Category Archives: Longevity

The Buck Institutes CEO Eric Verdin on why longevity research has transformative power, but the field must tread carefully between the hype and the noise.

The Buck Institute is all about living better for longer investigating and deciphering the biology of aging to end the threat of age-related disease. Aging is the number one risk factor for chronic disease, so the Buck deploys cutting edge science and technology and leading gerontologists in order to tackle it but searching for immortality is definitely not something on its agenda.

Longevity.Technology: The Buck Institute is headed up by Dr Eric Verdin; highly cited and with a Glenn Award for Research in Biological Mechanisms of Aging, over 210 scientific papers and more than 15 patents under his belt, he is first and foremost a scientist. As longevity goes mainstream, gaining longer air time and more column inches, there is a danger that the more fringe or extreme areas of the field become the focus, rather than the efforts to improve healthspan for people living today.

We sat down with Dr Verdin, President and CEO of The Buck Institute, to discuss these concerns and find out why searching for a philosophers stone might be good for Harry Potter but is the wrong direction for geroscience.

Its not my intention to sound like the big, grumpy old man of aging research, or a naysayer killing peoples hope! There are few people who are more excited by where this field is going and the acceleration of the research than I, but I also feel we are getting ahead of our skis a little bit when I read certain statements.

Immortality that word has unfortunately come back. Words like that, or statements like dont die are, in my opinion, completely out of place in a scientific discourse. We are not working on immortality frankly, its never going to happen. Theres no evidence it is going to happen, and Id question whether it would even be desirable. Talking about 150, 180-year lifespans is also completely premature. It doesnt help sure it creates hope, it creates clicks, sells books and might sell supplements, but its a distraction and one that alienates us from people who are serious about biomedical research.

But, living to 100 in good health is doable, and thats whats not being discussed enough that transformation. Gaining 25 years of lifespan in good health would be transformative.

If geroscience wants to be taken seriously, by the medical world, which will be critical in bringing this revolution to patients, we need to start making statements like that and work to implement what we know and really make a difference in peoples lives.

We can talk about living to 150 until were blue in the face, but were not going to deliver it anytime soon.

We will not implement this revolution without the help of physicians, working with them, understanding what its like to work with patients. With all the promise of aging research, you would have though that Pharma would jump in, but they are looking at the field with a degree of skepticism and hostility. VCs have an eye for detecting the best opportunities, but not many of them are in the aging space; some are dipping their toes, but they reference the hype and snake oil in the field. The serious scientists get drowned out by the noise of the crazy claims.

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The longevity revolution has the potential to transform healthcare in our lifetime - Longevity.Technology

Ahead of the Global Healthspan Summit, Hevolution CEO Mehmood Khan updates on the Foundations progress and explains why nothing happens without talent.

Next week, 100 international speakers and 1000 delegates will convene Riyadh at Hevolutions inaugural Global Healthspan Summit. As well as unveiling significant investments in the longevity sector, the Summit aims to catalyze global collaboration around extending healthspan, accelerate scientific progress for a rapidly aging world.

Longevity.Technology: Hevolution Foundation, which is delivering the summit, boasts an annual budget of up to $1 billion. The Foundation invests in grants for aging research and pioneers impact investments in early-stage biotech, driving acceleration and progress in the field. The Foundation is hoping the summit will serve as a seismic shift in how the world perceives and acts, catalyzing the discussion from lifespan to healthspan. To find out more, we sat down with Hevolutions CEO, Dr Mehmood Khan.

Whenever you convene the best minds of any field, and in this case, related to healthy lifespan, youre going to generate not only discussion, but youre looking for new ideas. The convergence of different disciplines allows you at that juncture to think about what are the innovations. In fact, if you look over scientific discoveries, most of them have happened when different disciplines have come together.

Were going to move this field forward into the marketplace, into the end consumers hands. That needs to have not only scientists, capital investors, large industry, small industry, but also policymakers, regulators, and bioethicists. This is what will happen at the Summit; it is unique bringing together as one meeting, people from all of these disciplines, to talk about healthy lifespan, thats not happened before.

Well also be sharing these ideas in a very public forum so that the discussion isnt just happening in a closed room. The idea is to engage and involve the media, because its telling the story so that people understand because at the end of the day, weve got to bring the public along.

We are facing some headwinds, some of which are general, but the general public has lost some of the trust in science. Following COVID, other recent discussions and, unfortunately, polarization in the political debate, we have to win the trust in science back. Innovation doesnt happen without that.

