Translating Aging

Today’s guest is Dr. Thomas Rando, Professor, Neurology; Molecular, Cell and Developmental Biology, and a pioneer in stem cell biology and the biology of aging. Dr. Rando is the Director of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at the University of California, Los Angeles, and the co-founder and Chair of the Board of Directors at Fountain Therapeutics. In today’s episode, he shares information surrounding cell cycle, parabiosis, and replacement therapy.Dr. Rando begins by explaining why the cell cycle is important and the place of aging cells in the world of cell cycle. He explains the quiescent states of cells and how heterochronic parabiosis has been tested on animals to determine if cells in a younger animal can be used to activate those in an older animal. He also discusses how three factors impact aging: genetics, diet, and exercise.In this episode, you’ll learn the meaning and importance of cell cycle and parabiosis and how they both relate to aging.Episode Highlights:Dr. Rando’s transition from neurology to stem cell biology The importance of cell cycle Why aging cells do not repair tissues Exploring the quiescent state How heterochronic parabiosis works Chronic inflammation in older people Does exercise benefit the tissues in the body? The connection between exercise and replacement therapy The relation between diet and longevity What are ketogenic diets? Dr. Rando’s thoughts on supplementation The future of stem cell therapy Can bone marrow be used to rejuvenate older people? Can stem cell therapy treat Alzheimer's disease? Transitioning from an academic to a founderQuotes:“Why is it that we heal our injuries and wounds less well as we age?”“The older we get, the more difficult it is to activate these cells out of that state. And you can imagine that if a cell is dormant, and you can't wake it up, it's not going to do very well in terms of repairing tissues.”“There's no free lunch here. What benefits the old animal hurts the young animal.”“The only reason why a species survives and thrives and continues is because of reproduction.”“No one wants to calorically restrict for their whole life. I mean, no one wants to go through their life eating 30%.”“Anything that we can do to find a healthy diet that is palatable and sustainable, and prevents obesity will be a good thing.”Links:Email questions, comments, and feedback to podcast@bioagelabs.comTranslating Aging on Twitter: @bioagepodcastBIOAGE Labs Website BIOAGELabs.comBIOAGE Labs Twitter @bioagelabsBIOAGE Labs LinkedInFountain Therapeutics

Dr. Marco Demaria is an Associate Professor in Cellular Ageing at the Medical Faculty of the University of Groningen. In 2018, he co-founded a start-up company, Cleara Biotech, devoted to developing anti-senescence drugs. Today, Dr. Demaria shares his insights and research on how senescence promotes aging and factors that promote the creation of senescent cells.In this episode, Dr. Demaria explains what cellular senescence means and discusses the good and bad that comes with having senescent cells in the body. He explains the role of senolytics in combating senescent cells and how senescent cells could be the cause of the severity of COVID in older people.In this episode, you’ll learn how senescent cells contribute to aging, the evolution of the senescent field, some current studies in the field, and what Dr. Demaria hopes to see in the field in years to come.Episode Highlights:What is cellular senescence?The positive and negative sides of senescent cells The role of senescent cells in agingWhat is the heterogeneity of senescence?Using senolytic drugs to eliminate senescent cellsHow does hypoxia affect senescent cells?The relation between senescence and COVID in the elderlyDr. Demaria’s progress in his study and work at Cleara BiotechThe evolution of the senescence field in the past 12 yearsExperiments Dr. Demaria would like to see doneQuotes:“A cell that is in an early senescence state seems to be different from a senescence cell in a late state.”“The next generation of senolytic drugs should definitely focus on dissecting the targets that they want to reach, because of the potential side effect of administering a general senolytic that could interfere with beneficial senescence.”“What we call senolytic drugs and compounds are mostly repurposed drugs.”“We also want to make this study of stem cell longevity in mice and in mouse tissues, because we think that might be another mechanism by which we can improve health, which is maintaining the stem cell pool because we retard the aging of the stem cells.”“There are two prominent senescence groups that are now using senolytics in the clinic for COVID-19 patients.”“There is no magic bullet so far that we have found but just because we haven't probably combined the right interventions at the right moment in the right context.”“The experiments I would like to see done are to combine approaches that target different aspects of aging.”Links:Email questions, comments, and feedback to podcast@bioagelabs.comTranslating Aging on Twitter: @bioagepodcastBIOAGE Labs Website BIOAGELabs.comBIOAGE Labs Twitter @bioagelabsBIOAGE Labs LinkedInCleara Biotech Website

