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Translating Aging

BioAge Labs

On Translating Aging, we talk with the worldwide community of researchers, entrepreneurs, and investors who are moving longevity science from the lab to the clinic. We bring you a commanding view of the entire field, in the words of the people and companies who are moving it forward today. The podcast is sponsored by BioAge labs, a clinical-stage biotechnology company developing therapies to extend human healthspan by targeting the molecular causes of aging.

  • 63 episodes
  • Updated June 17

Episodes63

  • May 18, 2022 · 34 min

    Bringing Talent into the Longevity Industry’s Workforce (Mark Hamalainen)

    In today’s episode of Translating Aging, Chris welcomes Mark Hamalainen, the founder and director of LessDeath, to discuss how to encourage the influx of talents into the longevity field. LessDeath is an organization on a mission to support the growth and effectiveness of the longevity industry’s workforce. Today, Mark shares with us his experience in the longevity space, why he founded LessDeath, and what to expect at the upcoming LessDeath Longevity Summer Camp. Noting that his experience in the longevity space was propelled by his fascination as a teenager, Mark goes on to share details about leaving his Ph.D. program to get hands-on experience in the longevity world and discover the many talents represented in the industry. He speaks about founding LessDeath, what the organization hopes to achieve, the inaugural LessDeath Longevity Summer Camp and the gap this event is hoping to bridge in the industry. Included in this episode are interviews with Stephanie Dainow and Kia Winslow, camp counselors for the Longevity Summer Camp, in which they share the kinds of talent they expect to attract to the event and the kinds of activities that will take place. Episode Highlights: How Mark got involved in the longevity space The biggest issue in the longevity field The different talents prospering in the biotech field Why gene delivery and gene therapy require more technological development The challenges with getting people into the longevity biotech field How LessDeath tackles the talent issue and encourages networking The LessDeath Longevity Summer Camp Interview with Stephanie Dainow How Stephanie got into the longevity space Interview with Kia Winslow Kia’s story of getting into biotech What is next for LessDeath? Quotes: “I started a Ph.D. at Cambridge working on some gene therapy development. But I quickly got a bit disillusioned with the pace and the amount of extra work involved in grant writing, bureaucracy, and academia.” “A lot of people would prefer to work on important problems like longevity, climate change, building a multiplanetary species. But it can be difficult to know where to start, and how to build a sustainable career out of it.” “I've never liked the idea of getting older and losing my faculties and physical capabilities.” “If you want to invest your time supporting initiatives that drive measurable improvement to the human condition, but you're really not sure where to start, this is the event for you.” 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 LessDeath Website LessDeath.Org Apply for LessDeath Longevity Summer Camp Mark’s LinkedIn

  • May 4, 2022 · 49 min

    VitaDAO - Democratizing Longevity Research through the Blockchain (Tyler Golato and Laurence Ion)

    On today’s episode of Translating Aging, Chris welcomes Tyler Golato and Laurence Ion to talk about VitaDAO, a collective accelerating research in human longevity and decentralized drug development. The pair start the conversation off by discussing their company’s roots - a previous business venture that sought to change the incentive structures around drug development. VitaDAO was created as a means to support biological longevity research through decentralized means. They go on to discuss VitaDAO’s future, how they can increase liquidity, and their goals to advance drug development. Golato and Ion argue that the present is a perfect time to create VitaDAO, given the current intersection between biotech, block chain, and longevity research. They conclude by recalling the early-life dreams that inspired them to enter this field. Episode Highlights: The essence of VitaDAO Changing the incentive structures around drug development The partners’ passion for longevity VitaDAO’s decentralized structure Project sourcing and funding Increasing liquidity Goals to end drug development The intersection of biotech, block chain, and longevity Why Tyler and Laurence are interested in longevity Quotes: “VitaDAO was born out of an early concept that we had been working on at a company called Molecule, which is a company that I co-founded about three years ago with a vision of doing decentralized drug development.” “It's not completely open, completely decentralized to the point where it's paralyzing for the organization, but we try to look at the things that are most valuable to decentralize in order to make the organization as maximally efficient as possible.” “We really try to make it as easy as possible for token holders to make informed decisions about whether or not something is ultimately worth funding. We like to do so once we're at the point where we ensure that we can actually progress with a deal.” “We are distinctly different from a venture fund in terms of our endpoint is not really ROI impact, it's really impact in the space. And that comes in many different forms, in terms of taking a diversified approach to funding longevity research.” “Even if we spin out a NewCo, these contributors can vote on what projects are funded, how they are spun out, and then they can co-invest and help these therapeutics eventually come to market.” “In the long term, we really hope to be able to do a lot of things within the decentralized science ecosystem as the space broadens and has liquidity to do so through partnerships with organizations like Molecule and LabDAO.” “Certain things like clinical trials don't yet have a business model. So we can create one by having either philanthropic groups, patient groups or even a government/life insurance company that has an economic incentive to improve health outcomes.” “Crypto has long been dismissed by the incumbents.” “People who are really looking at how technology and innovation can drive humanity forward and drive the way that we govern.” “What problem is more interesting than human aging? I mean, for me, it's so philosophical; it's so poetic.” 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 VitaDAO Homepage

  • Apr 6, 2022 · 34 min

    Building Community in the Longevity Biotech Space (Nathan Cheng)

    On today’s episode of Translating Aging, Chris welcomes Nathan Cheng, the program director at On Deck Longevity Biotech (ODLB), to discuss how ODLB is cultivating new founders and connecting people in the longevity biotech space. Nathan writes about the longevity biotech industry in his Longevity Marketcap Newsletter, is the founder of Longevity List which aims to connect job seekers, companies and investors in the longevity industry, and is on a self-professed mission to end biological aging, Today, he tells us about the purpose of ODLB, its achievements thus far, and the bridge it hopes to build in the longevity biotech industry. Nathan begins the conversation by discussing what On Deck is and why the company was formed. He briefly narrates his journey in tech, what increased his interest in the longevity space, and the mission of the ODLB, as well as how the fellowship works towards creating founders. He goes on to discuss the obstacles many face when they get accepted in the fellowship and how ODLB works to reduce those obstacles by promoting face-to-face interactions. Also contained in this episode are brief interviews with ODLB fellows Brian Hodge and Gabe Warshauer-Baker. Episode Highlights: What is On Deck? Nathan’s journey in the longevity space On Deck Longevity Biotech’s (ODLB) mission The importance of connecting those in the longevity biotech space How mentors contribute in ODLB Does the startup culture reward extroverts over introverts? Getting into the ODLB fellowship Interviews with ODLB fellows Feats the ODLB has achieved The future of the longevity biotech space Quotes: “At a high level, On Deck is where people come to start and accelerate their companies. It's also a place where people start and accelerate their careers in the startup economy.” “What makes On Deck unique is that it's a huge network of interconnected program communities. So we have communities centered around specific career goals.” “ODLB’s mission is to increase the number of people working to build longevity biotech startups.” “For some people coming from the scientific domain, this whole idea of networking is foreign to them or nebulous.” “We're gonna generate new founders, but among the people who decide for whatever reason not to become founders, we also want them to be encouraged and empowered to be involved in longevity biotech in some other capacity.” “Putting ourselves on the map for people who are interested in building longevity biotech, I think that is our greatest achievement so far. ” “So I think just more efforts in popularizing this geroscience paradigm, you know, actually targeting aging, I think there's a lot to be done there as well.” 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 On Deck Longevity Biotech Website Nathan Cheng Twitter