Sensationalism often leads to extreme statements billionaires living forever, and so on. We are absolutely nothing to do with that; our vision statement is clear: expand healthy lifespan for the benefit of all.

Benefit of all, for us, means democratizing everything we invest in, so it touches as many lives across the world, no matter where you are. Thats why this is important for every person on the planet, not just a few. The science is credible this is not just hocus pocus, pixie dust type of stuff. This is here now, the science is real, its happening now; whats been missing, somewhat, is the catalyzing of it, with also private capital, getting enough investment in it to bring it to market. The media needs to play its part, and its time to put the pieces together and change all that.

We want to catalyze the worlds talent to want to get behind taking the science from academic institutions and progressing it towards market. And I think its important to remember nothing will happen without talent.

Now, the field has been relatively small in terms of the number of scientists working in this field. We want to attract more scientists, younger scientists and scientists from adjacent fields who can understand the challenge and the opportunity and say: I absolutely want to commit a part of my career to progressing this field. We want to track that talent and showcase it, and at the summit, well be making some announcements that will get people to pay attention and say: Wow, I want to be part of it!

Everything we set out to do was to catalyze this field; our goal from the first hour was to build up to deploying $1 billion annually, but this is dependent on the organizations bandwidth and capacity of my organization. When I took over as CEO, there was myself and two people and you cant deploy a billion dollars responsibly managing with one CEO and two members of the team!

But, the team now has grown to be almost 70 people, and were on track by end of 2024 to be almost 200 people. So now we have the manpower and most importantly, the senior executives in place who have the experience to do this, whether its head of science, head of finance, head of investments, et cetera. The second part of this equation was the field itself is small, its nascent it cant absorb that much investment funding from the get-go. You have to build that capacity and thats exactly what weve been doing, and now, almost entering into our third year, weve been almost doubling every year to build to that. We are well on track and Im confident were going to get to that target number, and Ive always anticipated it will take three to five years to build to that. Were entering year three well on our way.

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Our vision statement is clear: Expand healthy lifespan for the benefit of all - Longevity.Technology

Do you want to live to 100? Thanks to modern medicine, you have a decent chance of doing so.

But if you want to live well to 100, physician and best-selling author Peter Attia says you may have some work to do so that your last decade of life - your "marginal decade," as he calls it - is healthful and rewarding, not limited by disease.

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If we adopt new ways of looking at our health, we can do a better job of matching our life span (how long we live) to our "health span" (how long we live free from chronic disease or other health problems), says Attia, the author of "Outlive: The Science & Art of Longevity."

In a phone interview, Attia talked about "the Four Horsemen of Chronic Disease" - cardiovascular disease, cancer, cognitive diseases (such as Alzheimer's) and metabolic diseases (such as Type 2 diabetes) - and new ways to plan for longevity. The following was edited for length and clarity.

Q: Many people fear living to be 100, imagining loneliness, poor health and solitude. Should living so long be our aim?

A: I don't think it should, actually. A lot of those fears are really valid. I think a better goal is to maximize health span. When you do that, you will automatically get a longer life span. If you improve your health span, so that when you're 80, you actually function like a 65-year-old, it's almost impossible to not also get five to 10 years of life-span extension.

Q: One of the ways to improve health span is through something you call "the Centenarian Decathlon." What is it, and how do we train for it?

A: It's a mental model which says that the greater the specificity with which you train for your physical goals, the more likely you are to achieve them.

I think back to the very first goal I ever had, which was to run five five-minute miles. That's a lot more specific than saying I want to be able to run five miles. If you want to achieve that, you have to train with far greater specificity than if you just want to able to run five miles. And this is true across the board. And it's what's necessary to achieve remarkable feats.

I ask patients to think specifically about what they want to be able to do when they are in their 80s or older, and to start training for that when they are in their 40s or 50s or 60s.

Q: You mean, for example, if you want to hike for two miles when you're 80.

A: Yes.

Q: Why won't just hiking every day in the years leading up to that prepare you to continue walking outdoors?

A: Because as you age, the degradation of strength, stamina, balance, lower leg variability is so profound that it is insufficient to just hike two miles when you're in your 40s and 50s, and assume that's going to get you doing the same thing when you're 80. When you're 80, you have to aim much higher. . . . The Centenarian Decathlon is asking, "What do you want to do in your marginal decade?" And the more specific you can make it, the better, because you'll be able to train for it, and increase the odds that you will be ready for it.