The TAME trial and beyond (Dr. Nir Barzilai)Dr. Nir Barzilai is the founding director of the Institute for Aging Research, the Nathan Shock Center of Excellence in the Basic Biology of Aging, and the Paul F. Glenn Center for the Biology of Human Aging Research at Albert Einstein College of Medicine of Yeshiva University. He is also the author of the book Age Later. Today, Dr. Nir brings his expertise to the podcast for a discussion regarding longevity and aging.Nir starts the conversation with a discussion on the existing regulatory frameworks that create impediments to the longevity biotech sector such as the FDA regulations. He also explores the use of metformin in combating age-related diseases, the clinical trials surrounding metformin being carried out in the Longevity Biotech Association, dealing with members of  the government, and his perspective regarding what longevity biotech will be like in 5 years.In this episode, you’ll learn the uses of metformin and its relation to age-related diseases and what Nir hopes to see in the longevity industry in years to come .Episode Highlights:The existing regulatory frameworks that create impediments to the longevity biotech sectorWhat is metformin and its relationship with age-related disease?Targeting aging with metformin — the TAME trialHow other biomarkers would be tracked in the studyThe future of the trials and what is set to happen after it endsExamining the economics The mission of the Longevity Biotech AssociationThe longevity industry in 5 yearsChallenges that come with conversing with the Government concerning longevity and aging Quotes:“Aging drives diseases and those diseases can be delayed.”“If aging drives all diseases, then it's the mother of diseases.”“After all, what are we trying to do? We are trying to prevent a cluster of age related diseases.”“Even if metformin doubles in price because of demand, it's still going to be the cheapest drug in the pharmacy.”“There are nine studies that show that people on metformin had less hospitalization, and less mortality from COVID if they were on metformin.”“Science is not a bipartisan issue.”“We need to extend the field and extend the actual funding to do it.”Links:Email questions, comments, and feedback to podcast@bioagelabs.comTranslating Aging on Twitter: @bioagepodcastBIOAGE Labs Website BIOAGELabs.comBIOAGE Labs Twitter @bioagelabsBIOAGE Labs LinkedInDr. Nir Barzilai’s Twitter

Professor Steven Austad is a distinguished researcher in geroscience and the Protective Life Endowed Chair in Healthy Aging at the University of Alabama at Birmingham. He's also the Director of the Nathan Shock Center at UAB and the Senior Scientific Director of the American Federation for Aging Research.Today, Professor Austad joins Bob Hughes to discuss the biology of aging. He begins by narrating the discovery that sparked his interest in aging and his transition from animal behavior to the biology of aging. He discusses how these discoveries led him to the rate of living theory—the idea that the rate of aging is determined by your metabolic rate—and explains a somewhat paradoxical aspect to this theory: the hummingbird, which has a high metabolic rate, is  relatively long-lived. He goes on to review evolutionary ideas to understand the rate of living theory, shares his striking discovery about how possums age more slowly in the absence of predation, and describes both why birds of flight live longer than terrestrial birds and the unusually long lifespan of bats.Professor Austad talks of how natural history observations can accelerate more molecular and pharmacologic insights into human health, explaining, “Evolution is smarter than you.” He shares his perspective of the research enterprise: what we do well, what we don't do well, and how we can be better. He also details where he stands on aging in the private sector and for-profit aging companies, the mechanisms of age-related decline, and gives details about his bet with Jay Olshansky about a 150-year-old person being alive by 2150. Finally, Professor Austad reveals his expectations on whether more people will live to be more than 120 or 150 in the second half of the century due to interventions, and shares what he would focus on if he was given $1 billion.In this episode, you'll learn about aging in animals and humans and the factors that determine their longevity. You also hear about aging in the private sector as well as  comparing today's interventions to aging with evolutionary stimulus.Episode Highlights:Professor Austad's transition from animal behavior to aging The striking differences  in aging between a South American species of opossums and mice The rate of living theory The constant heartbeat theory—understanding the impact of heartbeat rate and longevity An alternative to the rate of living theory—the evolutionary approach Professor Austad's study and discovery on the aging of possums without predator interference Why birds of flight live longer than terrestrial birds Current estimates on bat longevity and why bats have a long lifespan How natural history observations can accelerate more molecular or pharmacologic insights into human health How evolution is smarter than humans Professor Austad's view of the research enterprise Aging in the private sector and for-profit aging companies Mechanisms in age-related decline Professor Austad's bet with Jay Olshansky about a living 150-year-old person by 2150.Quotes:"The interesting thing is that project was about the sex ratio of the pups and was eventually published in Nature. And by the time it came out, I totally lost interest in that project, and I was off studying aging.""Evolution has this wonderful capacity to take a single-cell fertilized egg and have it develop into a healthy adult in some kind of species. It would seem to be just much easier to simply maintain