  • Mar 23, 2022 · 37 min

    Aging Goes to Washington! — The Alliance for Longevity Initiatives (Sonia Arrison and Dylan Livingston)

    In today's episode, Chris is joined by two leaders of the Alliance for Longevity Initiatives, A4LI, the first and only 501(c)(4) nonprofit organization founded with the goal of creating social and political action around the issues of combating age-related chronic conditions and increasing our number of healthy, disease-free years. Sonia Arrison is a best-selling author, analyst, entrepreneur, and investor who is founder of 100 Plus Capital, Chair of the Alliance for Longevity Initiatives, co-founder of Unsugarcoat Media (acquired by Medium), and an associate founder of Singularity University. Dylan Livingston, the founder and president of A4LI, has a background in political organizing at the state and national levels. The conversation begins with our guests reviewing their journey to the world of longevity science and ultimately A4LI. They then explore many aspects of their organization including the needs it will address, the obstacles it will encounter and how it will overcome them, and its plan for succeeding in its mission. They go on to share what they have already accomplished, their ties on both sides of the aisle in Congress, Silicon Valley's current perspective on their work, and how listeners can help them achieve their mission. Drawing the episode to a close, Sonia and Dylan share their vision for what success would look like for A4LI five years down the road. In this episode, you will learn about the need for an organization such as A4LI to create social and political action around age-related conditions, and how our guests plan to fill this need both now and into the future. Episode Highlights: Sonia and Dylan's journey to the area of longevity and longevity science How they both came to be involved with A4LI The unmet needs that A4LI will address The obstacles it will meet in pursuing its mission and how it will overcome them The sense in which biology of aging is underfunded A4LI's plan for succeeding in its mission The Regenerative Medicine Advanced Therapy designation What it has accomplished already The ties it has made with both Democrats and Republicans Silicon Valley's perspective on their work How researchers, entrepreneurs, and investors can help A4LI Sonia and Dylan's vision of success for A4LI in 5 years Quotes: “Sonia has been intimately involved since the organization's inception. And I'm really happy that she is able to be the chair of the board because her leadership and guidance has been absolutely crucial.” “Essentially A4LI will be establishing a line of communication between the longevity industry and elected officials.” “There's a lot of longevity companies out there who are doing some really cool things that are going to extend our health spans. And, and so we need to make sure that the atmosphere is right for that.” “We look to kind of educate, you know, not only politicians, but also the voting public on what's possible.” “What we're saying here is, what I hear you saying is, it should be okay for a company to say we're a longevity company.” “You'd think that the government would want to fund that more, and they should, because of the e massive impact that a drug that treats aging could have.” “Even if funding is coming in from the private sector, biotech companies still stand to gain from formalized efforts, because they're going to get a smoother regulatory environment and potentially greater legitimacy for the products and ideas that they're developing. “ “By simply doing what other advocacy efforts do - that is public persuasion campaigns, their advertising - I think we can really open some ears up and get people focused on this space a little more.” “One of the things that was really important to me about getting involved in this is that it remained bipartisan, and so far, we've managed to do a really good job of having people on both sides of the aisle.” “I think people in Silicon Valley are interested and excited, and are just sort of waiting to see what's going to happen, and, you know, just how interested Congress might be.” “Everything is going to change with the introduction of an effective longevity drug. So, you know, we need to help the government and institutions prepare for that.” “Once somebody starts stealing your idea, you know that it's gold.” 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 A4LI Homepage

  • Mar 9, 2022 · 46 min

    Measuring Biological Age (Dr. Morgan Levine)

    Today’s guest is Dr. Morgan Levine, an assistant professor of Pathology and Epidemiology at Yale School of Medicine. She is also a Founding Principal Investigator at Altos, a new biotechnology company focused on cellular rejuvenation programming to restore cell health and resilience. Dr. Levine shares her expertise on biological aging, aging clocks, cellular reprogramming, and a peek into the research she’s currently undertaking at Altos here today. She starts the conversation by explaining the differences between biological aging and chronological aging. She then delves into topics surrounding biological clocks such as DNA methylation, and discusses her work at Altos and how this will differ from an academic environment. Dr. Levine finishes up by highlighting what Altos hopes to bring to science and biotech in years to come. In today’s episode, you’ll learn the difference between biological and chronological aging, the nature of biological clocks, and some of the exciting work taking place in biotechnology these days. Episode Highlights: The difference between chronological aging and biological aging What is an epigenome? How DNA methylation is measured Using aging clocks for a particular demographics How to decide if a discovery slows the biological clock Applications of clocks as it pertains to aging and longevity The costs of individual measurements Dr. Morgan’s work at Altos How Altos was founded Deciding the direction of research Understanding cellular reprogramming The future at Altos Quotes: “Age measured in chronological time was the biggest risk factor for most diseases.” “I like to think of the epigenome as almost the operating system of a cell.” “The things that we assume should affect aging, in potentially an animal model, show effects when using the epigenetic clock.” “We've actually taken the human epigenetic clock and broken them out into.. what we would call different modules.” “If we're measuring biological age, it should first correlate with chronological age to some degree, but not perfectly.” “We’ve become much more interested in understanding the clocks rather than developing new clocks… What’s driving the changes that are captured by the clocks, and how do those link to the outcomes they’re associated with?” “My lab is really a combination of both experimental wet lab people and computational dry lab people.” “I think saying we just work on aging, or just work on longevity, is really constraining us to some degree.” 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. Morgan’s LinkedIn Altos Labs Website

  • Feb 23, 2022 · 47 min

    Stem Cell Biology and Longevity Research with Dr. Thomas Rando

    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 founder Quotes: “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.com Translating Aging on Twitter: @bioagepodcast BIOAGE Labs Website BIOAGELabs.com BIOAGE Labs Twitter @bioagelabs BIOAGE Labs LinkedIn Fountain Therapeutics

  • Feb 9, 2022 · 35 min

    Cellular senescence in aging and disease (Dr. Marco Demaria)