Q: And if you want to lift your great-grandchild when you're 80, you need to do what, exactly, when you're 50, 60 and 70?

A: To safely pick up a 30-pound child from the floor, you need hip flexibility and abdominal and spinal stability to get into a low squat position, then you need to be able to pick up a 30-pound weight. It's harder to do a squat with weight in front of you because it requires more core stabilization and more scapular stability [shoulder strength]. This essentially means you need to be able to do a 30-pound goblet squat at the age of 85. . . . By the time they're 85, most can't even do the goblet squat, without any additional weight. So just on that one metric of strength, we have something that we need to train for.

Q: You say exercise is the most important tactic for longevity, but more than 60 percent of Americans do not get enough exercise. Can sedentary people undertake the vigorous training that you recommend?

A: If you're starting from zero, just getting to 90 minutes a week of exercise will result in a 15 percent reduction in all-cause mortality [including the Four Horsemen]. That's dramatic. I mean, we don't have drugs that can reduce 15 percent all-cause mortality across the board. And the good news is it's not just like this abstract thing of "we're adding a couple of years to your life." No, no. You're going to feel better in three months.

Every person who saves for retirement, in my view, is doing something slightly more difficult. Because in the short term, you get nothing out of saving for retirement. . . . And I would say with these other changes that we ask people to make, at least they're getting a benefit today.

How is anybody supposed to find time for this? I would just say, if you're not going to make time for this, what are you making time for?

Q: Most of us succumb to one of those Four Horsemen. What do these diseases have in common?

A: Cancer, cardiovascular disease and neurogenerative diseases, Alzheimer's being the most common, are all exacerbated dramatically by metabolic disease. So, if you have Type 2 diabetes, your risk of those other diseases goes up dramatically.

Q: You suggest getting ahead of these diseases by screening, gene testing or digging deeply into bloodwork to uncover markers that, frankly, most insurance companies won't pay for. What do you say to patients, and your critics, about why these things are worth doing?

A: I guess the question is, what's the alternative? The alternative is continuing to do what we're doing. How is that working out? Not so well. So, if herculean preventive measurements are too expensive, treating them is costlier.

Is it expensive to get a $1,000 CT angiogram when you're 40? Yes, it is. Do you know what it costs to get a stent placed? Or to get a bypass when you're 65? Unfortunately, if you really want to take prevention seriously, you're on the hook for the cost.

Q: Does this mean that only rich people can live healthfully to 100?

A: Screening is simply one small part of this. Far more relevant to increasing your health span is not whether or not you're getting a CT angiogram, it's whether you're doing all of the other things that we talked about vis--vis sleep, nutrition and exercise. You don't have to be wealthy to do those things.

Q: Isn't it true that even if you do all of this, the Horsemen could still come for you?

A: Isn't there a chance that if you save for retirement, your investments will sour before you need to draw the money out? Yeah, of course, there is. But if you don't do these things, you dramatically increase the odds of things not going well.

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Want to live to a healthy 100? Longevity doctor Peter Attia has advice. - Yahoo News

In some pockets of the world, places with names like Okinawa, Sardinia, and Nicoya Peninsula, something truly remarkable is happening. People live longer, healthier lives than anywhere else on Earth. These regions, known as Blue Zones, have long been studied for their secrets to longevity, revealing key factors such as diet, community, active lifestyles, stress reduction, and a sense of purpose. However, one element often overlooked in these longevity paradises is bikeability. This article explores the profound connection between bikeability, health, and the remarkable longevity witnessed in Blue Zones.

Blue Zones are rare geographic areas where people live remarkably longer and healthier lives. These regions, first identified by National Geographic explorer and author Dan Buettner, have become the blueprint for longevity. With a focus on a plant-based diet, strong community ties, regular physical activity, and reduced stress, they offer valuable insights into how to extend life and improve well-being.

Bikeability refers to the ease and safety with which individuals can use bicycles for transportation and recreation within a community. It is a measure of how conducive an area is to cycling, taking into account factors such as infrastructure, safety, and accessibility.

Cycling is a fantastic cardiovascular exercise, promoting a strong heart and improving circulation. Regular cycling can significantly reduce the risk of heart disease and stroke.

The endorphins released during cycling enhance mental well-being, reduce stress, and combat anxiety and depression. In Blue Zones, stress reduction is a key factor in longevity, and cycling plays a role in promoting this.

Cycling is an excellent way to maintain a healthy weight or shed excess pounds, contributing to a lower risk of chronic diseases associated with obesity.