that healthy adult once you have it, but yet it's almost ubiquitous that when aging occurs, that healthy adult gradually loses its health.""One of the evolutionary ideas to understand that was that evolution is all about reproduction, and what evolution will favor is whatever physiology maximizes reproductive rate.""One of the things about possums that's important to note is that about 80% of them are ultimately killed by predators.""So it's clear that the lack of predators had really had an impact on those opossums because they were just like the animals of the Galapagos, completely unafraid of humans.""The longest-lived wild bat is reported to be 41 years. And that's an animal that's about a fifth the size of a mouse.""High-frequency hearing is one of the first things we lose, but bats have to maintain that year after year after year because getting their food depends on it. They find their animals in the dark by screaming and listening for the echoes. So the fact that a bat can live over 40 years in the wild strikes me as much more impressive than if it lived 60 years in a cave somewhere.""One of my favorite quotes is that evolution is smarter than you are. I think that's true because it's just so long to experiment. And so I think evolution will have come up with solutions to, let's say, how to maintain muscles better, maintain vision longer, or maintain nerves better in some species than we currently already do in humans.""I think scientists are increasingly conservative because they want to be able to do something that they know works. And most people I know have at least half of their next grant proposal already done, half the research done before submitting the proposal. And that, to me, is a good recipe for incremental advances, but not a recipe for major breakthroughs."Links:Email questions, comments, and feedback to podcast@bioagelabs.comTranslating Aging on Twitter: @bioagepodcastBIOAGE Labs Website BIOAGELabs.comBIOAGE Labs Twitter @bioagelabsBIOAGE Labs LinkedInProfessor Steven Austad LinkedInProfessor Steven Austad Wikipedia

Dr. Nabiha Saklayen is CEO & co-founder of Cellino, a personalized regenerative medicine company developing an AI-guided laser editing platform for autologous cell-based therapies. Cellino’s proprietary technology aims to make personalized stem cell-derived therapies scalable for the first time. Dr. Saklayen received her Ph.D. in Physics from Harvard University as a Howard Hughes Medical Institute (HHMI) International Fellow. In this episode, she joins Chris Patil to discuss autologous cell therapy and the strides Cellino has made in cell therapy using Machine Learning and laser technology. Dr. Saklayen talks about the challenges that come with autologous cell therapy, particularly in the manufacturing and cost aspect, and how Cellino infuses automation to make this procedure easier. She discusses how machine learning is integrated in the whole process and gives a brief insight into her career as a physicist and founding Cellino. She rounds up by discussing the future of Cellino and how Cellino strives to provide solutions in cell therapy that would change the world one patient at a time and at low cost. In this episode, you’ll learn what cell therapy is and how Dr. Saklayen, through Cellino, is reshaping the world of cell therapy and biotech as we know it. Episode Highlights: ●  What is cell therapy?●  Defining autologous cell therapies●  Examining the challenges with autologous cell therapy●  Cellino as a thought leader in the biotech industry●  The power of automation and laser therapy●  How machine learning contributes●  Dr. Saklayen’s career journey●  Going from a blood cell to a stem cell -  Sendai virus and  episomal vectors●  How to determine the success of an IPSC induction●  The future of Cellino●  Targeting diseases of aging●  How Cellino is providing solutions in aging aspects●  Cell therapies over small molecules●  Cellino’s goal for the next five years Quotes: “Cell therapy is a therapy where you make new cells for the patient and transplant them into the body to change the outcome of a disease or trajectory of a disease.” “It's about throughput. It's about yield. It's about consistency.” “The way we automate this process is by using machine learning algorithms that have been trained to look at images of cells and tell us which cells are high quality and which cells are not.” “It's really amazing to be able to tap into image-based machine learning algorithms and route the autonomous self-driving car industry towards advancing a lot of the neural nets that we're using in our training.” “I decided I want to be closer to real-world applications.” “Working together as an industry is going to be very important.” “Where we'd like to be in five years is we want to have our platform developed to a point where we can generate high quality patient specific cells in a reproducible manner, and do that for clinical doses.” Links: Email questions, comments, and feedback to podcast@bioagelabs.com Translating Aging on Twitter: @bioagepodcast BIOAGE Labs Website BIOAGELabs.com BIOAGE Labs Twitter @bioagelabs BIOAGE Labs LinkedIn Dr. Saklayen's TechCrunch Disrupt Talk Dr. Saklayen's LinkedIn  