    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 aging What is the heterogeneity of senescence? Using senolytic drugs to eliminate senescent cells How does hypoxia affect senescent cells? The relation between senescence and COVID in the elderly Dr. Demaria’s progress in his study and work at Cleara Biotech The evolution of the senescence field in the past 12 years Experiments Dr. Demaria would like to see done Quotes: “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.com Translating Aging on Twitter: @bioagepodcast BIOAGE Labs Website BIOAGELabs.com BIOAGE Labs Twitter @bioagelabs BIOAGE Labs LinkedIn Cleara Biotech Website

  • Jan 26, 2022 · 48 min

    The TAME trial and beyond (Dr. Nir Barzilai — AECOM)

    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 sector What is metformin and its relationship with age-related disease? Targeting aging with metformin — the TAME trial How other biomarkers would be tracked in the study The future of the trials and what is set to happen after it ends Examining the economics The mission of the Longevity Biotech Association The longevity industry in 5 years Challenges 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.com Translating Aging on Twitter: @bioagepodcast BIOAGE Labs Website BIOAGELabs.com BIOAGE Labs Twitter @bioagelabs BIOAGE Labs LinkedIn Dr. Nir Barzilai’s Twitter

  • Jan 12, 2022 · 36 min

    Natural history & the evolution of aging (Professor Steven Austad — University of Alabama)

    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.com Translating Aging on Twitter: @bioagepodcast BIOAGE Labs Website BIOAGELabs.com BIOAGE Labs Twitter @bioagelabs BIOAGE Labs LinkedIn Professor Steven Austad LinkedIn Professor Steven Austad Wikipedia

  • Dec 15, 2021 · 36 min

    Personalized cell therapies at scale (Dr. Nabiha Saklayen — Cellino)

    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

  • Dec 1, 2021 · 45 min

    DISCO: A New Model for Entrepreneurship in Longevity Biotech (Dr. James Peyer — Cambrian Biopharma)

    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

  • Nov 10, 2021 · 40 min

    Big Data and Human Health & Longevity (Prof. Michael Snyder — Stanford Medicine)

    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

  • Oct 27, 2021 · 42 min

    Accelerating drug discovery for aging and its diseases (Ben Kamens - Spring Discovery)

    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 Academy Introduction to Spring Discovery and how recent Series B funding will help the company advance its work to increase healthy lifespan and dramatically reduce disease His initial skepticism and passion for fighting disease Overcoming obstacles in the field of aging Building value and resources as a company over time Accelerating drug discovery and clinical development Machine learning approach Spring Discovery’s therapeutic pipeline Ben’s involvement running a nonprofit clinical trial for a generic drug against COVID, and what this taught him about testing drugs for age-related indications You can read Ben’s article “COVID-19 is the latest disease to point at our need to treat immune aging” here Favorite aspect of longevity science that his company is not currently working on Quotes: “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.com Translating Aging on Twitter: @bioagepodcast BIOAGE Labs Website BIOAGELabs.com BIOAGE Labs Twitter @bioagelabs BIOAGE Labs LinkedIn Spring Discovery Website springdiscovery.com

  • Oct 13, 2021 · 45 min

    The naked mole rat: A model of successful aging (Dr. Rochelle Buffenstein — Calico Life Sciences)

    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 aging How Dr. Buffenstein came to study these animals and what is unique about their aging process Naked mole rat’s reduced susceptibility to cardiovascular disease and cancer Research on whether they are resistant to neurodegeneration Central mechanism that provides generalized protection may be at play Nrf-2 signaling pathway and its role in maintaining optimal health Thinking beyond common model systems to learn about molecular processes of aging Studying aging in a long-lived system is more pertinent to humans Advantages of looking at slow aging process in a natural context The Methuselah Mouse Prize (Mprize) is being offered to the first person who can make mice live longer than five years Ultimate cause of death in naked mole rats is unknown Hallmarks of aging and inflammation process as they relate to naked mole rat Naked mole rats lack natural killer cells, which are very important for fighting viruses Innate and adaptive immune systems Unusual reproductive activity for naked mole rats They have adapted to a particularly harsh and hostile environment Dr. Buffenstein believes they contain the blueprint for how to stave off many of the adverse effects of aging Quotes: “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.com Translating Aging on Twitter: @bioagepodcast BIOAGE Labs Website BIOAGELabs.com BIOAGE Labs Twitter @bioagelabs BIOAGE Labs LinkedIn Calico Labs Website calicolabs.com

  • Sep 29, 2021 · 36 min

    Building networks and community around aging research (Leanne Jones and Saul Villeda of the Bakar Aging Research Institute)

    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 creation Spirit of community will help attract other institutions to collaborate Providing central resources and lowering barriers to research What inspired the Institute and founding vision of Barbara Bakar How BARI will enhance and promote translational medicine, translational applications Improving communication amongst scientists, clinicians, and healthcare workers who are interested in treating problems related to aging QB3 is a University of California hub for innovation and entrepreneurship in life science Path to commercialization for BARI Value of communicating with the community and including everyone in the conversation about improving human health Biggest challenges Dr. Jones and Dr. Villeda have had to overcome in getting BARI started Building a tangible community through a hybrid system of virtual/in-person interactions Top priorities moving forward and what they hope BARI will achieve in the next five to ten years Investing 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.com Translating Aging on Twitter: @bioagepodcast BIOAGE Labs Website BIOAGELabs.com BIOAGE Labs Twitter @bioagelabs BIOAGE Labs LinkedIn Bakar Aging Research Institute (BARI) Website geroscience.ucsf.edu

  • Sep 15, 2021 · 55 min

    Gene therapy screening to discover aging targets (Martin Borch Jensen - Gordian Biotechnology)