Cycling is an eco-friendly mode of transport that reduces air pollution and the related health risks, particularly in densely populated urban areas.

In Blue Zones, communities often incorporate cycling into daily life. Bikeability becomes not just a mode of transport but a way of living. For instance, Okinawa in Japan has an extensive network of cycling paths, making it easy for people of all ages to stay active on two wheels. The strong cycling culture in these areas complements the other elements that contribute to longevity.

Even in the United States, there are blue zone cities in small pockets such as in some California regions, which coincidentally have established or growing cycling networks such as San Francisco, Santa Barbara and San Diego.

Cycling in Okinawa, Japan (photo: visitokinawajapan.com)

Creating bikeable communities doesnt happen overnight, but there are strategies and best practices that can help cities and towns prioritize cycling. Local governments and urban planning have crucial roles to play in this process, from developing cycling infrastructure to promoting safety.

Challenges such as limited infrastructure, safety concerns, and cultural barriers can deter bikeability initiatives. However, innovative solutions and successful examples from different parts of the world show that these challenges can be overcome with determination and collaboration.

Incorporating bikeability into communities not only promotes physical health but also strengthens the sense of community, reducing stress and improving mental well-being. The extraordinary longevity seen in Blue Zones suggests that bikeability is more than just a means of transportation it is a pathway to a prosperous and healthy life.

The link between bikeability, health, and longevity in Blue Zones highlights the profound impact that simple, sustainable lifestyle choices can have on our well-being. By focusing on building bikeable communities and promoting cycling as a way of life, we can move closer to the health and longevity observed in these extraordinary regions. Its time to embrace the concept that cycling is not just an activity; its a path to prosperity, health, and a longer, fulfilling life.

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Here's why bicycles and blue zones are a perfect match - Momentum Mag

Researchers from Kumamoto University studied the cellular aging process in naked mole-rats (NMRs), discovering an NMR-specific natural senolytic mechanism that removes senescent cells, potentially contributing to their resistance to aging. The research, utilizing both in vitro and in vivo methods, identified the role of serotonin metabolism and the enzyme MAO in this process, offering insights into anti-aging strategies and treatments against age-related diseases.

The naked mole-rat (NMR), or Heterocephalus glaber, is a rodent native to East Africa that boasts a remarkable lifespan of over 37 years. This makes them the longest-lived rodents. Their remarkable resistance to aging and diseases like cancer has piqued the interest of the scientific community, leading researchers hoping to unravel the mechanisms contributing to their longevity.

Previous studies have explored the role of DNA repair mechanisms, protein stability, and translation accuracy (precise conversion of RNA to proteins) in this regard, but the molecular mechanisms/factors behind their aging resistance remain largely unclear. Moreover, the contribution of cellular senescence to their aging resistance is poorly understood.

Cellular senescence (cellular aging) is characterized by the irreversible arrest of cell division, which progresses with age. Senescent cells are less prone to cell death and accumulate in the tissues as they age, promoting chronic inflammation and compromising the function of these tissues. While cellular senescence plays an important role in aging, little is known about its function in NMRs.

A naked mole rat being bred at Miura Laboratory, Kumamoto University. Credit: Yoshimi Kawamura and Kyoko Miura from Kumamoto University, Japan

To this end, a team of researchers from Japan led by Professor Kyoko Miura from the Department of Aging and Longevity Research, Kumamoto University, conducted a series of experiments in vitro and in vivo to understand how cellular senescence occurs in NMRs and if there are any species-specific mechanisms that contribute to suppressing accumulation of senescent cells and their delayed aging. The Department of Aging and Longevity Research, Kumamoto University is the only center in Japan that breeds NMRs and conducts research on their resistance to aging and cancer.

Explaining the rationale behind their study recently published in The EMBO Journal, Professor Miura, states, Senolysis or the targeted removal of senescent cells has been shown to inhibit aging-related decline in mice. However, whether the findings in mice are generalizable, remains an open question. In this study, we discovered an NMR-specific natural senolytic mechanism that may provide an evolutionary rationale for removing senescent cells as a therapeutic strategy to prevent aging.

The research team used low concentrations of doxorubicin (DXR)a DNA-damaging agent to induce cellular senescence in NMR- and mouse-derived skin fibroblasts in vitro. They observed that induction of cellular senescence led to cessation of cell proliferation due to the arrest of the cell cycle with the activation of INK4a and RB (important factors for induction of cellular senescence), in both NMR- and mouse-fibroblasts. However, only NMR cells gradually and significantly activated cell death, suggesting that senescent cell accumulation in NMRs may be suppressed through their removal.