Dr. James Peyer, PhD, is the Founder and CEO of Cambrian Biopharma, a Distributed xDevelopment Company developing therapeutics targeting the biological drivers of aging.Cambrian Biopharma brings together experts, scientists, and experienced company builders in a new model of entrepreneurship related to health span and aging. Dr. Peyer was previously the founder of Apollo Ventures, a successful venture capital firm focused on the longevity biotech space. He has spoken on the topic of longevity biotech and investing for Bloomberg, The Economist, TEDx, Longevity Leaders, ETH Zurich, and the Max Planck Institute on the Biology of Aging. Today, Dr. Peyer joins host Chris Patil to discuss venture capitalism in the longevity space and the new models that are changing the game. After discussing his previous experiences with VC, Dr. Peyer introduces the Distributed Development Company (DISCO) model, which allows scientists to partner with an umbrella company (like Cambrian) instead of selling their discovery to a pharma company. He explains how this model allows investors to support scientists through the whole process of drug development, from initial idea to commercialization, while prioritizing the quality of the science above everything else. Dr. Peyer then goes on to give some details about Cambrian’s success so far and how it sources and supports up-and-coming talent in the longevity field. He finishes up by making some predictions about the future of biotech companies and how the DISCO model will have a big role to play. In this episode, you’ll learn about venture capitalism’s role in scientific discovery and development and why Dr. Peyer believes a new model is necessary to remove the inefficiencies in the current process. Episode Highlights: ·   Dr. Peyer’s experience with Apollo Ventures and why he’s moved on to Cambrian Biopharma·   The future of the longevity space will come in two stages: reusing insights into what makes us age to build drugs for today, and using those safe and effective drugs to slow down the rate of aging in healthy people·   In the long run, company-based models will be better than fund-based ones for the longevity space·   The Distributed Development Company model (aka DISCO)·   Cambrian started with three programs and has scaled up to over fourteen in two years·   Cambrian prioritizes the quality of the science over hype·   Cambrian has raised about $160 million since 2019, including $100 million Series C financing at the end of October·   Cambrian sources talent through constant monitoring of the scientific field·   The DISCO model was designed to correct inefficiencies in the process of getting funding for scientists and their discoveries·   Drug development is a risky process, and Cambrian ensures success by carefully monitoring progress at every stage·   Being a bona fide longevity biotech organization means being willing to support every single program from funding to commercialization·   There are opportunities to partner with big pharma companies, but commitment to the whole process is the default·   Cambrian’s two publicly-disclosed programs are with Vita Therapeutics, a cell engineering company run out of Johns Hopkins·   One of the advantages Cambrian can provide to scientists is the ability to keep their discoveries as trade secrets as long as possible to maximize their patent lifespan·   The potential for the DISCO model to be used in other fields beyond longevity·   The possibility of failure and how Cambrian works to avoid it by being realistic and strategic and bringing expertise on board·   DISCO works really well for asset-centric breakthroughs made by very small companies or at universities, but it’s not the catch-all solution for everything—for example, tech platforms may be a better choice for bigger biotechs, while founder-led biotechs are better for young entrepreneurs·   External factors in aging·   Predictions for the field ten years from now Quotes: “I like to say that we get to take the best parts of being a VC, a pharma company, and an entrepreneurial biotech, and very few of the negatives.” “When we raise capital into Cambrian, what we get to do is we have our Cambrian team, which cares exclusively about the quality of the science, right? Not the hype or the number of Twitter likes around some particular discovery, but exclusively about the quality of the science.” “Cambrian breaks apart the existing longevity biotech field at the academic level, into thirteen different focus areas that we are constantly monitoring.” “I think that our model was designed to correct some of the inefficiencies that happen for scientists and scientific founders first, and it also is a happy accident that that model is also, I think, the more investable and more scalable one.” “Creating an organization that can really assess a group on whether it’s sink or swim based on the science and not the ability to raise money, I think has been a huge advantage for us.” “The reality of the situation is when a drug starts its first human clinical trial, there is about a 10% chance that it will ultimately make it to approval. And if you select just on, like, venture-backed biotechs from really smart groups, that number only goes up to about 15-16%.” “With every single program that we get involved with, if the science continues to look great, that means we are going to be there with that group, providing the funding, the organizational structure, everything to see that all the way through to commercialization.” “The value of any drug is driven essentially by its patent life.” “Models like the DISCO model that we’re using with Cambrian are actually going to replace a big chunk of early-stage venture capital in the biotech space and particularly for asset-centric companies.” “I sometimes call this model of biotech, the ‘hungry beast’ model of building biotechs.” “We’re just much more hands-on, right? We want to be doing the research and development, and the funding, and a lot of the strategy, together with the scientists that we start things with, which doesn’t fit for everybody.” Links: Email questions, comments, and feedback to podcast@bioagelabs.com Translating Aging on Twitter: @bioagepodcast BIOAGE Labs Website BIOAGELabs.com BIOAGE Labs Twitter @bioagelabs BIOAGE Labs LinkedIn Cambrian Biopharma Homepage