    Gene therapy screening to discover aging targets (Martin Borch Jensen - Gordian Biotechnology) Gordian Biotechnology is a San Francisco Bay Area biotech company that has created the first in vivo therapeutic screening platform aimed at drug development for complex diseases of aging. Co-founder and Chief Science Officer, Dr. Martin Borch Jensen joins the show today to discuss Gordian’s unique in vivo pooled screening in animals, as well as which indications they are targeting, their strategy to bring drugs to market, and how Gordian is currently tackling the challenges inherent to animal models. Martin also speaks about his passion from an early age to help fight age-related disease, and making the transition from academia to entrepreneurship, giving up a K99 fellowship at the Buck Institute for Research on Aging to make the jump into biotech. You’ll also hear about Martin’s involvement in multiple efforts to promote longevity science and bring new people into the field, including his apprenticeship program, the newly announced Longevity Impetus Grants program, and recording his “Science of Aging” seminar. Next, Martin shares what’s next for Gordian as they get ready to scale to the next level, which areas of longevity science he is most interested in but not currently working on, and how he predicts the field will evolve over the next five to ten years. For more information on Martin’s apprenticeship program and Impetus Grants application process, please visit MartinBorchJensen.com or follow him on Twitter. Episode Highlights: Dr. Martin Borch Jensen is the co-founder and CSO of Gordian Biotechnology Gordian Biotechnology created the first in vivo therapeutic screening platform to radically improve drug development for complex diseases of aging Martin is also involved with an apprenticeship program and a newly announced grant program to catalyze rapid progress in aging research How Gordian’s unique in vivo pooled screening in animals works They’re focused on removing the diseases of aging, beginning with their three lead indications, NASH (nonalcoholic steatohepatitis or fatty liver), osteoarthritis and idiopathic pulmonary fibrosis How Gordian compiles their gene libraries While other companies start with in vitro models and then figure out ways to test them in living animals, Gordian starts with the second step They deliver hundreds of gene therapies at once to a single animal The drugs that they ultimately develop won't necessarily be gene therapy, but instead whatever is most appropriate to pursue the indication once they know the target (small molecule drugs, antibodies) What a cell needs depends on what a cell is Gene therapy has plenty of advantages, but the cost is very high How Gordian is overcoming challenges that are inherent to animal models Older mice are much more expensive and are rarely used in aging research Animal models can actually be useful if the animal has progressively developed a disease in the same way humans do, and has similar biology Example of studying osteoarthritis in horses, because the load-bearing structure of their joints is much more similar to humans, as is their cartilage thickness Gordian’s strategy to bring drugs to market Martin’s transition from academic to entrepreneur and what inspired him make the jump to biotech He gave up a K99 fellowship at the Buck Institute for Research on Aging He realized as a teenager that he wanted to try to fix aging Martin is good friends with Dr. Kristen Fortney, co-founder and CEO of BIOAGE; her journey showed him that it was possible to start his own company Martin is also involved in multiple efforts to promote longevity science, and to bring people into the field His apprenticeship program was developed as a way to bring people in, and train them to be able to work on direct projects Longevity Impetus Grants is a $21 million (update: $26 million as of the release of the podcast) program that provides funding for scientists to start working on what they consider the most important problems in aging biology without delay This was inspired by COVID-19 “Fast Grants,” created by Tyler Cowen, Patrick Collison, and Patrick Hsu Their goal is to take big bets on projects that could move the field forward, and recipients will be able to publish their findings regardless of what their results are Impetus Grants applications open on Monday, September 13, 2021 Martin also recorded a comprehensive seminar about the science of aging What’s next for Gordian as they get ready to scale to the next level Martin predicts that in 5-10 years, we will have ways of measuring biomarkers for aging in humans Quotes: “It's phenotypic screening, but also because it's gene therapies we're putting in, we know the target immediately. So I call it ‘pheno-target screening,’ combining the best of both discovery modalities that are used.” “At Gordian, we're focused on removing the diseases of aging. Right now we're doing that with three lead indications, and that number will grow, which are NASH and osteoarthritis and idiopathic pulmonary fibrosis.” “We've created the platform in order to be able to do somewhat unbiased screens or entirely unbiased screens, and just explore a lot more of the biology of these diseases than has ever been explored in vivo so far, because we have this higher throughput.” “The logistics of the other method simply don't allow you to test a wide range of things in the in vivo context.” “I'm very excited about gene therapy in the long run to treat aging, diseases of aging, and just the physiological processes of aging. Because it turns out that what a cell needs depends on what a cell is. And so you probably don't want the same treatment in every type of cell in your body.” “You need a targeted way to go in and give each type of cell and each tissue what it needs, if we're going to really exercise control over the aging process.” “Maybe animal models aren't so bad for many diseases, if you find an animal that has continuously developed, progressively, a disease in the same way that humans develop this disease, and has biology that resembles human biology and the relevant organ.” “We are a drug development company. We've developed this in vivo full screening platform in order to use it ourselves and discover the best drugs for each of the indications that we go into.” “We are in conversations with a whole bunch of pharma companies about partnering at the clinical stage around the assets that we are discovering with our platform.” “As a teenager, I came to the realization that I wanted to try to fix aging… The idea that everyone is going to get sick and be in pain, and then die, just seemed really bad.” “I wanted, with Gordian, not only to have the successful outcome of treating age-related diseases, but I also wanted to feel for myself that I was doing absolutely everything that I could towards the goal that I had decided.” “It's going to be really hard. There's going to be doubts and challenges… And so if you're doing it for reasons that won't compel you to push through all of that, it's probably not going to work out.” “[This apprenticeship program] is needed, because there are more things that should happen, and apparently could happen, than I could possibly ever go and do myself.” “The apprentices end up doing most of the legwork by far. And I'm kind of steering it.” “This is the real test of success for this apprenticeship - if the people in it end up running important projects within the longevity field overall, then it's a success.” “If there is something there, if the project does work out, that would actually be a really big push forward for the field, then we should try to fund those things. And many of them won't work out and that's okay. We can learn from that.” “Any nonprofit can apply from anywhere in the world. Or any researcher at a nonprofit.” “What you really have to explain to us is, How is what you're doing going to move the field forward, if it works, and why is the way that you're doing it, a good, robust, well thought-out experimental plan for doing it? Those are the main things that we look for.” “In five to 10 years, I think we will have drawn studies for biomarkers of human aging. So I think that in five to 10 years -hopefully more like five - we will have ways of measuring in humans, something that we choose to call aging.” 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 Martin Borch Jensen Website MartinBorchJensen.com Martin Borch Jensen on Twitter: @MartinBJensen Longevity Impetus Grants Website ImpetusGrants.org Gordian Biotechnology Website Gordian.bio

  • Sep 1, 2021 · 49 min

    Changing the Narrative on Women’s Reproductive Longevity (Dr. Jennifer Garrison, Buck Institute & GCRLE)

