a molecular biologist’s perspective, it doesn't make sense to say that somebody who has a lot of accumulated molecular damage that we could wipe out with modern technology is healthy. But from the clinician's perspective, they say, “Yeah, but this person is still functional. Why would you risk some clinical trial on the person who is not in a nursing home yet?”

Supertrends: Let's look now at the issue of longevity or aging from a bit different point of view. How do you envision the ethical implications of extending the human lifespan? Are there any potential problems that we should start to worry about? Like, for example, do we have enough resources?

VB: I don't think that is very expensive. I don’t think that is the main issue, because so many of our resources are already spent on keeping old people who are very sick alive a little bit longer. The costs for paying out pensions to people are very, very cheap compared to caring for sick people. I made some rough calculations, don’t quote me on exact numbers because I did it a few years ago. At least for my home country, Sweden, a person who retires at 65 and then lives on a pension until 150 is cheaper than a person who dies from Alzheimer's at age 85. So, from that angle, the amount of resource and capital that goes into administering diseases is so high that any prevention will definitely pay off by itself very quickly.

Supertrends: And is there any misconception about longevity or aging that you would like to address?

VB: Well, I do think that longevity is used very broadly for anything that somehow leads to better health, whatever aspect of health it is. But when I say longevity, I might more specifically mean the root causes behind the disease. For example, if you have high blood pressure and you take a drug for high blood pressure, you don't cure the underlying cause behind high blood pressure. With that drug, you might extend your life, but this is not really a longevity drug if it just treats the symptoms and not the cause.

Supertrends: And now a bit of a different type of question. If you met a time traveler coming back from let's say 50 years in the future, what question would you like to ask them about the future of technology and why?

VB: Well, I would like to see how the future would have evolved, and also to retrace and be able to analyze what led to what, because right now we do not know what the first major breakthrough is going to be. It is always easy when you look back and say, “Oh, we were really fools,” because you didn't know it back then. But who was the least foolish? Who was the closest to doing what was actually needed to impact something that could be highly interesting?I'm very optimistic about the progress that we can make because there's so much data in mice. We have targeted so many different aging processes. Somebody just has to pull everything together, because it's all scattered across thousands of labs worldwide. There's so much. I often say that aging is not a hard problem like physics. It's not like we're waiting for an Einstein to solve something that is impossible to understand. It's more like a very big book that is a billion pages long. But you can still read it. You can still understand everything in it. It's just very big, very complex, and very confusing. But it's not impossible to grasp. So, you have to just cooperate with many different scientists, many different people, and pull things together into actionable outcomes. That's how I view it.

Supertrends: I would like to ask if there is something you would like to add, something you think that is very important, but we didn't have a chance to touch on this topic.

VB: Yes, I'd like to inspire people to understand that we are very, very far on in the basic understanding of aging and longevity, and the lab work that is being done. But we are still very primitive when it comes to translating anything into humans. So it can often feel a bit like we are both in a sci-fi world and in the medieval times at the same point. There’s so much going on,: artificial intelligence, so many interesting things that show promise in mice. But the failure of putting things together and translating it and implementing it, that's where I think the main issue is at the moment. I wouldn't have said that 10 years ago. Then I would probably have been thinking that fundamental science is so hard by itself. But now, I will start saying that there's enough known that we can start really doing things, and we should simply be able to identify all the gaps and set up some framework to get things to work.

Supertrends: This is a great take-home message. Thank you, Victor, for this very insightful interview. It was a pleasure to have you as a guest.

VB: Thank you.

The text is a transcript of an interview  conducted as part of Supertrends “Interviews with Experts” series. Please note that the transcript may have been lightly edited for editorial reasons.

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