Professor Michael Snyder is the Chair of Genetics at Stanford School of Medicine, where his research group develops and uses technologies to study biological regulatory networks and applies these approaches to understand human variation and health. He's founded multiple biotech startups and has authored a book titled Genomics and Personalized Medicine: What Everyone Needs to Know. Today, Professor Snyder joins host Bob Hughes to discuss the impact of big data on human health. He reviews the results of his research, carried out on 109 people including himself, which entails collecting numerous types of health data and building an informative data profile, as opposed to the traditional approach of collecting just a few pieces of information. He goes on to share his personal story of how collecting deep data on himself helped him change his lifestyle after being diagnosed as a type two diabetic - using precision medicine to control diabetes. Professor Snyder also explores how DNA methylation can be used to track aging patterns and ageotypes, as well as the relationship between aging and Big Data collection, and also discusses health and longevity from his viewpoint, particularly from the standpoint of boosting the immune system. In this episode, you’ll learn how Big Data can influence our health, and why Professor Snyder believes that the transformation of healthcare begins with deep-diving into data. Episode Highlights: ●  Understanding precision medicine and personalized medicine●  How Big Data influences individual health●  Professor Snyder’s research results on 109 people●  The impacts of deep data profiles●  How Professor Snyder changed his lifestyle after deep-diving into his data●  Using precision medicine to control diabetes●  DNA Methylation and tracking aging patterns●  Selection criteria for the 109 research subjects●  Professor Snyder’s growth over the years from yeast biology●  Human health and longevity from Professor Snyder’s viewpoint Quotes: “We're actually much more focused, I would say, on precision health, trying to keep people healthy at an individualized level, and trying to use big data to do just that.” “We're in a world now where you can just collect so much deeper data on people.” “I liken it to a jigsaw puzzle. If I want to see what the picture is in a puzzle, looking at one or two pieces of a 1000 person puzzle isn't going to tell me the picture, even 15 pieces probably won't do it. But I want to look at as many pieces as possible. And that's what big data is all about.” “One aspect is to collect data, the other is to do it over time.” “A lot of people who survived the COVID infections wind up being type two diabetics on a 4% increase, which is a pretty large number of people.” “Everybody has different aging patterns, and so the way we think about this is like a car. Your car as a whole gets older over time, but some parts wear out first. ” “Having good biomarkers for aging, we think, is a big deal.” “Why are we measuring 15 things? We should be measuring thousands.” “There's a ton of investment going into longevity these days - billions of dollars now into these new startups.” “Your immune system starts plummeting in your 60s, as I say, and that just leaves you more and more vulnerable anytime after that.” “I think we can transform healthcare. I think you'll see big changes in the next 10 years in terms of home testing, all this sort of stuff.” Links: Email questions, comments, and feedback to podcast@bioagelabs.com Translating Aging on Twitter: @bioagepodcast BIOAGE Labs Website BIOAGELabs.com BIOAGE Labs Twitter @bioagelabs BIOAGE Labs LinkedIn The Snyder Lab Genomics and Personalized Medicine: What Everyone Needs to Know

Ben Kamens is the founder and CEO of Spring Discovery, a company devoted to accelerating therapies for aging and its diseases. Prior to that, Ben was the first engineer for Khan Academy, which provides free online education to millions of users around the world. Today Ben joins host Chris Patil to discuss Spring Discovery’s mission to increase healthy lifespan and dramatically reduce disease, his experience with Khan Academy and how it connected to his work in biotechnology, and overcoming challenges in the field of aging. Ben tells Chris about his pragmatic approach to building a company, how Spring Discovery plans to accelerate drug discovery and clinical development, and their collegial relationship with BioAge and other companies in the longevity biotech sector. Ben chats about Spring Discovery’s recent Series B funding, then offers a sneak peek into their therapeutic pipeline, and details his experience running a nonprofit clinical trial for a generic drug to fight against COVID, including what this taught him about testing drugs for age-related indications. Finally, Ben shares his favorite aspect of longevity science that his company is not currently working on, and where he sees the field of aging moving toward over the next five to ten years.To learn more about Ben and Spring Discovery’s work to accelerate drug discovery with