    On today’s episode is Dr. Jennifer Garrison, Professor at the Buck Institute for Research on Aging, and the Faculty Director of the Global Consortium for Reproductive Longevity and Equality (GCRLE), which is devoted to supporting breakthrough research on reproductive aging and women in science through funding, training, infrastructure, and collaborative intellectual networks. Dr. Garrison explains that while there are plenty of scientists working on aging and plenty who are working on reproductive biology, there are precious few who are working at the interface of these two fields, which is what they are trying to build at the GCRLE. She shares her fascination with ovarian biology and how it fits into the broader context of longevity research, and details the issue of equality in terms of women having to plan their life choices around reproductive longevity in ways that men do not, as well as funding for women’s health being traditionally overlooked. Dr. Garrison answers questions about menopause across the animal kingdom, the link between reproductive span and lifespan in women, and the most important question we need to answer in order to truly understand ovarian aging. Dr. Garrison describes the key role played by the brain in reproductive success, the need for better animal model systems to understand menopause, and how hormone replacement therapy can help mitigate the negative health consequences around menopause. You’ll also hear about the profound economic and societal impact of menopause globally, as well as Dr. Garrison’s goals for the future and dream outcomes she envisions for the Consortium as they continue their cutting-edge research on the causes of ovarian aging. To learn more about their important work, visit BuckInstitute.org/gcrle/. Episode Highlights: The goal of the Global Consortium for Reproductive Longevity and Equality (CGRLE) is to extend the female reproductive span The Global Consortium began at the Buck Institute for Research on Aging through a generous donation from Nicole Shanahan and the Sergey Brin Family Foundation There are plenty of scientists working on aging and others who are working on reproductive biology, but precious few who are working at the interface of those two fields - that’s what they are trying to build The GCRLE has three arms: Funding; providing resources to build out the field; and building a network communications platform to foster dialogue and collaboration among researchers working on female reproductive aging They’ve also opened the world’s first ovarian biology core facility at the Buck Institute Ovaries are a very complex structure, and they age at a precocious rate - they’re considered geriatric by the time a woman is in her late 20s, early 30s Nicole Shanahan’s became involved with starting the CGRLE to find out what causes ovaries to decline in function so early Ovarian biology as it relates to reproductive longevity has been traditionally overlooked in terms of receiving funding Women’s health has been looked at as a subcategory of medicine Equality is a key piece to what they do - women need to plan their life choices around reproductive health in a way that men do not Menopause accelerates the aging process It is relatively rare in the animal kingdom - humans are one of the only species that go through menopause Women who experience menopause later in life also tend to live longer and have an enhanced ability to repair their DNA There is a clear link between reproductive span and lifespan in women The key question is, What is the cue that tells a woman’s ovaries to start declining in her 20s? The brain is a crucial player in reproductive success We need better animal model systems to understand menopause Female reproductive health trajectory and how medical intervention fits in Hormone replacement therapy is one of the best band aids we have to mitigate the negative health consequences of menopause Studies show that there is a positive benefit to doing hormone replacement therapy on cognitive function Economic impact of menopause and related healthcare costs Emerging trend of reproductive aging in biotech industry Dr. Garrison’s goals for the future and dream outcomes she envisions for the Consortium Quotes: “We started a few years ago, with a really generous gift from Nicole Shanahan and the Sergey Brin Family Foundation. We started a center at the Buck Institute to study female reproductive aging.” “When we started the center, we realized right away that if we really wanted to have an impact, and truly move the needle, that we were going to have to do something bigger. And that's where the consortium came in.” “What's different about the ovary, compared to every other organ in the human body, is that it ages precociously, meaning that it's actually the first organ by far to age in the human body, and it's aging at about two and a half times the rate of the rest of the tissues.” “I think research on women's health is underfunded in general.” “I think that as we make progress and advances in extending healthy longevity and health span, or the number of years that someone's healthy, if we don't address reproductive longevity, then I think gender inequality is going to get worse, not better.” “From the minute I went through puberty, whether I wanted to have biological children or not, every decision that I made was overshadowed by the fact that I was going to go through this reproductive decline in midlife - this biological clock, so to speak, that was ticking in the background. Decisions about overall health, my career, family planning. This is an issue of equity. Men don't have these concerns.” “Humans are really weird. We're very unusual as a species. There's almost no other species - there's very few species that go through menopause.” “Women who have later menopause tend to live longer. They also have an enhanced ability to repair their DNA.” “There's no question that the brain is a key player for reproductive success. It controls all aspects of female reproduction: Puberty, menstruation, fertility, conception, pregnancy, childbirth, childcare, and ultimately menopause.” “That's the goal is to give women more choice and control over their own bodies.” “By the time a woman actually might want to use her ovaries, she's left with approximately 2 to 3% of the number of eggs that she started with.” “The bottom line is that hormone replacement therapy is probably the best band aid we have to mitigate the negative health consequences of menopause.” “I think the basic science has to happen first. I can't emphasize that more strongly. Otherwise, like I said, everything we're doing is a band aid.” “I really want people to think about a scenario where women aren't constrained by an immutable biological clock, to think about a world where women aren't subject to the detrimental health effects of menopause. And just to consider for a moment, the implications for social, economic and personal empowerment, that that freedom of choice and freedom from health risks would give to half the population.” 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 Global Consortium for Reproductive Longevity and Equality Website buckinstitute.org/gcrle/ Garrison Lab Website garrisonlab.com

  • Aug 18, 2021 · 39 min

    The Cures Within Us (Hanadie Yousef — Juvena Therapeutics)