Through further experiments, the researchers observed that there was an accumulation of serotonin (a neurotransmitter that sends signals between nerve cells) in the non-senescent NMR fibroblasts, but not in the mouse fibroblasts. Upon senescence induction, in NMR cells, serotonin was metabolized by monoamine oxidase (MAO; an enzyme highly activated in senescent NMR fibroblasts after induction of cellular senescence) and converted to 5-hydroxyindole acetic acid (5-HIAA; a metabolite), releasing large amounts of hydrogen peroxide (H2O2).

An infographic depicting a unique natural senolytic or natural senescent cell removal mechanism identified by Japanese researchers, in naked mole-rats, the longest-lived rodent species. They proposed a species-specific mechanism involving activation of INK4a-RB-signaling and serotonin metabolism, which increases intracellular oxidative damage and causes subsequent death of senescent NMR cells. Credit: Yoshimi Kawamura and Kyoko Miura from Kumamoto University, Japan

The team proposed that oxidative stress due to the intracellular production of H2O2predisposed the senescent NMR fibroblasts to the cell death pathway, thus leading to senolysis (selective removal of senescent cells). This was confirmed by the observation that the addition of MAO inhibitors and antioxidants inhibited cell death in NMR fibroblasts.

To confirm if a similar mechanism was also prevalent in vivo, the team induced cellular senescence in the lungs of mice and NMRs using bleomycin (a DNA-damaging agent). They observed that cell death, likely due to an acute response to DNA damage, initially increased on day 2 in both mouse and NMR lung cells. However, after an initial rise on day 2, a fall in cell death was observed and by day 21, cell death had increased again, only in NMR lung cells.

Furthermore, treatment with the MAO inhibitor significantly suppressed cell death but increased the number of senescent cells only in the NMR lung on day 21. This suggests that MAO plays a role in inducing cell death and reducing the number of senescent cells following the induction of cellular senescence in NMR lung cells. These results are consistent with the in vitro findings and suggest that MAO contributes to suppressing the accumulation of senescent cells in NMR tissues.

Further studies focusing on the senescent cell removal mechanism in NMR tissues are needed to understand which kind of senescent cells should be removed, when, and how. Such studies may aid the development of safer and targeted senolytic drugs,says Prof. Miura while discussing future steps.

Overall, these findings suggest that INK4a-RB-mediated cell death may facilitate the removal of senescent cells in NMRs, helping them resist aging-related degeneration. We are confident that by highlighting a natural senolytic mechanism in this long-lived species, this study would contribute to the development of anti-aging strategies and targeted therapies against age-related diseases such as cancer.

Reference: Cellular senescence induction leads to progressive cell death via the INK4a-RB pathway in naked mole-rats by Yoshimi Kawamura, Kaori Oka, Takashi Semba, Mayuko Takamori, Yuki Sugiura, Riyo Yamasaki, Yusuke Suzuki, Takeshi Chujo, Mari Nagase, Yuki Oiwa, Shusuke Fujioka, Sayuri Homma, Yuki Yamamura, Shingo Miyawaki, Minoru Narita, Takaichi Fukuda, Yusuke Sakai, Takatsugu Ishimoto, Kazuhito Tomizawa, Makoto Suematsu, Takuya Yamamoto, Hidemasa Bono, Hideyuki Okano and Kyoko Miura, 11 July 2023, The EMBO Journal. DOI: 10.15252/embj.2022111133

The study was funded by the Japan Science and Technology Agency, the Japan Agency for Medical Research and Development, the Japan Society for the Promotion of Science, the Takeda Science Foundation, the Mitsubishi Foundation, the Kanzawa Medical Research Foundation, the Japan Foundation for Aging and Health, the KOSE Cosmetology Research Foundation, the Princess Takamatsu Cancer Research Fund, the Nakatomi Foundation, the Naito Foundation, the Foundation for Promotion of Cancer Research, the Kato Memorial Bioscience Foundation, the MSD Life Science Foundation, the Inamori Foundation, the SGH Foundation, the Terumo Foundation for Life Sciences and Arts, the Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care, and the Frontier Salon Foundation.

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Nature's Anti-Aging Blueprint: How Naked Mole-Rats Are Redefining What We Know About Aging - SciTechDaily

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