machine learning, visit springdiscovery.com.Episode Highlights:Ben Kamens is the founder and CEO of Spring Discovery; he was also the first engineer for Khan AcademyIntroduction to Spring Discovery and how recent Series B funding will help the company advance its work to increase healthy lifespan and dramatically reduce diseaseHis initial skepticism and passion for fighting disease Overcoming obstacles in the field of agingBuilding value and resources as a company over timeAccelerating drug discovery and clinical developmentMachine learning approachSpring Discovery’s therapeutic pipelineBen’s involvement running a nonprofit clinical trial for a generic drug against COVID, and what this taught him about testing drugs for age-related indicationsYou can read Ben’s article “COVID-19 is the latest disease to point at our need to treat immune aging” hereFavorite aspect of longevity science that his company is not currently working onQuotes:“I couldn't think of a more important mission to try to enable than battling diseases of aging. And our mission is to give the best technology possible to these people who are doing what we think is the most important work possible.”“I came to this field as an outsider and somebody who's really a team builder, and interested in deploying the intersection of scientists and technology to try to fight disease.”“I am an extremely pragmatic person, especially when it comes to company building and entrepreneurialism.”“When you mention aging, you're immediately talking about this extremely broad array of biological phenomena, some of which are going to be relevant clinically, some of which are not.”“This presented a real opportunity to build the best company in the world at measuring the many changes that occur in us as we age.”“We've essentially taken an engineering throughput mindset to disentangling the many dimensions of age-related changes that accrue in our cells and tissues over time, and built a company around getting really, really good at that, and then using that to much more quickly search for therapies.”“You can think of it as a big engine that takes in a whole bunch of primary human samples, spits out this very multidimensional, complete view of cellular function, but does it in a big single screen that's combining tons of phenotypic imaging data with proteomics data, and then uses a set of models we built up to identify different cellular functions that are being identified in that raw data.”“I do not view that as competition whatsoever. I have nothing but respect for BIOAGE.”“We can cause all sorts of problems for ourselves. I don't really know what a competitor would do that would really dramatically change our trajectory.”“Our current focus is in the world of immune aging, and specifically how immune aging applies to both the pulmonary and skin therapeutic areas.”“We were following our standard path. And then, as you know, the more data that came out, the more it became very obvious that, more so than any other comorbidity, one's age defined one’s outcome with COVID. And it was almost looking like people who are much older who get COVID have an entirely different disease than people who are much younger.”“For most diseases, they are way worse for you if you're older, and so where is all the therapeutic effort that is focused on that huge fact in COVID?”“I am very uniquely proud that we found a way to do this.”“For me, this was just validation that there are ways to run pragmatic, cost effective, timely clinical trials for diseases that are exacerbated by the biology of aging.”Links:Email questions, comments and feedback to podcast@bioagelabs.comTranslating Aging on Twitter: @bioagepodcastBIOAGE Labs Website BIOAGELabs.comBIOAGE Labs Twitter @bioagelabsBIOAGE Labs LinkedInSpring Discovery Website springdiscovery.com

Rochelle Buffenstein is one of the world’s leading authorities on the naked mole rat, a fascinating animal that has emerged as an important model for research in longevity science. Dr. Buffenstein is currently a senior principal investigator at Calico Life Sciences, a subsidiary of Alphabet, that is seeking to better understand the biology that controls aging and lifespan. Today Dr. Buffenstein joins host Bob Hughes to explain why the naked mole rat is such a powerful model of successful aging. She talks about their resistance to cardiovascular disease, cancer, and neurodegeneration, and what this means for improving human health. You’ll hear about the role of Nrf-2 signaling in maintaining optimal health, looking beyond common animal model systems to understand aging more deeply, and the advantages of looking at health and longevity in naked mole rats versus mice. Dr. Buffenstein also discusses the typical hallmarks of aging and inflammation as they present in the naked mole rat, their unusual reproductive activity, and what this can teach us about human fertility. In this episode, you’ll learn why this unique and resilient creature is a “super organism” of sorts, and why Dr. Buffenstein believes they contain the blueprint for how to live long and successfully healthy lives.Episode Highlights:Introduction to naked mole rat as a powerful model of successful agingHow Dr. Buffenstein came to study these animals and what is unique about their aging processNaked mole rat’s reduced susceptibility to cardiovascular disease and cancerResearch on whether they are resistant to neurodegenerationCentral mechanism that provides generalized protection may be at playNrf-2 signaling pathway and its role in