    Dr. Hanadie Yousef is a scientist, aging biology expert and the co-founder and CEO of Juvena Therapeutics, a Palo Alto-based biopharma startup developing protein-based therapeutics to promote tissue regeneration and increase healthspan to prevent, reverse, and cure degenerative diseases. Dr. Yousef joins host Dr. Chris Patil to discuss Juvena’s premise, their use of a machine learning platform to identify proteins that have therapeutic potential, and what most excites her about turning signaling proteins into therapeutics. She answers questions about handling potential challenges within Juvena’s approach, their strategy for bringing drugs to market, and the first aging indication that they are targeting - muscular rejuvenation. Dr. Yousef outlines Juvena’s plans for a clinical study in patients with Myotonic Dystrophy Type 1 by 2023, and shares what’s coming down the pipeline next for her team. You’ll also hear about Dr. Yousef’s transition from academic science to becoming an entrepreneur, her involvement with the On Deck initiative, which seeks to increase the number of scientists, researchers, and inventors in the healthspan and longevity field, and why it’s so worthwhile to invest in anti-aging science. The interview concludes with Dr. Yousef’s advice for potential new founders in the biotech industry. She also shares the areas of longevity science that she is most fascinated by, and offers her thoughts on how the field of aging pharma will evolve over the next five to ten years. Episode Highlights: Tissues deteriorate as we get older and our ability to heal slows down - this leads to a wide variety of age-related diseases Juvena Therapeutics sets out to find regenerative cures for those diseases During the aging process, critical regenerative protein signaling pathways that are important for instructing cells and tissues within our bodies start to change They start becoming over-expressed or under-expressed There is a change and loss of healthy crosstalk between pathways that can instruct cells This leads to a loss of tissue homeostasis By understanding what is changing within us, we can use that information to target protein signaling pathways that are important for stem cell function, immune cell function, etc. in order to rejuvenate tissues and reverse the aging process Juvena uses a machine learning platform by combining several data modalities Their premise is to develop protein-based therapies that can target critical regenerative signaling pathways in our bodies to promote better regeneration They do this by mining secretome of the most po-regenerative source of cells, which are human embryonic, or pluripotent, stem cells Aging models that they use are cells derived from people who are themselves aged or who have an age-related disease There are challenges with every therapeutic intervention targeting the biology of aging Juvena’s strategy for bringing drugs to market and the first aging indication they are targeting They are looking to promote tissue-specific rejuvenation, for example, better muscle differentiation, reduced atrophy and improved strength and function They are hoping to have FDA approval as an investigative new drug within the next year and a half - this would lead to a Phase One/Two clinical study for patients with Myotonic Dystrophy Type 1 by 2023 Dr. Yousef’s academic background and transitioning to starting her own company She has a passion for both drug discovery and taking those inventions to build companies The inspiration and motivation behind starting Juvena Therapeutics with co-founder Dr. Jeremy O'Connell, as well as the process of pitching and acquiring funding Dr. Yousef was torn between an academic career and entrepreneurship, and she ultimately decided to embrace her role as CEO and focus on building the company How investors react to Juvena Therapeutics’ aging focus and how Dr. Yousef puts their minds at ease with regards to the expense of biotech and therapeutic investment It’s worth the risk - with a looming healthcare crisis of an aging population around the corner, the company that succeeds in anti-aging science could be one of the most lucrative and successful companies in the world Dr. Yousef’s involvement in the On Deck initiative - a fellowship program that seeks to increase the number of scientists, researchers, and inventors in the healthspan and longevity field Advice she would give new entrepreneurs in this field She is fascinated by the study of human centenarians, reproductive aging, and plant aging Her predictions for the field of aging pharma in the next 5-10 years Quotes: “As we all know, tissues deteriorate as we get older, and our ability to heal slows down, which leads to a wide range of age-related diseases. So Juvena Therapeutics sets out to find regenerative cures for these disorders.” “Through years of dedicated research, we discovered that the cures had been within us all along.” “By understanding what is changing within us, we can actually use that understanding to target those protein signaling pathways that are so important in regulating stem cell function, immune cell function, tissue regeneration and repair, in order to rejuvenate tissues, and to actually reverse the aging process and to bring our bodies back internally to a more healthy state.” “Ultimately, our premise at Juvena is to develop protein-based therapies that can target these critical regenerative signaling pathways in our bodies to promote better regeneration.” “What we're doing with our machine learning enhanced platform is really building a map of regenerative protein biology with a compounding database that's enabled by an array of in-house machinery and computational tools that we establish using these data modalities, to really identify the proteins that have therapeutic potential.” “What excites us about actually turning signaling proteins into therapeutics is their ability to really interact in more of a systems biology level with multiple pathways.” “Of course, ultimately, the goal is to calibrate homeostatic levels of signaling to more youthful levels, and not try to over induce any one particular pathway. And so by really recalibrating, and being careful about dosing, we'll be able to avoid things like oncogenic transformation.” “We are, right now, really interested in bringing our muscle regeneration protein therapeutic to market for a rare neuromuscular, muscle wasting disease, known as Myotonic Dystrophy Type 1.” “Our hope is that by 2023, we will be conducting what would be a combined Phase One/Two clinical study for patients with Myotonic Dystrophy Type 1 to test if our regenerative therapeutic can, in fact, do what it's doing in all the models and all the preclinical data to date.” “What's really coming is our ultimate goal of enhancing and promoting health span, and reversing multiple age-related and chronic diseases by developing a pipeline of protein therapies that act by rejuvenating your own body endogenous stem and precursor cell function to enhance regeneration and improve and rejuvenate your life.” “I am a neurobiologist, stem cell biologist and aging biologist by training.” “What came first for me was really a passion in general and biomedical research, and in the startup environment and in building companies.” “I really fell in love with the concept that actually understanding the mechanisms driving the aging process, and specifically, the changes in signaling that occur that lead to loss of stem cell function with age, we can actually use that understanding to reverse the process, to rejuvenate stem cell function to revitalize the body, and to then really reverse aging. And so that got me so excited. And I just fell in love with that and knew that that is what I want to dedicate the rest of my life to doing.” “It was this battle for me of, I love my research, I can really envision myself leading an academic lab and a faculty position to move this forward, really focus on brain aging. But then there was this also entrepreneurial opportunity to start my company and to instead really focus more on translational work, and really building the platform that enables a pipeline of protein therapeutics.” “The other things investors fear is just the expense associated with some of these indications.” “In the next decade, the largest demographic of people will be those over the age of 60. I think it's really in investors that just realize, it's worth the risk. Because the company that succeeds will be potentially one of the most lucrative, successful, and sought-after companies in the world.” “Some advice I wish I had going into this is really looking at what the target product profile of a drug you want to develop is, and as early as possible, creating a plan to really get to that preclinical stage in that translational stage where you need significantly more investment.” “I think in five to ten years, we'll get increasing acceptance of aging as a risk factor to diseases and more of an acceptance of therapeutics that can target the aging process.” 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 Juvena Therapeutics website