maintaining optimal healthThinking beyond common model systems to learn about molecular processes of agingStudying aging in a long-lived system is more pertinent to humansAdvantages of looking at slow aging process in a natural contextThe Methuselah Mouse Prize (Mprize) is being offered to the first person who can make mice live longer than five yearsUltimate cause of death in naked mole rats is unknownHallmarks of aging and inflammation process as they relate to naked mole ratNaked mole rats lack natural killer cells, which are very important for fighting virusesInnate and adaptive immune systemsUnusual reproductive activity for naked mole ratsThey have adapted to a particularly harsh and hostile environmentDr. Buffenstein believes they contain the blueprint for how to stave off many of the adverse effects of agingQuotes:“A naked mole rat is a mouse-sized rodent that stands out as an especially powerful model of successful aging, primarily because it is known to live an incredibly long time. It seems to be exceptionally resistant to most age-associated diseases like cancer and cardiovascular disease. And even reproductive senescence.”“We believe that given this phenotype that these animals are a very good example that aging does not need to be inevitable, and that they hold the blueprint for how to live long and successfully healthy lives.”“I got my first grant, looking at how it is that they're able to live 17 years. Little did I know then that these animals would be exceeding 39 years of age in my care.”“The fact that these animals don't seem to show any age-related change in cardiac function to me is remarkable. If we could understand the mechanism behind that, we might be able to come up with ways to improve human heart function and human health.”“[Naked mole rats] seem to be resistant to just about everything.”“We think that the mechanisms that protect them against aging might be the same as some mechanisms that protect them against cancer as well.”“We know that broccoli and the cruciferous vegetables all upregulate Nrf-2 naturally.”“I think the traditional model organisms have played a very important role in understanding aging. Because while evolutionary distance all of these models share an important feature, and that is, as they get older, their health declines and their probability of dying increases.”“I think that yes, we've learned a lot from mice, and we've learned how we can manipulate aging or health span, to some extent, but nowhere near the extent that you could, by looking at species that have already over a multimillion year evolutionary process, modified their biology and have features that enable them to live 10 times longer than a mouse. And that's where I think the naked mole rats are an important model.”“The real answer is we don't really know what it is that kills them. We just know what doesn't kill them are the common diseases that kill mice and rodents.”“Every time we've tried to induce some kind of stress, we see a very abrogated or attenuated inflammatory response. They don't seem to activate their inflammatory pathways to the same extent as other animals.”“Unlike mice, which have predominantly lymphoid cells, T cells and B cells, naked mole rats tend to rely much more on the innate immune system, on the myeloid cells.”“Both humans and more rats have about 40% of their immune cells being the slow responding adaptive immune cells.”“Any female in the colony can breed, but most of them are stuck in the suspended prepubescent state. When a female becomes the dominant breeding female, she continues to breed throughout her life. There's no sign of menopause.”“In most species, fertility declines as you get older. It's true of mice, and it's true of humans. And yet mole rats are showing the exact opposite pattern where the number of offspring produced in a litter increases with increasing age.”“The naked mole rat can survive 18 minutes in an oxygen-free environment without damaging its brain in any way. Whereas humans and mice after three minutes are brain dead.”“I think many of the effects that we see that pertain to their extreme longevity are byproducts of having to cope with such a harsh and hostile environment.”“The biology of the naked mole rat provides a proof of concept that it contains a blueprint for how to stave off many of the adverse effects of aging. The real problems with trying to figure out what that blueprint is.”“To me, the next steps are trying to successfully make transgenic naked mole rats, and being able to manipulate certain genes both in them, and giving their unique genetic makeup to mice to see if we can extend their longevity, or at least their health span in a significant kind of way.”Links:Email questions, comments and feedback to podcast@bioagelabs.comTranslating Aging on Twitter: @bioagepodcastBIOAGE Labs Website BIOAGELabs.comBIOAGE Labs Twitter @bioagelabsBIOAGE Labs LinkedInCalico Labs Website calicolabs.com