  • Aug 4, 2021 · 1 hr

    The Dog Aging Project: Understanding longevity in our canine companions

    The Dog Aging Project is an innovative initiative that brings together a community of dogs, owners, veterinarians, researchers, and volunteers to carry out the most ambitious canine health study in the world. The goal of the Dog Aging Project is to understand how genes, lifestyle, and environment influence aging, and to use that information to help pets and people increase their healthspan, the period of life spent free from disease. Co-directors Dr. Daniel Promislow and Dr. Matt Kaeberlein join the show to discuss the origins of the Dog Aging Project, the overall goals for their initiative, and why dogs are a particularly good model for human aging. They talk about their funding through the National Institutes of Health, the extensive scale of the Dog Aging Project, and its “Community Scientist” component, with canine participants still living at home with their owners. Professors Promislow and Kaeberlein explain their use of molecular biology measures to predict health outcomes for dogs, their commitment to making their data available to the scientific community as a whole, and the difference between how small dogs versus large dogs age, as well as what diseases or conditions different breeds age and die from. Today’s fascinating conversation also touches on the impact of living in a rural versus urban areas on aging, how veterinarians feel about participating in the Dog Aging Project, the test of rapamycin in aging dogs (TRIAD), and the intrinsic value of being able to increase the lifespan and healthspan of our pets. Professors Promislow and Kaeberlein share what drew them to the field of aging, and review the importance of putting safety first in their work with dogs. Finally, you’ll hear their exciting predictions for what we can expect to see in aging research over the coming decades. For more information on the Dog Aging Project, visit DogAgingProject.org. Thank you for listening. Episode Highlights: Professors Daniel Promislow and Matt Kaeberlein are co-directors of the Dog Aging Project at the University of Washington in Seattle Dog Aging Project started in 2007 to investigate whether IGF-1 was associated with aging for dogs Chief Veterinary Officer is Kate E. Creevy Overall goals are to understand how genes, environment, and lifestyle shape healthy aging in dogs and the mechanisms by which they do so, and to determine whether we can intervene and improve healthy aging in dogs Dogs are a very good model for human aging due to their similar environment (water quality, air quality, home setting) Dogs age seven to 10 times more rapidly than humans do, which means we have better success carrying out longitudinal studies with them They also get the same types of diseases that we do The Dog Aging Project is funded through the National Institutes of Health, and in particular, the National Institute on Aging The scale of this project is notable, as well as the fact that the dogs are not in laboratories, but are living at home with their owners It’s a “Citizen Scientist” or “Community Science Project” effort They now have upwards of 32,000 owners and dogs participating, and are still enrolling at DogAgingProject.org They collect information about the dogs’ health, disease, activity, diet every year, over the course of their entire lives These molecular biology measures will allow them to predict what might happen in the future for dogs, and to improve diagnosis and prognosis The samples are also stored in a biobank at Cornell, with the hopes that can be useful in studying overall aging as time goes on and new technologies become available The Dog Aging Project has always been an open science project, with data being made available to the scientific community on an annual basis The rate of aging for dogs varies depending on size and breed Biological aging is faster in dogs than in humans, but the relationship is not necessarily linear What different breeds die of is very different Large dogs frequently die of Osteosarcoma, which is rare in smaller breeds and humans Certain organs may age faster than others The Dog Aging Project is able to control for different breeds using their genetic data Dogs who live in rural areas spend more time outside and engage in more physical activity - soon we will be able to tell how this affects the aging process Veterinarians are very enthusiastic about participating in this study Test of rapamycin in aging dogs (TRIAD) clinical study looks at whether or not the drug Rapamycin can slow aging and increase healthy lifespan in dogs Translating this to humans and bridging this to human trial If they find success in increasing the healthspan of people’s pets, this could really change the way the field is perceived by the general public Challenges of collecting and curating massive amounts of data Dogs who were administered rapamycin became more active afterward How Professors Promislow and Kaeberlein became interested in the field of aging Dogs are becoming increasingly important models for understanding human health Safety is always first priority for the animals Professors Promislow and Kaeberlein share their predictions for aging breakthroughs and challenges in the coming years We will see advances in biomarkers or “precision geroscience” in the next decade It’s important to have realistic expectations and use consistent language when discussing aging - to use the term “curing aging” or “defeating aging” is misleading Quotes: “Dogs experience pretty much every aspect of the human environment.” “Dogs have the advantage, from the perspective of trying to understand aging, that they age about seven to 10 times more rapidly than people do. So that means that we can actually carry out longitudinal studies to understand the most important genetic and environmental risk factors in a few years, whereas in people it would take a few decades.” “A lot of what we know about human health and disease, we’ve learned from really simple organisms, like yeast, and nematode worms, and fruit flies.” “There is no upper limit. We hope to continue this project for many generations of dogs.” “The first, most important level is just to collect the information about health, disease, activity, diet from all the dogs. That's done through surveys, and all participants will be asked to contribute survey updates every year, so we follow the dogs throughout the course of their lives.” “Our scientists will also analyze what we call the Systems Biology Components - the epigenome, the microbiome, the metabolome. We're also looking at a panel of inflammatory markers, measuring frailty. So these are the sorts of things that we will track throughout the course of the life of these dogs. The hope is that these molecular biology measures that we collect will allow us to predict what might happen in the future for dogs and to improve diagnosis, and prognosis as well.” “Our expectation is that the samples that are collected and stored in the biobank will be useful to the field for exploring those other types of molecular markers that may be particularly predictive for overall aging, or certain age-related disease processes.” “The Dog Aging Project, from its inception, has been envisioned as an open science project. And so all of the data that we collect is being made available on an annual basis to the scientific community.” “The other thing about dogs is that a decade from now, when new technologies may be available, that's about the equivalent of 70 years of biological aging in people. So it's almost as if any human longitudinal study you had biobank samples for seven decades, we can get that sort of biological age resolution in a single decade of dogs.” “A Great Dane would be considered geriatric at seven years, whereas a Chihuahua might be considered geriatric at 12 or 14, and could very well live 18 or 19 years.” “The Dog Aging Project will eventually be able to tell us what the relationship is between the epigenetic age clock and actual aging of pathophysiological processes.” “There's just a lot to learn about how quickly different breeds age and what they age and die from.” “We shipped a kit to an owner to take to their veterinarian. And these kits are filled with, as I mentioned earlier, blood samples, hair, fecal samples, urine, and then they need to be delivered via FedEx, to our diagnostic lab. This was a rural veterinarian, and there wasn't a FedEx Office or drop-off point in that community. So the veterinarian, not the owner, but the veterinarian after work, drove 40 minutes to the next town over where there was a FedEx drop-off, so that they could deliver the kit. That's the kind of enthusiasm that we see from participating veterinarians.” “TRIAD is the Test of Rapamycin in Aging Dogs. That’s the only clinical trial the Dog Aging Project is carrying out right now. And the goal of that trial is really to test whether or not the drug Rapamycin can slow aging and increase healthy lifespan in dogs.” “Everybody on the Dog Aging Project team agrees that this isn't only about what we'll learn about human aging. There's intrinsic value in being able to increase the lifespan and healthspan of our pets. There's value to the pets and there's value to the owner.” “I think if we're successful in showing that it is possible to increase healthspan in people's pets, that will really be a watershed moment in the field in the way that we are perceived by the general public.” “There are lots of wearable devices on the market for dogs. And they're very much like the devices that humans were, typically though they go on the collar of the dog. And we will be putting those devices on the Precision dogs and the TRIAD dogs to measure their activity, how it changes with age.” “There are several companies now that are trying to develop therapies to treat aging or age-related indications with companion animals, at least as the first path to the market. Me personally, I think that's fantastic. Certainly, we view the Dog Aging Project as something that hopefully other people in the field will build off of.” “We would just want to encourage all of the companies that are considering moving forward in the companion animal space to keep that in mind, and make sure that whatever you are planning to bring to the market, that you do it in the context of safety. Because the last thing that any of us want to do is harm somebody's pet.” “We're excited to try and recruit these diverse populations to the Dog Aging Project, and maybe even to use that as a model for getting all communities excited about participating in this term that we'd like to use of ‘community science.’” “I fully expect that within the next decade, we will see the first geroscience intervention approved to treat an age-related indication.” 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 Dog Aging Project Website DogAgingProject.org

  • Jul 21, 2021 · 40 min

    Giving our best friends more time: Healthy aging for dogs (Celine Halioua, CEO of Loyal)