Earlier this year, the University of California San Francisco launched the Bakar Aging Research Institute (BARI), a scientific community that aims to translate breakthroughs in aging research across many disciplines into new approaches and treatments that help people remain healthy and vibrant in later life. Here to tell us about the Institute are Professor Leanne Jones, who moved from UCLA to UCSF to serve as Director of BARI, and Associate Professor and Associate Director of BARI, Saul Villeda. Today Dr. Jones and Dr. Villeda join host Chris Patil to discuss the mission and structure of the Institute, as well as their goal to bring people from different campuses together to push forward the field of aging research as a whole.Dr. Jones and Dr. Villeda talk about the collaborative culture at UCSF, lowering barriers to resources across disciplines, and what inspired the idea behind the Institute. They explain how they plan to foster communication between basic scientists, clinicians, and healthcare workers to enhance translational medicine, as well as the pathway to commercialization for BARI, and the value of building a community around improving human health together. Finally, Chris asks Dr. Jones and Dr. Villeda about the greatest challenges they’ve had to overcome in starting the Institute, their top priorities moving forward, and what they’re most excited to achieve through BARI over the next five to ten years.Episode Highlights:Mission and structure of the Bakar Aging Research Institute (BARI)Responsibilities and benefits of membership in the institute Connecting researchers across campuses Network creation and community creationSpirit of community will help attract other institutions to collaborateProviding central resources and lowering barriers to researchWhat inspired the Institute and founding vision of Barbara BakarHow BARI will enhance and promote translational medicine, translational applicationsImproving communication amongst scientists, clinicians, and healthcare workers who are interested in treating problems related to agingQB3 is a University of California hub for innovation and entrepreneurship in life sciencePath to commercialization for BARIValue of communicating with the community and including everyone in the conversation about improving human healthBiggest challenges Dr. Jones and Dr. Villeda have had to overcome in getting BARI startedBuilding a tangible community through a hybrid system of virtual/in-person interactionsTop priorities moving forward and what they hope BARI will achieve in the next five to ten yearsInvesting in the community and helping people jumpstart their research programs (e.g., Sandler Fellows Program)Quotes:“Our mission is broad, and really focused on building networks and community around aging. And, as we've said, improving the outcomes for older adults.”“It's exciting to think that our original vision of bringing people together from across all of the campuses is really coming to fruition.”“The requirement is that you're a full-time faculty member or equivalent at UCSF, and membership brings an ability to have first priority for funding opportunities, as well as the core resources that we're building up currently.”“What we quickly realized is that there are a lot of existing resources that people just don't know about. There was no centralized place, where you could just send an email and say, Hey, is anyone in Geriatrics...collecting blood from aging people?”“That's really one of the main things I think that people will get out of this - it's sort of a central place where you can make connections to facilitate and push your research forward.”“We really took it on as our charge to provide all of these resources for the community at UCSF, so that there's really lowering of any barrier to do the type of research that's related to the biology of aging, and also health span, and improvement of health ultimately, within the community.”“We're starting locally. But hopefully, we'll have an impact beyond the UCSF campuses soon.”“Really, I think that's the essence of the entire Institute is this idea of community.”“Here we have an institution where everyone is so close to each other, they have all the expertise, that just by building a series of bridges, I think we'll have an entire roadmap from beginning to end.”“We are improving the ability of everyone to take their discoveries, and hopefully have a much wider and a much more long lasting impact.”“We're really leveraging some of these resources to both facilitate questions that people have wanted to ask for a long time, but maybe didn't feel that they have the support to do it.”“We decided then that an institute would be the best way to sort of transfer this idea of community in a very tangible way across UCSF.”“In terms of infrastructure, we're trying to already lay the groundwork for setting up a program to do translational studies.”“We've got basic biologists, clinicians talking already, we are providing resources and funding for collaborative studies between these groups. And we're trying to go ahead and think about how we can provide a framework for translational neuroscience at UCSF.”“UCSF is a public university, and our mission is human health. And we want to be able to interact with and connect with the community.”“One thing that worked in our favor was actually the fact that we have been virtual for almost two years now, and that facilitated a number of town halls.”“What I'm really hopeful that we will be able to do is to be a place where an individual can come to get a personalized plan for improving their health or for maintaining their health.”“Every time you bring in someone new, it changes the landscape. So that makes me excited.”“I have no doubt the seeds that we are planting and sowing right now will really prove to be fruitful in the next five years.”Links:Email questions, comments and feedback to podcast@bioagelabs.comTranslating Aging on Twitter: @bioagepodcastBIOAGE Labs Website BIOAGELabs.comBIOAGE Labs Twitter @bioagelabsBIOAGE Labs LinkedInBakar Aging Research Institute (BARI) Website geroscience.ucsf.edu