    Loyal is a San Francisco-based startup that is seeking to treat the underlying causes of aging in dogs. Loyal has raised $11 million in seed funding so far, and is planning to start clinical trials of medications in 2022 and 2023. In this episode, BioAge VP-Media Chris Patil talks with Celine Halioua, CEO and founder of Loyal. Celine beginswith by describing the striking difference in lifespan among the dog species, with smaller breeds like the Chihuahua living twice as long as larger breeds like the Great Dane. She explains how historical inbreeding to create larger dogs actually caused them to age faster, and her plan to develop a drug that compensates for this accidental genetic disorder. Celine tells us about The Healthspan Study, which tracks aging markers in dogs, as well as what inspired her to start Loyal, and how their research complements the goals of the University of Washington Dog Aging Project. Celine breaks down the role of caloric restriction in anti-aging across species, why dogs are one of the best models for human aging as a disease, her background in neuroscience and longevity, and her passion for developing drugs for healthspan and lifespan extension. Celine also offers her perspective about encountering skepticism in the biotech industry, the unique challenges faced by young women founders, and overcoming sexist assumptions following the controversial story of Elizabeth Holmes. Finally, Celine shares what’s next for Loyal and her dream to build a consumer-focused pharmaceutical company that people love. To learn more about Loyal and their dedication to aging health for dogs, visit LoyalForDogs.com. Episode Highlights: Loyal is seeking to determine why, on average, the larger a dog breed is, the shorter their lifespan We do not see a 2X lifespan differential among varieties of other animals Loyal also looks at ways to pharmacologically improve metabolic resiliency and fitness in aged animals to give them a longer, healthier lifespan Historical inbreeding to create larger dogs led them to age faster once they were fully grown Loyal is developing a drug that plans to compensate for this accidental genetic disorder These drugs will enter clinical trials in 2022 to 2023 Loyal is also running “The Healthspan Study,” which tracks aging markers in dogs (register your dog here) Dogs are like family to their owners, and Celine noticed how heartbroken owners were about their larger dogs aging and dying so early This inspired her to start Loyal Distinction between healthspan versus simply adding years to life Thesis of Dr. Matt Kaeberlein of the University of Washington’s Dog Aging Project Most breeds have some sort of predisposition for some sort of disease LOY-001 specifically targets a cellular mechanism that is hypothesized to cause large and giant breed dogs to age faster and have shorter lifespans than their small-breed companions They are also developing a second drug that is explicitly for dogs of any size, who have already shown signs of aging Caloric restriction is one of the most fundamental agents of fighting aging - Loyal aims to replicate that effect with a drug, since most humans and dogs do not want to calorically restrict themselves Veterinary drugs need to be approved by the Veterinary FDA (Center for Veterinary Medicine or CVM) Dogs are one of the best models of human aging as a disease because they’ve largely evolved in the same environment as humans Because dogs have a shorter lifespan than we do, we can see whether longevity-based drugs have an impact on lifespan more rapidly than in an animal with an 80-year lifespan (like humans) Loyal has raised $11 million in seed funding - the largest amount for a woman solo founder Her goal is to show that pharmacological interventions to extend lifespan and healthspan are incredibly valuable and worthy of investment She has encountered skepticism in terms of both operational and societal barriers Going against the current helps her company stand apart in startup culture, which has been beneficial for recruiting an amazing team, 70% of which is female; but she also has to go above and beyond to prove her competence What’s next for Loyal and building a consumer-focused pharmaceutical company If they can succeed in developing a dog aging drug, it can help humans as well False fail risk The aging industry has a communal feel, rather than competitive, as we’re all pioneers in the field and individual successes are everyone’s success Quotes: “Fundamentally, we're developing various drug products that are targeting various concerned mechanisms by which dogs age to try to give them healthier years.” “Specifically, our first two products are looking at one of the underlying reasons as hypothesized why smallest dogs like a Chihuahua can live 18 or more years, while Great Danes on average will live seven to eight years.” “The larger a dog is, on average, the shorter that breed’s median lifespan, and that's abnormal. We don't see a 2x lifespan differential in humans, for example, or really any other species.” “It's actually a consequence of historical inbreeding of dogs, that was selecting for certain phenotypes like size, that basically looks to have created almost a genetic disorder for aging in these dogs.” “The drug that we're developing is hoping to compensate for the accidental genetic disease that we gave these dogs that causes them to become larger...and causes them to age faster after they're fully grown.” “We are basically doing a cross-sectional, observational - that means no drug, no intervention - study, looking at large and small, old and young dogs. And the idea of this study is basically to correlate various aging biomarkers of interest for our drug programs, and also just out of interest in general, to various dog sizes, breeds and conditions.” “There are different flavors of dog owners. But in general, people love their dogs. They see their dogs as family. They see their dogs as their furry children in some ways.” “Our first drug, LOY-001, is specifically indicated for large and giant breed dogs and extending their lifespan and healthspan and intervening while the dog is healthy.” “Caloric restriction is one of the most fundamental agent interventions there is. So the question is more, How do you emulate that with a drug? Because obviously, people don't really want to calorically restrict themselves or calorically restrict their dog.” “It's commonly accepted in the field that dogs are one of the best models, if not potentially the best model of human aging as a disease.” “Because dogs have a shorter lifespan than we do, if longevity-based drugs are efficacious in dogs, we could see whether they have an effect on lifespan much more rapidly in an animal with a 15-year lifespan than in an animal with an 80-year lifespan.” “Really my thing from, basically when I was 18, was how to develop better medicines for the worst diseases. And the worst diseases that I have always focused on, and been most interested in, were age-delayed diseases.” “I felt very strongly that my goal was to explicitly develop a drug for healthspan extension and lifespan extension.” “It's really fundamentally what I'm trying to do is prove a point to the broader population, to the medical community, to the development community, that yes, pharmacological interventions to extend lifespan and healthspan are incredibly valuable, and worthy of investment.” “I think when I walk into a room, there’s not necessarily an assumption of competency. And I've definitely also felt a requirement of almost like perfection.” “I'm very careful with how I word things because it's very easy, especially as a female founder, to get labeled as cocky or overconfident. So I'm much more conservative in my language than I might naturally be.” “Basically, people don't have very positive emotions or feelings towards pharmaceutical companies, which is understandable on some variables, but also disappointing because I think we want people to be excited about spending time...and working on developing new medicines. It's, in my opinion, one of the most important things to spend your life on because health is fundamental.” “I'm really interested in the opportunity of building a pharma company that people love.” “Actually if you think about it, aging encompasses probably the majority of cancers, plus nerve center disorders plus sarcopenia, arthritis, all these other diseases.” “Honestly, every company that's legitimate, that works on aging is only more helpful. It makes my life a little bit easier to prove that it's a valid thing to work on.” “We all win if we develop better medicines, and that's kind of where it's supposed to go.” “I feel like my only job is to help develop better medicines. So it means everything to me because I think it's the most important problem to work on.” 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 Loyal website LoyalForDogs.com